AHFS Class:

• Quinolones 8:12.18

Generic Name(s):

• Ciprofloxacin

• Ciprofloxacin Hydrochloride

Ciprofloxacin is a fluoroquinolone anti-infective agent.1,181,205,206,479,481,856

Ciprofloxacin is used orally or IV for the treatment of urinary tract infections (UTIs),1,178,180,205,296,297,300,319,323,326,327,329,332,336,337,338,339,340,341,342,343,345,351,352,353,354,359,375,379,380,429,435,466,479,481,504 chronic bacterial prostatitis,1,579 acute sinusitis,1,579 lower respiratory tract infections (including nosocomial pneumonia and acute exacerbations of chronic bronchitis), 1,178,205,296,297,300,315,324,326,333,335,345,346,347,355,356,357,358,359,375,380,433,435,466,479,481,491,579 GI infections,1,178,296,297,466,479,481 skin and skin structure infections,1,178,205,280,296,297,300,326,334,359,362,363,364,372,373,377,380,433,466,468,479,481,579 or bone and joint infections1,178,205,296,297,300,326,359,362,365,367,368,369,370,371,375,380,433,466,479,481,579,590,591,595 caused by susceptible gram-negative and gram-positive aerobic bacteria. Ciprofloxacin is used orally or IV for inhalational anthrax (postexposure) following suspected or confirmed exposure to aerosolized Bacillus anthracis spores1,292,579,671,672,673,678 and also is used for prophylaxis following ingestion of B. anthracis spores†662 and for the treatment of inhalational anthrax†, cutaneous anthrax†, or GI and oropharyngeal anthrax†.292,670,671,672,673,678 Ciprofloxacin is used orally or IV for the treatment or prophylaxis of plague.1,579,683,688 In addition, ciprofloxacin is used orally or IV in conjunction with metronidazole for the treatment of complicated intra-abdominal infections caused by Escherichia coli , Pseudomonas aeruginosa , Proteus mirabilis , Klebsiella pneumoniae , or Bacteroides fragilis .1,579 Because ciprofloxacin is inactive against most anaerobic bacteria, the drug is ineffective in and should not be used alone if a mixed aerobic-anaerobic bacterial infection is suspected.296,492,579 Ciprofloxacin has been used in conjunction with other anti-infectives for empiric anti-infective therapy in febrile neutropenic patients.579,786

Ciprofloxacin extended-release tablets containing both the hydrochloride and the base are used in adults for the treatment of uncomplicated UTIs (acute cystitis), complicated UTIs, or acute uncomplicated pyelonephritis.856 Safety and efficacy of ciprofloxacin extended-release tablets have been established only for infections involving the urinary tract;856 the extended-release tablets should not be used for the treatment of infections at other sites (e.g., respiratory tract, skin and skin structure, bone and joint, GI tract, intra-abdominal) that are treated with ciprofloxacin conventional tablets or oral suspension or with IV ciprofloxacin.856

Prior to initiation of ciprofloxacin therapy, appropriate specimens should be obtained for identification of the causative organism(s) and in vitro susceptibility tests.1,579 Ciprofloxacin therapy may be started pending results of susceptibility tests, but should be discontinued and other appropriate anti-infective therapy substituted if the organism is found to be resistant to ciprofloxacin.1,579 Because resistant strains of Pseudomonas aeruginosa have developed during ciprofloxacin therapy,99,122,128,137,138,139,144,180,205,280,300,346,359,361,362,363,370,371,424,435,458,466,479,579,596 in vitro susceptibility tests should be performed periodically when the drug is used in the treatment of infections caused by this organism.1,579,856 Because staphylococci may develop resistance to ciprofloxacin during prolonged therapy with the drug, in vitro susceptibility tests should be repeated during therapy,522,586 especially when infections are caused by methicillin-resistant strains of Staphylococcus aureus (MRSA; also known as oxacillin-resistant S. aureus or ORSA).522

Bone and Joint Infections

Ciprofloxacin (IV, conventional tablets, oral suspension) is used in adults for the treatment of bone and joint infections, including osteomyelitis,205,296,326,362,365,367,368,369,370,371,375,479,535,579,590,591,706 caused by susceptible E. aerogenes †,369,370,706 E. cloacae ,1,362,369,370,375,380,579,706 E. coli †,362,368,369,370,474,535 K. pneumoniae †,326,368,371,706 M. morganii †,369,370,706 P. mirabilis †,368,369,371,380,474,706 Ps. aeruginosa ,1,205,296,300,326,359,362,368,369,370,371,380,433,479,535,579,706 or S. marcescens .1,296,362,368,369,370,380,474,579

For the treatment of native vertebral osteomyelitis caused by Enterobacteriaceae or Ps. aeruginosa , the Infectious Diseases Society of America (IDSA) recommends ciprofloxacin as an alternative to the drugs of choice (cefepime, carbapenems).590 For the treatment of native vertebral osteomyelitis caused by Salmonella †, these experts recommend ciprofloxacin as the drug of choice and ceftriaxone as an alternative.590

For the treatment of prosthetic joint infections caused by Enterobacter or Ps. aeruginosa , IDSA states that cefepime or a carbapenem is preferred and ciprofloxacin is recommended as an alternative.591 These experts state that ciprofloxacin may be a preferred drug for the treatment of prosthetic joint infections caused by other Enterobacteriaceae.591

For additional information on management of bone and joint infections, current clinical practice guidelines from IDSA available at [Web] should be consulted.590,591

Clinical Experience

Clinical response has been reported in 61-86% and bacteriologic cure has been reported in 75-81% of patients with bone and joint infections (caused principally by gram-negative aerobes) who received oral ciprofloxacin.297,362,365,367,369,371,466,479,481,706 Treatment failures have been reported most frequently in patients with an underlying metal appliance at the site of infection362,367 and in patients with ciprofloxacin-resistant Ps. aeruginosa or S. aureus .363,369,371 However, there is evidence from a randomized, controlled study in patients with culture-proven staphylococcal infections associated with stable orthopedic implants that a long-term regimen (3-6 weeks) of ciprofloxacin and rifampin given after initial debridement and a 2-week IV regimen of flucloxacillin (not commercially available in the US) or vancomycin with rifampin or placebo can result in cure of the infection without removal of the implant.595

Endocarditis

Endocarditis Caused by the HACEK Group

Ciprofloxacin is used as an alternative for the treatment of endocarditis† (native or prosthetic valve or other prosthetic material) caused by fastidious gram-negative bacilli known as the HACEK group ( Haemophilus , Aggregatibacter , Cardiobacterium hominis , Eikenella corrodens , Kingella ).450 The HACEK group accounts for up to 10% of cases of community-acquired native valve endocarditis in patients who are not IV drug abusers.450 These organisms should be considered ampicillin-resistant, but may be susceptible to third or fourth generation cephalosporins or fluoroquinolones.450

The American Heart Association (AHA) and IDSA recommend ceftriaxone (or other third or fourth generation cephalosporin) for the treatment of endocarditis caused by the HACEK group,450 but state that a fluoroquinolone (ciprofloxacin, levofloxacin, moxifloxacin) may be considered in patients who cannot tolerate cephalosporins.450 Because only limited data are available regarding use of fluoroquinolones for the treatment of HACEK endocarditis, an infectious disease specialist should be consulted when treating such infections in patients who cannot tolerate cephalosporins.450

GI Infections

Infectious Diarrhea

Ciprofloxacin is used in adults for the treatment of infectious diarrhea caused by susceptible enterotoxigenic E. coli ,1,211,297 Campylobacter ,1,211,297,350,440,477 Salmonella †,440,477 Shigella 197,297,440,477,612 ( S. flexneri ,1,612 S. boydii , S. sonnei ,1 S. dysenteriae ),1,612 or Vibrio †197,477,664,756,757,758,759 (see Uses: Vibrio Infections).

Because ciprofloxacin is active in vitro against many pathogens associated with infectious diarrhea, including some strains of Campylobacter , E. coli , Shigella , Salmonella , Aeromonas , Vibrio , and Yersinia enterocolitica , some clinicians suggest that it may be a drug of choice for empiric treatment of the disease in adults.296,305,350,378,440,477,493,522,610,611 However, because of concerns about increasing emergence of fluoroquinolone-resistant strains in some enteric pathogens (e.g., Campylobacter , Salmonella , Shigella ) secondary to widespread use of the drugs, a decision to use a fluoroquinolone for empiric treatment of infectious diarrhea should be based on local susceptibility patterns.477,588,589

Campylobacter Infections

Ciprofloxacin is used for the treatment of campylobacteriosis caused by susceptible Campylobacter .292,440,477

Optimal treatment of campylobacteriosis in patients with human immunodeficiency virus (HIV) infection has not been identified.440 Some clinicians withhold anti-infective treatment in HIV-infected patients with CD4⁺ T-cell counts exceeding 200 cells/mm³ if they have only mild campylobacteriosis, but initiate treatment if symptoms persist for more than several days.440 In HIV-infected patients with mild to moderate campylobacteriosis, treatment with a fluoroquinolone (preferably ciprofloxacin or, alternatively, levofloxacin or moxifloxacin) or azithromycin is reasonable.440 Anti-infective therapy should be modified based on results of in vitro susceptibility testing.440 In the US, resistance to fluoroquinolones has been reported in 22% of C. jejuni and 35% of C. coli isolates tested.440 To limit emergence of resistance, some clinicians suggest that it may be prudent to use an aminoglycoside concomitantly in patients with bacteremic infections.440

Cyclospora Infections

Ciprofloxacin is recommended by some clinicians as an alternative to co-trimoxazole for the treatment of cyclosporiasis† caused by Cyclospora cayetanensis .134

Cystoisospora Infections

Ciprofloxacin has been used for the treatment of cystoisosporiasis† (formerly isosporiasis) caused by Cystoisospora belli (formerly Isospora belli ).440,477,533

Although co-trimoxazole is the drug of choice for the treatment of cystoisosporiasis,134,440,441,477 pyrimethamine, ciprofloxacin, and nitazoxanide are recommended as alternatives.440,441,477 Ciprofloxacin may not be as effective as co-trimoxazole,440,533 but may be useful for the treatment of cystoisosporiasis in patients who cannot tolerate co-trimoxazole.533

In HIV-infected patients, ciprofloxacin is recommended as an alternative to co-trimoxazole for treatment and chronic maintenance therapy (secondary prophylaxis) of cystoisosporiasis.440,441

Salmonella Gastroenteritis

Ciprofloxacin is used for the treatment of Salmonella gastroenteritis† (with or without bacteremia).440,477

Anti-infective therapy is not usually indicated in otherwise healthy individuals with uncomplicated (noninvasive) gastroenteritis caused by Salmonella since such therapy may prolong the duration of fecal excretion of the organism and there is no evidence that it shortens the duration of the disease; however, the US Centers for Disease Control and Prevention (CDC), American Academy of Pediatrics (AAP), IDSA, and others recommend anti-infective therapy in individuals with severe Salmonella gastroenteritis and in those who are at increased risk of invasive disease.197,292,440,477,525,681 These individuals include infants younger than 3-6 months of a individuals older than 50 years of a individuals with hemoglobinopathies, severe atherosclerosis or valvular heart disease, prostheses, uremia, chronic GI disease, or severe colitis; and individuals who are immunocompromised because of malignancy, immunosuppressive therapy, HIV infection, or other immunosuppressive illness.197,292,440,477 When an anti-infective agent is considered necessary in an individual with Salmonella gastroenteritis, CDC, AAP, IDSA, and others recommend ceftriaxone, cefotaxime, ciprofloxacin, ampicillin, amoxicillin, co-trimoxazole, chloramphenicol, or azithromycin depending on the susceptibility of the causative organism.197,292,477,525,681 If invasive disease is suspected or confirmed, IDSA recommends ceftriaxone over ciprofloxacin because of the increasing incidence of resistance to fluoroquinolones.477

Because HIV-infected individuals with Salmonella gastroenteritis are at high risk for bacteremia, CDC, National Institutes of Health (NIH), and the HIV Medicine Association of IDSA recommend that such patients receive anti-infective treatment.440 These experts state that the initial drug of choice for the treatment of salmonella gastroenteritis (with or without bacteremia) in HIV-infected adults is ciprofloxacin;440 other fluoroquinolones (levofloxacin, moxifloxacin) also are likely to be effective in these patients, but clinical data are limited.440 Depending on results of in vitro susceptibility testing of the causative organism, alternatives for treatment of Salmonella gastroenteritis in HIV-infected adults are co-trimoxazole or third generation cephalosporins (ceftriaxone, cefotaxime).440

The role of long-term treatment (secondary prophylaxis) against Salmonella in HIV-infected individuals is not well established, and possible benefits of such prophylaxis should be weighed against the risks of long-term anti-infective exposure.440 CDC, NIH, and IDSA state that secondary prophylaxis should be considered in those with recurrent bacteremia and may also be considered in those with recurrent gastroenteritis (with or without bacteremia) and in those with CD4⁺ T-cell counts less than 200 cells/mm³ and severe diarrhea.440 These experts state that secondary prophylaxis should be discontinued if the Salmonella infection resolves and there has been a sustained response to antiretroviral therapy with CD4⁺ T-cell counts greater than 200 cells/mm³.440

Shigella Infections

Ciprofloxacin is used for the treatment of shigellosis caused by susceptible Shigella .440,477

Infections caused by S. sonnei usually are self-limited (48-72 hours), and mild cases may not require treatment with anti-infectives.292 However, because there is some evidence that anti-infectives may shorten the duration of diarrhea and the period of fecal excretion of Shigella , anti-infective treatment generally is recommended in addition to fluid and electrolyte replacement in patients with severe shigellosis, dysentery, or underlying immunosuppression.292,440 An empiric treatment regimen can be used initially,292 but in vitro susceptibility testing of clinical isolates is indicated since resistance is common.292,477 A fluoroquinolone (preferably ciprofloxacin or, alternatively, levofloxacin or moxifloxacin) generally has been recommended for the treatment of shigellosis.440 However, fluoroquinolone-resistant Shigella have been reported in the US, especially in international travelers, the homeless, and men who have sex with men (MSM).440 Depending on in vitro susceptibility, other drugs recommended for the treatment of shigellosis include co-trimoxazole, ceftriaxone, azithromycin (not recommended in those with bacteremia), or ampicillin.197,292,440,477

Yersinia Infections

Although GI infections caused by Y. enterocolitica or Y. pseudotuberculosis usually are self-limited and anti-infective therapy is unnecessary, some experts recommend use of anti-infectives in immunocompromised individuals or for the treatment of severe infections or when septicemia or other invasive disease occurs.292,681 GI infections caused by Y. enterocolitica or Y. pseudotuberculosis can occur as the result of ingesting undercooked pork, unpasteurized milk, or contaminated water; infection has occurred in infants whose caregivers handled contaminated chitterlings (raw pork intestines) or tofu.681 When treatment is considered necessary, some clinicians recommend co-trimoxazole as the drug of choice and cefotaxime and ciprofloxacin as alternatives.477

Travelers' Diarrhea

Ciprofloxacin is used for the short-term treatment of travelers' diarrhea† and has been used for the prevention of travelers' diarrhea† in adults traveling for relatively short periods of time to high-risk areas.305,378,399,525,650,651,677,679

The most common cause of travelers' diarrhea worldwide is noninvasive enterotoxigenic strains of E. coli (ETEC), but travelers' diarrhea also can be caused by various other bacteria including enteroaggregative and other E. coli pathotypes, C. jejuni , Shigella , Salmonella , Aeromonas , Plesiomonas , Y. enterocolitica , or V. parahaemolyticus or non-O-group 1 V. cholerae , and, possibly, Acrobacter , Larobacter , and enterotoxigenic Bacteroides fragilis .305,525,610,611,612,650,651,677 In some cases, travelers' diarrhea is caused by parasitic enteric pathogens (e.g., Giardia , Cryptosporidium , Entamoeba histolytica ) or viral enteric pathogens (e.g., rotavirus, norovirus, astrovirus).305,525

Countries where travelers are at low risk of travelers' diarrhea include the US, Canada, Australia, New Zealand, Japan, and countries in Northern and Western Europe.525 Travelers are at intermediate risk for travelers' diarrhea in Eastern Europe, South Africa, and some of the Caribbean islands, but are at high risk in most of Asia, the Middle East, Africa, Mexico, and Central and South America.525

Treatment

Travelers' diarrhea caused by bacteria may be self-limited and often resolves within 3-7 days without anti-infective treatment.305,525,650,651,677,679 CDC states that anti-infective treatment is not recommended in patients with mild travelers' diarrhea.525 However, CDC and other clinicians state that empiric short-term anti-infective treatment (single dose or up to 3 days) may be used if diarrhea is moderate or severe, associated with high fever or bloody stools, or extremely disruptive to travel plans.305,525,650,651,677,679 Since bacteria are the most common cause of travelers' diarrhea (80-90% of cases), an anti-infective directed against enteric bacterial pathogens usually is used.525 Fluoroquinolones (e.g., ciprofloxacin, levofloxacin) generally have been considered the anti-infectives of choice for empiric treatment, including self-treatment, of travelers' diarrhea in adults;305,525,611,612,650,677,679 alternatives include azithromycin and rifaximin.305,525

If the causative pathogen is susceptible to the anti-infective chosen for empiric treatment, the duration of illness may be reduced by about a day.525 However, the increasing incidence of enteric bacteria resistant to fluoroquinolones and other anti-infectives may limit the usefulness of empiric treatment in individuals traveling in certain geographic areas, and the possible adverse effects of the anti-infective and adverse consequences of such treatment (e.g., development of resistance, effect on normal gut microflora) should be considered.525

Prophylaxis

CDC and most experts do not recommend anti-infective prophylaxis to prevent travelers' diarrhea in most individuals traveling to areas of risk.305,525,611,677,679 However, anti-infective prophylaxis may be considered for short-term travelers who are high-risk individuals (e.g., HIV-infected or other immunocompromised individuals, travelers with poorly controlled diabetes mellitus or chronic renal failure) and those who are taking critical trips during which even a short period of diarrhea could adversely affect the purpose of the trip.305,525

The risks of use of anti-infective prophylaxis in travelers should be weighed against the use of prompt, early self-treatment with an empiric anti-infective if moderate to severe travelers' diarrhea occurs.525 If anti-infective prophylaxis is used, fluoroquinolones (e.g., ciprofloxacin, levofloxacin) usually have been recommended;305,525 alternatives include azithromycin and rifaximin.305,525 The increasing incidence of fluoroquinolone resistance in pathogens that cause travelers' diarrhea (e.g., Campylobacter , Salmonella , Shigella ) should be considered and may limit their potential usefulness.305,525

Intra-abdominal Infections

Ciprofloxacin (IV, conventional tablets, oral suspension) is used in conjunction with metronidazole for the treatment of complicated intra-abdominal infections caused by E. coli , Ps. aeruginosa , P. mirabilis , K. pneumoniae , or Bacteroides fragilis .1,579

For additional information on management of intra-abdominal infections, the current clinical practice guidelines from IDSA available at [Web] should be consulted.708

Meningitis and Other CNS Infections

IV ciprofloxacin has been used for the treatment of meningitis† caused by gram-negative bacteria.366,418,707,762,763,764,765,818

Ciprofloxacin has been effective when used alone or in conjunction with other drugs (e.g., antipseudomonal aminoglycosides) to treat meningitis and other CNS infections† caused by susceptible Ps. aeruginosa .366,818 Some clinicians suggest that a regimen of ciprofloxacin (with or without an aminoglycoside) can be used as an alternative for the treatment of Ps. aeruginosa meningitis when cefepime or ceftazidime cannot be used.418

Ciprofloxacin has been recommended as a preferred alternative for the treatment of healthcare-associated ventriculitis and meningitis† caused by Enterobacteriaceae or Ps. aeruginosa when the drugs of choice cannot be used.416

Ciprofloxacin also has been used for the treatment of meningitis and other CNS infections† caused by susceptible Salmonella .762,763,764,765 Some clinicians suggest that ciprofloxacin alone or in conjunction with a third generation cephalosporin (cefotaxime, ceftriaxone) may be a drug of choice for the treatment of Salmonella meningitis in pediatric patients†, especially when the causative organism is resistant to other drugs.762,763

Because only low concentrations of ciprofloxacin are distributed into CSF1,436 and because efficacy and safety of the drug for the treatment of CNS infections have not been established,211,481 fluoroquinolones (including ciprofloxacin) should be considered for the treatment of meningitis only when the infection is caused by multidrug-resistant gram-negative bacilli or when the usually recommended anti-infectives cannot be used or have been ineffective.418,818

For additional information on management of meningitis and other CNS infections, the current clinical practice guidelines from IDSA available at [Web] should be consulted.416,418

Ophthalmic and Otic Infections

Oral or IV ciprofloxacin is used in the treatment of malignant otitis externa† caused by Ps. aeruginosa .781,782,783,784,816 Bacterial otitis externa usually is caused by Ps. aeruginosa or S. aureus .782,783,784,785,816 Although acute bacterial otitis externa localized in the external auditory canal may be effectively treated using topical anti-infectives (e.g., ciprofloxacin otic suspension, ofloxacin otic solution), malignant otitis externa is an invasive, potentially life-threatening infection, especially in immunocompromised patients such as those with diabetes mellitus or HIV infection, and requires prompt diagnosis and long-term treatment with systemic anti-infectives.781,782,783,784 The treatment of choice for malignant otitis externa usually is ciprofloxacin or an antipseudomonal β-lactam (e.g., ceftazidime, imipenem).781,782,783,784 Because ciprofloxacin-resistant Ps. aeruginosa have been reported with increasing frequency in patients with malignant otitis externa and has been associated with treatment failure,783,784,785 clinical isolates should be tested for in vitro susceptibility, especially if there is an inadequate response to treatment.785

Respiratory Tract Infections

Ciprofloxacin (IV, conventional tablets, oral suspension) is used in adults for the treatment of respiratory tract infections, including acute sinusitis,1,579 acute exacerbations of chronic bronchitis), 1,178,205,296,297,300,324,326,333,335,345,346,347,355,356,357,358,359,375,380,433,435,466,479,481,491,579 bronchiectasis,333,479,596 lung abscess,474,596 and pneumonia,205,326,333,346,347,356,357,435,466,479,491,596 caused by susceptible E. aerogenes †,474 E. cloacae ,1,333,474,579 E. coli ,1,333,345,355,491,579 Haemophilus influenzae ,1,297,301,324,333,346,351,380,427,491,596,579 H. parainfluenzae ,1,297,579 K. oxytoca †,474 K. pneumoniae ,1,297,301,333,345,351,380,474,579 P. mirabilis ,1,380,579 Ps. aeruginosa ,1,300,301,324,333,346,359,380,427,433,579 S. aureus †,333,345,380,491 or S. pneumoniae (penicillin-susceptible strains).1,324,326,333,345,346,355,356,357,425,427,491 The drug also is used for the treatment of respiratory tract infections caused by susceptible Moraxella catarrhalis .1,324,333,346,356,395,427,491,579

IV ciprofloxacin is used for the treatment of nosocomial pneumonia caused by susceptible H. influenzae or K. pneumoniae and for the treatment of acute bacterial sinusitis caused by H. influenzae , S. pneumoniae (penicillin-susceptible strains), or M. catarrhalis .579

Ciprofloxacin should be used for the treatment of acute bacterial sinusitis or acute bacterial exacerbations of chronic bronchitis only when there are no other treatment options. 1,140,145,579Because systemic fluoroquinolones, including ciprofloxacin, have been associated with disabling and potentially irreversible serious adverse reactions (e.g., tendinitis and tendon rupture, peripheral neuropathy, CNS effects) that can occur together in the same patient 1,140,145,579,856and because acute bacterial sinusitis and acute bacterial exacerbations of chronic bronchitis may be self-limiting in some patients, 1,579the risks of serious adverse reactions outweigh the benefits of fluoroquinolones for patients with these infections. 140,145

In controlled studies in adults with respiratory tract infections, oral ciprofloxacin therapy was as effective as therapy with oral amoxicillin,356 oral ampicillin,335 IV cefamandole,491 oral doxycycline,347 or IV imipenem and cilastatin sodium.361 Oral ciprofloxacin therapy generally resulted in a bacteriologic cure rate of 80-98% in adults with respiratory tract infections.297,355,356,466,479,481 Oral ciprofloxacin has been most effective in the treatment of respiratory tract infections caused by H. influenzae or M. catarrhalis ;178,296,298,479,596 treatment failures have occurred when the drug was used in the treatment of infections caused by S. pneumoniae 178,324,358,425,427,479 or Ps. aeruginosa .178,324,346,358,427,479,596 Treatment failure of S. pneumoniae respiratory tract infections may be related to the moderate in vitro susceptibility of this organism to ciprofloxacin.324,355,427 Although ciprofloxacin may be effective, it is not a drug of first choice for the treatment of presumed or confirmed pneumonia secondary to S. pneumoniae ,1,579 and some clinicians suggest that ciprofloxacin generally not be used for empiric treatment of community-acquired pneumonia when S. pneumoniae is likely or suspected as the causative organism.5,178,296,356,427,479,522,621 A β-lactam antibiotic generally is preferred for empiric treatment of these infections and also is preferred in other respiratory tract infections known or suspected to be caused by pneumococci or streptococci.197,211,294,296,522 Ciprofloxacin probably should not be used in the treatment of aspiration pneumonia because these infections generally involve anaerobic bacteria.211,296,621

Acute Exacerbations of Chronic Bronchitis

Clinical improvement has occurred when oral ciprofloxacin was used alone for the treatment of acute exacerbations of bronchopulmonary Ps. aeruginosa infections in adults with cystic fibrosis.99,103,178,205,289,296,299,301,307,308,309,310,311,359,424,479 As with other anti-infectives, Ps. aeruginosa may be cleared temporarily from the sputum, but a bacteriologic cure rarely is obtained and should not be expected in these patients.205,306,307,309,310,312,424,425,466,479

Resistant strains of Ps. aeruginosa have developed during ciprofloxacin therapy;99,137,138,139,178,180,296,299,424,435,479,481,596 in one study, up to 45% of cystic fibrosis patients developed resistance after 2 weeks of therapy with the drug.180,308 Clinical improvement occurred in some patients despite the emergence of resistant Ps. aeruginosa ;178,296,308,309,312,479 in some cases, the resistant organisms reverted to being susceptible after ciprofloxacin therapy was discontinued.479 Further study is necessary to determine if emergence of resistance will limit use of ciprofloxacin in the treatment of Ps. aeruginosa infections in cystic fibrosis patients.99,137,211,289,296,299,307,308,309,310,311,312,324,358,359,424,481 Some clinicians caution against long-term use of ciprofloxacin in these patients and recommend that the drug be used in short courses (e.g., 14 days), alternated with other anti-infectives active against Ps. aeruginosa (e.g., aztreonam, extended-spectrum penicillins, third generation cephalosporins)211,294,296,479 and/or used in conjunction with one of these agents.211,296,479,522 If ciprofloxacin is used, it is important that susceptibility of isolates be tested carefully in subsequent exacerbations.481

Nosocomial Pneumonia

IV ciprofloxacin is used for the treatment of nosocomial pneumonia,315,579 including hospital-acquired pneumonia (HAP) not associated with mechanical ventilation and ventilator-associated pneumonia (VAP).315

Local susceptibility data should be used when selecting initial empiric regimens for the treatment of nosocomial pneumonia, including HAP and VAP.315

For initial empiric treatment of HAP in adults, IDSA states that ciprofloxacin should be used in conjunction with an anti-infective active against MRSA (vancomycin, linezolid) if factors that increase the likelihood of MRSA are present or if the patient is at high risk of mortality or has received IV anti-infectives during the prior 90 days.315

For initial empiric treatment in adults with clinically suspected VAP and factors that increase the risk of MRSA or multidrug-resistant gram-negative bacteria, IDSA states that ciprofloxacin should be used in conjunction with an anti-infective active against MRSA (vancomycin, linezolid) plus an antipseudomonal β-lactam (fixed combination of piperacillin and tazobactam [piperacillin/tazobactam], cefepime, ceftazidime, imipenem, meropenem, aztreonam).315

For additional information on management of nosocomial pneumonia, the current clinical practice guidelines from IDSA available at [Web] should be consulted.315

Skin and Skin Structure Infections

Ciprofloxacin (IV, conventional tablets, oral suspension) is used in adults for the treatment of skin and skin structure infections caused by susceptible C. freundii ,1,372,579 E. cloacae ,1,362,474,579 E. coli ,1,326,372,375,377,380,579 K. oxytoca †,474 K. pneumoniae ,1,362,372,377,380,474,579 M. morganii ,1,579 P. mirabilis ,1,362,364,372,377,380,579 P. vulgaris ,1,372,579 P. stuartii ,1,377,474,579 Ps. aeruginosa ,1,280,300,326,359,362,372,375,377,382,433,579 Serratia marcescens †,362,380 S. aureus (methicillin-susceptible strains),1,326,362,364,372,373,375,377,382,466,579 S. epidermidis (methicillin-susceptible strains),1,364,372,375,377,382,474,579 or S. pyogenes (group A β-hemolytic streptococci).1,362,373,579 The drug has been effective in the treatment of cellulitis,297,326,334,372,373,381,382,466,474 abscesses,205,297,334,364,372,373 folliculitis,364 furunculosis,205,364 pyoderma,205 postoperative wound infections,326,334,372,373,375,382 and infected ulcers,297,326,334,372,377,382,466 burns,297,373,474 or wounds.205,297,364,466

Ciprofloxacin may be particularly useful as an oral agent for the treatment of skin and skin structure infections caused by susceptible gram-negative bacteria.334,363,372,479,481 Because staphylococci, streptococci, and anaerobes are only moderately susceptible to ciprofloxacin, ciprofloxacin generally should not be used alone and other anti-infectives remain the drugs of choice for skin and skin structure infections caused by these bacteria.197,211,468,481,492,522 Treatment failures have been reported in patients with skin or skin structure infections caused by S. aureus and the increasing emergence of strains of staphylococci resistant to quinolones limits the usefulness of the drugs in the treatment of these infections.122,144,362,548,549 Some clinicians suggest that ciprofloxacin therapy may be particularly useful for the treatment of hospital-acquired decubitus ulcers when anti-infective therapy is indicated.211,296,334,479,522

In several controlled studies, oral ciprofloxacin was at least as effective as IV cefotaxime in the treatment of skin and skin structure infections caused by susceptible organisms.334,372,373 Oral ciprofloxacin resulted in a bacteriologic cure rate of 80-92% in patients with skin and skin structure infections.297,466,468

Although ciprofloxacin is active in vitro against most common aerobic pathogens isolated from animal and human bite wounds, including Flavobacterium † and Eikenella corrodens †, the in vitro activity of the drug against streptococci, which frequently are isolated from such wounds (usually in mixed cultures), and against anaerobes generally is poor.492 Therefore, use of the drug as monotherapy in these infections is not recommended pending accumulation of additional efficacy data.492,522

For additional information on management of skin and skin structure infections, the current clinical practice guidelines from IDSA available at [Web] should be consulted.543,544

Urinary Tract Infections and Prostatitis

Uncomplicated and Complicated Urinary Tract Infections

Ciprofloxacin extended-release tablets containing both the hydrochloride and the base are used only for the treatment of uncomplicated UTIs (acute cystitis) caused by susceptible E. faecalis , E. coli , P. mirabilis , or S. saprophyticus , complicated UTIs caused by susceptible E. coli , K. pneumoniae , P. mirabilis , Ps. aeruginosa , or E. faecalis , or acute uncomplicated pyelonephritis caused by E. coli in adults.856

Ciprofloxacin (IV, conventional tablets, oral suspension) is used in adults for the treatment of complicated or uncomplicated UTIs caused by susceptible Citrobacter koseri (formerly C. diversus ),1,579 C. freundii ,1,339,340,341,375,380,474,579 Enterobacter cloacae ,1,327,332,380,474,579 E. aerogenes †,474 E. coli ,1,297,326,327,329,332,336,338,339,340,351,352,353,375,380,504,579 Klebsiella oxytoca †,474 K. pneumoniae ,1,297,327,329,336,338,340,341,353,375,504,579 Morganella morganii ,1,340,341,474,579 Proteus mirabilis ,1,327,332,336,340,352,353,504,579 Providencia rettgeri ,1,579 P. stuartii †,326,474 Pseudomonas aeruginosa ,1,197,297,300,326,327,336,338,339,340,341,351,353,359,375,379,380,579 or Serratia marcescens .1,340,341,353,380,504,579 The drug also is used in adults for the treatment of UTIs caused by susceptible gram-positive bacteria, including Staphylococcus aureus †,327,353,380 S. epidermidis (methicillin-susceptible strains),1,327,336,340,579 S. saprophyticus ,1,332,579 or E. faecalis .1,197,327,336,339,340,341,353,579

Ciprofloxacin (IV, conventional tablets, oral suspension) is used in pediatric patients 1 year of age or older for the treatment of complicated UTIs and pyelonephritis caused by susceptible E. coli .1,579 Although effective in UTIs,1,579 ciprofloxacin is not a drug of first choice for these infections in pediatric patients because of the risk of adverse effects (e.g., musculoskeletal effects) reported in this patient population.1,292,579

Ciprofloxacin should be used for the treatment of uncomplicated UTIs only when there are no other treatment options. 1,140,145,856Because systemic fluoroquinolones, including ciprofloxacin, have been associated with disabling and potentially irreversible serious adverse reactions (e.g., tendinitis and tendon rupture, peripheral neuropathy, CNS effects) that can occur together in the same patient 1,140,145,856and because uncomplicated UTIs may be self-limiting in some patients, 1,856the risk of serious adverse reactions outweigh the benefits of fluoroquinolones for patients with uncomplicated UTIs. 140,145

Some clinicians suggest that ciprofloxacin be reserved for the treatment of complicated UTIs, especially those caused by multidrug-resistant bacteria.299,336,379,425,481,551 IDSA and other experts state that fluoroquinolones (ciprofloxacin, levofloxacin, ofloxacin) generally should be considered alternatives for the treatment of uncomplicated UTIs (e.g., acute cystitis) and should be used in these infections only when other urinary anti-infectives are likely to be ineffective or are contraindicated or not tolerated.143,299,522,551,585

Clinical Experience

In controlled studies in men and women, oral ciprofloxacin therapy was as effective as therapy with oral co-trimoxazole in the treatment of uncomplicated UTIs;296,353,354 bacteriologic cure rates and rate of relapse and/or reinfection were similar with both drugs.479 Oral ciprofloxacin therapy generally results in a bacteriologic cure in 80-100% of patients with UTIs.178,297,319,323,329,336,337,340,342,353,354,466,479 Oral ciprofloxacin is more effective in the treatment of uncomplicated UTIs than in complicated infections,323,479 and most treatment failures occur in patients with underlying structural abnormalities of the urinary tract (e.g., obstructions, neurogenic bladder) or indwelling catheters.296,479

Oral ciprofloxacin has been as effective as oral co-trimoxazole in the treatment of complicated UTIs,296,466,479 and has been effective in the treatment of UTIs caused by organisms resistant to co-trimoxazole.338,353,474 Prolonged, high-dose oral ciprofloxacin therapy (500-750 mg every 12 hours) has been effective in the treatment of complicated UTIs caused by multidrug-resistant Ps. aeruginosa .178,211,339,338,341,425

A 3-day regimen of oral ciprofloxacin (conventional tablets) generally is effective for the treatment of acute, uncomplicated cystitis caused by susceptible E. coli , E. faecalis , P. mirabilis , or S. saprophyticus (bacteriologic eradication rate 81-100%).1 Oral ciprofloxacin (conventional tablets) has been effective in women for the treatment of uncomplicated UTIs when given as a single 100- or 250-mg dose†.332 However, efficacy of a single dose of the drug for the treatment of these infections has not been clearly established; single-dose therapy was less effective in the treatment of UTIs caused by gram-positive bacteria than in those caused by gram-negative bacteria.332

Safety and efficacy of ciprofloxacin extended-release tablets for the treatment of uncomplicated UTIs (acute cystitis) have been evaluated in a randomized, double-blind, controlled study in adults.856 In this study, adults were randomized to receive ciprofloxacin extended-release tablets (500 mg once daily for 3 days) or conventional ciprofloxacin tablets (250 mg twice daily for 3 days).856 The bacteriologic eradication rate with no new infections or superinfections at the time of test of cure (post-therapy day 4-11) was 94.5% in those who received the extended-release tablets and 93.7% in those who received conventional tablets.856 Safety and efficacy of ciprofloxacin extended-release tablets for the treatment of complicated UTIs or acute uncomplicated pyelonephritis also have been evaluated in a randomized, double-blind study.856 In this study, adults were randomized to receive ciprofloxacin extended-release tablets (1 g once daily for 7-14 days) or conventional ciprofloxacin tablets (500 mg twice daily for 7-14 days).856 In the per-protocol population, the bacteriologic eradication rate with no new infections or superinfections at the time of test of cure (post-therapy day 5-11) in those who received the extended-release tablets was 89.2 or 87.5% in those with complicated UTIs or uncomplicated pyelonephritis, respectively; in those who received the conventional tablets, the rates were 81.4 or 98.1%, respectively.856

In clinical studies evaluating IV or oral ciprofloxacin for the treatment of complicated UTIs and pyelonephritis in pediatric patients 1-17 years of age, the bacteriologic eradication rate was about 84% in those receiving ciprofloxacin compared with about 78% in those receiving a cephalosporin.1,579

Prostatitis

Ciprofloxacin (IV, conventional tablets, oral suspension) is used in men for the treatment of recurrent UTIs and chronic prostatitis caused by E. coli or P. mirabilis .1,180,294,296,339,343,379,466,579 Ciprofloxacin has been most effective in the treatment of prostatitis caused by E. coli or other Enterobacteriaceae, and has been effective in infections that did not respond to co-trimoxazole therapy.339,343,466 Prostatitis caused by Ps. aeruginosa , enterococci, or staphylococci may respond poorly to the drug.211,296,343,479 Because high concentrations of ciprofloxacin are attained in prostatic tissues, the drug may become a drug of choice for the treatment of recurrent UTIs associated with prostatitis;180,338,339,343,466,479 however, further study is needed to compare efficacy of ciprofloxacin with that of other anti-infectives used in the treatment of these infections.180,294,296

Anthrax

Ciprofloxacin (conventional tablets, oral suspension) is used for inhalational anthrax (postexposure) to reduce the incidence or progression of disease following suspected or confirmed exposure to aerosolized Bacillus anthracis spores in adults and pediatric patients.1,579,678 Ciprofloxacin (IV, conventional tablets, oral suspension) is used for the treatment of clinically apparent inhalational anthrax†,668,670,671,672,673,683,686 other systemic anthrax infections (GI, meningitis, or cutaneous with systemic involvement, head or neck lesions, or extensive edema),671,672,673,681 or uncomplicated cutaneous anthrax†,668,671,672,673,686 and for prophylaxis following ingestion of B. anthracis spores in contaminated meat†.662

Naturally occurring or endemic cutaneous anthrax in humans can occur after exposure to B. anthracis spores following contact with contaminated soil or infected animals (e.g., goats, sheep, cattle, swine, horses, buffalo, deer) or animal by-products (e.g., hides, hair, wool, carcasses, bone meal); GI or oropharyngeal anthrax can occur after ingestion of anthrax spores (e.g., in contaminated, raw or undercooked meat); and inhalational anthrax can occur after exposure to B. anthracis spores aerosolized during industrial processing of contaminated animal by-products or in the laboratory.292,579,662,663,670,678,680,681,683 Inhalational or cutaneous anthrax also may occur as the result of exposure to aerosolized B. anthracis spores in the context of biologic warfare or bioterrorism, including exposure to mail or other fomites contaminated with anthrax spores.292,663,668,671,672,673,678,682,683

Following exposure to aerosolized B. anthracis spores, inhalational anthrax may develop if spore-containing particles are deposited into alveolar spaces.663,683,668,680 Macrophages ingest the spores663,668 and some undergo lysis and destruction.668 Surviving spores are transported via the lymph system to mediastinal lymph nodes where germination and vegetative growth may occur after a period of spore dormancy.663,668 Monkey studies have demonstrated that viable spores can persist in a dormant state in alveolar surface epithelium and mediastinal lymph nodes for up to 100 days after inhalation.663,683,668,680 The process responsible for the delayed transformation of spores to vegetative cells remains to be elucidated.668 Once germination occurs, disease follows rapidly.668 Replicating B. anthracis release toxins that can result in hemorrhage, edema, and necrosis.663,668 Cutaneous anthrax may occur if B. anthracis spores are introduced into a cut or abrasion (e.g., on the face, neck, or arms).663,668,670 Septicemia and meningeal anthrax result from hematogenous spread of the organism from the primary cutaneous, GI, or inhalation site.292,663,683 Although discharge from cutaneous lesions might be infectious, the risk for person-to-person transmission of cutaneous anthrax is low.663 Person-to-person transmission and secondary cases of anthrax (e.g., in medical personnel) have not been documented to date.292,663,668,678

For the treatment of clinically apparent inhalational, GI, or meningeal anthrax and anthrax septicemia that occurs as the result of natural or endemic exposures to B. anthracis , parenteral penicillin historically has been considered the drug of choice and IV ciprofloxacin or IV doxycycline have been suggested as alternatives.197,292,670,680,682,683,686 However, it has been postulated that exposures to B. anthracis that occur in the context of biologic warfare or bioterrorism may involve bioengineered resistant strains and this concern should be considered when selecting initial anti-infective regimens for the treatment of anthrax that occurs as the result of bioterrorism-related exposures or when selecting anti-infectives for postexposure prophylaxis following such exposures.668,686 B. anthracis with natural resistance to penicillins have been reported and there are published reports of B. anthracis strains that have been engineered to have tetracycline and penicillin resistance as well as resistance to other anti-infectives (e.g., macrolides, chloramphenicol, rifampin).668,699 In addition, reduced susceptibility to ofloxacin (4-fold increase in MICs from baseline) has been produced in vitro following sequential subculture of the Sterne strain of B. anthracis in subinhibitory concentrations of the fluoroquinolone.713

Recommendations for the treatment and prophylaxis of anthrax have evolved based on experience gained in treating US patients who developed inhalational or cutaneous anthrax during September and October 2001 following bioterrorism-related exposures to B. anthracis spores as well results of animal studies and concerns related to treating large numbers of individuals in a mass casualty setting.683,668,671,672,673,682,683,686,695,703,710

For additional information on management of anthrax, including postexposure prophylaxis of anthrax, the current guidelines from CDC and AAP should be consulted.671,672,673

Postexposure Prophylaxis of Anthrax

Ciprofloxacin is used for inhalational anthrax (postexposure) to reduce the incidence or progression of disease following suspected or confirmed exposure to aerosolized B. anthracis spores in adults and pediatric patients.1,579,668,671,672,673,682,683 CDC, AAP, US Working Group on Civilian Biodefense, and US Army Medical Research Institute of Infectious Diseases (USAMRIID) recommend oral ciprofloxacin and oral doxycycline as the initial drugs of choice for postexposure prophylaxis following exposure to aerosolized anthrax spores, including exposures that occur in the context of biologic warfare or bioterrorism.668,671,672,673,683 Other oral fluoroquinolones (levofloxacin, moxifloxacin, ofloxacin) are alternatives for postexposure prophylaxis when ciprofloxacin or doxycycline cannot be used.668,671,672,673

Following natural, occupational, or bioterrorism-related exposures to aerosolized B. anthracis spores, anti-infective postexposure prophylaxis should be initiated immediately or as soon as possible.668,671,672,673,683 Postexposure vaccination with anthrax vaccine (if available) may be indicated in conjunction with anti-infective postexposure prophylaxis in some individuals.663,668,683 Vaccine-induced immunity provides protection if there are issues related to the anti-infective postexposure prophylaxis regimen (e.g., poor adherence, early discontinuance because of adverse effects) or if there are residual spores that germinate after the anti-infective regimen has been completed.663,683

Because of the possible persistence of anthrax spores in lung tissue following an aerosol exposure, prolonged postexposure prophylaxis usually is required.668,671,672,673,682,683 Based on a competing-risks model, some clinicians suggest that the optimum duration of prophylaxis depends on the dose of inhaled spores.767 These clinicians state that a duration of 60 days may be adequate for a low-dose exposure, but that a duration exceeding 4 months may be necessary to reduce the risk following a high-dose exposure.767 CDC, AAP, US Working Group on Civilian Biodefense, and USAMRIID recommend that postexposure prophylaxis following a confirmed exposure (including in laboratory workers with confirmed exposures to B. anthracis cultures) should be continued for 60 days.668,671,672,673,682,683

Postexposure anti-infective prophylaxis may be indicated in laboratory workers and other individuals who work in occupations that result in exposure to B. anthracis and may also be considered following a naturally occurring GI exposure to B. anthracis (e.g., ingestion of meat from an undercooked carcass of an anthrax-infected animal).663

Pediatric Patients

Ciprofloxacin (IV, conventional tablets, oral suspension) is labeled by FDA for inhalational anthrax (postexposure) in neonates, infants, and children 17 years of age or younger.1,579 Although ciprofloxacin generally is not recommended for use in infants and children, the benefits of ciprofloxacin in reducing the incidence or progression of disease following exposure to aerosolized B. anthracis spores outweigh the risks in pediatric patients.1,579,668,671,683,703

For initial anti-infective prophylaxis following a suspected exposure to B. anthracis spores that occurs in the context of biologic warfare or bioterrorism, AAP states that oral ciprofloxacin is the drug of choice in neonates 4 weeks of age or younger and oral ciprofloxacin or oral doxycycline are the drugs of choice in pediatric patients 1 month of age or older (prior to susceptibility testing and when penicillin-resistant strains have been identified).671 If exposure has been confirmed and in vitro tests indicate that the organism is susceptible to penicillin, the postexposure prophylaxis regimen in pediatric patients may be switched to oral amoxicillin or, alternatively, oral penicillin V.671

Pregnant and Breast-feeding Women

If anti-infective postexposure prophylaxis following a suspected exposure to aerosolized B. anthracis spores in the context of biologic warfare or bioterrorism is indicated in pregnant women, postpartum women, and women who are breast-feeding, CDC states that oral ciprofloxacin is preferred over oral doxycycline, unless oral ciprofloxacin is unavailable.672 If in vitro studies indicate that the organism is susceptible to penicillin, consideration can be given to changing the postexposure regimen to oral amoxicillin or oral penicillin V.672

Individuals at Contaminated Sites

For the bioterrorism-related exposures to B. anthracis spores that occurred in the US during the fall of 2001, CDC recommended that anti-infective prophylaxis be initiated (pending additional information) in individuals exposed to an air space where a suspicious material may have been aerosolized (e.g., near a suspicious powder-containing letter during opening) and in individuals who shared the air spaces likely to be the source of an inhalational anthrax case.701 While culture of nasal swabs can occasionally document exposure and provide clues to help assess the exposure circumstances, these nasal swabs are investigative tools only and results cannot be used to rule out exposure to B. anthracis .686,699 Following confirmation of the presence of B. anthracis spores, CDC recommended that a full 60-day postexposure regimen be completed in individuals exposed to an air space known to be contaminated with aerosolized B. anthracis , in individuals exposed to an air space known to be the source of an inhalational anthrax case, and in individuals along the transit path of an envelope or other vehicle containing B. anthracis that may have been aerosolized (e.g., a postal sorting facility in which an envelope containing B. anthracis was processed).701

Remediation workers with repeated entries into contaminated sites over a prolonged period of time may require anti-infective prophylaxis for considerably longer than the 60 days recommended for individuals with a single exposure.714 Some remediation workers exposed during the bioterrorism-related events that occurred in the US during the fall of 2001 received anti-infective prophylaxis for more than 6 months.714 At that time, CDC recommended that anti-infective prophylaxis be continued throughout the period of risk and for 60 days after the risk of exposure ended, unless a 6-dose series of anthrax vaccine had been completed and annual boosters were up to date.714

Laboratory Workers and Other Individuals

Laboratory workers and other individuals who work in occupations that might result in repeated exposure to aerosolized B. anthracis spores should receive preexposure vaccination with anthrax vaccine adsorbed.663 ACIP states that anti-infective postexposure prophylaxis is not necessary in fully vaccinated workers who wear appropriate personal protective equipment (PPE) while working in environments contaminated with B. anthracis spores, unless PPE is disrupted.663 If there is any type of disruption of PPE in a worker who is fully or partially vaccinated against anthrax, ACIP recommends that anti-infective postexposure prophylaxis be given for at least 30 days in conjunction with any remaining indicated doses of anthrax vaccine.663 Following an occupational exposure to B. anthracis spores in previously unvaccinated workers, ACIP recommends that anti-infective postexposure prophylaxis be given for 60 days in conjunction with postexposure vaccination and states that the anti-infective prophylaxis regimen should be continued for 14 days after the third vaccine dose (even if this results in more than 60 days of anti-infective prophylaxis).663

Following a bioterrorism-related event, use of anti-infective prophylaxis in asymptomatic individuals in the general population is not indicated unless appropriate public health or law-enforcement agencies have ascertained that a risk of exposure to B. anthracis spores exists.699 In addition, CDC states that postexposure prophylaxis is not indicated for the prevention of cutaneous anthrax, for autopsy personnel examining bodies infected with anthrax when appropriate isolation precautions and procedures are followed, for hospital personnel caring for patients with anthrax, or for individuals who routinely open or handle mail in the absence of a suspicious letter or credible threat.701

Clinical Experience

Although controlled studies evaluating ciprofloxacin for aerosolized anthrax exposure in humans have not been conducted for ethical reasons, the indication for use of ciprofloxacin is based on serum concentrations of the drug achieved in humans, a surrogate end point reasonably likely to predict clinical benefit.1,579 Efficacy of ciprofloxacin has been evaluated in a rhesus monkey model of inhalational anthrax.1,579,684 In this study, rhesus monkeys were exposed to an inhaled mean dose of 11 LD₅₀ (approximately 5.5 x 10⁵) spores (range: 5-30 LD₅₀) of B. anthracis and then received a 30-day regimen of placebo or oral ciprofloxacin beginning 24 hours after exposure.1,579,684 Mortality due to anthrax was significantly lower in monkeys that received ciprofloxacin (1/9) compared with those that received placebo (9/10); the one ciprofloxacin-treated monkey that died of anthrax did so following the 30-day drug administration period.1,579,684 In the monkeys studied, mean serum concentrations of ciprofloxacin 1 hour after dosing (at the expected time of peak serum concentrations) following oral dosing to steady state ranged from 0.98-1.69 mcg/mL; mean steady-state trough concentrations at 12 hours after dosing ranged from 0.12-0.19 mcg/mL.1,579 The mean serum concentrations of ciprofloxacin associated with a statistically significant improvement in survival in this rhesus monkey model of inhalational anthrax are reached or exceeded in adult and pediatric patients receiving oral or IV ciprofloxacin.1,579,685

Some data regarding efficacy of ciprofloxacin for postexposure prophylaxis in humans following exposure to aerosolized B. anthracis spores is available since the drug was used for postexposure prophylaxis in individuals in the US who were exposed to B. anthracis spores in bioterrorism-related incidences that occurred during September and October 2001.1,579,686,696 Approximately 300 postal or other facilities were tested for B. anthracis spores and anti-infective prophylaxis with ciprofloxacin or other anti-infectives was initiated in approximately 32,000 individuals in Florida, New Jersey, New York, and the District of Columbia who had potential exposures.700 A full 60-day postexposure prophylaxis regimen was recommended for approximately 8424 of these individuals.700,709 To date, no individual who received anti-infective prophylaxis following these bioterrorism-related exposures developed microbiologically confirmed anthrax.1,579,668,696 Although ciprofloxacin postexposure prophylaxis generally was well tolerated, the incidence of adverse effects was higher than that reported previously in controlled clinical trials evaluating the drug for other indications.1,579,700,709

Treatment of Systemic Anthrax

The rapid course of symptomatic inhalational anthrax and high mortality rate make early initiation of anti-infective therapy essential.668,682,683 Because of the difficulty in making a rapid microbiologic diagnosis of anthrax, high-risk individuals who develop fever or other evidence of systemic infection should promptly receive therapy for possible anthrax infection while waiting for results of laboratory studies.668,683

Based on clinical experience from the bioterrorism-related anthrax exposures of 2001 and the possibility that a B. anthracis strain resistant to one or more anti-infectives might be used in a future bioterrorism event, CDC, AAP, and other experts (e.g., US Working Group on Civilian Biodefense, USAMRIID) state that treatment of clinically apparent systemic anthrax (inhalational, GI, meningitis, or cutaneous with systemic involvement, head or neck lesions, or extensive edema) in adults and pediatric patients that occurs as the result of exposure to anthrax spores in the context of biologic warfare or bioterrorism should be initiated with a multiple-drug parenteral regimen that includes ciprofloxacin or doxycycline and 1 or 2 additional anti-infectives predicted to be effective.668,671,672,673,683,686,703 Other drugs to be included in the initial treatment regimen with ciprofloxacin or doxycycline should be selected based on in vitro susceptibility, possibility of efficacy, adverse effects, and cost.668,683,696 Based on in vitro data, other drugs that have been suggested as possibilities to augment ciprofloxacin or doxycycline in such multiple-drug regimens include carbapenems (doripenem, imipenem, meropenem), penicillin G, ampicillin, linezolid, clindamycin, rifampin, chloramphenicol, vancomycin, macrolides (azithromycin, clarithromycin, erythromycin), daptomycin, quinupristin and dalfopristin, and aminoglycosides (gentamicin).671,672,673,683,686,668

For initial empiric treatment of systemic anthrax (with possible or confirmed meningitis), CDC and AAP recommend use of a multiple-drug parenteral regimen that includes at least 3 anti-infectives with activity against B. anthracis and good CNS penetration, including at least one drug that has bactericidal activity against the organism and at least one drug classified as a protein synthesis inhibitor.671,672,673 These experts state that IV ciprofloxacin is recommended as the primary bactericidal component of these regimens.671,672,673 The preferred multiple-drug regimen for the treatment of systemic anthrax (with possible or confirmed meningitis) in adults and pediatric patients (including neonates) is IV ciprofloxacin in conjunction with another IV bactericidal anti-infective (preferably meropenem) and an IV protein synthesis inhibitor (preferably linezolid).671,672,673

For initial empiric treatment of systemic anthrax when meningitis has been excluded, CDC and AAP recommend use of a multiple-drug parenteral regimen that includes at least 2 anti-infectives with activity against B. anthracis , including at least one drug with bactericidal activity against the organism and at least one drug classified as a protein synthesis inhibitor.671,672,673 The preferred multiple-drug regimen for the treatment of systemic anthrax in adults and pediatric patients (including neonates) when meningitis has been excluded is IV ciprofloxacin in conjunction with an IV protein synthesis inhibitor (preferably clindamycin or linezolid in adults or clindamycin in pediatric patients).671,672,673

If the B. anthracis strain is tested and found to be susceptible to penicillin, CDC and AAP state that IV penicillin G and IV ampicillin are acceptable alternatives for the second bactericidal agent (i.e., the carbapenem) used in multiple-drug regimens for the treatment of systemic anthrax (with possible or confirmed meningitis) or the bactericidal agent used in multiple-drug regimens for the treatment of systemic anthrax when meningitis has been excluded.671,672,673

Some experts suggest that oral ciprofloxacin or other oral fluoroquinolones (levofloxacin, moxifloxacin, ofloxacin) can be considered for the treatment of inhalational anthrax† when a parenteral regimen is not available.668,683 Although a multiple-drug parenteral regimen should be used for the treatment of inhalational anthrax that occurs as the result of exposure to B. anthracis spores in the context of biologic warfare or bioterrorism,668,671,672,673,683 use of these parenteral regimens may not be possible if large numbers of individuals require treatment in a mass casualty setting and it may be necessary to use an oral regimen.668,683

Because of the possible persistence of anthrax spores in lung tissue, anti-infective therapy for the treatment of systemic anthrax that occurs as the result of exposure to aerosolized B. anthracis spores in the context of biologic warfare or bioterrorism should be continued for 60 days.668,671,672,673,683 The initial multiple-drug parenteral regimen should be continued for at least 2-3 weeks until the patient is clinically stable and can be switched to an appropriate oral anti-infective.671,672,673

Clinical Experience

A multiple-drug parenteral regimen that was used in 2 patients who survived inhalational anthrax following the bioterrorism-related exposures in 2001 was a 3-drug regimen of ciprofloxacin (400 mg every 8 hours), rifampin (300 mg every 12 hours), and clindamycin (900 mg every 8 hours).702,710 Other multiple-drug regimens that were used for the initial treatment of patients who survived inhalational anthrax following these bioterrorism-related anthrax exposures were ciprofloxacin/cefotaxime/azithromycin (1 patient); levofloxacin/rifampin initially then ciprofloxacin rifampin/vancomycin (1 patient); and oral levofloxacin (prior to diagnosis), then ciprofloxacin/azithromycin, then clindamycin/ceftriaxone/azithromycin, then doxycycline (1 patient).702,710 Although it is unclear whether the deaths were related to ineffective regimens and/or delays in initiation of therapy, the regimens used in patients who died of inhalational anthrax following these exposures were levofloxacin/clindamycin/penicillin G (1 patient, initiated on the second day of hospitalization after various anti-infectives, died 3 days after admission); levofloxacin monotherapy (1 patient, died day of admission); levofloxacin/rifampin/penicillin G/ceftriaxone (1 patient, died day of admission); levofloxacin monotherapy, then levofloxacin/rifampin/gentamicin/nafcillin, then ciprofloxacin/rifampin/clindamycin/ceftazidime (1 patient, died 3 days after admission); ampicillin-sulbactam/ciprofloxacin/clindamycin (1 patient, initiated on the third day of hospitalization after various other regimens, died 4 days after admission) and ampicillin-sulbactam/ciprofloxacin (1 patient, initiated on the day of hospitalization and clindamycin added on the third day, died 4 days after admission).710,711,773

Results of in vitro susceptibility testing of strains of B. anthracis that were associated with cases of inhalational or cutaneous anthrax that occurred in the US (Florida, New York, District of Columbia) during September and October 2001 in the context of bioterrorism-related exposures to anthrax spores indicated that these strains were susceptible to ciprofloxacin, doxycycline, tetracycline, rifampin, clindamycin, vancomycin, and chloramphenicol.686 Isolates were susceptible to clarithromycin, azithromycin (borderline susceptibility), and imipenem, but had only intermediate susceptibility to erythromycin.686 Although these B. anthracis strains were susceptible to penicillin and amoxicillin in vitro, additional tests indicated that some of these strains had constitutive and inducible β-lactamases and there is in vitro evidence that exposure of some penicillin-susceptible B. anthracis strains to penicillins can induce β-lactamases.686 Therefore, CDC states that use of a penicillin alone is not recommended for the treatment of anthrax that occurs as the result of biologic warfare or bioterrorism when high concentrations of the organism are likely to be present, although penicillin can be included in appropriate combination regimens.686 B. anthracis strains resistant to sulfamethoxazole, trimethoprim, cephalosporins (i.e., cefuroxime, cefotaxime, ceftazidime), or aztreonam have been reported, and these anti-infectives should not be used in the treatment of anthrax.668,682,687

Treatment of Uncomplicated Cutaneous Anthrax

Natural penicillins (e.g., oral penicillin V, IM penicillin G benzathine, IM penicillin G procaine) generally have been considered drugs of choice for the treatment of mild, uncomplicated cutaneous anthrax caused by susceptible B. anthracis that occurs as the result of naturally occurring or endemic exposure to anthrax, although some clinicians suggest use of oral fluoroquinolones (ciprofloxacin, levofloxacin, ofloxacin), oral amoxicillin, or oral doxycycline if in vitro tests indicate susceptibility.668,670,680

For the treatment of uncomplicated cutaneous anthrax† (without systemic involvement) that occurs following exposure to B. anthracis spores in the context of biologic warfare or bioterrorism, CDC recommends that adults receive an oral regimen of ciprofloxacin, doxycycline, levofloxacin, or moxifloxacin;672,673 alternatives include oral amoxicillin or penicillin V (if penicillin susceptibility is confirmed) or oral clindamycin.672,673

For the treatment of uncomplicated cutaneous anthrax† (without systemic involvement) that occurs following exposure to B. anthracis spores in the context of biologic warfare or bioterrorism, AAP recommends that pediatric patients (including neonates) receive an oral regimen of ciprofloxacin;671 alternatives include oral amoxicillin or penicillin V (if penicillin susceptibility is confirmed) or oral doxycycline, clindamycin, or levofloxacin.671

CDC, AAP, and other experts recommend that anti-infective treatment be continued for 60 days if the cutaneous infection occurred as the result of exposure to aerosolized anthrax spores since the possibility of inhalational anthrax would also exist.668,671,672,673,683 For the treatment of mild, uncomplicated cutaneous anthrax that occurs as the result of natural or endemic exposures to anthrax (e.g., known exposure to infected livestock or their products), a treatment duration of 3-10 days may be sufficient.668,680,683 Anti-infective therapy may limit the size of the cutaneous anthrax lesion and it usually becomes sterile within the first 24 hours of treatment, but the lesion will still progress through the black eschar stage despite effective treatment.668,670,680

Treatment of GI and Oropharyngeal Anthrax Following Natural or Endemic Exposures

Although penicillin usually is considered the drug of choice for the treatment of GI anthrax† that occurs as the result of ingesting contaminated, undercooked meat, ciprofloxacin is considered an alternative for the treatment of these infections.681 Ciprofloxacin has been used for prophylaxis following ingestion of B. anthracis spores† in contaminated meat.662

Brucellosis

Ciprofloxacin has been used in the treatment of brucellosis† caused by Brucella melitensis ,624,771 and some clinicians suggest that a regimen of ciprofloxacin and rifampin can be used as an alternative regimen for the treatment of the disease.197,683,771,772 Most experts recommend a regimen of doxycycline and streptomycin (or gentamicin) or a regimen of doxycycline and rifampin; alternative regimens include co-trimoxazole with or without gentamicin or rifampin; ciprofloxacin (or ofloxacin) and rifampin; or chloramphenicol with or without streptomycin.176,197,683,772 Monotherapy with any drug usually is associated with a high relapse rate and is not recommended.683,772

In a study in adults with brucellosis, a 30-day regimen of oral ciprofloxacin (500 mg twice daily) and rifampin (600 mg once daily) was as effective as a regimen of oral doxycycline (100 mg twice daily) and rifampin (600 mg once daily).771 Oral ciprofloxacin has been used in patients with acute brucellosis or acute brucella arthritis-diskitis†.624 Although oral ciprofloxacin therapy resulted in an initial apparent response in most patients and defervescence within 7 days, at least one patient was considered a treatment failure because blood cultures remained positive and about 25% of patients (generally those with arthritis-diskitis) had relapse or reinfection within 8-32 weeks after the drug was discontinued.624

Chancroid

Ciprofloxacin (conventional tablets, oral suspension) has been effective in men for the treatment of chancroid†, genital ulcers caused by Haemophilus ducreyi .321,462 Although a single 500-mg oral dose of the drug was effective in some men for the treatment of chancroid, multiple-dose regimens generally have been associated with fewer treatment failures.321

CDC states that a single IM dose of ceftriaxone, a single oral dose of azithromycin, a 3-day regimen of oral ciprofloxacin (not recommended in pregnant or lactating women), or a 7-day regimen of oral erythromycin are the regimens of choice for the treatment of chancroid.344

HIV-infected patients and patients who are uncircumcised may not respond to treatment as well as those who are HIV-negative or circumcised.344 Clinicians should consider that, although treatment failures can occur with any of these recommended regimens, only limited data are available regarding efficacy of the single-dose ceftriaxone and single-dose azithromycin regimens in HIV-infected patients.344 Because treatment failures and slow healing of ulcers are more likely in HIV-infected individuals,344 such patients should be monitored closely and more prolonged treatment or retreatment may be necessary.344

Data are limited regarding the prevalence of H. ducreyi resistant to the anti-infectives recommended for treatment.344 Isolates of H. ducreyi with intermediate resistance to ciprofloxacin have been reported rarely.344

For additional information on management of chancroid, current CDC sexually transmitted diseases treatment guidelines available at [Web] should be consulted.344

Chlamydial and Mycoplasmal Infections

Multiple-dose oral ciprofloxacin therapy has been used for the treatment of nongonococcal urethritis†, but results have been conflicting.178,180,211,294,296,448 Although 7-10 days of oral ciprofloxacin appeared to be effective for the treatment of nongonococcal urethritis in some men,313,320,322,325 efficacy of the drug was unpredictable when Chlamydia was present, and the rate of relapse was high.320 If a fluoroquinolone is used as an alternative for the treatment of nongonococcal urethritis when the regimens of choice (azithromycin, doxycycline) are not used, CDC recommends a 7-day regimen of oral ofloxacin or oral levofloxacin.344

Oral ciprofloxacin was used with some success in a limited number of women for the treatment of urethral and cervical infections caused by C. trachomatis or Mycoplasma hominis †.296,478 The drug generally has been ineffective in both men and women for the treatment of urogenital infections caused by Ureaplasma urealyticum †.296,478 If a fluoroquinolone is used as an alternative for the treatment of C. trachomatis urogenital infections, CDC recommends a 7-day regimen of oral levofloxacin or oral ofloxacin.344

Crohn's Disease

Oral ciprofloxacin (administered with737,742,744,745,746,748 or without metronidazole)743,747 has been used for induction of remission of mildly to moderately active Crohn's disease†;737,742,743,744,745,746,747 748 the drug also has been used for refractory perianal Crohn's disease.737,739,750,751 Because intestinal flora appear to have an association with intestinal inflammation,743,744,745,747 and because ciprofloxacin appears to have immunosuppressive effects,743,748 the drug may be useful in the management of Crohn's disease as an adjunct to conventional therapies.739,743,744,745,747 However, there currently is no established standard therapy with ciprofloxacin for the management of active Crohn's disease, and further larger studies are needed to confirm study results to date and to establish management criteria and safety considerations for the disease.747

Results of several open-label,744,746 comparative,743,745 retrospective,742 and at least 1 placebo-controlled study747 indicate that ciprofloxacin (with737,742,744,745,746,748 or without metronidazole743,747 ) can result in clinical response (e.g., improvement of clinical condition, clinical remission) in patients with mildly to moderately active Crohn's disease.744,745,746 It appears that the combination of ciprofloxacin and metronidazole is more effective than ciprofloxacin alone.739,742 Safety and efficacy of ciprofloxacin in the management of active Crohn's disease were evaluated in a small 6-month preliminary, placebo-controlled, randomized study that included 47 adults with moderately active Crohn's disease who had an inadequate response to conventional therapies (e.g., prednisone, mesalamine, mercaptopurine).747 To be included in the study, patients had to have had symptomatic disease and a Crohn's Disease Activity Index [CDAI]) greater than 150 at the time of study entry.747 The CDAI score is based on subjective observations by the patient (e.g., the daily number of liquid or very soft stools, severity of abdominal pain, general well-being) and objective evidence (e.g., number of extraintestinal manifestations, presence of an abdominal mass, use or nonuse of antidiarrheal drugs, the hematocrit, body weight).753 Patients were randomized to receive ciprofloxacin 500 mg twice daily or placebo while they continued to receive conventional therapy for the disease.747 Clinical response was described as achievement of a CDAI score of less than 150.747 Only 37 patients completed the study; 25 of those were receiving ciprofloxacin and 12 were receiving placebo.747 Mean CDAI score at the end of 6 months was 112 or 205 in those receiving ciprofloxacin or placebo, respectively.747

Results of a small, randomized, comparator-drug (ciprofloxacin versus mesalamine) controlled study (patients having a median CDAI score of 217 [ range:160-305]) indicate that clinical improvement in patients receiving ciprofloxacin in a dosage of 1 g daily was similar to that in those receiving mesalamine controlled-release capsules in a dosage of 4 g daily.738,743 At 6 weeks of therapy, complete remission (defined as a CDAI score of 150 or less, associated with a reduction from baseline CDAI of more than 75 points) was reported in 56 or 55% of patients receiving ciprofloxacin or mesalamine, respectively, while partial remission (defined as a CDAI score of 150 or less, associated with a reduction from baseline CDAI of greater than 50 but less than 70 points) was reported in 17 (3 out of 18 patients) or 4.5% (1 out of 22) patients receiving ciprofloxacin or mesalamine, respectively.743

In addition, safety and efficacy of concomitant use of ciprofloxacin and metronidazole have been evaluated in a 12-week comparative (versus methylprednisolone) study in 41 patients with active Crohn's disease (CDAI of more than 200 at the time of study entry).738,745 Patients were randomized to receive ciprofloxacin 500 mg twice daily in conjunction with metronidazole 250 mg 4 times daily (22 patients) or methylprednisolone (0.7-1 mg/kg daily initially, followed by variable tapering to 40 mg, and subsequent tapering of 4 mg weekly; 19 patients).738,745 At 12 weeks of therapy, clinical remission (defined as a CDAI of 150 points or less) was reported in 63 or 46% of patients receiving the corticosteroid or the combination therapy, respectively.745 It has been suggested that combination therapy with ciprofloxacin and metronidazole could be an alternative to corticosteroids, although a high incidence of adverse effects (27% discontinued therapy because of such effects) was associated with the anti-infectives.745

Limited data indicate that ciprofloxacin may be more effective in patients with ileitis than in those with colitis.739,742 It has been suggested that reduced efficacy of ciprofloxacin in colitis may be associated with the low activity of the drug against anaerobic bacteria.739,742

Ciprofloxacin has been used in the management of refractory perianal Crohn's disease†.737,739,750,751 Anecdotal reports suggest that ciprofloxacin may be useful in the long-term treatment of active perianal Crohn's disease;739 however, the drug generally is used for short-term administration for this condition.750,751 Relapse usually occurs when the anti-infective is discontinued.739,750 Limited data indicate that short-term (8 weeks) combination therapy with ciprofloxacin and metronidazole given with, or followed by, azathioprine (up to about 20 weeks) in patients with perianal Crohn's disease may result in rapid reduction of fistula drainage (induced by the anti-infectives) and beneficial maintenance (associated with the azathioprine).751

Gonorrhea and Associated Infections

Although oral ciprofloxacin (conventional tablets, oral suspension) was used in the past for the treatment of uncomplicated urethral, endocervical, rectal†, or pharyngeal† gonorrhea caused by susceptible Neisseria gonorrhoeae ,1,314,317,322,428,619 quinolone-resistant N. gonorrhoeae (QRNG) is widely disseminated throughout the world, including in the US.114,344,632,634,635,637,638,639,669,754,835,839,857 Therefore, CDC states that fluoroquinolones are no longer recommended for the treatment of gonorrhea and should not be used routinely for any associated infections that may involve N. gonorrhoeae (e.g., pelvic inflammatory disease [PID], epididymitis).114,344,839

From 1993-2000, CDC recommended fluoroquinolones as drugs of choice for the treatment of uncomplicated gonorrhea in the US; however, because of reports of QRNG, subsequent CDC recommendations regarding use of the drugs for the treatment of gonorrhea became more restrictive.114 Beginning in 2000, CDC no longer recommended use of fluoroquinolones for the treatment of gonorrhea in individuals who acquired their infections in Asia or the Pacific Islands (including Hawaii) because of the high incidence QRNG in these areas.114 In 2002, this restriction was broadened to include individuals who acquired gonorrhea in California.114 In 2004, CDC recommended that fluoroquinolones not be used to treat gonorrhea in men who have sex with men because of the increased prevalence of QRNG in this population.114 Beginning in April 2007, CDC stated that fluoroquinolones should not be used for the treatment of gonorrhea or any associated infections that may involve N. gonorrhoeae (e.g., PID, epididymitis).114

Granuloma Inguinale (Donovanosis)

Oral ciprofloxacin is considered an alternative for the treatment of granuloma inguinale (donovanosis)† caused by Klebsiella granulomatis (formerly Calymmatobacterium granulomatis ).344

CDC recommends that granuloma inguinale be treated with a regimen of oral azithromycin or, alternatively, a regimen of oral doxycycline, oral ciprofloxacin, oral erythromycin, or oral co-trimoxazole.344 Anti-infective treatment should be continued until all lesions have healed completely; a minimum duration of 3 weeks usually is necessary.344 If improvement is not evident within the first few days of treatment, CDC states that consideration can be given to adding a parenteral aminoglycoside (e.g., IV gentamicin) to the regimen.344 Anti-infective therapy appears to halt progression of lesions, although prolonged duration of therapy often is required to enable granulation and re-epithelization of ulcers.344 Despite effective anti-infective therapy, granuloma inguinale may relapse 6-18 months later.344

Individuals with HIV infection should receive the same treatment regimens recommended for other individuals with granuloma inguinale; however, CDC suggests that addition of a parenteral aminoglycoside to the regimen can be considered if improvement is not evident within the first few days of treatment.344

For additional information on management of granuloma inguinale, current CDC sexually transmitted diseases treatment guidelines available at [Web] should be consulted.344

Legionnaires' Disease

Ciprofloxacin has been used for the treatment of Legionnaires' Disease† caused by Legionella pneumophila ,734 including in immunocompromised patients (e.g., transplant recipients).197,512,622,704,734,735

Malaria

Although ciprofloxacin reportedly has some activity in vitro against Plasmodium falciparum , oral ciprofloxacin (750 mg every 12 hours) has been ineffective when used alone in the treatment of uncomplicated malaria caused by chloroquine-resistant P. falciparum †.623

Mycobacterial Infections

Treatment of Active Tuberculosis

Ciprofloxacin has been used in multiple-drug regimens for the treatment of active tuberculosis† caused by Mycobacterium tuberculosis .601,615,804,805,806,807,817

Although the potential role of fluoroquinolones and the optimal length of therapy have not been fully defined, the American Thoracic Society (ATS), CDC, IDSA, and others state that use of fluoroquinolones as alternative (second-line) agents can be considered for the treatment of active tuberculosis in patients intolerant of certain first-line agents and in those with relapse, treatment failure, or M. tuberculosis resistant to certain first-line agents.218,440 If a fluoroquinolone is used in multiple-drug regimens for the treatment of active tuberculosis, ATS, CDC, IDSA, and others recommend levofloxacin or moxifloxacin.218,231,276,440 Some experts state that ciprofloxacin is no longer recommended for treatment of tuberculosis.231,276

The most recent ATS, CDC, and IDSA recommendations for the treatment of tuberculosis should be consulted for more specific information.218

Other Mycobacterial Infections

Ciprofloxacin has been used alone or in conjunction with amikacin for the treatment of cutaneous infections caused by M. fortuitum †.607,817 Although ciprofloxacin appeared to be effective in a few patients with M. fortuitum infections, ciprofloxacin-resistant strains of the organism have developed when the drug was used alone or in conjunction with amikacin in the treatment of these infections.607,817 Although optimum regimens have not been identified, ATS and IDSA recommend that M. fortuitum pulmonary infections be treated with a regimen consisting of at least 2 anti-infectives selected based on results of in vitro susceptibility testing and tolerability (e.g., amikacin, ciprofloxacin or ofloxacin, a sulfonamide, cefoxitin, imipenem, doxycycline).675

Ciprofloxacin has been used in multiple-drug regimens for the treatment of pulmonary and extrapulmonary (localized or disseminated) M. avium complex† (MAC) infections.197,602,607,614,616,617,817,819 However, ATS and IDSA state that the role of fluoroquinolones in the treatment of MAC infections has not been established.675 If a fluoroquinolone is included in a treatment regimen (e.g., for macrolide-resistant MAC infections), moxifloxacin may be preferred, although many strains are resistant in vitro.675

Based on results of in vitro susceptibility testing, ciprofloxacin may be considered for use in combination antimycobacterial regimens used for the treatment of infections caused by M. chelonae †, M. haemophilum †, or M. terrae †.675 Optimal treatment regimens for these infections have not been identified.675 Because of considerations related to resistance, ciprofloxacin is not recommended for treatment of M. marinum infections.675

The most recent ATS, CDC, and IDSA recommendations for the treatment of other mycobacterial infections should be consulted for more specific information.675

Neisseria meningitidis Infections

Ciprofloxacin (conventional tablets, oral suspension) is used in adults to eliminate nasopharyngeal carriage of Neisseria meningitidis †292,376,406,409,411,538,545,569 and for chemoprophylaxis to prevent meningococcal disease in household or other close contacts of patients with invasive disease†.292,374,376

Patients with invasive meningococcal disease who have been treated with penicillin G or any anti-infective other than ceftriaxone or another third generation cephalosporin may still be carriers of N. meningitidis and should receive an anti-infective regimen to eradicate nasopharyngeal carriage of the organism prior to hospital discharge.292,374,376 The treatments of choice to eradicate nasopharyngeal carriage of N. meningitidis are ceftriaxone (single IM dose), rifampin (2-day regimen), and ciprofloxacin (single oral dose).292,376 These regimens are all 90-95% effective and any of these is an acceptable regimen in appropriate patients.374,376

Chemoprophylaxis in close contacts of a patients with invasive meningococcal disease is an important means of preventing secondary cases in household and other close contacts.292,374,376 Recommended regimens for chemoprophylaxis against meningococcal disease include a single dose of IM ceftriaxone, 2-day regimen of oral rifampin (not recommended in pregnant women), or a single dose of oral ciprofloxacin (not recommended in individuals younger than 18 years of age unless no other regimen can be used and not recommended for pregnant or lactating women).292,374,376 These regimens are all 90-95% effective and any of these is an acceptable regimen for chemoprophylaxis.376 AAP suggests that rifampin may be the drug of choice for chemoprophylaxis in most children.292

The attack rate for household contacts who do not receive chemoprophylaxis has been estimated to be 4 cases per 1000 individuals exposed, which is 500-800 times greater than that for the general population.376 A decision to administer chemoprophylaxis to close contacts of an individual with invasive meningococcal disease is based on the degree of risk.292,376 Throat and nasopharyngeal cultures are not useful in determining the need for chemoprophylaxis and may unnecessarily delay administration of the regimen.292,376

When chemoprophylaxis is indicated in high-risk contacts, it must be administered promptly (ideally within 24 hours after identification of the index case) since the attack rate of secondary disease is greatest in the few days following disease onset in the index case.292,374,376 All high-risk contacts should be informed that even if chemoprophylaxis is taken or started, the development of any suspicious clinical manifestation warrants early, rapid medical attention.374 Chemoprophylaxis probably is of limited or no value if administered more than 14 days after contact with the index case.374,376 If high-risk exposure to a new index case occurs more than 2 weeks after initial chemoprophylaxis, additional chemoprophylaxis is indicated.374

Fluoroquinolone-resistant N. meningitidis has been reported rarely in the US and elsewhere (e.g., India).853,854 Ciprofloxacin should not be used for prophylaxis in close contacts of individuals with meningococcal disease in areas where fluoroquinolone-resistant strains have been reported (e.g., selected counties of North Dakota and Minnesota).292,853

Plague

Ciprofloxacin (IV, conventional tablets, oral suspension) is used for the treatment of plague, including pneumonic and septicemic plague, caused by Yersinia pestis and for postexposure prophylaxis of plague in adults and children.1,292,579,683,688 Based on results of in vitro and animal testing,674,683,688,694 fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin, ofloxacin) are recommended as alternatives for the treatment of plague and for postexposure prophylaxis following a high-risk exposure to Y. pestis , including exposures that occur in the context of biologic warfare or bioterrorism.683,688

Efficacy of ciprofloxacin for treatment or prophylaxis of plague has not be evaluated in clinical trials in humans for ethical and feasibility reasons.1,579 The drug is labeled by FDA for this indication based on an efficacy study in animals that demonstrated a survival benefit.1,579 In a placebo-controlled study, African green monkeys were exposed to an inhaled dose of Y. pestis (mean dose of 110 LD₅₀ [range 92-127 LD₅₀]) and then randomized to receive either ciprofloxacin (15 mg/kg IV for 10 days) or placebo initiated when fever started or 76 hours post-challenge, whichever occurred first.1,579 In vitro testing indicated that the Y. pestis strain used in this study (CO92 strain) had a ciprofloxacin MIC of 0.015 mcg/mL.1,579 Pharmacokinetic data indicated that mean peak serum concentrations of ciprofloxacin attained in the monkeys at the end of a single 60-minute IV infusion of the drug were approximately 3.5, 3.9, and 4 mcg/mL on days 2, 6, and 10 of treatment, respectively;1,579 trough concentrations on these days were all less than 0.5 mcg/mL.1,579 Study results indicated that mortality in the ciprofloxacin treatment group was significantly lower (1 out of 10) compared with the placebo group (2 out of 2).1,579 The single ciprofloxacin-treated monkey that died had not received the protocol-directed ciprofloxacin dosage because of a failure of the administration catheter; ciprofloxacin serum concentrations in this monkey were less than 0.5 mcg/mL at all time points tested.1,579 Although this monkey became culture negative on day 2 of treatment and terminal blood cultures were negative, the animal had a resurgence of low grade bacteremia on day 6 after initiation of ciprofloxacin.1,579

Treatment of Plague

For the treatment of plague, IM streptomycin (or IM or IV gentamicin) historically has been considered the regimen of choice.197,292,683,688 Alternatives recommended for the treatment of plague when aminoglycosides are not used include IV doxycycline (or IV tetracycline), IV chloramphenicol (a drug of choice for plague meningitis), an IV fluoroquinolone (ciprofloxacin [a drug of choice for plague meningitis], levofloxacin, moxifloxacin), or co-trimoxazole (may be less effective than other alternatives).197,292,683,688

Anti-infective regimens recommended for the treatment of naturally occurring or endemic bubonic, septicemic, or pneumonic plague also are recommended for the treatment of plague that occurs following exposure to Y. pestis in the context of biologic warfare or bioterrorism.683,688 Such exposures would most likely result in primary pneumonic plague,688 and prompt initiation of anti-infective therapy (within 18-24 hours of onset of symptoms) is essential in the treatment of pneumonic plague.683,688 Some experts (e.g., US Working Group on Civilian Biodefense, USAMRIID) recommend that treatment of plague in the context of biologic warfare or bioterrorism be initiated with a parenteral anti-infective regimen of streptomycin (or gentamicin) or, alternatively, doxycycline, a fluoroquinolone (ciprofloxacin, levofloxacin, moxifloxacin) or chloramphenicol.683,688 However, an oral regimen of doxycycline (or tetracycline) or a fluoroquinolone (ciprofloxacin, levofloxacin, moxifloxacin, ofloxacin) may be substituted when the patient's condition improves or when a parenteral regimen is unavailable (e.g., when there are supply or logistic problems because large numbers of individuals require treatment in a mass casualty setting); oral chloramphenicol is considered an alternative in these situations.688

Postexposure Prophylaxis of Plague

In the context of biologic warfare or bioterrorism, some experts (e.g., US Working Group on Civilian Biodefense, USAMRIID) recommend that asymptomatic individuals with exposure to plague aerosol or asymptomatic individuals with household, hospital, or other close contact (within about 2 m) with an individual who has pneumonic plague receive an oral anti-infective regimen for postexposure prophylaxis; however, any exposed individual who develops a temperature of 38.5°C or higher or new cough should promptly receive a parenteral anti-infective for treatment of the disease.683,688 If postexposure prophylaxis is indicated, these experts recommend a regimen of oral doxycycline (or tetracycline) or an oral fluoroquinolone (ciprofloxacin, levofloxacin, moxifloxacin, ofloxacin).683,688

Although plague vaccine (no longer commercially available in the US) was previously recommended to provide protection against Y. pestis infection, the vaccine was effective for preventing or ameliorating bubonic plague but was not effective for prophylaxis against exposure to aerosolized Y. pestis and therefore did not provide protection against pneumonic plague.683,688

Rickettsial Infections

Ciprofloxacin has been used with some success in a limited number of patients for the treatment of various rickettsial infections†,393,568,625 including Mediterranean spotted fever† caused by Rickettsia conorii .393,568 CDC and other clinicians state that doxycycline is the drug of choice for the treatment of all tickborne rickettsial diseases.197,500,683 Although some fluoroquinolones have in vitro activity against Rickettsiae500 and some clinicians have suggested that fluoroquinolones (e.g., ciprofloxacin, ofloxacin) may be considered alternatives for the treatment of some rickettsial infections (e.g., Rocky Mountain spotted fever caused by R. rickettsii ) when doxycycline cannot be used,197,683 CDC states that fluoroquinolones are not recommended for the treatment of Rocky Mountain spotted fever.500

Ciprofloxacin has been used for the long-term treatment of Q fever endocarditis caused by Coxiella burnetii †.625 However, CDC states that doxycycline is the drug of choice when treatment of acute Q fever is indicated and doxycycline in conjunction with hydroxychloroquine is the regimen of choice for the treatment of chronic Q fever, including endocarditis.495

Tularemia

Treatment of Tularemia

Ciprofloxacin (IV, conventional tablets, oral suspension) is recommended as an alternative to aminoglycosides (streptomycin or gentamicin) for the treatment of tularemia† caused by Francisella tularensis .292,683,689 Streptomycin generally has been considered the drug of choice for the treatment of tularemia; however, gentamicin is more readily available and is considered an alternative drug of choice when streptomycin is unavailable.197,292,683,689 Other alternatives for the treatment of tularemia include tetracyclines (doxycycline), chloramphenicol, or ciprofloxacin.197,292,683,689 Anti-infective regimens recommended for the treatment of naturally occurring or endemic tularemia also are recommended for the treatment of tularemia that occurs following exposure to F. tularensis in the context of biologic warfare or bioterrorism.683,689 However, the fact that a fully virulent streptomycin-resistant strain of F. tularensis was developed in the past for use in biologic warfare should be considered.683,689 Exposures to F. tularensis in the context of biologic warfare or bioterrorism would most likely result in inhalational tularemia with pleuropneumonitis, although the organism also can infect humans through the skin, mucous membranes, and GI tract.689

Postexposure Prophylaxis of Tularemia

Postexposure prophylaxis with anti-infectives usually is not recommended after possible exposure to natural or endemic tularemia (e.g., tick bite, rabbit or other animal exposure) and is unnecessary in close contacts of tularemia patients since human-to-human transmission of the disease is not known to occur.683 However, postexposure prophylaxis is recommended following a high-risk laboratory exposure to F. tularensis (e.g., spill, centrifuge accident, needlestick injury).689 In the context of biologic warfare or bioterrorism, some experts (e.g., US Working Group on Civilian Biodefense, USAMRIID) recommend that asymptomatic individuals with exposure to F. tularensis receive postexposure anti-infective prophylaxis; however, any individual who develops an otherwise unexplained fever or flu-like illness within 14 days of presumed exposure should promptly receive a parenteral anti-infective for treatment of the disease.683,689 Oral ciprofloxacin or oral doxycycline (or oral tetracycline) usually is recommended for postexposure prophylaxis of tularemia† following such exposures.683,689

Typhoid Fever and Other Invasive Salmonella Infections

Ciprofloxacin (conventional tablets, oral suspension) is used in adults for the treatment of typhoid fever (enteric fever) or paratyphoid fever† caused by susceptible Salmonella enterica serovars Typhi or Paratyphi, respectively.1,197,326,396,408,443,479,493,494,525,603,654,655,656,657,658,659,660 Although fluoroquinolones have been recommended for empiric treatment of Salmonella enteric fever in adults, resistance to fluoroquinolones has been reported in more than 80% of such infections in travelers to South and Southeast Asia and treatment failures will occur.525

Oral ciprofloxacin has been effective when used to treat chronic typhoid carriers†;197,211,292,391,403,438,466,473,603 however, the manufacturer of ciprofloxacin cautions that efficacy of the drug in the eradication of the chronic typhoid carrier state has not been demonstrated.1

Ciprofloxacin is recommended as a drug of choice for the treatment of native vertebral osteomyelitis caused by Salmonella †.590

Ciprofloxacin has been used to treat meningitis caused by susceptible Salmonella †.762,763,764,765

Vibrio Infections

Cholera

Ciprofloxacin has been used for the treatment of cholera† caused by Vibrio cholerae 01 or 0139 in adults or children†.664,756,757,758 Doxycycline generally is considered the drug of choice when anti-infective therapy is indicated as an adjunct to fluid and electrolyte replacement in patients with cholera;197,292,477,664,758 alternatives include azithromycin, co-trimoxazole, ciprofloxacin, or ceftriaxone.197,292,477,664,758

In a controlled study in adults, a 1-g oral dose of oral ciprofloxacin (given as a single dose or in 2 divided doses 12 hours apart) was at least as effective as a 3-day regimen of oral doxycycline (100 mg twice daily for 3 days) for the treatment of cholera.664 In another study in adults, a single 1-g dose of oral ciprofloxacin was more effective than a single 300-mg oral dose of doxycycline in eradicating V. cholerae from stool;664 although there was no difference between the regimens in terms of duration of diarrhea in those with V. cholerae 0139 infections, the duration of diarrhea was shorter in those with V. cholerae 01 infections who received ciprofloxacin.664

Although further study is needed to evaluate safety and efficacy in children, a single dose of oral ciprofloxacin (20 mg/kg) was as effective as a 3-day regimen of oral erythromycin (12.5 mg/kg every 6 hours) for the treatment of V. cholerae 01 or 0139 in children 2-15 years of age.758 The overall clinical success rate was 60% for ciprofloxacin and 55% for erythromycin; although the bacteriologic eradication rate was lower with ciprofloxacin (42%) than with erythromycin (70%) and erythromycin was associated with a more rapid clearance of V. cholerae , there was no difference in duration of diarrhea.758

Other Vibrio Infections

Some clinicians suggest that fluoroquinolones (e.g., ciprofloxacin) may be an alternative to tetracyclines for the treatment of other Vibrio infections, including gastroenteritis or wound infections caused by V. parahaemolyticus † or V. vulnificus †.197,759

Although optimum anti-infective therapy for V. vulnificus infections has not been identified, a tetracycline or third generation cephalosporin (e.g., cefotaxime, ceftazidime), a fluoroquinolone, or aminoglycoside has been recommended.759 Because the case fatality rate associated with V. vulnificus is high, anti-infective therapy should be initiated promptly if indicated.759

Perioperative Prophylaxis

Ciprofloxacin is used for perioperative prophylaxis† to reduce the risk of postoperative infections in patients undergoing certain genitourinary surgery.360

Perioperative prophylaxis is not recommended for patients with sterile urine undergoing cystoscopy without manipulation.360 However, if the patient has positive (or unavailable) urine cultures or an indwelling urinary catheter or is undergoing cystoscopy with manipulation (dilation, biopsy, fulguration, resection, or ureteral instrumentation), some clinicians recommend pretreatment to sterilize the urine before surgery or perioperative prophylaxis with a single preoperative dose of an anti-infective (e.g., ciprofloxacin) active against the most likely urologic pathogens.360

Perioperative prophylaxis using an appropriate anti-infective (e.g., ciprofloxacin) is recommended in patients undergoing transurethral prostatectomy, transrectal prostatic biopsies, ureteroscopy, shock wave lithotripsy, percutaneous renal surgery, open laparoscopic procedures, or procedures that involve placement of a urologic prosthesis (e.g., penile implant, artificial sphincter, synthetic pubovaginal sling, bone anchors for pelvic floor reconstruction).360 Because of increasing resistance of E. coli to fluoroquinolones, local susceptibility patterns should be considered when selecting an anti-infective for prophylaxis in patients undergoing genitourinary surgery.360

Empiric Therapy in Febrile Neutropenic Patients

Ciprofloxacin is used for empiric therapy of presumed bacterial infections in febrile neutropenic patients.579,786,787

IV ciprofloxacin has been used in conjunction with IV piperacillin sodium (no longer commercially available in the US as a single-entity preparation) for empiric anti-infective therapy in febrile neutropenic patients.579 Safety and efficacy of combination therapy with ciprofloxacin and piperacillin sodium for empiric therapy in febrile neutropenic patients have been evaluated in a multicenter, randomized study in adults.579 Patients were randomized to receive a regimen of ciprofloxacin (400 mg IV every 8 hours) and piperacillin sodium (50 mg/kg IV every 4 hours) or a regimen of tobramycin (2 mg/kg IV every 8 hours) and piperacillin sodium (50 mg/kg IV every 4 hours).579 There was clinical resolution of the initial febrile episode (resolution of fever, microbiologic eradication of infection if such infection was microbiologically documented, resolution of signs and symptoms of infection) without modification of the empiric regimen in 27% of those who received ciprofloxacin and piperacillin and in 21.9% of those who received tobramycin and piperacillin; the overall survival rate was 96.1 or 94.1%, respectively.579

Anti-infective prophylaxis with a fluoroquinolone during periods of expected neutropenia is recommended by some experts in patients who are at high risk for febrile neutropenia or profound, protracted neutropenia (e.g., most patients with acute myeloid leukemia/myelodysplastic syndromes [AML/MDS] or hematopoietic stem-cell transplantation [HSCT] treated with myeloablative conditioning regimens).786 These experts state that prophylaxis with a fluoroquinolone is not routinely recommended in patients with solid tumors because the benefits do not outweigh risks in these patients, but may be considered for some patients with solid tumors or lymphoma who are expected to experience profound neutropenia for at least 7 days and are not receiving granulocyte colony-stimulating factor (G-CSF).786

An empiric regimen that includes a fluoroquinolone (ciprofloxacin or levofloxacin) in conjunction with the fixed combination of amoxicillin and clavulanate potassium (or clindamycin in those with penicillin allergy) has been recommended for outpatient management of febrile neutropenic adults receiving treatment for malignancy.787 Use of a fluoroquinolone alone is not recommended for initial empiric therapy for outpatient management in febrile neutropenic patients; however, some studies have shown that monotherapy may be effective in low-risk outpatients.787

Published protocols on anti-infective prophylaxis in febrile neutropenic patients should be consulted for specific recommendations regarding when anti-infective prophylaxis is appropriate for immunosuppressed patients with cancer and options for such prophylaxis.786,787

Administration

Ciprofloxacin is administered orally as conventional tablets containing the hydrochloride,1 as a conventional oral suspension containing the base,1 and as extended-release tablets containing both the hydrochloride and the base.856 Ciprofloxacin is given by IV infusion as the base.579

Patients receiving initial therapy with IV ciprofloxacin may be switched to oral ciprofloxacin (conventional tablets, oral suspension) when clinically appropriate.579

Ciprofloxacin extended-release tablets are used only for the treatment of certain urinary tract infections (UTIs) in adults and should not be used for any indication in pediatric patients.856 The extended-release tablets are not interchangeable with other oral ciprofloxacin preparations (conventional tablets, oral suspension).856

Patients receiving oral or IV ciprofloxacin should be adequately hydrated and should be instructed to drink fluids liberally to prevent highly concentrated urine and formation of crystals in urine.1,579,856

Oral Administration

Ciprofloxacin conventional tablets, extended-release tablets, or oral suspension may be given without regard to meals.1,856

Ciprofloxacin conventional tablets, extended-release tablets, or oral suspension should not be administered concurrently with dairy products (e.g., milk, yogurt) or calcium-fortified products (e.g., juices) alone (without a meal) since absorption of the drug may be substantially reduced.1,856 Doses should preferably be taken 2 hours before or after these calcium-fortified products or substantial calcium intake (greater than 800 mg).1,856

Conventional tablets1 and extended-release tablets856 should be swallowed whole and should not be split, crushed, or chewed.1,856

Following reconstitution, ciprofloxacin oral suspension containing 250 or 500 mg of ciprofloxacin per 5 mL should be administered using the graduated spoon provided by the manufacturer that has markings for 2.5 and 5 mL.1 The microcapsules contained in the reconstituted oral suspensions should be swallowed whole and should not be chewed.1 Water may be ingested after the oral suspension is swallowed.1

Reconstitution

Ciprofloxacin microcapsules for oral suspension are provided in a kit that contains a bottle of microcapsules, a bottle of oral suspension diluent, and a graduated dosing spoon.1 At the time of dispensing, the bottle containing the microcapsules (either 5 or 10 g of ciprofloxacin) should be added to the bottle of diluent according to the manufacturer's directions and shaken vigorously for about 15 seconds to provide a suspension containing 250 or 500 mg of ciprofloxacin per 5 mL, respectively.1 Only the diluent supplied in the kit should be used;1 water should not be added to the oral suspension.1

Prior to administration of each dose, the reconstituted oral suspension should be shaken vigorously for about 15 seconds.1

IV Infusion

Prior to IV infusion, commercially available ciprofloxacin concentrate for injection containing 10 mg/mL must be diluted with a compatible IV solution (e.g., sterile water for injection, 5% or 10% dextrose injection, 0.9% sodium chloride injection, 5% dextrose and 0.225 or 0.45% sodium chloride injection, or lactated Ringer's injection) to provide a solution containing 1-2 mg/mL.579

Alternatively, commercially available premixed ciprofloxacin injection for IV infusion containing 2 mg/mL in 5% dextrose injection may be used without further dilution.579

IV infusions should be given into a large vein to minimize discomfort and reduce the risk of venous irritation.579 If a Y-type administration set is used, the other IV solution flowing through the tubing should be discontinued while ciprofloxacin is being infused.579 If concomitant use of IV ciprofloxacin and another parenteral drug is necessary, each drug should be given separately.579

Rate of Administration

IV infusions of ciprofloxacin should be infused over 1 hour.579

Because local reactions (e.g., thrombophlebitis, burning, pain, pruritus, paresthesia, erythema, swelling) at the site of IV infusion are more frequent when the drug is administered rapidly (e.g., over 30 minutes or less) or via a small vein, ciprofloxacin should be infused IV slowly over a period of 1 hour as a dilute solution (1-2 mg of ciprofloxacin per mL) via a large vein.579 If such reactions occur despite these precautions, they generally resolve rapidly following completion of the infusion; the manufacturers state that subsequent IV administration of ciprofloxacin is not contraindicated unless the reaction recurs or worsens.579

Dosage

Dosage of ciprofloxacin hydrochloride and ciprofloxacin is expressed in terms of ciprofloxacin.1,579

Unless otherwise specified, oral ciprofloxacin dosage is for the conventional tablets or oral suspension of the drug.1

The extended-release tablets are not interchangeable with the conventional tablets or oral suspension.856

Dosage of oral and IV ciprofloxacin is not identical.1,579 Based on pharmacokinetic parameters (i.e., area under the plasma concentration-time curve [AUC]), the following oral and IV ciprofloxacin regimens are considered equivalent: 250 mg orally every 12 hours (conventional tablets) is equivalent to 200 mg IV every 12 hours; 500 mg orally every 12 hours (conventional tablets) is equivalent to 400 mg IV every 12 hours; and 750 mg orally every 12 hours (conventional tablets) is equivalent to 400 mg IV every 8 hours.1,579

The duration of ciprofloxacin therapy depends on the type and severity of infection, and should be determined by the clinical and bacteriologic response of the patient.1,579

Pediatric Dosage

Complicated Urinary Tract Infections and Pyelonephritis

If ciprofloxacin is used for the treatment of complicated UTIs or pyelonephritis in pediatric patients 1-17 years of age, dosage and route of administration should be based on infection severity.1,579 The manufacturers recommend a total treatment duration of 10-21 days;1,579 the mean total duration of treatment (IV and/or oral) in clinical trials was 11 days (range 10-21 days).1,579

If IV ciprofloxacin is used for the treatment of complicated UTIs or pyelonephritis in pediatric patients 1-17 years of age, the manufacturer recommends a dosage of 6-10 mg/kg (up to 400 mg) every 8 hours.579

If oral ciprofloxacin is used for the treatment of complicated UTIs or pyelonephritis in pediatric patients 1-17 years of age, the manufacturer recommends a dosage of 10-20 mg/kg (up to 750 mg) every 12 hours.1

If ciprofloxacin oral suspension containing 250 mg/5 mL is used for the treatment of complicated UTIs or pyelonephritis in pediatric patients 1-17 years of age, the manufacturer recommends a dosage of 125 mg every 12 hours in those weighing 9-12 kg, 250 mg every 12 hours in those weighing 13-18 kg, 250-375 mg every 12 hours in those weighing 19-24 kg, 375-500 mg every 12 hours in those weighing 25-31 kg, 375-625 mg every 12 hours in those weighing 32-37 kg, and 500-750 mg every 12 hours in those weighing 38 kg or more.1

If ciprofloxacin oral suspension containing 500 mg/5 mL is used for the treatment of complicated UTIs or pyelonephritis in pediatric patients 1-17 years of age, the manufacturer recommends a dosage of 250 mg every 12 hours in those weighing 13-24 kg, 250-500 mg every 12 hours in those weighing 25 kg, 500 mg every 12 hours in those weighing 26-37 kg, and 500-750 mg every 12 hours in those weighing 38 kg or more.1

Postexposure Prophylaxis of Anthrax

If oral ciprofloxacin is used for inhalational anthrax (postexposure) to reduce the incidence or progression of disease following exposure to aerosolized Bacillus anthracis spores in the context of biologic warfare or bioterrorism, the manufacturer recommends that neonates, infants, and children 17 years of age or younger receive 15 mg/kg (up to 500 mg) every 12 hours.1

If ciprofloxacin oral suspension containing 250 mg/5 mL is used for inhalational anthrax (postexposure) in neonates, infants, and children 17 years of age or younger, the manufacturer recommends a dosage of 125 mg every 12 hours in those weighing 9-12 kg, 250 mg every 12 hours in those weighing 13-18 kg, 250-375 mg every 12 hours in those weighing 19-24 kg, and 500 mg every 12 hours in those weighing 25 kg or more.1

If ciprofloxacin oral suspension containing 500 mg/5 mL is used for inhalational anthrax (postexposure) in neonates, infants, and children 17 years of age or younger, the manufacturer recommends a dosage of 250 mg every 12 hours in those weighing 13-24 kg and 500 mg every 12 hours in those weighing 25 kg or more.1

If IV ciprofloxacin is used for inhalational anthrax (postexposure) in neonates, infants, and children 17 years of age or younger, the manufacturer recommends a dosage of 10 mg/kg (up to 400 mg) every 12 hours.579

For postexposure prophylaxis of anthrax in neonates up to 4 weeks of age following an exposure that occurred in the context of biologic warfare or bioterrorism, the American Academy of Pediatrics (AAP) recommends that oral ciprofloxacin be given in a dosage of 10 mg/kg every 12 hours in preterm neonates (gestational age 32-37 weeks) and 15 mg/kg every 12 hours in full-term neonates.671 AAP recommends that pediatric patients 1 month of age or older receive oral ciprofloxacin in a dosage of 15 mg/kg (up to 500 mg) every 12 hours for such postexposure prophylaxis.671

Postexposure anti-infective prophylaxis should be initiated as soon as possible following suspected or confirmed anthrax exposure.1,579,668,673,683

Because of possible persistence of B. anthracis spores in lung tissue following an aerosol exposure, the US Centers for Disease Control and Prevention (CDC), AAP, and others recommend that anti-infective prophylaxis be continued for 60 days following a confirmed exposure.1,579,668,671,672,673,683

Treatment of Systemic Anthrax

If IV ciprofloxacin is used in neonates up to 4 weeks of age as part of a multiple-drug parenteral regimen for initial treatment of systemic anthrax† (inhalational, GI, meningitis, or cutaneous with systemic involvement, extensive edema, or head or neck lesions) that occurs in the context of biologic warfare or bioterrorism, AAP recommends a dosage of 10 mg/kg every 12 hours in preterm neonates (gestational age 32-37 weeks) and 15 mg/kg every 12 hours in full-term neonates.671

If IV ciprofloxacin is used in pediatric patients 1 month of age or older as part of a multiple-drug parenteral regimen for initial treatment of systemic anthrax† (inhalational, GI, meningitis, or cutaneous with systemic involvement, lesions on the head or neck, or extensive edema) that occurs in the context of biologic warfare or bioterrorism, AAP recommends a dosage of 10 mg/kg (up to 400 mg) every 8 hours.671

The multiple-drug parenteral regimen should be continued for at least 2-3 weeks until the patient is clinically stable and treatment can be switched to an appropriate oral anti-infective.671 If systemic anthrax occurred as the result of exposure to aerosolized B. anthracis spores (e.g., in the context of biologic warfare or bioterrorism), the oral follow-up regimen should be continued until 60 days after onset of the illness.671

When oral ciprofloxacin is used for follow-up treatment of systemic anthrax after an initial parenteral regimen in neonates up to 4 weeks of age, AAP recommends a dosage of 10 mg/kg every 12 hours in preterm neonates (gestational age 32-37 weeks) and 15 mg/kg every 12 hours in full-term neonates.671 AAP recommends a dosage of 15 mg/kg (up to 500 mg) every 12 hours when oral ciprofloxacin is used for such follow-up treatment in pediatric patients 1 months of age or older.671

Treatment of Uncomplicated Cutaneous Anthrax

If oral ciprofloxacin is used in neonates up to 4 weeks of age for the treatment of uncomplicated cutaneous anthrax† (without systemic involvement) that occurs in the context of biologic warfare or bioterrorism, AAP recommends a dosage of 10 mg/kg every 12 hours in preterm neonates (gestational age 32-37 weeks) and 15 mg/kg every 12 hours in full-term neonates.671

If oral ciprofloxacin is used in pediatric patients 1 month of age or older for the treatment of uncomplicated cutaneous anthrax† (without systemic involvement) that occurs in the context of biologic warfare or bioterrorism, AAP recommends a dosage of 15 mg/kg (up to 500 mg) every 12 hours.671

If uncomplicated cutaneous anthrax occurred after exposure to aerosolized B. anthracis spores in the context of biologic warfare or bioterrorism, anti-infective treatment should be continued for 60 days after onset of the illness.671 A treatment duration of 7-10 days may be sufficient if uncomplicated cutaneous anthrax occurred as the result of naturally occurring or endemic exposures.671

Treatment of Plague

When IV ciprofloxacin is used for the treatment of plague (including pneumonic and septicemic plague) caused by Yersinia pestis , the manufacturer recommends that neonates, infants, and children 17 years of age or younger receive a dosage of 10 mg/kg (up to 400 mg) every 8-12 hours.579

If oral ciprofloxacin is used for the treatment of plague, the manufacturer recommends that neonates, infants, and children 17 years of age or younger receive a dosage of 15 mg/kg (up to 500 mg) every 8-12 hours.1

If ciprofloxacin oral suspension containing 250 mg/5 mL is used for the treatment of plague in neonates, infants, and children 17 years of age or younger, the manufacturer recommends a dosage of 125 mg every 12 hours in those weighing 9-12 kg, 250 mg every 12 hours in those weighing 13-18 kg, 250-375 mg every 12 hours in those weighing 19-24 kg, 375-500 mg every 12 hours in those weighing 25-31 kg, 375-625 mg every 12 hours in those weighing 32-37 kg, and 500-750 mg every 12 hours in those weighing 38 kg or more.1

If ciprofloxacin oral suspension containing 500 mg/5 mL is used for the treatment of plague in neonates, infants, and children 17 years of age or younger, the manufacturer recommends a dosage of 250 mg every 12 hours in those weighing 13-24 kg, 250-500 mg every 12 hours in those weighing 25 kg, 500 mg every 12 hours in those weighing 26-37 kg, and 500-750 mg every 12 hours in those weighing 38 kg or more.1

Some experts (e.g., US Working Group on Civilian Biodefense, US Army Medical Research Institute of Infectious Diseases [USAMRIID]) recommend that children receive IV ciprofloxacin in a dosage of 15 mg/kg every 12 hours (up to 1 g daily) for the treatment of pneumonic plague that occurs as the result of exposure to Y. pestis in the context of biologic warfare or bioterrorism.683,688 If oral ciprofloxacin is used for the treatment of plague when the patient's clinical condition improves or when a parenteral regimen is not available (e.g., in mass casualty settings), some experts (e.g., US Working Group on Civilian Biodefense) recommend that children receive 20 mg/kg twice daily (up to 1 g daily).688

A parenteral regimen is preferred for initial treatment of plague;683,688 an oral regimen can be used after clinical improvement occurs or when a parenteral regimen is not available (e.g., mass casualty setting).683,688

The manufacturer recommends a total treatment duration (IV and oral) of 10-21 days in pediatric patients;579 some experts state that the total treatment duration should be 10-14 days.683,688

Postexposure Prophylaxis of Plague

When oral ciprofloxacin is used for prophylaxis of plague, the manufacturer recommends that neonates, infants, and children 17 years of age or younger receive a dosage of 15 mg/kg (up to 500 mg) every 8-12 hours for 10-21 days.1

If ciprofloxacin oral suspension containing 250 mg/5 mL is used for prophylaxis of plague in neonates, infants, and children 17 years of age or younger, the manufacturer recommends a dosage of 125 mg every 12 hours in those weighing 9-12 kg, 250 mg every 12 hours in those weighing 13-18 kg, 250-375 mg every 12 hours in those weighing 19-24 kg, 375-500 mg every 12 hours in those weighing 25-31 kg, 375-625 mg every 12 hours in those weighing 32-37 kg, and 500-750 mg every 12 hours in those weighing 38 kg or more.1

If ciprofloxacin oral suspension containing 500 mg/5 mL is used for the prophylaxis of plague in neonates, infants, and children 17 years of age or younger, the manufacturer recommends a dosage of 250 mg every 12 hours in those weighing 13-24 kg, 250-500 mg every 12 hours in those weighing 25 kg, 500 mg every 12 hours in those weighing 26-37 kg, and 500-750 mg every 12 hours in those weighing 38 kg or more.1

If IV ciprofloxacin is used for prophylaxis of plague, the manufacturer recommends that neonates, infants, and children 17 years of age or younger receive a dosage of 10 mg/kg (up to 400 mg) every 8-2 hours for 10-21 days.579

Some experts (e.g., US Working Group on Civilian Biodefense, USAMRIID) recommend that children receive oral ciprofloxacin in a dosage of 20 mg/kg twice daily (up to 1 g daily) for postexposure prophylaxis following exposure to Y. pestis in the context of biologic warfare or bioterrorism.683,688

Postexposure prophylaxis of plague should be initiated as soon as possible after a suspected or confirmed exposure to Y. pestis .1,579

In close contacts of patients with pneumonic plague or individuals exposed to plague aerosol (e.g., in the context of biologic warfare or bioterrorism), prophylaxis should be continued for 7 days or for the duration of the risk of exposure plus 7 days.683,688 If fever or cough develops during prophylaxis, the regimen should be switch to that used for treatment of plague.683,688

Treatment of Tularemia

If IV ciprofloxacin is used for the treatment of tularemia† that occurs as the result of exposure to Francisella tularensis in the context of biologic warfare or bioterrorism, some experts (e.g., US Working Group on Civilian Biodefense, USAMRIID) recommend that children receive 15 mg/kg every 12 hours (up to 1 g daily) for at least 10-14 days.683,689 Oral therapy may be substituted when the patient's condition improves.683,689

If oral ciprofloxacin is used for the treatment of tularemia when the patient's clinical condition improves or if a parenteral regimen is not available, experts recommend that children receive 15 mg/kg twice daily (up to 1 g daily) for a total treatment duration of at least 10-14 days.683,689

Postexposure Prophylaxis of Tularemia

If oral ciprofloxacin is used for postexposure prophylaxis of tularemia† following exposure to F. tularensis that occurs in the context of biologic warfare or bioterrorism, some experts (e.g., US Working Group on Civilian Biodefense, USAMRIID) recommend that children receive 15 mg/kg orally twice daily (up to 1 g daily).683,689

Postexposure prophylaxis of tularemia ideally should be initiated within 24 hours of exposure and continued for at least 14 days.683,689

Cystoisospora Infections

If oral ciprofloxacin is used as an alternative for the treatment of infections caused by Cystoisospora belli † (formerly Isospora belli ) in pediatric patients with human immunodeficiency virus (HIV) infection, the recommended dosage is 10-20 mg/kg (up to 500 mg) twice daily for 7 days.441

If oral ciprofloxacin is used for chronic maintenance therapy (secondary prophylaxis) of cystoisosporiasis in HIV-infected pediatric patients†, a dosage of 10-20 mg/kg (up to 500 mg) 3 times weekly is recommended.441 Consideration can be given to discontinuing such prophylaxis in pediatric patients if there is no evidence of active Cystoisospora infection and there has been sustained improvement in immunologic status (CDC immunologic category 1 or 2) for more than 6 months in response to antiretroviral therapy.441

Meningitis and Other CNS Infections

Although safety and efficacy have not been established, if use of IV ciprofloxacin is considered necessary for the treatment of healthcare-associated ventriculitis and meningitis† caused by susceptible gram-negative bacteria when the drugs of choice cannot be used, the Infectious Diseases Society of America (IDSA) recommends that pediatric patients receive a dosage of 30 mg/kg daily given in divided doses every 8-12 hours.416

Neisseria meningitidis Infections

If use of ciprofloxacin is considered necessary in children and infants 1 month of age or older to eliminate nasopharyngeal carriage of Neisseria meningitidis † or for chemoprophylaxis in household or other close contacts of individuals with invasive meningococcal disease† when other anti-infectives (e.g., rifampin, ceftriaxone) cannot be used, AAP recommends a single oral dose of 20 mg/kg (up to 500 mg).292 Ciprofloxacin should be used only if fluoroquinolone-resistant N. meningitis have not been identified in the community.292

Vibrio Infections

If use of ciprofloxacin is considered necessary in pediatric patients for the treatment of cholera†, AAP recommends a dosage of 15 mg/kg (up to 500 mg) twice daily for 3 days.292 Children 2-12 years of age have received a single oral ciprofloxacin dose of 20 mg/kg (up to 750 mg) for the treatment of cholera caused by V. cholerae 01 or 0139.758

Adult Dosage

Bone and Joint Infections

If IV ciprofloxacin is used for the treatment of bone and joint infections in adults, the manufacturer recommends a dosage of 400 mg every 8 to 12 hours for 4-8 weeks.579

If oral ciprofloxacin is used for the treatment of bone and joint infections in adults, the manufacturer recommends a dosage of 500-750 mg every 12 hours for 4-8 weeks.1

For the treatment of native vertebral osteomyelitis, IDSA recommends that IV ciprofloxacin be given in a dosage of 400 mg every 8 hours for 6 weeks for infections caused by Ps. aeruginosa or a dosage of 400 mg every 12 hours for the treatment of infections caused by Enterobacteriaceae.590 If oral ciprofloxacin is used for the treatment of native vertebral osteomyelitis, IDSA recommends a dosage of 750 mg every 12 hours for 6 weeks for infections caused by Ps. aeruginosa , 500 mg every 12 hours for 6-8 weeks for infections caused by Salmonella , and 500-750 mg every 12 hours for 6 weeks for infections caused by other Enterobacteriaceae.590

For the treatment of prosthetic joint infections, IDSA recommends that IV ciprofloxacin be given in a dosage of 400 mg every 12 hours for 4-6 weeks for infections caused by Ps. aeruginosa or Enterobacter .491 If oral ciprofloxacin is used for the treatment of prosthetic joint infections, IDSA recommends a dosage of 750 mg twice daily for 4-6 weeks for infections caused by Ps. aeruginosa and for infections caused by Enterobacter or other Enterobacteriaceae.591

Endocarditis

For the treatment of endocarditis† (native or prosthetic valve or other prosthetic material) caused by fastidious gram-negative bacilli of the HACEK group when ceftriaxone (or other third or fourth generation cephalosporin) cannot be used, the American Heart Association (AHA) and IDSA suggest that adults receive IV ciprofloxacin in a dosage of 800 mg daily given in 2 equally divided doses or oral ciprofloxacin in a dosage of 1 g daily given in 2 equally divided doses.450

Treatment should be continued for 4 weeks in those with native valve endocarditis or for 6 weeks in those with endocarditis involving prosthetic cardiac valves or other prosthetic cardiac material.450 Because only limited data are available regarding use of ciprofloxacin for the treatment of these infections, AHA and IDSA recommend that patients with HACEK endocarditis who cannot receive ceftriaxone be treated in consultation with an infectious disease specialist.450

Infectious Diarrhea

The usual oral dosage of ciprofloxacin for the treatment of infectious diarrhea in adults is 500 mg every 12 hours for 5-7 days.1,350,378,612

Campylobacter Infections

For the treatment of campylobacteriosis caused by susceptible Campylobacter in HIV-infected adults, the recommended dosage of oral ciprofloxacin is 500-750 mg every 12 hours.440 If IV ciprofloxacin is used, the recommended dosage is 400 mg every 12 hours.440

The recommended duration of treatment in HIV-infected adults is 7-10 days for gastroenteritis or at least 14 days for bacteremic infections.440 A duration of 2-6 weeks is recommended for recurrent infections.440

Cyclospora Infections

If oral ciprofloxacin is used for the treatment of infections caused by Cyclospora cayetanensis †, some clinicians recommend that adults receive 500 mg twice daily for 7 days.134

Cystoisospora Infections

If oral ciprofloxacin is used as an alternative for the treatment of infections caused by C. belli † (formerly I. belli ) in HIV-infected adults, the recommended dosage is 500 mg twice daily for 7 days.440

If oral ciprofloxacin is used as an alternative for chronic maintenance therapy (secondary prophylaxis) of cystoisosporiasis† in HIV-infected adults with CD4⁺ T-cell counts less than 200 cells/mm³, a dosage of 500 mg 3 times weekly is recommended based on limited data.440 Consideration can be given to discontinuing such prophylaxis if CD4⁺ T-cell counts exceed 200 cells/mm³ for more than 6 months in response to antiretroviral therapy.440

Salmonella Gastroenteritis

For the treatment of Salmonella gastroenteritis† (with or without bacteremia) in HIV-infected adults, the recommended dosage of oral ciprofloxacin is 500-750 mg every 12 hours.440 Alternatively, 400 mg can be given IV every 12 hours.440

The recommended duration of treatment in HIV-infected adults is 7-14 days in those with CD4⁺ T-cell counts of 200 cells/mm³ or greater (14 days or longer if the patient is bacteremic or the infection is complicated) or 2-6 weeks in those with CD4⁺ T-cell counts less than 200 cells/mm³.440

Shigella Infections

For the treatment of shigellosis caused by susceptible Shigella in HIV-infected adults, the recommended dosage of oral ciprofloxacin is 500-750 mg every 12 hours.440 Alternatively, 400 mg can be given IV every 12 hours.440

The recommended duration of treatment in HIV-infected adults is 7-10 days for gastroenteritis or at least 14 days for bacteremic infections.440 Recurrent infections, especially in patients with CD4⁺ T-cell counts less than 200 cells/mm³, may require up to 6 weeks of treatment.440

Travelers' Diarrhea

If oral ciprofloxacin (conventional tablets or oral suspension) is used for the treatment of travelers' diarrhea† in adults, some clinicians recommend a dosage of 500 once or twice daily for 1-3 days or 750 mg once daily for 1-3 days.305 Alternatively, if ciprofloxacin extended-release tablets are used, some clinicians recommend a dosage of 500 mg or 1 g once daily for 1-3 days.305

If ciprofloxacin is used for empiric treatment of travelers' diarrhea† in HIV-infected adults, an oral dosage of 500-750 mg every 12 hours or IV dosage of 400 mg every 12 hours is recommended.440 If there is no clinical response after 3-4 days of treatment, stool culture and in vitro susceptibility testing should be considered.440

Although the use of anti-infectives for prophylaxis of travelers' diarrhea† generally is discouraged,305,525 if oral ciprofloxacin (conventional tablets or oral suspension) is used, the recommended adult dosage is 500 mg once daily during the period of risk (not exceeding 2-3 weeks) beginning the day of travel and continuing for 1 or 2 days after leaving the area of risk.305,650,651,677

Intra-abdominal Infections

When IV ciprofloxacin is used for the treatment of complicated intra-abdominal infections, the recommended dosage for adults is 400 mg every 12 hours given in conjunction with metronidazole.579 If oral ciprofloxacin is used for the treatment of complicated intra-abdominal infections, the recommended dosage for adults is 500 mg every 12 hours in conjunction with metronidazole.1

The manufacturers recommend a total treatment duration of 7-14 days.1,579 IDSA states that the usual duration of treatment for intra-abdominal infections is 4-7 days.773 A longer duration of treatment has not been associated with improved outcome and is not recommended unless adequate source control is difficult to achieve.773

Meningitis and Other CNS Infections

Although efficacy and safety have not been established, some clinicians suggest that adults can receive IV ciprofloxacin in a dosage of 400 mg every 8 hours for the treatment of meningitis† caused by susceptible gram-negative bacteria.766 Other clinicians recommend a dosage of 800-1200 mg daily for the treatment of meningitis in adults.418

If IV ciprofloxacin is used for the treatment of healthcare-associated ventriculitis and meningitis† caused by susceptible gram-negative bacteria when the drugs of choice cannot be used, IDSA recommends that adults receive a dosage of 800-1200 mg daily given in divided doses every 8-12 hours.416

Malignant Otitis Externa

If oral ciprofloxacin is used for the treatment of malignant otitis externa†, some clinicians recommend a dosage of 750 mg twice daily.784,816 Although there may be rapid relief of symptoms (pain, otorrhea), treatment should be continued for 6-8 weeks.784,816

Because ciprofloxacin-resistant Pseudomonas aeruginosa have been isolated from patients with malignant otitis externa with increasing frequency,783,784,785 in vitro susceptibility testing is indicated, especially if there is an inadequate response to treatment.785

Acute Sinusitis

If oral ciprofloxacin is used for the treatment of acute sinusitis, dosage in adults is 500 mg every 12 hours for 10 days.1

The usual IV dosage of ciprofloxacin for the treatment of acute sinusitis in adults is 400 mg every 12 hours for 10 days.579

Lower Respiratory Tract Infections

The usual dosage of oral ciprofloxacin for the treatment of lower respiratory tract infections in adults is 500-750 mg every 12 hours for 7-14 days.1

The usual IV dosage of ciprofloxacin for the treatment of lower respiratory tract infections in adults is 400 mg every 8 to 12 hours;579 severe or complicated lower respiratory tract infections should be treated with 400 mg IV every 8 hours. The usual duration of treatment is 7-14 days.579

Nosocomial Pneumonia

The usual dosage of IV ciprofloxacin for the treatment of nosocomial pneumonia in adults, including hospital-acquired pneumonia (HAP) not associated with mechanical ventilation and ventilator-associated pneumonia (VAP), is 400 mg every 8 hours.315,579

The manufacturer recommends a treatment duration of 10-14 days.579 IDSA states that a treatment duration of 7 days is recommended in patients with HAP or VAP; however, a longer or shorter duration may be indicated depending on clinical response.315

Skin and Skin Structure Infections

For the treatment of skin and skin structure infections, the usual dosage of oral ciprofloxacin for adults is 500-750 mg every 12 hours for 7-14 days.1

The usual IV dosage of ciprofloxacin for the treatment of skin and skin structure infections in adults is 400 mg every 8 to 12 hours for 7-14 days.579

Acute, Uncomplicated Cystitis

If ciprofloxacin (conventional tablets or oral suspension) is used for the treatment of acute, uncomplicated cystitis, dosage in adults is 250 mg every 12 hours for 3 days.1

If ciprofloxacin extended-release tablets are used for the treatment of uncomplicated UTIs (acute cystitis) caused by susceptible E. faecalis , Escherichia coli , Proteus mirabilis , or Staphylococcus saprophyticus , the recommended dosage in adults is 500 mg once every 24 hours for 3 days.856

Complicated Urinary Tract Infections and Pyelonephritis

The usual oral dosage of ciprofloxacin (conventional tablets or oral suspension) for the treatment of UTIs in adults is 250-500 mg every 12 hours for 7-14 days.1

If ciprofloxacin extended-release tablets are used for the treatment of complicated UTIs or acute, uncomplicated pyelonephritis caused by susceptible bacteria, the usual adult dosage is 1 g once every 24 hours for 7-14 days.856

The usual IV dosage of ciprofloxacin for the treatment of UTIs in adults is 200-400 mg every 8 to 12 hours for 7-14 days.

Prostatitis

For the treatment of chronic bacterial prostatitis in men, the usual oral dosage of ciprofloxacin (conventional tablets or oral suspension) is 500 mg every 12 hours for 28 days.1

The usual IV dosage of ciprofloxacin for the treatment of chronic bacterial prostatitis is 400 mg every 12 hours for 28 days.579

Postexposure Prophylaxis of Anthrax

When oral ciprofloxacin is used for inhalational anthrax (postexposure) to reduce the incidence or progression of disease following exposure to aerosolized B. anthracis spores in the context of biologic warfare or bioterrorism, adults should receive 500 mg every 12 hours.1,668,682,683 If IV ciprofloxacin is used for inhalational anthrax (postexposure), adults should receive 400 mg IV every 12 hours.579

CDC recommends that adults (including pregnant and postpartum women) receive oral ciprofloxacin in a dosage of 500 mg every 12 hours for postexposure prophylaxis of anthrax.672,673

Postexposure anti-infective prophylaxis should be initiated as soon as possible following suspected or confirmed anthrax exposure.1,579,668,673,683

Because of possible persistence of B. anthracis spores in lung tissue following an aerosol exposure, CDC and other experts recommend that anti-infective prophylaxis be continued for 60 days following a confirmed exposure.668,672,673,682,683

For prophylaxis following ingestion of B. anthracis spores† in contaminated meat, a ciprofloxacin dosage of 500 mg orally twice daily has been recommended for adults.662

If anti-infective prophylaxis is used following a naturally occurring GI exposure to B. anthracis (e.g., ingestion of meat from an undercooked carcass of an anthrax-infected animal), ACIP states that a duration of 7-14 days can be considered.663

Treatment of Systemic Anthrax

When IV ciprofloxacin is used in a multiple-drug parenteral regimen for initial treatment of systemic anthrax† (inhalational, GI, meningitis, or cutaneous anthrax with systemic involvement, lesions on the head or neck, or extensive edema) that occurs in the context of biologic warfare or bioterrorism, CDC recommends that adults (including pregnant and postpartum women) receive a dosage of 400 mg every 8 hours.672,673

The multiple-drug parenteral regimen should be continued for at least 2-3 weeks until the patient is clinically stable and treatment can be switched to an oral anti-infective.672,673 If systemic anthrax occurred as the result of exposure to aerosolized B. anthracis spores (e.g., in the context of biologic warfare or bioterrorism), the oral follow-up regimen should be continued until 60 days after onset of the illness.668,672,673

If oral ciprofloxacin is used for follow-up after an initial parenteral regimen or as an alternative for the treatment of inhalational anthrax† when a parenteral regimen is not available (e.g., when there are supply or logistic problems because large numbers of individuals require treatment in a mass casualty setting), some experts (US Working Group on Civilian Biodefense, USAMRIID) recommend that adults receive an oral dosage of 500 mg every 12 hours.668,683

Treatment of Uncomplicated Cutaneous Anthrax

For the treatment of uncomplicated cutaneous anthrax† (without systemic involvement) that occurs in the context of biologic warfare or bioterrorism, CDC recommends that adults (including pregnant and postpartum women) receive oral ciprofloxacin in a dosage of 500 mg every 12 hours.672,673

If uncomplicated cutaneous anthrax occurred after exposure to aerosolized B. anthracis spores in the context of biologic warfare or bioterrorism, anti-infective treatment should be continued for 60 days after onset of the illness.672,673 A treatment duration of 3-10 days may be sufficient if uncomplicated cutaneous anthrax occurred as the result of naturally occurring or endemic exposures.668,672,673,680,683

Treatment of GI or Oropharyngeal Anthrax

For treatment of GI and oropharyngeal anthrax† that occurs in the context of biologic warfare or bioterrorism, CDC and other experts (US Working Group on Civilian Biodefense, USAMRIID) recommend that therapy be initiated with the same parenteral multiple-drug regimen recommended for treatment of inhalational anthrax.668,683,686,703

Brucellosis

For the treatment of brucellosis† caused by Brucella melitensis , some clinicians recommend that oral ciprofloxacin be given in a dosage of 500 mg twice daily in conjunction with oral rifampin (600 mg once daily).771,772 Oral ciprofloxacin also has been given in a dosage of 500 mg 2 or 3 times daily for 6-12 weeks or 750 mg 3 times daily for 6-8 weeks for the treatment of brucellosis or acute brucella arthritis-diskitis†.624 Monotherapy or treatment regimens shorter than 4-6 weeks are not recommended.683,772

Chancroid

When oral ciprofloxacin is used in the treatment of chancroid†, CDC recommends that adults receive 500 mg twice daily for 3 days.344

Crohn's Disease

Oral ciprofloxacin has been given in a dosage of 500 mg twice daily (with or without metronidazole) for induction of remission of mildly to moderately active Crohn's disease†.742,744,745,746,749

Gonorrhea and Associated Infections

Although ciprofloxacin is no longer recommended for the treatment of gonorrhea, the manufacturer recommends a single 250-mg dose of oral ciprofloxacin for the treatment of uncomplicated urethral or endocervical gonorrhea caused by susceptible Neisseria gonorrhoeae .1

Granuloma Inguinale (Donovanosis)

For the treatment of granuloma inguinale† (donovanosis) caused by Klebsiella granulomatis (formerly Calymmatobacterium granulomatis ), 750 mg of oral ciprofloxacin should be given twice daily for at least 3 weeks and until all lesions have completely healed.344 Consideration can be given to adding a parenteral aminoglycoside (e.g., gentamicin 1 mg/kg IV every 8 hours) if improvement is not evident within the first few days of treatment.344

Legionnaires' Disease

For the treatment of Legionnaires' disease†, some clinicians recommend that 500 mg of ciprofloxacin be given orally every 12 hours or 400 mg be given IV every 12 hours for 2-3 weeks.622

Mycobacterial Infections

When used in multiple-drug regimens for the treatment of Mycobacterium avium complex (MAC) infections†, oral ciprofloxacin has been given to adults in a dosage of 750 mg twice daily. 616,617,675

Neisseria meningitidis Infections

When ciprofloxacin is used to eliminate nasopharyngeal carriage of N. meningitidis † or for chemoprophylaxis in household or other close contacts of individuals with invasive meningococcal disease†, adults should receive a single 500-mg oral dose.376

Treatment of Plague

When IV ciprofloxacin is used for the treatment of plague caused by Y. pestis , the manufacturer recommends that adults receive a dosage of 400 mg every 8 to 12 hours for 14 days.579

If oral ciprofloxacin is used for the treatment of plague, the manufacturer recommends that adults receive a dosage of 500-750 mg orally every 12 hours for 14 days.1

Some experts (e.g., US Working Group on Civilian Biodefense, USAMRIID) recommend that adults receive a dosage of 400 mg every 12 hours if IV ciprofloxacin is used for as an alternative for the treatment of pneumonic plague that occurs as the result of exposure to Y. pestis in the context of biologic warfare or bioterrorism.683,688 If oral ciprofloxacin is used for the treatment of plague when the patient's clinical condition improves or when a parenteral regimen is not available (e.g., in mass casualty settings), these experts recommend that adults receive 500-750 mg orally twice daily.683,688

A parenteral regimen is preferred for initial treatment of plague; an oral regimen can be used after clinical improvement occurs or when a parenteral regimen is not available (e.g., mass casualty setting).683,688

The manufacturer recommends a total treatment duration (IV and oral) of 14 days in adults;579 some experts state that the total treatment duration should be 10-14 days.683,688

Postexposure Prophylaxis of Plague

When oral ciprofloxacin is used for prophylaxis of plague, the manufacturer recommends that adults receive a dosage of 500-750 mg orally every 12 hours for 14 days.1

If IV ciprofloxacin is used for prophylaxis of plague, the manufacturer recommends that adults receive a dosage of 400 mg every 8 to 12 hours for 14 days.579

Some experts (e.g., US Working Group on Civilian Biodefense, USAMRIID) recommend that oral ciprofloxacin be given in a dosage of 500 mg twice daily if the drug is used for postexposure prophylaxis following exposure to Y. pestis in the context of biologic warfare or bioterrorism.683,688

Postexposure prophylaxis of plague should be initiated as soon as possible after a suspected or confirmed exposure to Y. pestis .1,579

In close contacts of patients with pneumonic plague or individuals exposed to plague aerosol (e.g., in the context of biologic warfare or bioterrorism), prophylaxis should be continued for 7 days or for the duration of the risk of exposure plus 7 days.683,688 If fever or cough develops during prophylaxis, the regimen should be switch to that used for treatment of plague.683,688

Treatment of Tularemia

If IV ciprofloxacin is used for the treatment of tularemia† that occurs as the result of exposure to F. tularensis in the context of biologic warfare or bioterrorism, some experts (e.g., US Working Group on Civilian Biodefense, USAMRIID) recommend that adults receive a dosage of 400 mg every 12 hours.683,689 Oral therapy may be substituted when the patient's condition improves.683,689

If oral ciprofloxacin is used for the treatment of tularemia when the patient's clinical condition improves or if a parenteral regimen is not available, adults should receive 500 mg orally twice daily.683,689

Postexposure Prophylaxis of Tularemia

If oral ciprofloxacin is used for postexposure prophylaxis of tularemia† following exposure to F. tularensis that occurs in the context of biologic warfare or bioterrorism, some experts (e.g., US Working Group on Civilian Biodefense, USAMRIID) recommend that adults receive 500 mg orally every 12 hours.683,689

Postexposure prophylaxis ideally should be initiated within 24 hours of exposure and continued for at least 14 days.683,689

Typhoid Fever and Other Invasive Salmonella Infections

The usual adult oral dosage of ciprofloxacin for the treatment of mild to moderate typhoid fever is 500 mg every 12 hours for 10 days.1

Although the optimum dosage and duration of therapy have not been established, oral ciprofloxacin dosages of 750 mg twice daily for 28 days have been used in adults for the treatment of chronic typhoid carriers†.391,403,438,466,473

Vibrio Infections

For the treatment of cholera† caused by Vibrio cholerae 01 or 0139, adults have received oral ciprofloxacin in a dosage of 1 g given either as a single dose or in 2 divided doses 12 hours apart.664,757

Perioperative Prophylaxis

If ciprofloxacin is used for perioperative prophylaxis† in high risk patients undergoing genitourinary procedures, some clinicians recommend that a single 500-mg oral dose or a single 400-mg IV dose of ciprofloxacin be given prior to the procedure.360 If IV ciprofloxacin is used, the dose should be given within 1-2 hours prior to the procedure or initial incision.360 Postoperative doses generally are unnecessary and should not be used.360

Empiric Therapy in Febrile Neutropenic Patients

For empiric anti-infective therapy in febrile neutropenic patients, the manufacturer recommends that adults receive ciprofloxacin in a dosage of 400 mg IV every 8 hours for 7-14 days given in conjunction with piperacillin sodium (50 mg/kg IV every 4 hours, not to exceed 24 g/daily or 300 mg/kg daily; no longer commercially available in the US as a single-entity preparation).579

Dosage in Renal and Hepatic Impairment

Renal Impairment

Dosage adjustments may be necessary when ciprofloxacin is used in adults with renal impairment, especially those with severe impairment.1,579,856

Dosage recommendations are not available for use of ciprofloxacin in pediatric patients with impaired renal function (creatinine clearances less than 50 mL/minute).1,579

When ciprofloxacin conventional tablets or oral suspension is used in adults, modification of the usual dosage is unnecessary in patients with creatinine clearances exceeding 50 mL/minute.1 However, dosage should be decreased in adults with creatinine clearances of 50 mL/minute or less.1 (See Table 1.) The manufacturer states that a dosage of 750 mg administered at the intervals noted in Table 1 may be used with close monitoring in adults with severe infections and severe renal impairment.1

Dosage adjustments are not needed when ciprofloxacin 500-mg extended-release tablets are used for the treatment of uncomplicated UTIs (acute cystitis) in adults with renal impairment.856 However, a decreased dosage of 500 mg once daily is recommended when extended-release tablets are used for the treatment of complicated UTIs or acute uncomplicated pyelonephritis in adults with creatinine clearances of 30 mL/minute or less.856 (See Table 2.) The maximum dosage of ciprofloxacin extended-release tablets in adults undergoing hemodialysis or peritoneal dialysis (including continuous ambulatory peritoneal dialysis) is 500 mg once daily.856 The manufacturers state that the 1-g extended-release tablets are not recommended in adults who have creatinine clearances of 30 mL/minute or less or are undergoing hemodialysis or peritoneal dialysis.856

Dosage adjustments are not needed when IV ciprofloxacin is used in adults with creatinine clearances exceeding 30 mL/minute.579 However, dosage should be decreased in those with creatinine clearances less than 30 mL/minute.579 (See Table 3.)

Hepatic Impairment

The manufacturers make no specific dosage recommendations for patients with impaired hepatic function.1,579 Patients with both hepatic and renal impairment should be carefully monitored.579

In preliminary studies in patients with stable chronic liver cirrhosis, no clinically important changes in ciprofloxacin pharmacokinetics were observed; however, the pharmacokinetics of the drug in patients with acute hepatic insufficiency have not been fully studied.1,579,856

Adverse effects reported with ciprofloxacin are similar to those reported with other fluoroquinolone anti-infectives (e.g., gemifloxacin, levofloxacin, moxifloxacin, ofloxacin).1,177,178,297,301,317,355,422,424,426,579,596 Adverse effects have been reported in 5-14% of patients receiving ciprofloxacin,1,177,178,183,297,426,466,474,479 and have been severe enough to require discontinuance in up to 3.5% of patients.1,177,178,183,425,426,474,479,579,856 The most frequent adverse effects of the drug include nausea, diarrhea, vomiting, abnormal liver function test results and rash.1,177,178,180,183,297,333,426,466,474,479,579,856

Systemic fluoroquinolones, including ciprofloxacin, have been associated with disabling and potentially irreversible serious adverse reactions (e.g., tendinitis and tendon rupture, peripheral neuropathy, CNS effects) that can occur together in the same patient.1,140,145,579,856 These serious reactions may occur within hours to weeks after a systemic fluoroquinolone is initiated and have occurred in all age groups and in patients without preexisting risk factors for such adverse reactions.1,579,856

Tendinitis and Tendon Rupture

Systemic fluoroquinolones, including ciprofloxacin, are associated with an increased risk of tendinitis and tendon rupture in all age groups.1,579,851,852,856

The risk of developing fluoroquinolone-associated tendinitis and tendon rupture is increased in older adults (usually those older than 60 years of age), individuals receiving concomitant corticosteroids, and kidney, heart, or lung transplant recipients.1,579,856 Other factors that may independently increase the risk of tendon rupture include strenuous physical activity, renal failure, and previous tendon disorders such as rheumatoid arthritis.1,579,856 However, tendinitis and tendon rupture have been reported in patients receiving fluoroquinolones who did not have any risk factors for such adverse effects.1,579,856

Fluoroquinolone-associated tendinitis and tendon rupture most frequently involve the Achilles tendon and have also been reported in the rotator cuff (shoulder), hand, biceps, thumb, and other tendon sites.1,579,856 Tendinitis or tendon rupture can occur within hours or days after ciprofloxacin is initiated or as long as several months after completion of therapy and can occur bilaterally.1,579,856

Ciprofloxacin should be discontinued immediately if pain, swelling, inflammation, or rupture of a tendon occurs.1,579,856

Peripheral Neuropathy

Systemic fluoroquinolones, including ciprofloxacin, have been associated with an increased risk of peripheral neuropathy.1,579,856

Sensory or sensorimotor axonal polyneuropathy affecting small and/or large axons resulting in paresthesias, hypoesthesias, dysesthesias, and weakness has been reported in patients receiving systemic fluoroquinolones, including ciprofloxacin.1,130,579,856 Symptoms may occur soon after initiation of ciprofloxacin and, in some patients, may be irreversible.1,130,579,856

Ciprofloxacin should be discontinued immediately if symptoms of peripheral neuropathy (e.g., pain, burning, tingling, numbness, and/or weakness) occur or if there are other alterations in sensations (e.g., light touch, pain, temperature, position sense, vibratory sensation).1,579,856

CNS Effects

Systemic fluoroquinolones, including ciprofloxacin, have been associated with an increased risk of adverse psychiatric effects, including toxic psychosis,1,579 psychotic reactions progressing to suicidal ideations/thoughts,1,579 hallucinations,1,579 paranoia,1,579 depression,1,579 self-injurious behavior such as attempted or completed suicide,1,579 anxiety,1,579 agitation,1,171,579 delirium,1,171,579 confusion,1,579 disorientation,1,171,579 disturbances in attention,1,171,579 nervousness,1,171,579 insomnia,1,579 nightmares,1,579 and memory impairment.1,171,579 These adverse effects may occur after the first dose.1,579

Systemic fluoroquinolones, including ciprofloxacin, have been associated with an increased risk of seizures (convulsions), increased intracranial pressure (including pseudotumor cerebri), dizziness, and tremors.1,579,856 Ciprofloxacin, like other fluoroquinolones, is known to trigger seizures or lower the seizure threshold.1,579,856 Status epilepticus has been reported.1,579,856

Headache,1,178,183,237,333,336,425,428,466,474,479,856 dizziness,1,178,183,237,333,425,426,466,474,479,856 and restlessness1,178,426,466,474,479 have been reported in 1-3% or more of patients receiving ciprofloxacin.1,183,856 Lightheadedness,1,308,474 insomnia,1,466,474,479,856 nightmares,1,474,856 hallucinations,1,466,474,479,856 paranoia,856 manic reaction,1,474 toxic psychosis,579,856 irritability,1,474 tremor,1,178,426,466,474,479,856 ataxia,1,474 seizures,1,466,474,479,579,856 lethargy,1,474,479 drowsiness,1,474,479 vertigo,368 anxiety,479,856 nervousness,479,856 agitation,856 confusion,1,479,856 weakness,1,474,479 malaise,1,474,535,856 phobia,1,474 depersonalization,1 depression,1,474,856 psychotic reactions,856 suicidal thoughts or acts,1,579,856 paresthesia,1,474,535 and increased intracranial pressure (including pseudotumor cerebri)1,579,856 have also been reported.

Some adverse nervous system effects of ciprofloxacin may be related to the fact that the drug, like other fluoroquinolones, is a γ-aminobutyric acid (GABA) inhibitor.185,208,455,542,550,553 In addition, it has been suggested that some CNS stimulant effects reported in patients receiving the drug may have resulted from ciprofloxacin-induced alterations in caffeine pharmacokinetics.522

If psychiatric or other CNS effects occur during ciprofloxacin therapy, the drug should be discontinued immediately and appropriate measures instituted.1,579,856

Exacerbation of Myasthenia Gravis

Fluoroquinolones, including ciprofloxacin, have neuromuscular blocking activity and may exacerbate muscle weakness in individuals with myasthenia gravis.1,579,856 Use of fluoroquinolones in myasthenia gravis patients has resulted in requirements for ventilatory support and in death.1,579,856

Dermatologic and Sensitivity Reactions

Mild, transient rash1,251,308,311,425,426,466,473,474,479,583,584,612 has been reported in 1-4%1,479 and eosinophilia,1,251,297,334,339,368,466,479 pruritus,1,466,474,479,582,583 urticaria,1,473,474,479,582,583 cutaneous candidiasis,1,474 hyperpigmentation,1,474 erythema nodosum,1,474 angioedema,1,474,479,582 and edema of the face, neck, lips, conjunctivae, or hands1,474,479,583,612 have been reported in less than 1% of patients.1 Flushing,1,474 fever,1,474,479,582,583 and chills1,474 also have been reported in less than 1% of patients receiving the drug.1

Hypersensitivity Reactions

Severe hypersensitivity reactions characterized by rash, fever, eosinophilia, jaundice, and hepatic necrosis and that were fatal have been reported rarely in patients receiving ciprofloxacin and other drugs concomitantly.579,581,583 Toxic epidermal necrolysis (Lyell's syndrome) also has been reported rarely in patients receiving ciprofloxacin.1,643,644 The possibility that these reactions were related to ciprofloxacin therapy could not be excluded.579,581 Other serious and occasionally fatal hypersensitivity (anaphylactic and anaphylactoid) reactions have occurred, some with the initial dose, in patients receiving quinolone therapy, including ciprofloxacin.1,579,581,582,583,645,856

Some hypersensitivity reactions reported in patients receiving fluoroquinolones, including ciprofloxacin, have been accompanied by cardiovascular collapse, loss of consciousness, paresthesia, pharyngeal or facial edema, dyspnea, urticaria, and/or pruritus.579,581,582,583,856

Other serious and sometimes fatal adverse reactions that have been reported with fluoroquinolones, including ciprofloxacin, and that may or may not be related to hypersensitivity reactions include one of more of the following: fever, rash or severe dermatologic reaction (e.g., toxic epidermal necrolysis, Stevens-Johnson syndrome); vasculitis, arthralgia, myalgia, serum sickness; allergic pneumonitis; interstitial nephritis, acute renal insufficiency or failure; hepatitis, jaundice, acute hepatic necrosis or failure; anemia (including hemolytic and aplastic anemia), thrombocytopenia (including thrombotic thrombocytopenic purpura), leukopenia, agranulocytosis, pancytopenia, and/or other hematologic abnormalities.1,579,856

Ciprofloxacin should be discontinued immediately at the first appearance of rash, jaundice, or any other sign of hypersensitivity.1,579,856 Appropriate therapy (e.g., epinephrine, corticosteroids, maintenance of an adequate airway, oxygen, maintenance of blood pressure) should be initiated as indicated.1,579,856

Photosensitivity Reactions

Moderate to severe photosensitivity/phototoxicity reactions have been reported in patients receiving fluoroquinolones, including ciprofloxacin.1,183,311,390,424,474,479,535,579,856

Phototoxicity may manifest as exaggerated sunburn reactions (e.g., burning, erythema, exudation, vesicles, blistering, edema) on areas exposed to sun or artificial ultraviolet (UV) light (usually the face, neck, extensor surfaces of forearms, dorsa of hands).1,579,856

Ciprofloxacin should be discontinued if photosensitivity or phototoxicity (sunburn-like reaction, skin eruption) occurs.1,579,856

Hepatotoxicity

Severe hepatotoxicity, including hepatic necrosis, life-threatening hepatic failure, and fatal events, has been reported in patients receiving ciprofloxacin.1,579,856 Most fatalities have occurred in adults older than 55 years of age.1,579,856

Acute liver injury has a rapid onset (range 1-39 days) and is often associated with hypersensitivity.1,579,856 The pattern of injury can be hepatocellular, cholestatic, or mixed.1,579,856 Temporary increase in aminotransferase or alkaline phosphatase concentrations or cholestatic jaundice may occur, especially in patients with previous liver damage.1,579,856

Increased serum concentrations of AST (SGOT)1,361,426,435,462,474,479,856 and ALT (SGPT)1,361,426,474,479,856 have been reported in about 2%1 and increased serum concentrations of alkaline phosphatase,1,474,479,856 LDH,1,479,856 bilirubin,1,435,474,479,856 and γ-glutamyltransferase (GGT, γ-glutamyl transpeptidase, GGTP)1,435,479,856 have been reported in less than 1% of patients receiving the drug.1,856 In addition, fulminant and occasionally fatal hepatic failure has occurred rarely in patients receiving ciprofloxacin.646,647

Ciprofloxacin should be discontinued immediately if any signs or symptoms of hepatitis (e.g., anorexia, jaundice, dark urine, pruritus, tender abdomen) occur.1,579,856

Aortic Aneurysm and Dissection

Rupture or dissection of aortic aneurysms has been reported in patients receiving systemic fluoroquinolones.172 Epidemiologic studies indicate an increased risk of aortic aneurysm and dissection within 2 months following use of systemic fluoroquinolones, particularly in elderly patients.1,579 The cause for this increased risk has not been identified.1,172,579

If a patient reports adverse effects suggestive of aortic aneurysm or dissection, fluoroquinolone treatment should be discontinued immediately.172

Cardiovascular Effects

Prolonged QT interval leading to ventricular arrhythmias, including torsades de pointes, has been reported with some fluoroquinolones, including ciprofloxacin.1,579,856 Patients with known prolongation of the QT interval or with risk factors for QT interval prolongation or torsades de pointes, patients receiving drugs known to prolong the QT interval (e.g., class IA or III antiarrhythmic agents, tricyclic antidepressants, macrolides, antipsychotics), and geriatric patients may be more susceptible to drug-associated effects on the QT interval.1,579,856

Palpitation,1,466,474,479 atrial flutter,1,474 ventricular ectopy,1,474 syncope,1,474,479 hypertension,1,474,479 angina pectoris,1,474 chest pain,479 myocardial infarction,1,474 cardiopulmonary arrest,1,474,479 and cerebral thrombosis1,474 have been reported in less than 1% of patients receiving ciprofloxacin.1

Hypoglycemia or Hyperglycemia

Systemic fluoroquinolones, including ciprofloxacin, have been associated with alterations in blood glucose concentrations, including symptomatic hypoglycemia and hyperglycemia.1,171,579 Blood glucose disturbances during fluoroquinolone therapy usually have occurred in patients with diabetes mellitus receiving an oral antidiabetic agent (e.g., glyburide) or insulin.1,171,579

Severe cases of hypoglycemia resulting in coma or death have been reported with some systemic fluoroquinolones.1,171,579 Although most reported cases of hypoglycemic coma have involved patients with risk factors for hypoglycemia,(e.g., older age, diabetes mellitus, renal insufficiency, concomitant use of antidiabetic agents [especially sulfonylureas]), some cases have occurred in patients receiving a fluoroquinolone who were not diabetic and were not reported to be receiving an oral antidiabetic agent or insulin.171

If a hypoglycemic reaction occurs, ciprofloxacin should be discontinued and appropriate therapy initiated immediately.1,579

GI Effects

Nausea, 1,178,183,237,289,297,301,307,308,317,329,336,363,424,425,426,428,462,466,473,474,478,479,856 diarrhea,1,183,237,251,297,301,307,329,425,428,435,466,474,479,856 vomiting,1,178,183,237,251,297,336,363,426,466,474,479,856 and abdominal pain/discomfort1,178,183,329,424,425,426,462,473,474,478,479,535 have been reported in 1-10% of patients receiving ciprofloxacin.1,333,474,479,856 These effects generally are mild and transient1,180,183,424,466,479,856 and occur most frequently in geriatric patients466 and/or when high dosage is used.466,479 Anorexia,1,333,474,479 dyspepsia,479,856 flatulence,435,479 GI erosion and bleeding,1,473,474 dysphagia,1,474 bad taste,1,474,479 intestinal perforation,1,474 painful oral mucosa,1,474 and oral candidiasis1,474 have been reported in less than 1% of patients receiving the drug.

Effects on Fecal Flora

Ciprofloxacin exerts a selective effect on normal bowel flora.220,349,386,479

Total bacterial counts of normal anaerobic fecal flora generally are unaffected during or following ciprofloxacin therapy.201,210,220,263,349,386,387,388,479 However, total bacterial counts of normal aerobic fecal flora are decreased within 2-5 days following initiation of therapy with the drug201,210,220,263,348,349,386,387,479 and generally return to pretreatment levels within 1-4 weeks after the drug is discontinued.220,263,349,479 Ciprofloxacin therapy generally markedly reduces or completely eradicates normal fecal Enterobacteriaceae; the drug reduces fecal aerobic gram-positive bacteria to a lesser extent.210,220,263,349,386,479 Ciprofloxacin therapy does not appear to affect total bacterial counts of normal salivary flora, including streptococci, staphylococci, and anaerobic bacteria.263,479

C. difficile-associated Diarrhea and Colitis

Treatment with anti-infectives alters normal colon flora and may permit overgrowth of Clostridioides difficile (formerly known as Clostridium difficile .1,302,303,304,348,579,796,856

C. difficile infection (CDI) and C. difficile -associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) have been reported with nearly all anti-infectives, including ciprofloxacin, and may range in severity from mild diarrhea to fatal colitis.1,302,303,304,579,792,793,797,798,856C. difficile produces toxins A and B, which contribute to the development of CDAD; hypertoxin-producing strains of C. difficile are associated with increased morbidity and mortality since they may be refractory to anti-infectives and colectomy may be required.1,579,856

C. difficile generally is resistant to ciprofloxacin.10,29,44,49,65,66,87,97 When fluoroquinolones were first marketed, there appeared to be a relative lack of association between use of the drugs and CDAD and the risk of CDAD appeared to be lower than that reported with some other anti-infectives.297,466,526 However, there now is some evidence that increasing use of the drugs may have resulted in emergence of C. difficile that are more resistant and/or more virulent than previous strains.792,793,794,795,797,798 Outbreaks of severe CDAD caused by fluoroquinolone-resistant C. difficile have been reported in US health-care facilities with increasing frequency over the last several years.792,793,794,795,797 Many of these CDAD cases occurred in patients who had received a fluoroquinolone (ciprofloxacin, gatifloxacin [no longer commercially available in the US], levofloxacin, moxifloxacin) or cephalosporin within the prior 4-6 weeks.793,797

Genitourinary Effects

Increased serum creatinine1,297,339,425,426,438,479,539,596 and BUN1,297,339,426,435,479,596 concentrations have occurred in about 1% of patients receiving ciprofloxacin.1 Interstitial nephritis,1,165,297,425,426,474 nephritis,1,297,474,479 renal failure,1,297,368,426,474,479,539 dysuria,479 polyuria,1,474 urinary retention,1,474 albuminuria,479 urethral bleeding,1,474 vaginitis,1,297,474,479 and acidosis1,474,479 have been reported in less than 1% of patients receiving the drug.1 In at least one patient, acute renal failure associated with interstitial nephritis occurred within about 2 weeks after initiating ciprofloxacin and appeared to be a hypersensitivity reaction to ciprofloxacin; renal biopsy showed marked interstitial edema, with extensive lymphocytic infiltrations and occasional eosinophils.165

Crystalluria,1,234,339,355,373,426,466,479,856 cylindruria,1,856 and hematuria1,183,191,479,856 have been reported rarely in patients receiving ciprofloxacin. Crystalluria generally occurs in patients with alkaline urine who receive high dosage of the drug,183,188,455,479 and has not been associated with changes in renal function.466 The risk of crystal formation and crystalluria in patients receiving usual recommended dosages of the drug (250-750 mg) is low if urine pH is within the usual range (i.e., less than 6.8).188 Patients receiving the drug, particularly at relatively high dosages, should maintain adequate fluid intake; in addition, alkaline urine should be avoided.1,455,856 Crystalluria, sometimes associated with nephropathy, occurs in animals receiving ciprofloxacin.1,455,479,579,856 This may be related to the fact that ciprofloxacin has reduced solubility under alkaline conditions and the urine of test animals (e.g., rats, monkeys) is predominantly alkaline.1,455,479,579,856 In studies in rhesus monkeys, crystalluria (without evidence of nephropathy) has occurred after a single oral ciprofloxacin dose as low as 5 mg/kg (approximately 0.07 times the highest recommended therapeutic dosage based on body surface area [BSA]).1,579 Nephropathy did not occur when these monkeys received 6 months of IV ciprofloxacin at a dosage of 10 mg/kg daily; however, nephropathy occurred after 6 months of therapy at a dosage of 20 mg/kg daily (approximately 0.2 times the highest recommended therapeutic dosage based on BSA).1,579

Musculoskeletal Effects

Arthralgia,183,361,425,479,612 joint or back pain,1,474,479 joint inflammation,474,612 joint stiffness,1,297,474 achiness,1,474 vasculitis,572 neck or chest pain,1,474 and flare-up of gout1,474 have been reported in less than 1% of patients receiving ciprofloxacin.1

An increased incidence of musculoskeletal disorders related to joints and/or surrounding tissues (e.g., arthralgia, abnormal gait, abnormal joint exam, joint sprains, leg pain, back pain, arthrosis, bone pain, myalgia, arm pain, decreased range of motion in a joint) has been reported in pediatric patients receiving ciprofloxacin.1,579,856 These events usually were mild to moderate in intensity and those that occurred by week 6 usually resolved (clinical resolution of signs and symptoms) within 30 days after treatment ended.1,579

Fluoroquinolones, including ciprofloxacin, cause arthropathies (arthrosis) in immature animals of various species.1,183,186,213,455,479,579,841,842,843,844,845,846,847,848,849,850,856 In young beagles, ciprofloxacin given in a dosage of 100 mg/kg daily for 4 weeks caused degenerative articular changes of the knee joint; in a daily dosage of 30 mg/kg, effects on the joint were minimal,1,579,856 although some damage to weight-bearing joints was observed even at the lower dosage.455 In another study, removal of weight bearing from the joint reduced the lesions, but did not totally prevent them.1,579,856 In a subsequent study in young beagle dogs, oral ciprofloxacin in a dosage of 30 mg/kg or 90 mg/kg daily for 2 weeks (approximately 1.3 or 3.5 times the pediatric dosage based on comparative plasma AUCs) caused articular changes that were still evident on histologic evaluation after a treatment-free period of 5 months.1,579,856 However, a dosage of 10 mg/kg (approximately 0.6 times the pediatric dosage based on comparative plasma AUCs) had no effects on joints and was not associated with arthrotoxicity after an additional treatment-free period of 5 months.1,579,856

Morphologic changes observed in animals with quinolone-induced arthropathies include erosions in joint cartilage accompanied by noninflammatory, cell-free effusion of the joint space; the cartilage is incapable of regeneration and may serve as a site for the development of arthropathy deformans.455 In addition, breakdown products of the cartilage may irritate the synovia.455 The relationship of these effects in animals and the rheumatologic symptoms associated with use of ciprofloxacin in humans is unknown.185,213

Hematologic Effects

Eosinophilia,1,183,251,334,339,368,479,535 leukopenia,1,368,474,479 neutropenia,183 increased or decreased platelet count,1,183,251,479 and pancytopenia1 have been reported in less than 1% of patients receiving ciprofloxacin.1,479 Anemia,1,479 decreased hemoglobin,1,473 increased monocytes,1,479 leukocytosis,1 and bleeding diathesis1 have been reported in less than 1% of patients receiving the drug.1 In at least one patient, decreased hemoglobin was associated with GI bleeding, although there was no evidence of such bleeding in some other patients with hemoglobin reductions.473 In addition, transient acquired von Willebrand's disease has been reported rarely in patients receiving ciprofloxacin; factor VIII concentration returned to normal values several months (i.e., 5-6 months) following discontinuance of the drug in these patients.652

Local Effects

Local adverse effects have been reported at the site of infusion following IV administration of ciprofloxacin.579,596 These reactions generally resolve rapidly after completion of the infusion and have been reported most frequently when IV infusions of the drug were given over 30 minutes or less.579 The manufacturers state that adverse local reactions to IV ciprofloxacin do not contraindicate subsequent IV administration of the drug, unless the reactions recur or worsen.579

Other Adverse Effects

Epistaxis,1,474 laryngeal or pulmonary edema,1,474,479 hiccups,1,474 hemoptysis,1,474 dyspnea,1,474,479 bronchospasm,1,474 and pulmonary embolism1,474 have been reported in less than 1% of patients receiving ciprofloxacin.1

Blurred vision,1,466,474,479 disturbed vision (e.g., change in color perception, overbrightness of lights),1,474,535 decreased visual acuity,1,474 diplopia,1,466,474 and eye pain1,474,479 have been reported in less than 1% of patients receiving ciprofloxacin.1 Although reported with some other quinolones,183,186,455,466,474,479 there has been no evidence of ocular toxicity in animal studies using ciprofloxacin.1,186,474 Tinnitus,1,474,479,612 increased serum amylase, and increased serum uric acid concentrations have been reported rarely (i.e., in less than 0.1% of patients).1,579

Adverse Effects Reported when Used for Inhalational Anthrax (Postexposure)

Some information regarding the safety of ciprofloxacin for long-term postexposure prophylaxis of anthrax are available based on use of the drug in the fall of 2001 following bioterrorism-related exposures to Bacillus anthracis spores.1,579,700,709 Among individuals surveyed by the US Centers for Disease Control and Prevention (CDC), adverse GI effects (nausea, vomiting, diarrhea, stomach pain), neurologic effects (problems sleeping, nightmares, headache, dizziness, lightheadedness), and musculoskeletal effects (muscle or tendon pain and joint swelling or pain) were reported more frequently than in controlled clinical studies evaluating the drug for other indications.1,579 This higher incidence in the absence of a control group could be the result of report bias, concurrent medical conditions, other concomitant drug therapy, emotional stress or other confounding factors, and/or the long duration of ciprofloxacin treatment required for prophylaxis.1,579 In response to a questionnaire given to 490 such individuals in Florida on approximately day 7 or 14 of anti-infective prophylaxis, 19% sought medical attention for any anti-infective related adverse effect or reported one or more of the following: pruritus, breathing problems, or swelling of the face, neck, or throat.700 Although the percentage of patients in this subgroup who received ciprofloxacin versus other anti-infectives was not reported, 86% of all patients (i.e., those who did or did not answer the questionnaire) received ciprofloxacin and 80% continued to receive prophylaxis beyond 14 days.700

In an epidemiologic evaluation in 8424 postal workers who were offered 60 days of prophylaxis for anthrax and given a questionnaire in New Jersey, New York City, and the District of Columbia on days 7-10 of anti-infective prophylaxis, 5819 completed or were administered the questionnaire, of whom 3863 had initiated prophylaxis (3428 with ciprofloxacin).709 Of the ciprofloxacin-treated individuals, 19% reported severe nausea, vomiting, diarrhea, and/or abdominal pain; 14% reported fainting, lightheadedness, and/or dizziness; 7% reported heartburn or acid reflux; 6% reported rash, urticaria, and/or pruritus; and 8% discontinued therapy with the drug (3% for adverse effects, 1% for fear of developing an adverse effect, and 1% because they were confused about the need).709 Only 2% of those on any anti-infective sought medical attention for possible manifestations of anaphylaxis, none of whom required hospitalization.709

Precautions and Contraindications

Ciprofloxacin is contraindicated in patients with a history of hypersensitivity to the drug, other quinolones, or any ingredient in the formulation.1,579,856

Systemic fluoroquinolones, including ciprofloxacin, have been associated with disabling and potentially irreversible serious adverse reactions (e.g., tendinitis and tendon rupture, peripheral neuropathy, CNS effects) that can occur together in the same patient.1,140,145,579,856 These serious reactions may occur within hours to weeks after a systemic fluoroquinolone is initiated and have occurred in all age groups and in patients without preexisting risk factors for such adverse reactions.1,579,856 Patients receiving ciprofloxacin should be informed about these serious adverse reactions and advised to immediately discontinue ciprofloxacin and contact a clinician if they experience any signs or symptoms of serious adverse effects (e.g., unusual joint or tendon pain, muscle weakness, a “pins and needles” tingling or pricking sensation, numbness of the arms or legs, confusion, hallucinations) while taking the drug.1,140,145,579,856 Systemic fluoroquinolones, including ciprofloxacin, should be avoided in patients who have experienced any of the serious adverse reactions associated with fluoroquinolones.1,140,145,579,856

Because fluoroquinolones, including ciprofloxacin, are associated with an increased risk of tendinitis and tendon rupture in all age groups, patients receiving ciprofloxacin should be informed of this potentially irreversible adverse effect and the drug should be discontinued immediately if pain, swelling, inflammation, or rupture of a tendon occurs.1,579,851,852,856 The risk of developing fluoroquinolone-associated tendinitis and tendon rupture is increased in adults older than 60 years of age, individuals receiving concomitant corticosteroids, and kidney, heart, or lung transplant recipients.1,579,856 Patients should be advised to rest and refrain from exercise at the first sign of tendinitis or tendon rupture (e.g., pain, swelling, or inflammation of a tendon or weakness or inability to use a joint) and advised to immediately discontinue the drug and contact a clinician.1,579,851,852,856 Systemic fluoroquinolones, including ciprofloxacin, should be avoided in patients who have a history of tendon disorders or have experienced tendinitis or tendon rupture.1,579,856

Because fluoroquinolones, including ciprofloxacin, are associated with an increased risk of peripheral neuropathy, ciprofloxacin should be discontinued immediately if symptoms of peripheral neuropathy (e.g., pain, burning, tingling, numbness, and/or weakness) occur or if there are other alterations in sensations (e.g., light touch, pain, temperature, position sense, vibratory sensation) and/or motor strength since this may minimize development of an irreversible condition.1,130,579,856 Patients receiving ciprofloxacin should be advised that peripheral neuropathies have been reported in patients receiving systemic fluoroquinolones, including ciprofloxacin, and that symptoms may occur soon after initiation of therapy and, in some patients, may be irreversible.1,130,579,856 Patients should be advised of the importance of immediately discontinuing the drug and contacting a clinician if such symptoms occur.1,130,579,856 Systemic fluoroquinolones, including ciprofloxacin, should be avoided in patients who have experienced peripheral neuropathy.856

Because fluoroquinolones, including ciprofloxacin, have been associated with an increased risk of adverse CNS effects, ciprofloxacin should be used with caution in epileptic patients, in patients with known or suspected CNS disorders that predispose to seizures or lower the seizure threshold (e.g., severe cerebral arteriosclerosis, history of convulsions, reduced cerebral blood flow, altered brain structure, stroke), and in the presence of other risk factors that predispose to seizures or lower the seizure threshold (e.g., certain drug therapies, renal dysfunction).1,410,455,579,856 Patients should be informed that seizures have been reported in patients receiving ciprofloxacin and advised to inform their clinician of any history of seizures before initiating therapy with the drug.1,579,856 Because increased intracranial pressure has been reported, patients receiving ciprofloxacin should be advised to notify their clinician if persistent headache (with or without blurred vision) occurs.1,579,856 Patients receiving ciprofloxacin also should be advised that ciprofloxacin may cause dizziness or lightheadedness and cautioned not to engage in activities requiring mental alertness and motor coordination (e.g., driving or operating machinery) until they experience how the drug affects them.1,579,856 If seizures or other CNS effects occur, ciprofloxacin should be discontinued immediately and appropriate measures instituted.1,579,856 Systemic fluoroquinolones, including ciprofloxacin, should be avoided in patients who have experienced CNS effects associated with fluoroquinolones.1,579,856

Ciprofloxacin should be avoided in patients with a known history of myasthenia gravis since fluoroquinolones may exacerbate myasthenia gravis symptoms.1,579,856 Patients should be advised of the importance of informing their clinician of any history of myasthenia gravis.1,579,856 Patients also should be advised to immediately contact a clinician if any symptoms of muscle weakness, including respiratory difficulties, occur.1,579,856

Because severe hepatotoxicity, including acute hepatitis and fatalities, has been reported in patients receiving ciprofloxacin, the drug should be discontinued immediately if any sign or symptom of hepatitis (e.g., anorexia, jaundice, dark urine, pruritus, tender abdomen) occurs.1,579,856 Patients should be advised to contact their clinician if any sign or symptom of hepatotoxicity (e.g., loss of appetite, nausea, vomiting, fever, weakness, tiredness, right upper quadrant tenderness, itching, yellowing of skin or eyes, light colored bowel movements, dark colored urine) occurs.1,579,856

Because an increased risk of aortic aneurysm and dissection has been reported with systemic fluoroquinolones, ciprofloxacin should not be used in patients who have an aortic aneurysm or are at increased risk for an aortic aneurysm unless there are no other treatment options.1,172,579 This includes elderly patients and patients with peripheral atherosclerotic vascular disease, hypertension, or certain genetic conditions (e.g., Marfan syndrome, Ehlers-Danlos syndrome).172 Patients should be informed that systemic fluoroquinolones may increase the risk of aortic aneurysm and dissection and of the importance of informing their clinician of any history of aneurysms, blockages or hardening of the arteries, high blood pressure, or genetic conditions such as Marfan syndrome or Ehlers-Danlos syndrome.172 Patients receiving ciprofloxacin should be advised to seek immediate medical treatment if they experience sudden, severe, and constant pain in the stomach, chest, or back.1,172,579

Because prolongation of the QT interval has been reported in patients receiving ciprofloxacin, the drug should be avoided in patients with known prolongation of the QT interval or with risk factors for QT interval prolongation or torsades de pointes (e.g., congenital long QT syndrome, uncorrected electrolyte imbalance such as hypokalemia or hypomagnesemia, cardiac disease such as heart failure, myocardial infarction, or bradycardia).1,579,856 Ciprofloxacin also should be avoided in patients receiving drugs known to prolong the QT interval, including class IA antiarrhythmic agents (quinidine, procainamide), class III antiarrhythmic agents (amiodarone, sotalol), tricyclic antidepressants, macrolides, and antipsychotics.1,579,856 Patients should be advised of the importance of informing their clinician of a personal or family history of QT interval prolongation or proarrhythmic conditions (e.g., hypokalemia, bradycardia, recent myocardial ischemia) or current therapy with any class IA (e.g., quinidine, procainamide) or class III (amiodarone, sotalol) antiarrhythmic agents; patients should be advised to contact their clinician if any symptoms of prolongation of QT interval, including prolonged heart palpitations or loss of consciousness, occur.1,579,856

Blood glucose concentrations should be carefully monitored when systemic fluoroquinolones, including ciprofloxacin, are used in patients with diabetes mellitus receiving antidiabetic agents.1,171,579 Patients should be informed that hypoglycemia has been reported when systemic fluoroquinolones were used in some patients receiving antidiabetic agents.171 Patients with diabetes mellitus receiving oral antidiabetic agents or insulin should be advised to discontinue ciprofloxacin and contact a clinician if they experience hypoglycemia or symptoms of hypoglycemia.1,171 Appropriate therapy should be initiated immediately.1,579

Ciprofloxacin inhibits cytochrome P-450 (CYP) isoenzyme 1A2, and concomitant use with drugs metabolized by this enzyme (e.g., clozapine, methylxanthines [e.g., caffeine, theophylline], olanzapine, ropinirole, tizanidine) may result in increased plasma concentrations of the concomitant drug and could lead to clinically important adverse effects.1,579,856 Because of an increased risk of adverse effects, ciprofloxacin is contraindicated in patients receiving tizanidine.1,579,856 Concomitant use with theophylline should be avoided since serious and sometimes fatal reactions (e.g., cardiac arrest, seizures, status epilepticus, respiratory failure) have occurred in patients receiving the drugs concomitantly.1,195,297,579,856 In addition, concomitant use of ciprofloxacin and other drugs metabolized by CYP1A2 should be avoided or requires particular caution.1,297,426,466,479,507,508,509,511,513,528,542,856

Sensitivity Reactions

Ciprofloxacin, like other quinolones, can cause serious, potentially fatal hypersensitivity reactions, occasionally following the initial dose.579,645,856 Patients receiving ciprofloxacin should be advised of this possibility and instructed to immediately discontinue the drug and contact a clinician at the first sign of rash, hives, other skin reaction, jaundice, rapid heartbeat, difficulty swallowing or breathing, any swelling suggesting angioedema (e.g., swelling of lips, tongue, or face; tightness of throat; hoarseness), or any other sign of hypersensitivity.1,579,856 Serious anaphylactic reactions require immediate emergency treatment with epinephrine and other resuscitation measures (e.g., oxygen, IV fluids, IV antihistamines, corticosteroids, pressor amines, airway management such as intubation) as indicated.856

Because photosensitivity/phototoxicity reactions have been reported with fluoroquinolones, unnecessary or excessive exposure to sunlight or artificial UV light (sunlamps, tanning beds, UVA/UVB treatment) should be avoided during ciprofloxacin therapy.1,579,856 If the patient needs to be outdoors, they should use sunscreen and wear a hat and clothing that protects skin from sun exposure.1,579,856 Patients should be advised to discontinue ciprofloxacin and contact a clinician if photosensitivity or phototoxicity (sunburn-like reaction, skin eruption) occurs.1,579,856

Selection and Use of Anti-infectives

Ciprofloxacin should be used for the treatment of acute bacterial sinusitis, acute bacterial exacerbations of chronic bronchitis, or uncomplicated urinary tract infections (UTIs) only when no other treatment options are available.1,140,145,579,856 Because ciprofloxacin, like other systemic fluoroquinolones, has been associated with disabling and potentially irreversible serious adverse reactions (e.g., tendinitis and tendon rupture, peripheral neuropathy, CNS effects) that can occur together in the same patient, the risks of serious adverse reactions outweigh the benefits of ciprofloxacin for patients with these infections.140,145

To reduce development of drug-resistant bacteria and maintain effectiveness of ciprofloxacin and other antibacterials, the drug should be used only for the treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.1,579,856

Patients should be advised that antibacterials (including ciprofloxacin) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).1,579,856 Patients also should be advised about the importance of completing the full course of therapy, even if feeling better after a few days, and that skipping doses or not completing therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with ciprofloxacin or other antibacterials in the future.1,579,856

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.1,579,856 In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.1,579,856 Culture and susceptibility testing performed periodically during therapy provides information on the therapeutic effect of the anti-infective agent and the possible emergence of bacterial resistance.1,579,856

Information on test methods and quality control standards for in vitro susceptibility testing of antibacterial agents and specific interpretive criteria for such testing recognized by FDA is available at [Web].1

Superinfection/C. difficile-associated Diarrhea and Colitis

As with other anti-infectives, use of ciprofloxacin may result in overgrowth of nonsusceptible organisms,297,300,338,346,348,390,426,466,479,856 especially enterococci or Candida .300,336,338,348,390 Resistant strains of some organisms (e.g., Pseudomonas aeruginosa , staphylococci) have developed during ciprofloxacin therapy.99,122,128,137,138,139,144,180,205,280,300,346,359,361,362,363,368,370,371,424,435,458,466,479,505,856 Careful monitoring of the patient and periodic in vitro susceptibility tests are essential.481,856

Because CDAD has been reported with the use of nearly all anti-infectives, including ciprofloxacin, it should be considered in the differential diagnosis in patients who develop diarrhea during or after ciprofloxacin therapy.1,302,303,304,579,856 Careful medical history is necessary since CDAD has been reported to occur as late as 2 months or longer after anti-infective therapy is discontinued.1,302,303,304,579,856

If CDAD is suspected or confirmed, anti-infective therapy not directed against C. difficile should be discontinued as soon as possible.302 Patients should be managed with appropriate anti-infective therapy directed against C. difficile (e.g., vancomycin, fidaxomicin, metronidazole), supportive therapy (e.g., fluid and electrolyte management, protein supplementation), and surgical evaluation as clinically indicated.1,302,303,304,579,856

Patients should be advised that diarrhea is a common problem caused by anti-infectives and usually ends when the drug is discontinued; however, it is important to contact a clinician if watery and bloody stools (with or without stomach cramps and fever) occur during or as late as 2 months or longer after the last dose.1,579,856

Other Precautions and Contraindications

Crystalluria has been reported rarely in patients receiving ciprofloxacin.1,188,339,373,426,466,479,579,856 Although crystalluria is not expected to occur under usual conditions with the usual recommended dosages of the drug,1,188,479 patients should be instructed to drink sufficient quantities of fluids to ensure proper hydration and adequate urinary output during ciprofloxacin therapy.1,455,856 Measures also should be taken to avoid alkaline urine.1,455,579,856

Ciprofloxacin has not been shown to be effective in the treatment of syphilis.856 Because use of anti-infectives given in high dosage for short periods of time to treat gonorrhea may mask or delay symptoms of incubating syphilis, serologic tests for syphilis should be performed at the time of diagnosis of gonorrhea.856 If ciprofloxacin is used for the treatment of gonorrhea, follow-up serologic tests for syphilis should be performed 3 months after gonorrhea treatment is completed.856

Doses and/or frequency of administration of ciprofloxacin should be decreased in patients with severe renal impairment since serum concentrations of the drug are higher and prolonged in these patients compared with patients with normal renal function.1,524,856

Pediatric Precautions

Ciprofloxacin, like other fluoroquinolones, is associated with arthropathy and histopathologic changes in weight-bearing joints of juvenile animals.1,183,186,455,479,481,579,856 Oral ciprofloxacin caused lameness in immature dogs; histologic evaluation of the weight-bearing joints of these dogs revealed permanent lesions of the cartilage.1,579,455,856 When used in pediatric patients younger than 18 years of age, ciprofloxacin has been associated with an increased rate of adverse effects involving joints and/or surrounding tissue (e.g., tendons) compared with comparator anti-infectives.1,579

The manufacturers state that ciprofloxacin (IV, conventional tablets, oral suspension) should be used in pediatric patients younger than 18 years of age only for the treatment of complicated UTIs and pyelonephritis caused by susceptible Escherichia coli ,1,579 inhalational anthrax (postexposure),1,579 and treatment and prophylaxis of plague.1,579 However, the American Academy of Pediatrics (AAP) and other experts (e.g., the American Heart Association [AHA], Infectious Diseases Society of America [IDSA]) state that use of fluoroquinolones in pediatric patients younger than 18 years of age also may be justified in certain other infections (e.g., endocarditis, multidrug-resistant gram-negative infections).292,293,450,522,654 Parents should be advised to inform their child's clinician if the child has a history of joint-related problems present before ciprofloxacin is initiated or if such problems occur during or after therapy with the drug.1,579

Ciprofloxacin extended-release tablets should not be used in children and adolescents younger than 18 years of age since safety and efficacy of the extended-release preparation have not been established for any indication in pediatric patients.856

Urinary Tract Infections

Ciprofloxacin (IV, conventional tablets, oral suspension) is labeled by FDA for the treatment of complicated UTIs and pyelonephritis caused by susceptible E. coli in pediatric patients 1-17 years of age.1,579 However, ciprofloxacin is not considered a drug of first choice for these infections in pediatric patients because an increased incidence of adverse effects has been reported in such patients.1,292,579 In clinical studies evaluating IV or oral ciprofloxacin for the treatment of complicated UTIs and pyelonephritis in pediatric patients 1-17 years of age, the rate of adverse effects (including events related to joints and/or surrounding tissues) occurring during 6 weeks of follow-up was 9.3% in those receiving ciprofloxacin compared with 6% in those receiving a cephalosporin.1,579 The rate of adverse effects occurring at any time up to 1 year was 13.7% or 9.5%, respectively and the rate of all adverse effects (regardless of drug relationship) at 6 weeks was 41 or 31%, respectively.1,579

Anthrax

Ciprofloxacin (IV, conventional tablets, oral suspension) is labeled by FDA for inhalational anthrax (postexposure) to reduce the incidence or progression of disease following exposure to aerosolized Bacillus anthracis spores in pediatric patients from birth to 17 years of age.1,579 The manufacturers state that risk-benefit assessment indicates that use of ciprofloxacin is appropriate for this indication in pediatric patients.1,579 AAP states that ciprofloxacin is a drug of choice for postexposure prophylaxis of anthrax in pediatric patients.671 Because of potential adverse effects from prolonged use of ciprofloxacin in pediatric patients and because postexposure prophylaxis should be continued for 60 days following exposures to aerosolized B. anthracis spores that occur in the context of biologic warfare or bioterrorism, the postexposure prophylaxis regimen can be changed to oral amoxicillin or oral penicillin V if penicillin susceptibility is confirmed.671

AAP states that oral ciprofloxacin is a drug of choice for the treatment of cutaneous anthrax without systemic involvement† in pediatric patients.671 Because of potential adverse effects from prolonged use of ciprofloxacin in pediatric patients and because a treatment duration of 60 days is recommended when cutaneous anthrax occurs following exposures to aerosolized B. anthracis spores that occur in the context of biologic warfare or bioterrorism, the treatment regimen can be changed to oral amoxicillin or oral penicillin V if penicillin susceptibility is confirmed.671

IV ciprofloxacin also is considered a drug of choice for use in multiple-drug parenteral regimens for initial treatment of systemic anthrax† (inhalational, GI, meningitis, or cutaneous with systemic involvement, extensive edema, or head or neck lesions) that occurs in the context of biologic warfare or bioterrorism.671 Because of potential adverse effects from prolonged use of ciprofloxacin in pediatric patients, IV penicillin G or IV ampicillin can replace IV ciprofloxacin in the multiple-drug regimen if penicillin susceptibility is confirmed.671

Plague

Ciprofloxacin (IV, conventional tablets, oral suspension) is labeled by FDA for treatment of plague, including pneumonic and septicemic plague, and for prophylaxis of plague in pediatric patients from birth to 17 years of age.1,579 The manufacturers state that risk-benefit assessment indicates that use of ciprofloxacin is appropriate for this indication in pediatric patients.1,579

Other Infections

Some clinicians suggest that quinolones may be used cautiously in adolescents if skeletal growth is complete,455,522 and that the potential benefits of ciprofloxacin therapy may outweigh the possible risks in certain children 9-18 years of age with serious infections when the causative organism is resistant to other available anti-infectives.522,654

AAP states that use of a systemic fluoroquinolone may be justified in children younger than 18 years of age in certain specific circumstances when there are no safe and effective alternatives and the drug is known to be effective.292,293 AAP states that use of fluoroquinolones may be justified in pediatric patients when parenteral therapy is not practical and no other safe and effective oral agent is available or when the pediatric patient has an infection caused by a multidrug-resistant organism (e.g., Pseudomonas , Mycobacterium ) for which there is no safe and effective alternative.292,293 Therefore, in addition to use after exposure to aerosolized B. anthracis (to decrease the incidence or progression of the disease), other possible uses of fluoroquinolones in pediatric patients include the treatment of urinary tract infections caused by Ps. aeruginosa or other multidrug-resistant gram-negative bacteria, infections caused by multidrug-resistant Streptococcus pneumoniae , chronic suppurative otitis media or malignant otitis externa caused by Ps. aeruginosa , chronic or acute osteomyelitis or osteochondritis caused by Ps. aeruginosa or other multidrug-resistant gram-negative bacteria known to be susceptible to fluoroquinolones and resistant to other alternatives, mycobacterial infections caused by isolates known to be susceptible to fluoroquinolones, gram-negative bacterial infections in immunocompromised patients when oral therapy is desired or when the causative agent is resistant to other alternatives, GI infections known or suspected to be caused by multidrug-resistant Shigella , Salmonella , Vibrio cholerae , or Campylobacter , or serious infections caused by fluoroquinolone-susceptible pathogens in pediatric patients with severe allergy to alternative anti-infectives.292,293

Geriatric Precautions

Retrospective analysis of 23 multiple-dose controlled clinical studies evaluating ciprofloxacin in over 3500 patients revealed that 25% of patients included in these studies were 65 years of age or older and 10% were 75 years of age or older.1,579 In a large, prospective, randomized study evaluating use of ciprofloxacin extended-release tablets for treatment of complicated UTIs, 49% of patients were 65 years of age or older and 30% were 75 years of age or older.856 Although no overall differences in safety or efficacy were observed between geriatric individuals and younger adults in these studies and other clinical experience revealed no evidence of age-related differences, the possibility that some older patients may exhibit increased sensitivity to the drug cannot be ruled out.1,579,856

The risk of fluoroquinolone-associated tendon disorders, including tendon rupture, is increased in geriatric adults older than 60 years of age.1,579,851,852,856 This risk is further increased in those receiving concomitant corticosteroids.1,579,851,852,856 Ciprofloxacin should be used with caution in geriatric adults, especially those receiving concomitant corticosteroids.1,579,856

The risk of prolonged QT interval leading to ventricular arrhythmias may be increased in geriatric patients.1,579,856 Ciprofloxacin should be used with caution in those receiving concurrent therapy with drugs that can prolong the QT interval (e.g., class IA or III antiarrhythmic agents) or those with risk factors for torsades de pointes (e.g., known QT prolongation, uncorrected hypokalemia).1,579,856

The risk of fluoroquinolone-associated aortic aneurysm and dissection may be increased in geriatric patients.1

Ciprofloxacin is substantially eliminated by the kidney, and the risk of adverse reactions may be greater in patients with impaired renal function.1,579,856 Although dosage of ciprofloxacin does not need to be modified in individuals older than 65 years of age with normal renal function, the greater frequency of decreased renal function observed in the elderly should be considered and dosage carefully selected in geriatric patients; monitoring renal function may be useful in these patients.1,579,856

Mutagenicity and Carcinogenicity

Ciprofloxacin was not mutagenic in vivo in the rat hepatocyte DNA repair assay or dominant lethal or micronucleus tests in mice.1,579,856 Although ciprofloxacin was positive for mutagenicity in vitro in the mouse lymphoma cell forward mutation assay and rat hepatocyte DNA repair assay, the drug was not mutagenic in other in vitro studies, including the Salmonella microsome test, mouse lymphoma cell forward mutation assay, Escherichia coli DNA repair assay, Chinese hamster V-79 cell HGPRT test, Syrian hamster embryo cell transformation assay, Saccharomyces cerevisiae point mutation assay, and S. cerevisiae mitotic crossover and gene conversion assay.1,579,856

In 2-year carcinogenicity studies in rats or mice, there was no evidence of carcinogenic or tumorigenic potential with oral ciprofloxacin in a dosage of 250 or 750 mg/kg daily (equivalent to approximately 2 or 3 times, respectively, a human dosage of 1 g daily based on BSA).1,579,856

Pregnancy, Fertility, and Lactation

Pregnancy

There are no adequate and controlled studies to date using ciprofloxacin in pregnant women.1,579,856 Because ciprofloxacin, like most other fluoroquinolones, causes arthropathy in immature animals, the drug should not be used in pregnant women unless potential benefits justify potential risks to the fetus and mother.1,579,856

CDC states that oral ciprofloxacin is the preferred drug for initial anti-infective postexposure prophylaxis in pregnant and postpartum women following a suspected or confirmed exposure to aerosolized B. anthracis spores in the context of biologic warfare or bioterrorism.672 CDC also states that oral ciprofloxacin is the preferred drug for treatment of uncomplicated cutaneous anthrax and IV ciprofloxacin is the preferred bactericidal component of a multiple-drug regimen for treatment of systemic anthrax in pregnant and postpartum women when such infections occur in the context of biologic warfare or bioterrorism.672

An expert review of published data regarding clinical experience with use of ciprofloxacin during pregnancy concluded that therapeutic doses of the drug during pregnancy are unlikely to pose a substantial teratogenic risk, but that data are insufficient to state that there is no risk.1,579,856 Although some safety data are available from several postmarketing epidemiology studies involving short-term, first-trimester exposures to ciprofloxacin, these studies are insufficient to evaluate the risk for less common defects or to permit reliable and definitive conclusions regarding the safety of ciprofloxacin in pregnant women and their developing fetuses.1,579,856 In one controlled prospective observational study of 200 women exposed to fluoroquinolones during pregnancy (68% were first-trimester exposures, 52.5% of exposures involved ciprofloxacin), in utero exposure to fluoroquinolones during embryogenesis did not appear to be associated with an increased risk of major congenital malformations (incidence was 2.2% in the fluoroquinolone group and 2.6% in the control group; background incidence is 1-5%).1,579,856 There also was no evidence of increases in the rates of spontaneous abortion, prematurity, or low birthweight and no clinically important increase in musculoskeletal dysfunction in the ciprofloxacin-exposed children followed to 1 year of age.1,579,856 In another prospective follow-up study that included 549 pregnancies with fluoroquinolone exposure (93% were first-trimester exposures, 70 first-trimester exposures involved ciprofloxacin), there was no increase in the rates of spontaneous abortion, prematurity, or low birthweight, and the malformation rate was similar to the background incidence rate with no evidence of any specific patterns of congenital abnormalities.1,579,856

Reproduction studies in rats and mice using oral ciprofloxacin dosages up to 100 mg/kg (0.6 and 0.3 times, respectively, the maximum daily human dosage of 1 g based on BSA) have not revealed evidence of harm to the fetus.1,579,856 In rabbits, oral ciprofloxacin dosages of 30 and 100 mg/kg (approximately 0.4 and 1.3 times, respectively, the highest recommended therapeutic dosage based on BSA) caused GI toxicity resulting in maternal weight loss and an increased incidence of abortion, but there was no evidence of teratogenicity.1,579,856 IV ciprofloxacin given to rabbits at dosages up to 20 mg/kg (approximately 0.3 times the highest recommended therapeutic dosage based on BSA) has not resulted in maternal toxicity, embryotoxicity, or teratogenicity.1,579

Fertility

Fertility studies in rats using oral ciprofloxacin dosages up to 100 mg/kg (equivalent to the highest recommended daily human dose of 1 g based on BSA) did not reveal evidence of impaired fertility.1,579,856

Administration of high dosages (100 mg/kg daily) of some quinolones (e.g., norfloxacin [no longer commercially available in the US], pefloxacin [not commercially available in the US] and pipemidic acid [not commercially available in the US]) has been associated with impaired spermatogenesis and/or testicular damage (atrophy in rats and dogs) in chronic (for 3 months or longer) toxicity studies.455

Lactation

Ciprofloxacin is distributed into milk,1,567,579,830,856 but the amount of the drug absorbed by a nursing infant is unknown.1,579,856 Because of the potential for serious adverse effects of ciprofloxacin (including articular damage) in nursing infants, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.1,455,579,856

AAP considers ciprofloxacin to be usually compatible with breast-feeding since the amount of the fluoroquinolone potentially absorbed by nursing infants would be small and no observable change in infants associated with such exposure has been reported to date.703,705

CDC states that recommendations for use of ciprofloxacin in breast-feeding women for postexposure prophylaxis following a suspected or confirmed exposure to aerosolized B. anthracis spores in the context of biologic warfare or bioterrorism and for treatment of uncomplicated cutaneous anthrax or systemic anthrax in such situations are the same as those for other adults.672

Drugs Metabolized by Hepatic Microsomal Enzymes

Ciprofloxacin inhibits cytochrome P-450 (CYP) isoenzyme 1A2.1,579,856 Concomitant use with CYP1A2 substrates (e.g., clozapine, methylxanthines [e.g., caffeine, theophylline], olanzapine, ropinirole, tizanidine) may result in increased plasma concentrations and increased pharmacologic or adverse effects of the concomitant drug.1,579,856

Drugs that Prolong the QT Interval

Concomitant use of ciprofloxacin and drugs known to prolong the QT interval, including class IA antiarrhythmics (e.g., quinidine, procainamide), class III antiarrhythmics (e.g., amiodarone, sotalol), tricyclic antidepressants, macrolides, and antipsychotics, may result in additive effects on QT interval prolongation.1,579,856 Concomitant use with these drugs should be avoided;1,579,856 if concomitant use is necessary, caution is advised.1,579,856

Antacids

Antacids containing magnesium, aluminum, or calcium decrease absorption of oral ciprofloxacin, resulting in decreased serum and urine concentrations of the anti-infective agent.1,81,180,190,196,202,203,208,214,339,479,536,537,540,597,598,824,856 Ciprofloxacin bioavailability may be decreased by as much as 90%1,856 and serum ciprofloxacin concentrations generally are decreased by 14-50%180,190,196,202,203 in patients receiving an antacid concomitantly; anti-infective treatment failure may occur as a result of reduced quinolone absorption in these patients.522,537,540 The mechanism of this interaction has not been fully elucidated to date, but magnesium, aluminum, and other divalent ions may bind to, and form insoluble complexes with, quinolones in the GI tract.81,180,196,202,205,208,295,517,536

The manufacturers state that ciprofloxacin conventional tablets, extended-release tablets, or oral suspension should be administered at least 2 hours before or 6 hours after antacids containing magnesium or aluminum.1,856 Some clinicians suggest that patients be instructed not to ingest antacids containing magnesium, aluminum, or calcium concomitantly with or within 2-4 hours of a ciprofloxacin dose;81,522,536,540,597,598 however, other clinicians state that these antacids should not be used in patients receiving ciprofloxacin522,532 and that ciprofloxacin probably should not be used in patients with renal failure who require aluminum hydroxide or aluminum carbonate for intestinal binding of phosphate.180,190

Aminoglycosides

The antibacterial activities of ciprofloxacin and aminoglycosides have been additive or synergistic in vitro against some strains of Enterobacteriaceae and Pseudomonas aeruginosa .116,129,479 However, synergism between the drugs is unpredictable, and indifference generally occurs when ciprofloxacin is used in conjunction with amikacin, gentamicin, or tobramycin against Ps. aeruginosa or Enterobacteriaceae.85,126,129,135,205,479 Indifference also generally occurs when the drug is used in conjunction with tobramycin against Acinetobacter .123

Antiarrhythmic Agents

Use ciprofloxacin with caution in those receiving concurrent therapy with drugs that can prolong the QT interval (e.g., class IA or III antiarrhythmic agents).856,579,856

Anticoagulants

Initiation of oral ciprofloxacin therapy in patients stabilized on warfarin has resulted in prolongation of the prothrombin time; hematemesis occurred in at least 1 patient.558,823 The mechanism of this interaction has not been determined to date, but ciprofloxacin may displace the anticoagulant from serum albumin binding sites.558,823,856 The risk may vary with the underlying infection, age, and general status of the patient so that the contribution of ciprofloxacin to the increase in international normalized ratio (INR) is difficult to assess.1,579,856

Ciprofloxacin should be used with caution in patients receiving warfarin,1,558,559,579,823,856 and prothrombin time and international normalized ratio (INR) should be monitored frequently during and shortly after concomitant therapy.1,558,559,579,823,856

Antidiabetic Agents

Concomitant use of ciprofloxacin and oral antidiabetic agents (e.g., sulfonylurea agents such as glimepiride or glyburide) has resulted in hypoglycemia, presumably by potentiating the glucose-lowering effect of the antidiabetic agent.1,579,856 Severe hypoglycemia and some fatalities have been reported.1,579,856

Ciprofloxacin should be used with caution in patients receiving oral antidiabetic agents, and blood glucose concentrations should be monitored.1,579,856 Patients receiving an oral antidiabetic agent and ciprofloxacin concomitantly should be advised to contact their clinician if low blood glucose occurs during ciprofloxacin therapy so that the clinician can determine whether the anti-infective should be changed.1,579,856

Antimuscarinics

Although the clinical importance has not been determined and further study is needed to evaluate the interactions, concomitant administration of antimuscarinics (e.g., pirenzepine, scopolamine) delays GI absorption of the anti-infective.81,474,479

Bismuth Subsalicylate

Concomitant administration of a single dose of oral bismuth subsalicylate (428 mg) and a single dose of oral ciprofloxacin (750 mg) results in a slight decrease in peak plasma concentrations and area under the concentration-time curve (AUC) of ciprofloxacin, but this is not considered clinically important.821

Clindamycin

The combination of ciprofloxacin and clindamycin has been synergistic in vitro against many strains of Peptostreptococcus ,65 Lactobacillus ,65 and B. fragilis tested.479

Corticosteroids

Concomitant use of corticosteroids increases the risk of severe tendon disorders (e.g., tendinitis, tendon rupture), especially in geriatric patients older than 60 years of age.1,579,851,852,856

Clozapine

Concomitant use of ciprofloxacin (250 mg) and clozapine (304 mg) for 7 days increased serum concentrations of clozapine and N -desmethylclozapine by 29 and 31%, respectively,1,579,775,822,856 potentially resulting in adverse effects.775,822

Clozapine and ciprofloxacin should be used concomitantly with caution;1,579,856 patients should be carefully monitored for clozapine adverse effects during and shortly after concomitant therapy and appropriate clozapine dosage adjustments made.1,579,856

Cyclosporine

Concomitant use of cyclosporine and ciprofloxacin may result in transient increases in serum creatinine.1,579,856 Acute renal failure occurred within 4 days after initiation of ciprofloxacin in a patient receiving cyclosporine maintenance therapy.539 The mechanism of this potential interaction has not been elucidated,522,539 but could involve synergistic nephrotoxic effects of the drugs and/or interference of cyclosporine metabolism by ciprofloxacin.539

Cyclosporine and ciprofloxacin should be used concomitantly with caution and renal function (especially serum creatinine concentrations) should be monitored.1,579,856

Didanosine

Concomitant use of oral ciprofloxacin and buffered didanosine preparations (pediatric oral solution admixed with antacid) may decrease absorption of ciprofloxacin resulting in decreased serum and urine concentrations of the quinolone.1,856

The manufacturers state that ciprofloxacin conventional tablets, extended-release tablets, or oral suspension should be administered at least 2 hours before or 6 hours after buffered didanosine preparations.1,856

Duloxetine

Concomitant use of duloxetine and potent CYP1A2 inhibitors may result in increased mean peak concentrations and AUC of duloxetine.1,579,856 Although clinical data are not available regarding a possible interaction between duloxetine and ciprofloxacin, similar effects on duloxetine exposure can be expected if duloxetine and ciprofloxacin are administered concomitantly.1

Concomitant use of duloxetine and ciprofloxacin should be avoided.1,579,856 If concomitant use cannot be avoided, patients should be monitored for duloxetine toxicity.1,579,856

Histamine H2-receptor Antagonists

Histamine H₂-receptor antagonists do not appear to have a clinically important effect on bioavailability of ciprofloxacin.1,579,856 Concomitant cimetidine339,474 or ranitidine474,824 does not appear to alter GI absorption of ciprofloxacin.

Iron, Multivitamins, and Mineral Supplements

Oral multivitamin and mineral supplements containing divalent or trivalent cations such as calcium, iron, or zinc may interfere with oral absorption of ciprofloxacin resulting in decreased serum and urine concentrations of the quinolone.1,856 Therefore, these multivitamins and/or mineral supplements should not be ingested concomitantly with ciprofloxacin.1,856

The manufacturers state that ciprofloxacin conventional tablets, extended-release tablets, or oral suspension should be administered at least 2 hours before or 6 hours after preparations containing calcium, iron, or zinc.1,856,856

-Lactam Antibiotics

An additive or synergistic effect has occurred occasionally in vitro against some strains of Ps. aeruginosa and Ps. maltophilia when ciprofloxacin was used concomitantly with an extended-spectrum penicillin (e.g., mezlocillin [not commercially available], piperacillin).116,117,118,119,124,132,430,434,479 Indifference generally occurs when ciprofloxacin is used in conjunction with an extended-spectrum penicillin against Enterobacteriaceae.132,205,434

Ciprofloxacin used in conjunction with imipenem, cefoxitin, or a cephalosporin (e.g., cefotaxime, ceftazidime) has been reported to be additive or synergistic against some strains of Ps. aeruginosa or Enterobacteriaceae; however, these combinations generally are indifferent rather than additive or synergistic against these bacteria.116,120,124,126,129,479 Although the clinical importance has not been determined, ciprofloxacin used in conjunction with cefotaxime in vitro resulted in a synergistic effect against many strains of Bacteroides fragilis tested; antagonism did not occur.65,479

Lanthanum Carbonate

Concomitant administration of lanthanum carbonate may decrease GI absorption of ciprofloxacin and result in a substantial decrease in serum and urine concentrations of the anti-infective agent.1,856

The manufacturers state that ciprofloxacin conventional tablets, extended-release tablets, or oral suspension should be administered at least 2 hours before or 6 hours after lanthanum carbonate.1,856

Lidocaine

Concomitant use of IV lidocaine hydrochloride (1.5 mg/kg) and ciprofloxacin (500 mg twice daily) increased the peak concentrations and AUC of lidocaine by 12 and 26%, respectively.1,579,856 Although lidocaine treatment was well tolerated at this elevated exposure, a possible interaction with ciprofloxacin and increase in lidocaine-associated adverse effects should be considered if the drugs are used concomitantly.1,579,856

Methotrexate

Concomitant use of ciprofloxacin and methotrexate may result in increased plasma concentrations of methotrexate (as the result of renal tubular transport inhibition) and may increase the risk of methotrexate-associated toxic reactions.1,579,856

Methotrexate and ciprofloxacin should be used concomitantly with caution;1,579,856 patients should be carefully monitored.1,579,856

Metoclopramide

Although bioavailability of ciprofloxacin does not appear to be affected,1,579,856 concomitant use of metoclopramide reportedly accelerates the rate of GI absorption of ciprofloxacin resulting in a shorter time to peak plasma concentrations of the drug.1,81,479,579,856

Metronidazole

Concomitant use of metronidazole and ciprofloxacin does not affect serum concentrations of either drug.1,579,856

Nonsteroidal Anti-inflammatory Agents

Concomitant use of ciprofloxacin and a nonsteroidal anti-inflammatory agent (NSAIA) could increase the risk of CNS stimulation (e.g., seizures).522,542,550,815 In preclinical studies and during postmarketing experience, concomitant use of ciprofloxacin and very high doses of an NSAIA (except aspirin) provoked seizures.1,579,856 Animal studies suggest that the risk may vary depending on the specific NSAIA.815

NSAIAs and ciprofloxacin should be used concomitantly with caution.1,579,856

Omeprazole

Concomitant administration of a single 500-mg conventional tablet of ciprofloxacin and omeprazole (20 mg once daily for 4 days) resulted in a 16% decrease in mean peak concentration and AUC of ciprofloxacin.1,856 Concomitant administration of ciprofloxacin extended-release tablets (single 1-g dose) and omeprazole (40 mg once daily for 3 days) in healthy individuals reduced peak plasma concentrations and AUC of ciprofloxacin by 23 and 20%, respectively.856 The clinical importance of this interaction has not been determined.1,856

Phenytoin

Concomitant use of ciprofloxacin and phenytoin has resulted in altered serum concentrations of phenytoin (increased or decreased).1,579,856

Phenytoin and ciprofloxacin should be used concomitantly with caution.1,579,856 To avoid loss of seizure control and prevent adverse effects associated with phenytoin overdosage, phenytoin serum concentrations should be monitored during and shortly after concomitant therapy with ciprofloxacin.1,579,856

Phosphodiesterase Type 5 Inhibitors

Concomitant use of a single oral dose of sildenafil (50 mg) with ciprofloxacin (500 mg) in healthy individuals increased the mean peak concentration and AUC of sildenafil approximately twofold.1,579,856

Sildenafil and ciprofloxacin should be used concomitantly with caution;1,579,856 patients should be monitored for sildenafil toxicity.1,579,856

Probenecid

Concomitant administration of probenecid interferes with renal tubular secretion of ciprofloxacin, resulting in a 50% decrease in renal clearance of ciprofloxacin,1,81,856 a 50% increase in systemic ciprofloxacin concentrations,1,856 and a prolonged serum half-life of the drug.208,214,474 This effect may potentiate ciprofloxacin toxicity.1,579,856

Probenecid and ciprofloxacin should be used concomitantly with caution.1,579,856

Rifampin

Concomitant use of oral ciprofloxacin (750 mg twice daily) and oral rifampin (300 mg twice daily) does not appear to affect the pharmacokinetics of either drug.832

In vitro, the combination of ciprofloxacin and rifampin generally is indifferent against S. aureus ; however, antagonism also has been reported rarely.115,479,557

Ropinirole

Concomitant use of oral ciprofloxacin (500 mg twice daily) and oral ropinirole (6 mg daily) has resulted in 60 and 84% increases in peak concentrations and AUC of ropinirole, respectively.1,579,836,856

Ropinirole and ciprofloxacin should be used concomitantly with caution;1,579,856 patients should be monitored for ropinirole-associated adverse effects during and shortly after concomitant therapy and ropinirole dosage adjustments should be made as necessary.1,579,856

Sevelamer

Concomitant administration of sevelamer may decrease GI absorption of ciprofloxacin and result in a substantial decrease in serum and urine concentrations of the anti-infective agent.1,856

The manufacturers state that ciprofloxacin conventional tablets, extended-release tablets, or oral suspension should be administered at least 2 hours before or 6 hours after sevelamer.1,856

Sucralfate

Concomitant sucralfate, presumably because of its aluminum content, decreases GI absorption of ciprofloxacin and may result in a substantial (50-90%) decrease in serum concentrations of the anti-infective agent.1,532,576,825,856

The manufacturers state that ciprofloxacin extended-release tablets, conventional tablets, or oral suspension should be administered at least 2 hours before or 6 hours after sucralfate.1,856

Tizanidine

Concomitant use of tizanidine (single dose of 4 mg) and ciprofloxacin (500 mg twice daily for 3 days) increased peak serum concentrations and AUC of tizanidine by sevenfold and tenfold, respectively.1,579,856

Concomitant use of ciprofloxacin and tizanidine is contraindicated because the hypotensive and sedative effects of tizanidine are potentiated.1,579,856

Vancomycin

Synergism does not occur in vitro when ciprofloxacin is used in conjunction with vancomycin against Staphylococcus epidermidis ,27,131,423 S. aureus (including methicillin-resistant S. aureus ),27,131,423,479 Corynebacterium ,27 or Listeria monocytogenes .27

Xanthine Derivatives

Theophyllines

Concomitant administration of ciprofloxacin in patients receiving a theophylline derivative may result in higher and prolonged serum theophylline concentrations and may increase the risk of theophylline-related adverse effects.1,180,193,198,199,200,204,205,208,216,297,421,426,466,479,506,507,508,509,510,511,527,552,561,579,856,856 Alterations in theophylline pharmacokinetics have shown considerable interindividual variation, with serum theophylline concentrations reportedly increasing by 17-254% and theophylline clearance decreasing by 18-112% following initiation of ciprofloxacin.180,193,198,199,200,204,506,507,508,509,510,528,552 Generally, however, reductions in theophylline clearance induced by ciprofloxacin have averaged 20-35%.245,248,507,508,510 Alterations in theophylline pharmacokinetics may be related to inhibition of metabolism in the liver179,198,208,216,355,506,507,508,509,510,511,523,527,528,552 by the 4-oxo metabolites of these quinolones.199,216,523,528 However, the potential contribution of the 4-oxo metabolites to this interaction has not been fully elucidated, and there is some evidence that, while formation of these metabolites may correlate with inhibition of theophylline metabolism, the 4-oxo metabolites themselves may not be responsible for the observed inhibition.528,522 Theophyllines do not appear to affect the pharmacokinetics of quinolones.506,511 However, there is limited in vitro evidence that theophyllines may potentiate quinolone-induced inhibition of γ-aminobutyric acid (GABA), thus possibly potentiating CNS stimulation.542,550

Serious and sometimes fatal reactions (e.g., cardiac arrest, seizures, status epilepticus, respiratory failure) have occurred in patients receiving ciprofloxacin and theophylline concomitantly.1,195,297,579,856 Death in at least one patient was associated with seizures and atrial fibrillation during concomitant therapy with the drugs.552 Other adverse reactions reported during concomitant therapy with the drugs include nausea, vomiting, dizziness, headache, tremor, restlessness, agitation, irritability, confusion, hallucinations, tachycardia, and palpitations.1,195,297,426,435,479,506,507,509,511,528,552,579 These adverse effects apparently occurred as the result of increased serum theophylline concentrations.1,195,297,426,435,479,506,507,509,511,528,552,579 While similar effects also have been reported in theophylline-treated patients who were not receiving ciprofloxacin concomitantly, the possibility that such toxicity may have been potentiated by ciprofloxacin cannot be excluded.1,579,856

Concomitant use of ciprofloxacin and a theophylline derivative should be avoided, if possible, because of the risk of toxicity (e.g., CNS or other adverse effects) associated with increased plasma concentrations of theophylline.1,180,509,552,579,856 If concomitant use of theophylline and ciprofloxacin cannot be avoided, plasma theophylline concentrations should be monitored, the patient observed for manifestations of theophylline toxicity, and appropriate theophylline dosage adjustments made as needed,1,185,193,199,200,204,216,355,466,506,507,508,509,510,511,527,528,552,579,856 especially in geriatric patients.200,204,355,466,479,507,523,528,552 The need for theophylline dosage adjustment also should be considered when ciprofloxacin is discontinued since subtherapeutic concentrations may occur.506,507

Caffeine

Ciprofloxacin inhibits formation of paraxanthine after caffeine administration,1,579,856 resulting in increased serum concentrations, reduced clearance, and prolonged elimination half-life of caffeine.1,185,194,479,513,514,515,528,541,577,579,856

Caffeine and ciprofloxacin should be used concomitantly with caution.1,579,856 Patients receiving ciprofloxacin should be advised that regular consumption of large quantities of coffee, tea, or caffeine-containing soft drinks or drugs during therapy with the anti-infective may result in exaggerated or prolonged effects of caffeine.1,513,528,577,579,856 If excessive cardiac or CNS stimulation (e.g., nervousness, insomnia, anxiety, tachycardia) occurs, caffeine intake should be restricted.513 In addition, caffeine intake should be restricted during ciprofloxacin therapy in patients at risk of adverse effects from CNS or cardiac stimulation.514,528,577

Pentoxifylline

Concomitant use of pentoxifylline and ciprofloxacin results in increased serum concentrations, reduced clearance, and prolonged elimination half-life of pentoxifylline.1,579,856 Ciprofloxacin and pentoxifylline should be used concomitantly with caution; patients should be monitored for xanthine toxicity and dosage adjusted as necessary.1,579,856

Zolpidem

Concomitant use of zolpidem and ciprofloxacin may increase serum concentrations of zolpidem and is not recommended.1

Laboratory Test Interferences

Tests for Urinary Glucose

Ciprofloxacin hydrochloride does not interfere with urinary glucose determinations using cupric sulfate solution (e.g., Benedict's solution, Clinitest^®) or with glucose oxidase tests (e.g., Diastix^®, Tes-Tape^®).180,192

Acute Toxicity

The oral LD₅₀ of the drug is greater than 5 g/kg in mice and rats and approximately 2.5 g/kg in rabbits.474 In mice, rats, rabbits, and dogs, substantial toxicity (including tonic/clonic convulsions) was observed with IV ciprofloxacin doses between 125 and 300 mg/kg.579,856

Reversible renal toxicity has been reported in some cases of acute overdosage of ciprofloxacin.1,579,856 If acute oral overdosage of the drug occurs, the stomach should be emptied by inducing emesis or by gastric lava 1,856 administration of antacids containing magnesium, aluminum, or calcium may reduce oral absorption of ciprofloxacin.1,856 If the patient is comatose, having seizures, or lacks the gag reflex, gastric lavage may be performed if an endotracheal tube with cuff inflated is in place to prevent aspiration of gastric contents.516 Supportive and symptomatic treatment should be initiated.1,579,856 The patient should be observed carefully;1,579,856 renal function and urinary pH should be monitored and the urine acidified if needed.1,579,856 Adequate hydration must be maintained to minimize the risk of crystalluria.1,579,856

Only a small amount of ciprofloxacin (less than 10%) is removed by hemodialysis or peritoneal dialysis.1,178,180,214,252,254,256,412,479,579,856 Some clinicians suggest that the risks associated with hemodialysis or peritoneal dialysis do not justify their possible benefits in ciprofloxacin overdosage.522

Mechanism of Action

Ciprofloxacin usually is bactericidal in action.15,57,148,151,176,179,180,181,479,481 Like other fluoroquinolone anti-infectives, ciprofloxacin inhibits DNA synthesis in susceptible organisms via inhibition of the enzymatic activities of 2 members of the DNA topoisomerase class of enzymes, DNA gyrase and topoisomerase IV.47,147,148,149,154,167,180,181,467,479,481,497,519,722,723,724,725,726,834 DNA gyrase and topoisomerase IV have distinct essential roles in bacterial DNA replication.722,723,724,725,726 DNA gyrase, a type II DNA topoisomerase, was the first identified quinolone target; DNA gyrase is a tetramer composed of 2 GyrA and 2 GyrB subunits.722,723,724,725,726 DNA gyrase introduces negative superhelical twists in DNA, an activity important for initiation of DNA replication.724,726 DNA gyrase also facilitates DNA replication by removing positive super helical twists.724,726 Topoisomerase IV, another type II DNA topoisomerase, is composed of 2 ParC and 2 ParE subunits.722,723,724,725,726 DNA gyrase and topoisomerase IV are structurally related; ParC is homologous to GyrA and ParE is homologous to GyrB.722,723,724,725,726 Topoisomerase IV acts at the terminal states of DNA replication by allowing for separation of interlinked daughter chromosomes so that segregation into daughter cells can occur.722,723,724,725,726 Fluoroquinolones inhibit these topoisomerase enzymes by stabilizing either the DNA—DNA gyrase complex or the DNA—topoismerase IV complex; these stabilized complexes block movement of the DNA replication fork and thereby inhibit DNA replication resulting in cell death.722,723,724,725,726

Although all fluoroquinolones generally are active against both DNA gyrase and topoisomerase IV, the drugs differ in their relative activities against these enzymes.722,723,724,725,726 For many gram-negative bacteria, DNA gyrase is the primary quinolone target and for many gram-positive bacteria, topoisomerase IV is the primary target; the other enzyme is the secondary target in both cases.722,723,724,725,726,834 However, there are exceptions to this pattern.722,723,724,725,726 For certain bacteria (e.g., Streptococcus pneumoniae ), the principal target depends on the specific fluoroquinolone.722,725

The mechanism by which ciprofloxacin's inhibition of DNA gyrase or topoisomerase IV results in death in susceptible organisms has not been fully determined.167,467,722,723,724,725,726 Unlike β-lactam anti-infectives, which are most active against susceptible bacteria when they are in the logarithmic phase of growth, studies using Escherichia coli and Pseudomonas aeruginosa indicate that ciprofloxacin can be bactericidal during both logarithmic and stationary phases of growth;59,116,179,467,481 this effect does not appear to occur with gram-positive bacteria (e.g., Staphylococcus aureus ).116 In vitro studies indicate that ciprofloxacin concentrations that approximate the minimum inhibitory concentration (MIC) of the drug induce filamentation in susceptible organisms;8,147,467,481 high concentrations of the drug result in enlarged or elongated cells147,481 that may not be extensively filamented.147,481 Although the bactericidal effect of some fluoroquinolones evidently requires competent RNA and protein synthesis in the bacterial cell, and concurrent use of anti-infectives that affect protein synthesis (e.g., chloramphenicol, tetracyclines) or RNA synthesis (e.g., rifampin) inhibit the in vitro bactericidal activity of these drugs,47,59,147,148,151,467,481 the bactericidal effect of ciprofloxacin is only partially reduced in the presence of these anti-infectives.59,147,148,151,467,481 This suggests that ciprofloxacin has an additional mechanism of action that is independent of RNA and protein synthesis.59,147,148,151,467,479,481

For most susceptible organisms, the minimum bactericidal concentration (MBC) of ciprofloxacin is 1-4 times higher than the minimum inhibitory concentration (MIC), although the MBC occasionally may be 8 times higher.10,11,15,16,17,22,25,50,56,119,181,458,479,481,563

Mammalian cells contain type II topoisomerase similar to that contained in bacteria.89,148,151,168,205,478,479,724 At concentrations attained during therapy, quinolones do not appear to affect the mammalian enzyme,151,168,479,481,724 presumably because it functions differently than bacterial DNA gyrase and does not cause supercoiling of DNA.89,148,151,205,481

Although the clinical importance has not been determined, ciprofloxacin appears to have a postantibiotic inhibitory effect against most susceptible aerobic organisms.15,467,474,479,482,483,484 The duration of the postantibiotic inhibitory effect and the ciprofloxacin concentration required to produce the effect vary depending on the organism;474,482,483,484 the duration of this effect also varies according to length of exposure to the drug, increasing with increased exposure.479,482 In vitro studies in Mueller-Hinton broth using S. aureus , Enterobacteriaceae, and Ps. aeruginosa exposed for 1-2 hours to ciprofloxacin concentrations several times higher than the MIC indicate that there is a recovery period of about 1-6 hours before these organisms resume growth after the drug is removed.15,474,479,482,483,484 Equivocal results have been observed following in vitro exposure of Enterococcus faecalis (formerly Streptococcus faecalis ) to the drug, and it is unclear whether the drug exerts a postantibiotic inhibitory effect against this organism.15,479,482

In vitro studies, particularly those involving in vitro susceptibility tests, indicate that the antibacterial activity of ciprofloxacin is decreased in the presence of urine, especially acidic urine.174,179,447,479,481,485 The clinical importance of this in vitro effect has not been determined to date; however, because ciprofloxacin concentrations attained in urine are usually substantially higher than ciprofloxacin MICs for most urinary tract pathogens, the effect probably is not clinically important.174,179,211,447 The antibacterial activity of ciprofloxacin also is decreased slightly in unbuffered peritoneal dialysis fluid with a pH of 5.5 compared with its activity in dialysis fluid buffered to a pH of 7.4.121

Spectrum

Ciprofloxacin has a spectrum of activity similar to that of some other fluoroquinolones (e.g., ofloxacin).178,179,180,189,207,214,295,479,481 In vitro on a weight basis, the activity of ciprofloxacin is approximately equal to or slightly greater than that of ofloxacin against most susceptible organisms.3,181,182,205,610

Ciprofloxacin is active in vitro against most gram-negative aerobic bacteria, including Enterobacteriaceae and Pseudomonas aeruginosa .1,7,8,9,56,57,58,178,180,181,189,205,207,295,459,467,479,481 Ciprofloxacin also is active in vitro against many gram-positive aerobic bacteria,1,3,4,5,7,8,9,10,33,34,56,57,58,100,178,180,181,189,207,295,467,479,481 including penicillinase-producing, nonpenicillinase-producing, and methicillin-resistant staphylococci (also known as oxacillin-resistant staphylococci), although many strains of streptococci are relatively resistant to the drug. 3,4,5,7,8,9,10,17,20,21,22,25,33,34,45,46,50,56,57,58,60,100,178,180,181,189,207,295,467,479,481 The drug generally is less active against gram-positive than gram-negative bacteria.56,57,58,178,180,181,189,207,479,481 Ciprofloxacin has some activity in vitro against obligately anaerobic bacteria, but many of these organisms are considered resistant to the drug.180,181,189,205,459,460,467,479,481 The drug also has some activity in vitro against Chlamydia ,37,52,64,67,70,78,178,180,181,205,413,479,481 Mycoplasma ,64,69,78,180,181,213,479,481,609 Mycobacterium ,2,28,32,68,106,181,205,295,479,481,518,554,607,788 Plasmodium ,489,499,501 and Rickettsia .393 Ciprofloxacin is inactive against fungi.153

In Vitro Susceptibility Testing

Like those of other fluoroquinolones, results of ciprofloxacin in vitro susceptibility tests are affected by the pH of the media1,20,62,76,174,178,179,205,207,295,467,479,481,485 and the presence of certain cations (e.g., magnesium).295,447,467,479,481 There generally is little effect when the pH of the media is 6-8;20,179,205,479,481 however, minimum inhibitory concentrations (MICs) are at least 4-16 times greater when the pH of the media is less than 6.20,56,174,205,295,479,485 It has been suggested that ionization of the 7-piperazine group as pH decreases may interfere with access or binding to the drug's target enzyme.481,485

Ciprofloxacin MICs also are increased when high concentrations of magnesium are present in the media.295,447,467,479,481,485 The mechanism by which magnesium interferes with the antibacterial activity of ciprofloxacin is unclear,295,447,467,479,481,485 but it has been suggested that this cation may form complexes with the drug which may prevent access or binding to its target enzyme.295,447,467,481,485 Presence of calcium or zinc does not appear to affect results of ciprofloxacin susceptibility tests.447,479

Inoculum size generally does not affect in vitro susceptibility to ciprofloxacin.3,4,10,41,77,92,125,179,205,295,467,468,474,479 MICs for most organisms are only 2-4 times greater when the size of the inoculum is increased from 10² to 10⁸ colony-forming units (CFU) per mL;3,4,10,41,77,92,125,179,205,295,467,468,474,479 however, in some studies, an inoculum effect did occur with some strains of Enterobacteriaceae or Pseudomonas aeruginosa 56,119,147,447,481,486 and MIC and minimum bactericidal concentration (MBC) of the drug appeared to be equally affected by increased inoculum size.481,486 Presence of serum generally has no effect on results of ciprofloxacin in vitro susceptibility tests, but reportedly may slightly decrease MICs of the drug for some organisms.15,38,56,179,181,205,479

MICs of ciprofloxacin are higher when susceptibility tests are performed in pooled urine or urine agar rather than in nutrient broth or Mueller-Hinton media.56,62,76,174,178,179,205 The MIC of ciprofloxacin for Escherichia coli is less than 0.01 mcg/mL in Mueller-Hinton broth at pH 7.4, but is 1.6 mcg/mL in urine at pH 7.5 or 6.5 and 3.1 mcg/mL in urine at pH 5.5.56 The decreased antibacterial activity in the presence of urine probably occurs because of low pH and because urine contains a higher concentration of magnesium ions than nutrient broth or Mueller-Hinton media.205

MICs of ciprofloxacin are increased when activated charcoal is present in the media.555,556

When in vitro susceptibility testing is performed according to the standards of the Clinical and Laboratory Standards Institute (CLSI; formerly National Committee for Clinical Laboratory Standards [NCCLS]), clinical isolates identified as susceptible to ciprofloxacin are inhibited by drug concentrations usually achievable when the recommended dosage is used for the site of infection.586 Clinical isolates classified as intermediate have minimum inhibitory concentrations (MICs) that approach usually attainable blood and tissue concentrations and response rates may be lower than for strains identified as susceptible.586 Therefore, the intermediate category implies clinical applicability in body sites where the drug is physiologically concentrated or when a higher than usual dosage can be used.586 This intermediate category also includes a buffer zone that should prevent small, uncontrolled technical factors from causing major discrepancies in interpretation, especially for drugs with narrow pharmacotoxicity margins.586 If results of in vitro susceptibility testing indicate that a clinical isolate is resistant to ciprofloxacin, the strain is not inhibited by drug concentrations generally achievable with usual dosage schedules and/or MICs fall in the range where specific microbial resistance mechanisms are likely and clinical efficacy of the drug against the isolate has not been reliably demonstrated in clinical studies.586

Results of ciprofloxacin susceptibility tests should not be used to predict susceptibility to other fluoroquinolones.586

Gram-positive Aerobic Bacteria

Gram-positive Aerobic Cocci

Ciprofloxacin is active in vitro against most strains of Staphylococcus aureus ,1,4,5,7,8,9,20,21,33,34,38,41,45,56,57,58,60,84,90,100,187,189,205,447,459,460 S. epidermidis ,1,7,8,9,10,13,21,33,34,36,41,45,56,57,60,80,90,100,187,447,459 S. saprophyticus ,8,10,80,100,447 and S. hemolyticus .10 The drug is active against both penicillinase-producing and nonpenicillinase-producing staphylococci, and also is active in vitro against some methicillin-resistant strains, although to a lesser degree than against methicillin-susceptible strains.5,8,9,10,17,20,21,22,25,33,34,45,46,50,56,57,58,60,100,459,460 Ciprofloxacin is less active in vitro on a weight basis against streptococci than against staphylococci.7,8,9,10,33,56,57,58,100,180,205,447,459,460 Streptococcus pneumoniae ,3,5,7,8,9,10,20,23,33,34,38,41,56,57,58,60,189,447,459,460 S. pyogenes (group A β-hemolytic streptococci),3,5,6,9,10,20,33,34,41,46,56,58,60,100,187,189,459,460 S. agalactiae (group B streptococci),3,5,7,10,13,20,33,34,41,56,57,58,60,100,187,189,447,459,460 and viridans streptococci4,9,10,33,41,56,57,60,100,459,460 generally are inhibited in vitro by ciprofloxacin concentrations of 4 mcg/mL or less. Groups C, F, and G streptococci3,7,9,10,33,34,56,60,100,459,460 and nonenterococcal group D streptococci9,10,33,56 are inhibited in vitro by ciprofloxacin concentrations of 16 mcg/mL or less. Ciprofloxacin is active in vitro against some strains of enterococci, including Enterococcus faecalis (formerly S. faecalis ).1,3,4,5,7,8,9,10,13,18,20,33,34,38,41,45,46,57,58,60,80,84,90,94,96,100,187,189,205,447,459,460,563 The drug is more active in vitro against E. faecalis than against E. faecium or E. durans (formerly S. faecium and S. durans , respectively).5,10,18,60,563 Ciprofloxacin is bactericidal in vitro against enterococci and is active against some strains of E. faecalis resistant to penicillin combined with an aminoglycoside.563

Gram-positive Aerobic Bacilli

Ciprofloxacin is active in vitro against Bacillus anthracis ,1,686,692,712 and naturally occurring isolates have been inhibited in vitro by ciprofloxacin concentrations of 0.03-0.25 mcg/mL.692,712 The MIC of the drug reported for the strain of B. anthracis used in a study in the rhesus monkey model of inhalational anthrax was 0.08 mcg/mL.1,579 Results of in vitro susceptibility testing of 11 B. anthracis isolates that were associated with cases of inhalational or cutaneous anthrax that occurred in the US (Florida, New York, District of Columbia) during September and October 2001 in the context of an intentional release of anthrax spores (biologic warfare, bioterrorism) indicate that these strains had ciprofloxacin MICs of 0.06 mcg/mL or less.686 Based on interpretive criteria established for staphylococci, these strains are considered susceptible to ciprofloxacin.686 Anti-infectives are active against the germinated form of B. anthracis but are not active against the organism while it is still in the spore form.668,683 Strains of B. anthracis with naturally occurring resistance to ciprofloxacin have not been reported to date.668,668 However, reduced susceptibility to ofloxacin (4-fold increase in MICs from baseline) has been produced in vitro following sequential subculture of the Sterne strain of B. anthracis in subinhibitory concentrations of the fluoroquinolone.713 There are published reports of B. anthracis strains that have been engineered to have tetracycline and penicillin resistance as well as resistance to other anti-infectives (e.g., macrolides, chloramphenicol, rifampin).668,699

Ciprofloxacin is active in vitro against Corynebacterium .9,10,33,36,74,102,213,460 The MIC₉₀ of the drug reported for JK strains of Corynebacterium 9,10,33,36,74,460 and Corynebacterium D2102 is 0.5-1 mcg/mL.

Ciprofloxacin is active in vitro against Listeria monocytogenes , and the MIC₉₀ of the drug reported for this organism is 0.25-2 mcg/mL.5,9,10,33,34,41,56,60,100,213,447,459,460

The MIC₉₀ of ciprofloxacin for Nocardia asteroides is 8-16 mcg/mL; these organisms generally are considered resistant to the drug.10,108,213,447

Gram-negative Aerobic Bacteria

Neisseria

Ciprofloxacin is active in vitro against some strains of penicillinase- and nonpenicillinase-producing Neisseria gonorrhoeae 1,4,8,19,20,21,33,34,37,38,45,58,64,104,187,189,205,213,459,460,620 and N. gonorrhoeae with chromosomally mediated resistance to penicillin (CMRNG) or plasmid-mediated tetracycline resistance (TRNG).620 The MIC₉₀ of ciprofloxacin is 0.002-0.05 mcg/mL for most penicillinase- or nonpenicillinase-producing N. gonorrhoeae ,4,8,19,20,21,33,34,37,38,45,58,74,104,187,189,205,213,459,460,633,635 CMRNG, and TRNG.620 However, strains of N. gonorrhoeae with decreased susceptibility to ciprofloxacin and other fluoroquinolones have been reported with increasing frequency.632,634,635,637,638,639,857

Ciprofloxacin is active in vitro against N. meningitidis ,1,20,46,56,58,100,213,447 and the MIC₉₀ of the drug for this organism usually is 0.004-0.06 mcg/mL.4,8,20,21,33,34,37,38,45,58,189,205,213,459,460