VA Class:AM900
Levofloxacin is a fluoroquinolone anti-infective agent.1, 2, 8, 4
Levofloxacin is used for the treatment of acute bacterial sinusitis caused by susceptible Streptococcus pneumoniae , Haemophilus influenzae , or Moraxella catarrhalis .1, 2, 8, 18, 90
Levofloxacin should be used for the treatment of acute bacterial sinusitis only when there are no other treatment options. 1, 2, 8, 140, 145Because systemic fluoroquinolones, including levofloxacin, 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 (see Cautions)1, 2, 8, 140, 145and because acute bacterial sinusitis may be self-limiting in some patients, 1, 2, 8the risks of serious adverse reactions outweigh the benefits of fluoroquinolones for patients with acute sinusitis. 140, 145
In one open study in adults with acute bacterial sinusitis, therapy with oral levofloxacin (500 mg once daily) or oral amoxicillin and clavulanate potassium (500 mg of amoxicillin 3 times daily) resulted in success rates of 88 or 87%, respectively.18
In a double-blind, prospective study in adults with acute bacterial sinusitis randomized to receive levofloxacin in a dosage of 500 mg once daily for 10 days or a dosage of 750 mg once daily for 5 days, safety and efficacy of both regimens were similar.1, 90 The clinical success rate (defined as complete or partial resolution of pretreatment signs and symptoms of sinusitis to such an extent that no further anti-infective treatment was indicated) in the microbiologically evaluable patient population at the test-of-cure visit was 88.6% in those who received the 10-day regimen compared with 91.4% in those who received the 5-day regimen.1, 90 When results were stratified according to pathogen, the clinical success rate was 96.3 or 92.6% in those with S. pneumoniae , 92.6 or 90.5% in those with H. influenzae , and 100 or 90.9% in those with M. catarrhalis .1, 90
Acute Exacerbations of Chronic Bronchitis
Levofloxacin is used for the treatment of acute bacterial exacerbations of chronic bronchitis1, 8, 19, 20 caused by susceptible Staphylococcus aureus (methicillin-susceptible [oxacillin-susceptible] strains), S. pneumoniae , H. influenzae , H. parainfluenzae , or M. catarrhalis .1, 8
Levofloxacin should be used for the treatment of acute bacterial exacerbations of chronic bronchitis only when there are no other treatment options. 1, 8, 140, 145Because systemic fluoroquinolones, including levofloxacin, 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 (see Cautions)1, 8, 140, 145and because acute bacterial exacerbations of chronic bronchitis may be self-limiting is some patients, 1, 8the risks of serious adverse reactions outweigh the benefits of fluoroquinolones for patients with these infections. 140, 145
In controlled clinical studies in adults with acute bacterial exacerbations of chronic bronchitis, levofloxacin was as effective as therapy with cefaclor or cefuroxime.19, 20 Levofloxacin therapy generally resulted in bacterial cure rates of 95-97% in patients with acute bacterial exacerbations of chronic bronchitis.19, 20 The most prevalent pathogens in these studies were H. influenzae , H. parainfluenzae , M. catarrhalis , and S. pneumoniae .19, 20
Levofloxacin is used for the treatment of community-acquired pneumonia (CAP) caused by susceptible S. aureus (methicillin-susceptible [oxacillin-susceptible] strains), S. pneumoniae (including multidrug-resistant S. pneumoniae [MDRSP]), H. influenzae , H. parainfluenzae , Klebsiella pneumoniae , Legionella pneumophila , M. catarrhalis , Chlamydophila pneumoniae (formerly Chlamydia pneumoniae ), or Mycoplasma pneumoniae .1, 2, 8, 21, 512
Initial treatment of CAP generally involves use of an empiric anti-infective regimen based on the most likely pathogens and local susceptibility patterns;512 treatment may then be changed (if possible) to provide a more specific regimen (pathogen-directed therapy) based on results of in vitro culture and susceptibility testing.512 The most appropriate empiric regimen varies depending on the severity of illness at the time of presentation, whether outpatient treatment or hospitalization in or out of an intensive care unit (ICU) is indicated, and the presence or absence of cardiopulmonary disease and other modifying factors that increase the risk of certain pathogens (e.g., methicillin-resistant S. aureus [MRSA; also known as oxacillin-resistant S. aureus or ORSA], penicillin-resistant S. pneumoniae , MDRSP, enteric gram-negative bacilli, Ps. aeruginosa ).512
For additional information on management of CAP, the current clinical practice guidelines from the Infectious Diseases Society of America (IDSA) available at [Web] should be consulted.512
In one controlled clinical study in adults with CAP, a 7- to 14-day regimen that included IV and/or oral levofloxacin was as effective as a regimen that included IV ceftriaxone and/or oral cefuroxime.1, 21 Levofloxacin generally resulted in clinical success (cure or improvement) 5-7 days following completion of therapy in 93-95% of adults with CAP.1, 21 In a randomized study in CAP patients 65 years of age or older (mean age 77.9 years), the clinical cure rate at the test-of-cure visit (5-21 days after end of treatment) was 92.9% in those who received moxifloxacin and 87.9% in those who received levofloxacin; the bacteriologic success rate was 81% in those who received moxifloxacin and 75% in those who received levofloxacin.95
In controlled clinical studies, presumptive bacteriologic eradication 5-7 days following completion of therapy was evident in 98% of patients with H. influenzae infection, 95% of those with H. parainfluenzae infection, 100% of those with K. pneumoniae infection, 94% of those with M. catarrhalis infection, 88% of those with S. aureus infection, and 95% of those with S. pneumoniae infection.1, 21 Clinical success rate 5-7 days following completion of therapy in patients with atypical pneumonia caused by C. pneumoniae , M. pneumoniae , or L. pneumoniae was 96, 96, or 70%, respectively.1, 21
Safety and efficacy of a 5-day regimen of levofloxacin (750 mg IV or orally once daily for 5 days) was compared with that of a 10-day regimen of the drug (500 mg IV or orally once daily for 10 days) in a double-blind, randomized, prospective study in adults with clinically or radiologically confirmed mild to severe CAP.1 The clinical success rate (cure and improvement) was about 91% in both groups.1
A clinical and bacteriologic success rate of 95% has been reported when levofloxacin was used in adults for the treatment of CAP caused by multidrug-resistant S. pneumoniae .1
Levofloxacin is used for the treatment of nosocomial pneumonia caused by susceptible S. aureus (methicillin-susceptible [oxacillin-susceptible] strains), S. pneumoniae , H. influenzae , Escherichia coli , K. pneumoniae , Ps. aeruginosa , or Serratia marcescens .1, 2, 8 Adjunctive therapy should be used as clinically indicated.1, 2, 8 If the infection is known or suspected of being caused by Ps. aeruginosa , concomitant therapy with an antipseudomonal β-lactam anti-infective is recommended.1, 2, 8
Local susceptibility data should be used when selecting initial empiric regimens for the treatment of hospital-acquired pneumonia (HAP) not associated with mechanical ventilation or the treatment of ventilator-associated pneumonia (VAP).315
For initial empiric treatment of HAP in adults who are not at high risk of mortality and have no factors that increase the likelihood of MRSA, IDSA and the American Thoracic Society (ATS) state that levofloxacin is one of several options that can be considered.315 However, these experts state that levofloxacin should be used in conjunction with an antibacterial 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
In adults with clinically suspected VAP, IDSA and ATS state that levofloxacin is one option that can be considered for initial empiric treatment in those not at increased risk for MRSA.315 However, in patients with factors that increase the risk of MRSA or multidrug-resistant gram-negative bacteria, these experts state that levofloxacin 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
In a multicenter, randomized, open-label study in adults with clinical and radiologically documented nosocomial pneumonia, patients were randomized to receive a 7- to 15-day regimen of IV levofloxacin (750 mg once daily) following by oral levofloxacin (750 mg once daily) or IV imipenem and cilastatin sodium (500-1000 mg every 6-8 hours) followed by oral ciprofloxacin (750 mg every 12 hours).1 Patients with documented Ps. aeruginosa infections received adjunctive therapy with ceftazidime or piperacillin and tazobactam sodium (for those receiving levofloxacin) or an aminoglycoside (for those receiving the comparator regimen); those with suspected MRSA received concomitant vancomycin.1 The overall clinical success rate 3-15 days after completion of therapy was 58.1% for those receiving levofloxacin and 60.6% for those receiving the comparator regimen; the overall microbiologic eradication rate was 66.7 and 60.6%, respectively.1
Skin and Skin Structure Infections
Levofloxacin is used for the treatment of mild to moderate uncomplicated skin and skin structure infections caused by susceptible S. aureus (methicillin-susceptible [oxacillin-susceptible] strains) or S. pyogenes (group A β-hemolytic streptococci)1, 2, 8, 23, 27, 543 and for the treatment of complicated skin and skin structure infections caused by susceptible S. aureus (methicillin-susceptible [oxacillin-susceptible] strains), Enterococcus faecalis , S. pyogenes , or Proteus mirabilis .1, 2, 8, 46, 58
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
Levofloxacin has been effective for the treatment of uncomplicated abscesses, cellulitis, erysipelas, furuncles, impetigo, pyoderma, and wound or surgical infections caused by susceptible bacteria.1, 23, 27 In 2 controlled studies, oral levofloxacin was as effective as oral ciprofloxacin in the treatment of mild to moderate skin infections caused by susceptible bacteria, mainly S. aureus and S. pyogenes .23, 27 Levofloxacin resulted in a bacteriologic cure rate of 93-97.5% in patients with mild to moderate skin and skin structure infections.23, 27
In an open-label, randomized study in patients with complicated skin and skin structure infections, the overall success rate (improved or cured) in clinically evaluable patients at 2-5 days after completion of treatment was 84.1% in those randomized to receive levofloxacin (750 mg once daily for 7-14 days given IV and/or orally as indicated) and 80.3% in those randomized to the comparator regimen (fixed combination of IV ticarcillin and clavulanate [no longer commercially available in the US] followed by oral amoxicillin and clavulanate for a total duration of 7-14 days).1, 58 Success rates varied depending on the diagnosis, ranging from 69% in those with infected diabetic ulcers to 90% in those with infected abscesses.58 In the microbiologically evaluable population, the overall rate of eradication was 83.7% in those who received levofloxacin and 71.4% in those who received the comparator regimen.58
Urinary Tract Infections and Prostatitis
Uncomplicated Urinary Tract Infections
Levofloxacin is used for the treatment of mild to moderate uncomplicated urinary tract infections (UTIs) caused by susceptible E. coli , K. pneumoniae , or S. saprophyticus .1, 2, 8
Levofloxacin should be used for the treatment of uncomplicated UTIs only when there are no other treatment options. 1, 2, 8, 140, 145Because systemic fluoroquinolones, including levofloxacin, 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 (see Cautions)1, 2, 8, 140, 145and because uncomplicated UTIs may be self-limiting in some patients, 1, 8the risks of serious adverse reactions outweigh the benefits of fluoroquinolones for patients with uncomplicated UTIs. 140, 145
IDSA and other experts state that fluoroquinolones (ciprofloxacin, levofloxacin, ofloxacin) should be considered alternative agents 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
Complicated Urinary Tract Infections
Levofloxacin is used for the treatment of mild to moderate complicated UTIs caused by susceptible E. faecalis , Enterobacter cloacae , E. coli , K. pneumoniae , P. mirabilis , or Ps. aeruginosa and acute pyelonephritis caused by susceptible E. coli , including cases with concurrent bacteremia.1, 2, 8
In controlled clinical studies, levofloxacin therapy was as effective as ciprofloxacin in the treatment of complicated UTIs or pyelonephritis.1, 24, 25 In one study in adults with complicated UTIs, bacterial eradication 5-9 days following completion of therapy was evident in 93% of patients with E. coli infection, 97% of those with K. pneumoniae infection, and 90% of those with P. mirabilis infection.25
Levofloxacin is used for the treatment of chronic prostatitis caused by susceptible E. coli , E. faecalis , or S. epidermidis (methicillin-susceptible [oxacillin-susceptible] strains).1, 2, 8
In one double-blind controlled study, adults with prostatitis were randomized to receive a 28-day regimen of oral levofloxacin (500 mg once daily) or ciprofloxacin (500 mg twice daily).1 The overall microbiologic eradication rate 5-18 days after completion of treatment was 75% in those who received levofloxacin and 76.8% in those who received ciprofloxacin.1 In those with infections caused by E. coli , E. faecalis , or S. epidermidis , the eradication rate was 93.3, 72.2, or 81.8%, respectively, in those who received levofloxacin and 81.8, 75, or 78.6%, respectively, in those who received ciprofloxacin.1
Levofloxacin 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 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
Levofloxacin has been recommended as an alternative for the treatment of campylobacteriosis† caused by susceptible Campylobacter .440
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 and 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
Levofloxacin is used for the treatment of Salmonella gastroenteritis† (with or without bacteremia).440
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.292, 440, 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.292, 440
Because HIV-infected individuals with Salmonella gastroenteritis are at high risk for bacteremia, CDC, National Institutes of Health (NIH), and 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
Levofloxacin is used as an alternative for the treatment of shigellosis† caused by susceptible Shigella .440
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, but in vitro susceptibility testing of clinical isolates is indicated since resistance is common.292 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
Oral levofloxacin has been used for the short-term treatment of travelers' diarrhea†305, 525, 677, 679 and has been used for the prevention of travelers' diarrhea† in adults traveling for relatively short periods of time to high-risk areas.305
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 , and, possibly, Acrobacter , Larobacter , and enterotoxigenic Bacteroides fragilis .305, 525 In some cases, travelers' diarrhea is caused by parasitic enteric pathogens (e.g., Giardia , Cryptosporidium , Entamoeba histolytica ) or viral enteric pathogens (e.g., norovirus, rotavirus, 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
Travelers' diarrhea caused by bacteria may be self-limited and often resolves within 3-7 days without anti-infective treatment.305, 525 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 fever or bloody stools, or extremely disruptive to travel plans.305, 525 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, 440, 525, 677, 679 alternatives include azithromycin and rifaximin.305, 525
If the causative pathogen is susceptible to the anti-infective chosen for empiric therapy, 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
CDC and most experts do not recommend prophylactic use of anti-infectives to prevent travelers' diarrhea in most individuals traveling to areas of risk.305, 525 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 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
Levofloxacin has been used as a component of various multiple-drug regimens for the treatment of infections caused by Helicobacter pylori †.235, 236, 237
Although safety and efficacy of levofloxacin-containing regimens have not been established, a 3-drug regimen that includes a proton-pump inhibitor (PPI), levofloxacin, and amoxicillin has been suggested as a first-line option for the treatment of H. pylori infection.235 In addition, a 4-drug regimen that includes a PPI, levofloxacin, nitazoxanide, and doxycycline and a sequential regimen that includes initial treatment with a PPI and amoxicillin followed by treatment with a PPI, levofloxacin, and a nitroimidazole (either tinidazole or metronidazole) have been suggested as other possible first-line options.235 Levofloxacin-containing regimens also have been recommended for second-line or salvage therapy in patients with persistent H. pylori infection.235, 237 Data are limited regarding the prevalence of fluoroquinolone-resistant H. pylori in the US; the possible impact of such resistance on the efficacy of fluoroquinolone-containing regimens used for the treatment of H. pylori infections is not known.235
Levofloxacin 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, 2, 8, 671, 672, 673 Although efficacy of levofloxacin for postexposure prophylaxis to prevent inhalational anthrax has not been evaluated in human clinical trials, the drug is labeled by FDA for this indication based on a surrogate end point derived from a primate model of inhalational anthrax that predicts clinical benefit based on plasma levofloxacin concentrations achievable in humans with recommended oral or IV dosages.1, 2, 8, 93
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, 686 Other oral fluoroquinolones (levofloxacin, moxifloxacin, ofloxacin) are alternatives for postexposure prophylaxis when ciprofloxacin or doxycycline cannot be used.668, 671, 672, 673
Oral levofloxacin is one of several options recommended for the treatment of uncomplicated cutaneous anthrax† (without systemic involvement) that occurs in the context of biologic warfare or bioterrorism.671, 672, 673 CDC recommends that adults receive an oral regimen of ciprofloxacin, doxycycline, levofloxacin, or moxifloxacin for the treatment of such infections.672, 673 AAP recommends that pediatric patients receive oral ciprofloxacin for the treatment of such infections and states that oral amoxicillin or penicillin V (if penicillin susceptibility is confirmed) or oral doxycycline, clindamycin, or levofloxacin are alternatives.671
IV levofloxacin is recommended as an alternative to IV ciprofloxacin 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.668, 671, 672, 673 CDC, AAP, US Working Group on Civilian Biodefense, and USAMRIID recommend that treatment be initiated with a multiple-drug parenteral regimen that includes a fluoroquinolone (preferably ciprofloxacin) or doxycycline and 1 or 2 additional anti-infective agents predicted to be effective;668, 671, 672, 673, 683 after the patient is clinically stable, treatment can be changed to an oral anti-infective.668, 671, 672, 673, 683 For initial treatment of systemic anthrax with possible or confirmed meningitis, CDC and AAP recommend a regimen of IV ciprofloxacin in conjunction with another IV bactericidal anti-infective (preferably meropenem) and an IV protein synthesis inhibitor (preferably linezolid).671, 672, 673 If meningitis has been excluded, these experts recommend an initial regimen of IV ciprofloxacin in conjunction with an IV protein synthesis inhibitor (preferably clindamycin or linezolid).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,668, 671, 672, 673, 683, 686 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
Levofloxacin is considered an alternative for the treatment of urogenital infections caused by Chlamydia trachomatis †.344 CDC states that a single oral dose of azithromycin or a 7-day regimen of oral doxycycline are the recommended regimens for the treatment of C. trachomatis urogenital infections in adults and adolescents;344 a 7-day regimen of oral erythromycin base or ethylsuccinate or a 7-day regimen of oral levofloxacin or ofloxacin are alternative regimens.344
Individuals with HIV infection should receive the same treatment regimens recommended for other individuals with C. trachomatis urogenital infections.344
Any individual who had sexual contact with a patient with C. trachomatis urogenital infection during the 60 days preceding the patient's onset of symptoms or diagnosis should be referred for evaluation, testing, and presumptive treatment with a regimen effective against Chlamydia .344 To minimize transmission and avoid reinfection, individuals treated for C. trachomatis urogenital infections should abstain from sexual intercourse until they and their partner(s) have been adequately treated (i.e., for 7 days after a single-dose regimen or after completion of a 7-day regimen) and symptoms have resolved.344
Gonorrhea and Associated Infections
Although levofloxacin was used in the past for the treatment of uncomplicated gonorrhea† caused by susceptible Neisseria gonorrhoeae ,114 quinolone-resistant N. gonorrhoeae (QRNG) is widely disseminated throughout the world, including in the US.53, 114, 116, 344, 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, 116, 344
Levofloxacin is considered an alternative agent for the treatment of PID†.344 (See Uses: Pelvic Inflammatory Disease.)
Levofloxacin is considered an alternative agent for the treatment of acute epididymitis†.344 Although acute epididymitis in sexually active men younger than 35 years of age is most frequently caused by C. trachomatis or N. gonorrhoeae , epididymitis can also be caused by other organisms (e.g., sexually transmitted enteric bacteria, Mycoplasma , Ureaplasma , mycobacteria, fungi).344 Presumptive treatment is usually initiated prior to availability of all diagnostic laboratory test results, and the anti-infective regimen is selected based on the patient's risk for chlamydia, gonorrhea, and/or sexually transmitted enteric bacteria (e.g., E. coli ).344 For treatment of acute epididymitis most likely caused by sexually transmitted chlamydia and gonorrhea, CDC recommends a single IM dose of ceftriaxone used in conjunction with a 10-day regimen of oral doxycycline.344 For treatment of acute epididymitis most likely caused by sexually transmitted chlamydia and gonorrhea and enteric bacteria (e.g., in men who practice insertive anal sex), CDC recommends a single IM dose of ceftriaxone given in conjunction with a 10-day regimen of oral levofloxacin or ofloxacin.344 If acute epididymitis is most likely caused by enteric bacteria (e.g., in men who have undergone prostate biopsy, vasectomy, or other urinary tract instrumentation procedure) and gonorrhea has been ruled out (e.g., by gram, methylene blue, or gentian violet stain), CDC states that a 10-day regimen of oral levofloxacin or ofloxacin can be used alone.344
For information on current recommendations for the treatment of gonorrhea and associated infections,see Uses: Gonorrhea and Associated Infections in Ceftriaxone 8:12.06.12. For additional information on quinolone-resistantN. gonorrhoeae (QRNG),see Uses: Gonorrhea and Associated Infections in Ciprofloxacin 8:12.18.
Treatment of Active Tuberculosis
Levofloxacin is used in multiple-drug regimens for the treatment of active tuberculosis† caused by Mycobacterium tuberculosis .73, 76, 77, 78, 79, 218, 231, 276, 440
Although the potential role of fluoroquinolones and the optimal length of therapy have not been fully defined, 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
Although levofloxacin (or moxifloxacin) has been used instead of ethambutol during the intensive phase of treatment in adults who could not receive ethambutol and has been used instead of isoniazid throughout the course of treatment in adults who could not receive isoniazid, ATS, CDC, and IDSA state that there is no evidence that levofloxacin (or moxifloxacin) can be used to replace a rifamycin or pyrazinamide while maintaining a 6-month treatment regimen.218
The fact that there are reports of fluoroquinolone-resistant M. tuberculosis and increasing reports of extensively drug-resistant tuberculosis (XDR tuberculosis) should be considered.70, 71, 72, 74, 75 XDR tuberculosis is caused by strains that are resistant to rifampin and isoniazid (multiple-drug resistant strains) and also are resistant to a fluoroquinolone and at least one parenteral second-line antimycobacterial (capreomycin, kanamycin, amikacin).71, 72
The most recent ATS, CDC, and IDSA recommendations for the treatment of tuberculosis should be consulted for more specific information.218
Other Mycobacterial Infections
Levofloxacin has been used in multiple-drug regimens for the treatment of disseminated M. avium complex† (MAC) infections.440
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 multiple-drug treatment regimen (e.g., for macrolide-resistant MAC infections), levofloxacin or moxifloxacin may be preferred,440, 675 although many strains are resistant in vitro.675
The most recent ATS, CDC, and IDSA recommendations for the treatment of other mycobacterial infections should be consulted for more specific information.440, 675
Levofloxacin is considered as an alternative agent for the treatment of nongonococcal urethritis† (NGU).344 NGU can be caused by various organisms (e.g., Chlamydia , M. genitalium , Trichomonas vaginalis , Ureaplasma , enteric bacteria) and is treated presumptively at the time of diagnosis.344 CDC states that a single dose of oral azithromycin or a 7-day regimen of oral doxycycline are the recommended regimens for the treatment of NGU;344 a 7-day regimen of oral erythromycin base or ethylsuccinate or a 7-day regimen of oral levofloxacin or ofloxacin are alternative regimens.344
CDC states that men with persistent or recurrent NGU who were not compliant with the treatment regimen or were reexposed to untreated sexual partner(s) can be retreated with the initial regimen.344 In other patients, symptoms alone (without documentation of signs or laboratory evidence of urethral inflammation) are not a sufficient basis for retreatment and an objective diagnosis of persistent or recurrent NGU should be made before considering additional treatment.344 Because there is some evidence that M. genitalium is the most frequent cause of persistent or recurrent NGU, CDC states that those initially treated with doxycycline should receive retreatment with a single dose of oral azithromycin and those initially treated with azithromycin should receive retreatment with a 7-day regimen of oral moxifloxacin.344 However, if the patient with persistent or recurrent urethritis has sex with women and is in an area where T. vaginalis is prevalent, CDC recommends presumptive retreatment with a single 2-g dose of oral metronidazole or tinidazole and referral of their partner(s) for evaluation and appropriate treatment.344
NGU may facilitate transmission of HIV and men diagnosed with NGU should be tested for HIV.344 Individuals with HIV infection should receive the same treatment regimens recommended for other individuals with NGU.344
Any individual who had sexual contact with a patient with NGU within the preceding 60 days should be referred for evaluation, testing, and presumptive treatment with a regimen effective against Chlamydia .344 To minimize transmission and avoid reinfection, men treated for NGU should abstain from sexual intercourse until they and their sexual partner(s) have been adequately treated.344
Levofloxacin is considered an alternative agent for the treatment of acute pelvic inflammatory disease† (PID),344 but should not be used routinely for treatment of PID or any infections that may involve N. gonorrhoeae .114, 116, 344
When a combined IM and oral regimen is used for the treatment of mild to moderately severe acute PID, CDC recommends a single IM dose of ceftriaxone, cefoxitin (with oral probenecid), or cefotaxime given in conjunction with a 14-day regimen of oral doxycycline (with or without a 14-day regimen of oral metronidazole).344 If parenteral cephalosporins are not feasible (e.g., because of cephalosporin allergy), CDC states that a 14-day regimen of oral levofloxacin, ofloxacin, or moxifloxacin given in conjunction with a 14-day regimen of oral metronidazole can be considered if the community prevalence and individual risk of gonorrhea are low and diagnostic testing for gonorrhea is performed.344 If culture results are positive for N. gonorrhoeae , the PID treatment regimen should be selected based on results of in vitro susceptibility testing.344 If QRNG are identified or if in vitro susceptibility cannot be determined (e.g., only nucleic acid amplification test [NAAT] for gonorrhea is available), consultation with an infectious disease specialist is recommended.344
Levofloxacin 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 6 months of age or older.1, 2, 8 Based on results of in vitro and animal testing, 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 levofloxacin for treatment or prophylaxis of plague has not been evaluated in clinical trials in humans for ethical and feasibility reasons.1, 2, 8 The drug is labeled by FDA for this indication based on an efficacy study in animals that demonstrated a survival benefit.1, 2, 8 In a placebo-controlled study, African green monkeys were exposed to an inhaled dose of Y. pestis (mean dose of 65 LD50 [ range 3-145 LD50]) and then randomized to receive a 10-day regimen of levofloxacin or placebo initiated within 6 hours after the onset of fever.1, 2, 8 In vitro testing indicated that the Y. pestis strain used in this study had a levofloxacin MIC of 0.03 mcg/mL.1, 2, 8 Pharmacokinetic data from the monkeys indicated that mean levofloxacin plasma concentrations at the end of a single 30-minute IV infusion of the drug ranged from 2.84-3.5 mcg/mL and trough concentrations 24 hours after the dose ranged from less than 0.03 to 0.06 mcg/mL.1, 2, 8 Study results indicated that mortality in the levofloxacin treatment group (1 out of 17) was significantly lower compared with mortality in the placebo group (7 out of 7).1, 2, 8 One of the levofloxacin-treated monkeys was euthanized on day 9 after exposure to Y. pestis because of a gastric complication;1, 2, 8 blood cultures in this monkey were positive for Y. pestis on day 3, but all subsequent daily blood cultures from days 4 through 7 were negative.1, 2, 8
For the treatment of plague, IM streptomycin (or IM or IV gentamicin) historically has been considered the drug of choice.197, 292, 683, 688 Alternatives recommended for the treatment of plague when aminoglycosides are not used include an IV fluoroquinolone (ciprofloxacin [a drug of choice for plague meningitis], levofloxacin, moxifloxacin), IV doxycycline (or IV tetracycline), IV chloramphenicol (a drug of choice for plague meningitis), or co-trimoxazole (may be less effective than other alternatives).50, 197, 292, 683, 688
Anti-infective regimens recommended for treatment of naturally occurring or endemic bubonic, septicemic, or pneumonic plague also are recommended for 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, a fluoroquinolone (ciprofloxacin, levofloxacin, moxifloxacin), doxycycline, 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).688
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
Levofloxacin is administered orally1, 8 or by IV infusion.2 The drug should not be given IM, subcutaneously, intrathecally, or intraperitoneally.2
IV administration of levofloxacin generally is reserved for patients who do not tolerate or are unable to take the drug orally and in other patients in whom the IV route offers a clinical advantage.2 Because the pharmacokinetics of levofloxacin are similar following oral and IV administration, these routes of administration are considered interchangeable.1, 2, 8
Patients receiving oral or IV levofloxacin should be well hydrated and instructed to drink fluids liberally to prevent highly concentrated urine and formation of crystals in urine.1, 2, 8
Levofloxacin tablets and oral solution are bioequivalent.8
Levofloxacin tablets may be given without regard to meals;1 however, levofloxacin oral solution should be given 1 hour before or 2 hours after meals.8
When levofloxacin tablets are given with a standard high-fat breakfast (e.g., 2 eggs fried in butter, 2 strips of bacon, hash brown potatoes, 2 slices of toast with butter, 180 mL of milk), peak serum levofloxacin concentrations are decreased approximately 14% (not considered clinically important).1, 86 When given with calcium-fortified orange juice, peak serum concentrations are decreased 18%;88 when given with a breakfast of calcium-fortified orange juice and whole grain, fortified, ready-to-eat cereal with skim milk, peak concentrations are decreased 24% and the time to peak concentrations is increased 46%.87 When levofloxacin is given as an oral solution, food decreases peak serum concentrations of the drug by approximately 25%.8
Levofloxacin (tablets or oral solution) should be administered orally at least 2 hours before or 2 hours after antacids containing magnesium or aluminum, metal cations (e.g., iron), sucralfate, multivitamins or dietary supplements containing iron or zinc, or buffered didanosine (pediatric oral solution admixed with antacid).1, 5, 8 These drugs may interfere with oral absorption of levofloxacin, resulting in subtherapeutic systemic concentrations of the quinolone.1, 5, 7, 8 (See Drug Interactions.)
The manufacturer states that levofloxacin tablets should not be used in pediatric patients weighing less than 30 kg.1
Commercially available levofloxacin premixed injection for IV infusion containing 5 mg/mL in 5% dextrose injection in single-use flexible containers is used without further dilution.2
Alternatively, if commercially available levofloxacin concentrate for injection containing 25 mg/mL in single-use vials is used, the concentrate must be diluted prior to IV infusion with a compatible IV solution (e.g., 0.9% sodium chloride injection, 5% dextrose injection, 5% dextrose in lactated Ringer's injection or 0.9% sodium chloride injection, Plasma-Lyte 56 and 5% dextrose injection) to provide a solution containing 5 mg/mL.2
Levofloxacin should not be admixed with other drugs or infused simultaneously through the same tubing with other drugs.2 Fluoroquinolones, including levofloxacin, should not be infused through the same tubing with any solution containing multivalent cations (e.g., magnesium).2 If the same administration set is used for sequential infusion of several different drugs, the tubing should be flushed before and after administration of levofloxacin with an IV solution that is compatible with both levofloxacin and the other drug(s).2
Levofloxacin solutions should be inspected visually for particulate matter prior to administration whenever solution and container permit;2 the solutions should be discarded if they are cloudy or contain precipitates.2
Levofloxacin premixed injection for IV infusion in 5% dextrose and levofloxacin concentrate for injection for IV infusion contain no preservatives;2 any unused portions of the solutions should be discarded.2
Levofloxacin doses of 250 or 500 mg should be administered by IV infusion over a period of 60 minutes;2 doses of 750 mg should be administered by IV infusion over a period of 90 minutes.2
Rapid IV infusion or injection has been associated with hypotension and must be avoided.2
Dosage of oral and IV levofloxacin is identical.1, 2, 8
When IV levofloxacin is used initially, therapy may be changed to oral levofloxacin (when appropriate) using the same dosage to complete therapy.1, 2, 8
Safety of levofloxacin for treatment durations longer than 28 days in adults and longer than 14 days in pediatric patients has not been studied;1, 2, 8 therefore, the manufacturers state that the drug should be given for prolonged periods only when potential benefits outweigh risks.1, 2, 8
Postexposure Prophylaxis of Anthrax
If levofloxacin is used for inhalational anthrax (postexposure) to reduce the incidence or progression of disease following suspected or confirmed exposure to aerosolized Bacillus anthracis spores, including exposures in the context of biologic warfare or bioterrorism, the manufacturers recommend that pediatric patients 6 months of age or older weighing less than 50 kg receive 8 mg/kg (up to 250 mg) every 12 hours and that pediatric patients 6 months of age or older weighing more than 50 kg receive a dosage of 500 mg once daily for 60 days.1, 2, 8
If oral levofloxacin is used for postexposure prophylaxis of anthrax in the context of biologic warfare or bioterrorism, the American Academy of Pediatrics (AAP) suggests that pediatric patients as young as 1 month of age† can receive a dosage of 8 mg/kg (up to 250 mg) every 12 hours if they weigh less than 50 kg or 500 mg once daily if they weigh more than 50 kg.671
Postexposure prophylaxis should be initiated as soon as possible following suspected or confirmed exposure to aerosolized B. anthracis .1, 2, 8, 668, 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 postexposure prophylaxis be continued for 60 days following a confirmed exposure.668, 671, 672, 673, 683
Treatment of Uncomplicated Cutaneous Anthrax
If oral levofloxacin is used for the treatment of uncomplicated cutaneous anthrax without systemic involvement† that occurs in the context of biologic warfare or bioterrorism, AAP recommends that pediatric patients 1 month of age or older† receive a dosage of 8 mg/kg (up to 250 mg) every 12 hours if they weigh less than 50 kg or 500 mg once daily if they weigh more than 50 kg.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
If IV levofloxacin is used in 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 (see Uses: Anthrax), AAP recommends that pediatric patients 1 month of age or older† receive a dosage of 8 mg/kg (up to 250 mg) every 12 hours if they weigh less than 50 kg or 500 mg once daily if they weigh more than 50 kg.671 If meningitis has been excluded, these experts recommend that IV levofloxacin be given in a dosage of 10 mg/kg (up to 250 mg) every 12 hours in those weighing less than 50 kg or 500 mg once daily in those weighing more than 50 kg.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 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
If oral levofloxacin is used for follow-up therapy of systemic anthrax after completion of the initial multiple-drug parenteral regimen, AAP recommends that pediatric patients 1 month of age or older† receive a dosage of 8 mg/kg (up to 250 mg) every 12 hours if they weigh less than 50 kg or 500 mg once daily if they weigh 50 kg or more.671
For the treatment or prophylaxis of plague caused by Yersinia pestis in pediatric patients 6 months of age or older weighing less than 50 kg, the manufacturers recommend a dosage of 8 mg/kg (up to 250 mg) every 12 hours for 10-14 days.1, 2, 8
For the treatment or prophylaxis of plague in pediatric patients 6 months of age or older weighing more than 50 kg, the manufacturers recommend a dosage of 500 mg once daily for 10-14 days and state that these individuals can receive a higher dosage (i.e., 750 mg once daily) if clinically indicated.1, 2, 8
The drug should be initiated as soon as possible after suspected or known exposure to Y. pestis .1, 2, 8
If levofloxacin is used for the treatment of acute bacterial sinusitis, the usual adult dosage is 500 mg once every 24 hours for 10-14 days.1, 2, 8 Alternatively, adults can receive a dosage of 750 mg once every 24 hours for 5 days.1, 2, 8 (See Acute Sinusitis under Uses: Respiratory Tract Infections.)
Acute Exacerbations of Chronic Bronchitis
If levofloxacin is used for the treatment of acute bacterial exacerbations of chronic bronchitis, the usual adult dosage of levofloxacin is 500 mg once every 24 hours for 7 days.1, 2, 8 (See Acute Exacerbations of Chronic Bronchitis under Uses: Respiratory Tract Infections.)
For the treatment of community-acquired pneumonia (CAP) caused by Staphylococcus aureus , Streptococcus pneumoniae (including multidrug-resistant S. pneumoniae [MDRSP]), Haemophilus influenzae , H. parainfluenzae , Klebsiella pneumoniae , Legionella pneumophila , Moraxella catarrhalis , Chlamydophila pneumoniae , or Mycoplasma pneumoniae , the usual adult dosage of levofloxacin is 500 mg once every 24 hours for 7-14 days.1, 2, 8 Alternatively, adults with CAP caused by S. pneumoniae (except MDRSP), H. influenzae , H. parainfluenzae , C. pneumoniae , or M. pneumoniae can receive a dosage of 750 mg once every 24 hours for 5 days.1, 2, 8
When used in empiric regimens for the treatment of CAP or for treatment of CAP caused by Pseudomonas aeruginosa , the Infectious Diseases Society of America (IDSA) and American Thoracic Society (ATS) recommend that levofloxacin be given in a dosage of 750 mg once daily.512
IDSA and ATS state that CAP should be treated for a minimum of 5 days and patients should be afebrile for 48-72 hours before discontinuing anti-infective therapy.512
For the treatment of nosocomial pneumonia, the usual adult dosage of levofloxacin is 750 mg once every 24 hours for 7-14 days.1, 2, 8
Skin and Skin Structure Infections
For the treatment of uncomplicated skin and skin structure infections, the usual adult dosage of levofloxacin is 500 mg once every 24 hours for 7-10 days.1, 2, 8
For the treatment of complicated skin and skin structure infections, the usual adult dosage of levofloxacin is 750 mg once every 24 hours for 7-14 days.1, 2, 8
Urinary Tract Infections and Prostatitis
If levofloxacin is used for the treatment of uncomplicated urinary tract infections (UTIs), the usual adult dosage is 250 mg once every 24 hours for 3 days.1, 2, 8 (See Uncomplicated Urinary Tract Infections under Uses: Urinary Tract Infections and Prostatitis.)
For the treatment of complicated UTIs caused by Enterococcus faecalis , E. cloacae , Escherichia coli , K. pneumoniae , Proteus mirabilis , or Ps. aeruginosa or the treatment of acute pyelonephritis caused by E. coli , the usual adult dosage of levofloxacin is 250 mg once every 24 hours for 10 days.1, 2, 8 Alternatively, adults with complicated UTIs caused by E. coli , K. pneumoniae , or P. mirabilis or acute pyelonephritis caused by E. coli can receive 750 mg once every 24 hours for 5 days.1, 2, 8
The usual adult dosage of levofloxacin for the treatment of chronic prostatitis is 500 mg once every 24 hours for 28 days.1, 2, 8
For the treatment of campylobacteriosis† caused by susceptible Campylobacter in adults with human immunodeficiency virus (HIV) infection, the recommended dosage of oral or IV levofloxacin is 750 mg once daily.440
The recommended duration of fluoroquinolone treatment in HIV-infected patients 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
For the treatment of Salmonella gastroenteritis† (with or without bacteremia) in HIV-infected adults, the recommended dosage of oral or IV levofloxacin is 750 mg once daily.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
For the treatment of shigellosis† caused by susceptible Shigella in HIV-infected adults, the recommended dosage of oral or IV levofloxacin is 750 mg once daily.440
The recommended duration of fluoroquinolone treatment in these patients 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
If oral levofloxacin is used for the treatment of travelers' diarrhea† (see Travelers' Diarrhea under Uses: GI Infections), some clinicians recommend adults receive 500 mg once daily for 1-3 days.305, 679
Although the use of anti-infectives for prophylaxis of travelers' diarrhea† generally is discouraged (see Travelers' Diarrhea under Uses: GI Infections), 305, 525 if oral levofloxacin 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, 677
When used as a component of various multiple-drug regimens for the treatment of infections caused by Helicobacter pylori † (see Helicobacter pylori Infection under Uses: GI Infections), levofloxacin usually has been given in a dosage of 500 mg once daily.235, 236, 237 A dosage of 250 mg once daily has been used in some regimens.235
Postexposure Prophylaxis of Anthrax
If levofloxacin is used for inhalational anthrax (postexposure) to reduce the incidence or progression of disease following suspected or confirmed exposure to aerosolized B. anthracis spores, including exposures in the context of biologic warfare or bioterrorism, the manufacturers recommend that adults receive a dosage of 500 mg once daily.1, 2, 8
CDC recommends that adults (including pregnant and postpartum women) receive oral levofloxacin in a dosage of 750 mg once daily for postexposure prophylaxis of anthrax in the context of biologic warfare or bioterrorism.672, 673
Anti-infective prophylaxis should be initiated as soon as possible following suspected or confirmed exposure to aerosolized B. anthracis .1, 2, 8, 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, 683
Treatment of Uncomplicated Cutaneous Anthrax
If oral levofloxacin is used for the treatment of uncomplicated cutaneous anthrax without systemic involvement†, CDC recommends that adults (including pregnant and postpartum women) receive a dosage of 750 mg once daily.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 illness.668, 672, 673, 683, 686
If IV levofloxacin is used as an alternative to IV ciprofloxacin in 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, CDC recommends that adults (including pregnant and postpartum women) receive a dosage of 750 mg once daily.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 regimen.672, 673 The oral follow-up regimen should be continued until 60 days after onset of the illness.668, 672, 673
If oral levofloxacin is used as an alternative for the treatment of urogenital infections caused by Chlamydia trachomatis † in adults and adolescents, CDC recommends a dosage of 500 mg once daily for 7 days.344
For the treatment of acute epididymitis† most likely caused by sexually transmitted enteric bacteria (e.g., E. coli ) and when Neisseria gonorrhoeae has been ruled out, CDC recommends that oral levofloxacin be given a dosage of 500 mg once daily for 10 days.344
Levofloxacin should not be used alone for treatment of epididymitis unless N. gonorrhoeae has been ruled out.114, 344 (See Uses: Gonorrhea and Associated Infections.)
Treatment of Active Tuberculosis
If levofloxacin is used as an alternative (second-line) agent in multiple-drug regimens for the treatment of active tuberculosis†, ATS, CDC, and IDSA recommend that adults receive 0.5-1 g daily.218 These experts state that data are insufficient to support intermittent regimens of levofloxacin for the treatment of tuberculosis.218
Treatment of Other Mycobacterial Infections
If oral levofloxacin is used as an alternative in multiple-drug regimens for the treatment of disseminated infections caused by Mycobacterium avium complex† (MAC) in HIV-infected adults, CDC, National Institutes of Health (NIH), and IDSA recommend a dosage of 500 mg once daily.440
If oral levofloxacin is used as an alternative for the treatment of nongonococcal urethritis† (NGU), CDC recommends a dosage of 500 mg once daily for 7 days.344 (See Uses: Nongonococcal Urethritis.)
If oral levofloxacin is used as an alternative for the treatment of mild to moderately severe acute pelvic inflammatory disease (PID), CDC recommends a dosage of 500 mg once daily for 14 days given in conjunction with oral metronidazole (500 mg twice daily for 14 days).344
Levofloxacin should be used for the treatment of PID only when parenteral cephalosporins are not feasible, the community prevalence and individual risk of gonorrhea are low, and in vitro susceptibility has been confirmed.344 (See Uses: Pelvic Inflammatory Disease.)
If levofloxacin is used for the treatment or prophylaxis of plague caused by Y. pestis in adults, the manufacturers recommend a dosage of 500 mg once daily for 10-14 days and state that these individuals can receive a higher dosage (i.e., 750 mg once daily) if clinically indicated.1, 2, 8
The drug should be initiated as soon as possible after suspected or known exposure to Y. pestis .1, 2, 8
Adjustment of levofloxacin dosage is not be expected to be necessary in patients with hepatic impairment because most of the drug is excreted unchanged in urine.1, 2, 8
Dosage of levofloxacin should be modified according to the degree of renal impairment when the drug is used in adults with creatinine clearances less than 50 mL/minute.1, 8 The only exception is when levofloxacin is used for the treatment of uncomplicated UTIs.1, 2, 8 (See Table 1.)
The manufacturers make no dosage recommendations for pediatric patients with renal insufficiency.1, 2, 8
Usual Daily Dosage for Normal Renal Function (Creatinine Clearance ≥50 mL/minute or greater) | Creatinine Clearance (mL/minute) | Dosage for Renal Impairment |
|---|---|---|
250 mg | 20-49 | Dosage adjustment not required |
250 mg | 10-19 | Uncomplicated UTIs: Dosage adjustment not required |
Other infections: 250 mg once every 48 hours | ||
250 mg | Hemodialysis or CAPD patients | Information not available |
500 mg | 20-49 | Initial 500-mg dose, then 250 mg once every 24 hours |
500 mg | 10-19 | Initial 500-mg dose, then 250 mg once every 48 hours |
500 mg | Hemodialysis or CAPD patients | Initial 500-mg dose, then 250 mg once every 48 hours; supplemental doses not required after dialysis |
750 mg | 20-49 | 750 mg once every 48 hours |
750 mg | 10-19 | Initial 750-mg dose, then 500 mg once every 48 hours |
750 mg | Hemodialysis or CAPD patients | Initial 750-mg dose, then 500 mg once every 48 hours; supplemental doses not required after dialysis |
Adjustment of levofloxacin dosage based solely on age is not necessary in geriatric patients.1, 2, 8 However, dosage of the drug should be selected carefully since geriatric patients are more likely to have decreased renal function than younger adults.1, 2, 8 (See Geriatric Use under Warnings/Precautions: Specific Populations, in Cautions.)
Levofloxacin is contraindicated in patients with known hypersensitivity to levofloxacin or other quinolones.1, 2, 8
Disabling and Potentially Irreversible Serious Adverse Reactions
Systemic fluoroquinolones, including levofloxacin, 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, 2, 8, 140, 145 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, 2, 8
Levofloxacin should be discontinued immediately at the first signs or symptoms of any serious adverse reactions.1, 2, 8, 140, 145
Systemic fluoroquinolones, including levofloxacin, should be avoided in patients who have experienced any of the serious adverse reactions associated with fluoroquinolones.1, 2, 8, 140, 145
Systemic fluoroquinolones, including levofloxacin, are associated with an increased risk of tendinitis and tendon rupture in all age groups.1, 2, 8, 128, 129
The risk of developing fluoroquinolone-associated tendinitis and tendon rupture is increased in older adults (usually those over 60 years of age), individuals receiving concomitant corticosteroids, and kidney, heart, or lung transplant recipients.1, 2, 8 (See Geriatric Use under Warnings/Precautions: Specific Populations, in Cautions.)
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, 2, 8 Tendinitis and tendon rupture have been reported in patients receiving fluoroquinolones who did not have any risk factors for such adverse reactions.1, 2, 8
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, 2, 8 Tendinitis or tendon rupture can occur within hours or days after levofloxacin is initiated or as long as several months after completion of therapy and can occur bilaterally.1, 2, 8
Levofloxacin should be discontinued immediately if pain, swelling, inflammation, or rupture of a tendon occurs.1, 2, 8
Systemic fluoroquinolones, including levofloxacin, should be avoided in patients who have a history of tendon disorders or have experienced tendinitis or tendon rupture.1, 2, 8
Systemic fluoroquinolones, including levofloxacin, have been associated with an increased risk of peripheral neuropathy.1, 2, 8
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 levofloxacin.1, 2, 8 Symptoms may occur soon after initiation of levofloxacin and, in some patients, may be irreversible.1, 2, 8, 130
Levofloxacin 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, 2, 8, 130 (See Advice to Patients.)
Systemic fluoroquinolones, including levofloxacin, should be avoided in patients who have experienced peripheral neuropathy.1, 2, 8
Systemic fluoroquinolones, including levofloxacin, have been associated with an increased risk of psychiatric adverse effects, including toxic psychosis,1, 2, 8 hallucinations,1, 2, 8 paranoia,1, 2, 8 depression,1, 2, 8 suicidal thoughts or acts,1, 2, 8 anxiety,1, 2, 8 agitation,1, 2, 8, 171 restlessness,1, 2, 8 nervousness,1, 2, 8, 171 confusion,1, 2, 8 delirium,1, 2, 8, 171 disorientation,1, 2, 8, 171 disturbances in attention,1, 2, 8, 171 insomnia,1, 2, 8 nightmares,1, 2, 8 and memory impairment.1, 2, 8, 171 Attempted or completed suicides have been reported, especially in patients with a history of depression or an underlying risk factor for depression.1, 2, 8 These adverse effects may occur after the first dose.1, 2, 8
System fluoroquinolones, including levofloxacin, have been associated with an increased risk of seizures (convulsions), increased intracranial pressure (including pseudotumor cerebri), dizziness, and tremors.1, 2, 8
Levofloxacin, like other fluoroquinolones, should be used with caution in patients with known or suspected CNS disorders that predispose to seizures or lower the seizure threshold (e.g., severe cerebral arteriosclerosis, epilepsy) or with other risk factors that predispose to seizures or lower the seizure threshold (e.g., certain drugs, renal impairment).1, 2, 8
If psychiatric or other CNS effects occur, levofloxacin should be discontinued immediately and appropriate measures initiated.1, 2, 8 (See Advice to Patients.)
Exacerbation of Myasthenia Gravis
Fluoroquinolones, including levofloxacin, have neuromuscular blocking activity and may exacerbate muscle weakness in individuals with myasthenia gravis.1, 2, 8 Use of fluoroquinolones in myasthenia gravis patients has resulted in requirements for ventilatory support and in death.1, 2, 8
Levofloxacin should be avoided in patients with a known history myasthenia gravis.1, 2, 8 Patients should be advised to immediately contact a clinician if they experience any symptoms of muscle weakness, including respiratory difficulties.1, 2, 8 (See Advice to Patients.)
Serious and occasionally fatal hypersensitivity and/or anaphylactic reactions have been reported in patients receiving fluoroquinolones, including levofloxacin.1, 2, 8 These reactions often occur with the first dose.1, 2, 8
Some hypersensitivity reactions have been accompanied by cardiovascular collapse, hypotension or shock, seizures, loss of consciousness, tingling, angioedema (e.g., edema or swelling of the tongue, larynx, throat, or face), airway obstruction (e.g., bronchospasm, shortness of breath, acute respiratory distress), dyspnea, urticaria, pruritus, and other severe skin reactions.1, 2, 8
Other serious and sometimes fatal adverse reactions that have been reported with fluoroquinolones, including levofloxacin, and that may or may not be related to hypersensitivity reactions include one or more of the following: fever, rash or other severe dermatologic reactions (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 effects.1, 2, 8
Levofloxacin should be discontinued immediately at the first appearance of rash, jaundice, or any other sign of hypersensitivity.1, 2, 8 Appropriate therapy should be initiated as indicated.1, 2, 8 (See Advice to Patients.)
Moderate to severe photosensitivity/phototoxicity reactions have been reported with fluoroquinolones, including levofloxacin.1, 2, 8
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, 2, 8
As with other fluoroquinolones, patients should be advised to avoid unnecessary or excessive exposure to sunlight or artificial UV light (e.g., tanning beds, UVA/UVB treatment) while receiving levofloxacin.1, 2, 8 If a patient needs to be outdoors, they should wear loose-fitting clothing that protects skin from sun exposure and use other sun protection measures (sunscreen).1, 2, 8
Levofloxacin should be discontinued if photosensitivity or phototoxicity (sunburn-like reaction, skin eruption) occurs.1, 2, 8
Severe hepatotoxicity, including acute hepatitis, has occurred in patients receiving levofloxacin and sometimes resulted in death.1, 2, 8 Most cases of severe hepatotoxicity occurred within 6-14 days of initiation of levofloxacin therapy and were not associated with hypersensitivity reactions.1, 2, 8 The majority of fatal cases of hepatotoxicity were in geriatric patients 65 years of age or older.1, 2, 8 (See Geriatric Use under Warnings/Precautions: Specific Populations, in Cautions.)
Levofloxacin should be discontinued immediately in any patient who develops signs or symptoms of hepatitis (e.g., loss of appetite, nausea, vomiting, fever, weakness, tiredness, right upper quadrant tenderness, itching, yellowing of the skin or eyes, light colored bowel movements, or dark colored urine).1, 2, 8
Prolonged QT interval leading to ventricular arrhythmias, including torsades de pointes, has been reported with some fluoroquinolones, including levofloxacin.1, 2, 8, 37
Levofloxacin should be avoided in patients with a history of prolonged QT interval, in those with uncorrected electrolyte disorders (e.g., hypokalemia), and in those receiving class IA (e.g., quinidine, procainamide) or class III (e.g., amiodarone, sotalol) antiarrhythmic agents.1, 2, 8
The risk of prolonged QT interval may be increased in geriatric patients.1, 2, 8 (See Geriatric Use under Warnings/Precautions: Specific Populations, in Cautions.)
Risk of 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 geriatric patients.1, 2, 8 The cause for this increased risk has not been identified.1, 2, 8, 172
Unless there are no other treatment options, systemic fluoroquinolones, including levofloxacin, should not be used in patients who have an aortic aneurysm or are at increased risk for an aortic aneurysm.1, 2, 8, 172 This includes geriatric patients and patients with peripheral atherosclerotic vascular disease, hypertension, or certain genetic conditions (e.g., Marfan syndrome, Ehlers-Danlos syndrome).172
If a patient reports adverse effects suggestive of aortic aneurysm or dissection, fluoroquinolone treatment should be discontinued immediately.172 (See Advice to Patients.)
Systemic fluoroquinolones, including levofloxacin, have been associated with alterations in blood glucose concentrations, including symptomatic hypoglycemia and hyperglycemia.1, 2, 8, 171 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, 2, 8, 171
Severe cases of hypoglycemia resulting in coma or death have been reported with some systemic fluoroquinolones.1, 2, 8, 171 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
Blood glucose concentrations should be carefully monitored when systemic fluoroquinolones, including levofloxacin, are used in patients with diabetes mellitus receiving antidiabetic agents.1, 2, 8, 82, 171
If a hypoglycemic reaction occurs, levofloxacin should be discontinued and appropriate therapy initiated immediately.1, 2, 8 (See Advice to Patients.)
An increased incidence of musculoskeletal disorders (arthralgia, arthritis, tendinopathy, gait abnormality) has been reported in pediatric patients receiving levofloxacin.1, 2, 8 The manufacturers state that levofloxacin should be used in pediatric patients only for inhalational anthrax (postexposure) or treatment or prophylaxis of plague and only in those 6 months of age or older.1, 2, 8 (See Pediatric Use under Warnings/Precautions: Specific Populations, in Cautions.)
Fluoroquinolones, including levofloxacin, cause arthropathy and osteochondrosis in immature animals of various species.1, 2, 8, 118, 119, 120, 121, 122, 125, 126 Persistent lesions in cartilage reported in levofloxacin studies in immature dogs;1, 2, 8 similar erosions in weight-bearing joints and other signs of arthropathy have been reported with other fluoroquinolones.1, 2, 8
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, 2, 8, 302, 303, 304 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 levofloxacin, and may range in severity from mild diarrhea to fatal colitis.1, 2, 8, 102, 106, 107, 302, 303, 304 C. difficile produces toxins A and B which contribute to development of CDAD;1, 2, 8, 302 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, 2, 8
CDAD should be considered if diarrhea develops during or after therapy and managed accordingly.1, 2, 8, 105, 302, 303, 304 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, 8, 302, 303, 304
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, 2, 8, 302, 303, 304
Selection and Use of Anti-infectives
Levofloxacin 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, 2, 8, 140, 145 Because levofloxacin, 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 levofloxacin for patients with these infections.140, 145
To reduce development of drug-resistant bacteria and maintain effectiveness of levofloxacin and other antibacterials, use only for treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.1, 2, 8
When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.1, 2, 8 In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.1, 2, 8
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, 2, 8
There are no adequate and well-controlled studies of levofloxacin in pregnant women, and the drug should be used during pregnancy only if potential benefits justify potential risks to the fetus.1, 2, 8
Reproduction studies in rats or rabbits have not revealed evidence of teratogenicity at oral doses 9.4 or 1.1 times the maximum recommended human dose, respectively, or IV doses 1.9 or 0.5 times the maximum human dose, respectively, based on relative body surface area.1, 2, 8
Levofloxacin is distributed into milk following oral or IV administration.80
Because of the potential for serious adverse reactions in the infant, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.1, 2, 8
Safety and efficacy of levofloxacin have not been established for any indication in infants younger than 6 months of age.1, 2, 8
Levofloxacin is labeled by FDA for inhalational anthrax (postexposure) or for treatment or prophylaxis of plague in adolescents and children 6 months of age or older.1, 2, 8 Safety and efficacy of the drug have not been established for any other indication in this age group.1, 2, 8
Quinolones, including levofloxacin, cause arthropathy and osteochondrosis in juvenile animals of various species.1, 2, 8, 118, 119, 120, 121, 122, 125, 126 (See Musculoskeletal Disorders under Warnings/Precautions: Other Warnings/Precautions, in Cautions.)
The American Academy of Pediatrics (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.110, 292 For information regarding when fluoroquinolones may be a preferred option in children, see Cautions: Pediatric Precautions in Ciprofloxacin 8:12.18.
No overall differences in safety and efficacy were observed between geriatric patients and younger adults in clinical trials, but increased sensitivity in some older individuals cannot be ruled out.1, 2, 8
The risk of fluoroquinolone-associated tendon disorders, including tendon rupture, is increased in older adults (usually those older than 60 years of age).1, 2, 8, 128, 129 This risk is further increased in those receiving concomitant corticosteroids.1, 2, 128, 129 (See Tendinitis and Tendon Rupture under Warnings/Precautions: Warnings, in Cautions.) Caution is advised if levofloxacin is used in geriatric adults, especially those receiving concomitant corticosteroids.1
Severe and sometimes fatal hepatotoxicity has been reported in patients receiving levofloxacin, and the majority of fatalities have occurred in geriatric patients 65 years of age or older.1, 2, 8 (See Hepatotoxicity under Warnings/Precautions: Other Warnings/Precautions, in Cautions.)
The risk of prolonged QT interval leading to ventricular arrhythmias may be increased in geriatric patients, especially those receiving concurrent therapy with other drugs that can prolong QT interval (e.g., class IA or III antiarrhythmic agents) or with risk factors for torsades de pointes (e.g., known QT prolongation, uncorrected hypokalemia).1, 2, 8 (See Prolongation of QT Interval under Warnings/Precautions: Other Warnings/Precautions, in Cautions.)
The risk of fluoroquinolone-associated aortic aneurysm and dissection may be increased in geriatric patients.1, 2, 8 (See Risk of Aortic Aneurysm and Dissection under Warnings/Precautions: Other Warnings/Precautions, in Cautions.)
Because levofloxacin is substantially eliminated by the kidneys, age-related decreases in renal function should be considered when selecting dosage for geriatric patients and it may be useful to monitor renal function.1, 2, 8 (See Geriatric Patients under Dosage and Administration: Special Populations.)
Pharmacokinetics of levofloxacin have not been studied in patients with hepatic impairment, but pharmacokinetic alterations are unlikely.1, 2, 8
Levofloxacin clearance is substantially reduced and plasma elimination half-life of the drug is substantially prolonged in patients with impaired renal function (creatinine clearance less than 50 mL/minute).1, 2, 8
Levofloxacin should be used with caution in patients with renal impairment.1, 2, 8 Appropriate renal function tests should be performed prior to and during levofloxacin therapy and dosage adjusted as needed.1, 2, 8 (See Renal Impairment under Dosage and Administration: Special Populations.)
Adverse effected reported in 3% or more of patients receiving levofloxacin include GI effects (nausea, diarrhea, constipation), headache, insomnia, and dizziness.1, 2, 8
Drugs That Prolong QT Interval
Potential pharmacologic interaction between levofloxacin and drugs that prolong the QT interval (additive effects on QT interval prolongation).1, 2, 8 Concomitant use of levofloxacin and class IA (e.g., quinidine, procainamide) or class III (e.g., amiodarone, sotalol) antiarrhythmic agents should be avoided.1, 2, 8 (See Prolongation of QT Interval under Warnings/Precautions: Other Warnings/Precautions, in Cautions.)
Potential pharmacokinetic interaction between levofloxacin (tablets or oral solution) and antacids containing magnesium or aluminum (decreased absorption of oral levofloxacin).1, 2, 5, 7, 8 Data are not available regarding concomitant use of IV levofloxacin and antacids.2
Levofloxacin tablets or oral solution should be administered at least 2 hours before or 2 hours after such antacids.1, 8
Potential pharmacologic interaction between levofloxacin and antiarrhythmic agents (additive effect on QT interval prolongation).1, 2, 8 Levofloxacin should be avoided in patients receiving class IA (e.g., quinidine, procainamide) or class III (e.g., amiodarone, sotalol) antiarrhythmic agents.1, 2, 8 (See Prolongation of QT Interval under Warnings/Precautions: Other Warnings/Precautions, in Cautions.)
Pharmacokinetic interaction between levofloxacin and procainamide (increased half-life and decreased clearance of procainamide).84
Potential pharmacologic interaction between levofloxacin and fluoxetine or imipramine (additive effect on QT interval prolongation).85
Potential pharmacodynamic interaction (altered blood glucose concentrations and symptomatic hyperglycemia or hypoglycemia) in diabetic patients receiving levofloxacin concomitantly with antidiabetic agents (e.g., insulin, glyburide).1, 2, 8 (See Hypoglycemia or Hyperglycemia under Warnings/Precautions: Other Warnings/Precautions, in Cautions.)
Careful monitoring of blood glucose concentrations is recommended;1, 2, 8 levofloxacin should be discontinued if a hypoglycemic reaction occurs.1, 8
Pharmacokinetic interaction between levofloxacin and cimetidine (slightly increased levofloxacin area under the plasma concentration-time curve [AUC] and half-life).1, 2, 8 This interaction is not considered clinically important, and levofloxacin dosage adjustments are not warranted.1, 2, 8
Concomitant use of levofloxacin and corticosteroids increases the risk of severe tendon disorders (e.g., tendinitis, tendon rupture), especially in geriatric patients older than 60 years of age.1, 2, 8 Levofloxacin and corticosteroids should be used concomitantly with caution.1, 2, 8 (See Tendinitis and Tendon Rupture under Warnings/Precautions: Warnings, in Cautions.)
Possible pharmacokinetic interactions between levofloxacin and cyclosporine or tacrolimus (increased AUC of the immunosuppressive agent).92
The manufacturers of levofloxacin state that concomitant use of cyclosporine and levofloxacin did not have a clinically important effect on the pharmacokinetics of the immunosuppressive agent and dosage adjustments are not required for either drug.1, 2, 8 Some clinicians suggest that plasma concentrations of cyclosporine or tacrolimus should be monitored if used concomitantly with levofloxacin.92
Potential pharmacokinetic interaction between levofloxacin (tablets and oral solution) and buffered didanosine preparations (decreased GI absorption of oral levofloxacin).1, 8 Data are not available regarding concomitant use of IV levofloxacin and buffered didanosine preparations.2
Levofloxacin tablets or oral solution should be administered at least 2 hours before or 2 hours after buffered didanosine (pediatric oral solution admixed with antacid).1, 8
Concomitant use of levofloxacin and digoxin did not result in any clinically important effects on the pharmacokinetics of either drug.1, 2, 8, 83 Dosage adjustments are not necessary for either drug if levofloxacin and digoxin are used concomitantly.1, 2, 8
Iron, Multivitamins, and Mineral Supplements
Potential pharmacokinetic interaction between levofloxacin (tablets and oral solution) and iron, multivitamins, or mineral supplements (decreased absorption of oral levofloxacin).1, 8, 94 Data are not available regarding concomitant use of IV levofloxacin and such preparations.2
Levofloxacin tablets or oral solution should be administered at least 2 hours before or 2 hours after iron preparations or multivitamins or dietary supplements containing zinc, calcium, magnesium, or iron.1, 8, 94
Nonsteroidal Anti-inflammatory Agents
Potential pharmacologic interaction between levofloxacin and nonsteroidal anti-inflammatory agents (NSAIAs) (possible increased risk of CNS stimulation and seizures).1, 2, 8, 91 Animal studies suggest the risk may be less than that associated with some other fluoroquinolones and that risk varies depending on the specific NSAIA.91
Pharmacokinetic interaction between levofloxacin and probenecid (slightly increased levofloxacin AUC and half-life).1, 2, 8 This interaction is not considered clinically important;1, 8 levofloxacin dosage adjustments are not warranted.1, 2, 8
Potential pharmacokinetic interaction between levofloxacin (tablets or oral solution) and sucralfate (decreased absorption of oral levofloxacin);1, 8 no pharmacokinetic interaction if given 2 hours apart.86 Data are not available regarding concomitant use of IV levofloxacin and sucralfate.2
Levofloxacin tablets or oral solution should be administered at least 2 hours before or 2 hours after sucralfate.1, 8
Concomitant use of levofloxacin and theophylline did not have a clinically important effect on the pharmacokinetics of either drug.1, 2, 8 However, pharmacokinetic interactions (increased theophylline half-life and increased risk of theophylline-related adverse effects) have been reported with some other quinolones.1, 2, 8
If levofloxacin and theophylline are used concomitantly, serum theophylline concentrations should be closely monitored and theophylline dosage adjusted accordingly;1, 2, 8 clinicians should consider that adverse theophylline effects (e.g., seizures) may occur with or without elevated theophylline concentrations.1, 2, 8
Concomitant use of levofloxacin in patients receiving warfarin has resulted in increased prothrombin time (PT);1, 2, 8 clinical episodes of bleeding have been reported.1 Patients receiving the drugs concomitantly should be monitored for evidence of bleeding and PT and international normalized ratio (INR) should be monitored.1, 2, 8
Levofloxacin is rapidly absorbed from the GI tract.1, 8 Following a 500- or 750-mg dose of levofloxacin given as tablets, absolute bioavailability of the drug is approximately 99%.1, 8
Peak plasma concentrations of levofloxacin usually are attained 1-2 hours after an oral dose;1, 8 steady-state plasma concentrations are attained within 48 hours with once-daily regimens.1, 8
Levofloxacin tablets and oral solution are bioequivalent.8
Plasma concentrations of levofloxacin and area under the plasma concentration-time curve (AUC) of the drug after oral administration of tablets are similar to those after IV administration.1, 2, 8
Food slightly prolongs the time to peak plasma concentration and decreases peak concentrations of levofloxacin.1, 86, 87, 89 The effect varies depending on whether the drug is administered as tablets or oral solution.1, 8
Tablets: When a 500-mg tablet of levofloxacin is given with a standard high-fat breakfast (e.g., 2 fried eggs in butter, 2 strips of bacon, hash brown potatoes, 2 slices of toast with butter, 180 mL of milk), peak serum concentrations of the drug are decreased approximately 14% (not considered clinically important).1, 86 When levofloxacin is given with calcium-fortified orange juice, peak serum concentrations of the drug are decreased 18%;88 when given with a breakfast of calcium-fortified orange juice and whole grain, fortified, ready-to-eat cereal with skim milk, peak concentrations are decreased 24% and time to peak concentrations is increased 46%.87
Oral solution: When a 500-dose of levofloxacin is given as an oral solution with food, peak concentrations of the drug are decreased by approximately 25%.1, 8
Levofloxacin is widely distributed into body tissues and fluids, including skin, blister fluid, and lungs.1, 2, 8
Levofloxacin is distributed into CSF.5, 64, 65 Following IV administration of 400 or 500 mg of levofloxacin twice daily, CSF concentrations have been reported to be up to 47% of concurrent plasma concentrations.64, 65
The drug is distributed into milk following oral or IV administration.80
Levofloxacin is 24-38% bound to serum proteins, principally albumin.1, 2, 8
Levofloxacin undergoes limited metabolism to inactive metabolites.1, 2, 8
Levofloxacin is eliminated principally as unchanged drug in urine by glomerular filtration and active tubular secretion.1, 2, 8 Approximately 87% of an oral dose is eliminated in urine and less than 4% is eliminated in feces.1, 8
Levofloxacin is not removed by hemodialysis or continuous ambulatory peritoneal dialysis (CAPD).1, 2, 8
The terminal elimination half-life of levofloxacin is approximately 6-8 hours after oral or IV administration.1, 2, 8
In pediatric patients 6 months to 16 years of age, clearance of levofloxacin is increased and plasma concentrations of the drug are decreased compared with adults.1, 2, 8
Levofloxacin pharmacokinetics in geriatric individuals with normal renal function are similar to that reported in younger adults.1, 2, 8
Levofloxacin pharmacokinetics have not been studied in patients with hepatic impairment, but pharmacokinetic alterations are unlikely.1, 2, 8
In patients with impaired renal function, levofloxacin clearance is decreased and plasma half-life is prolonged.1, 8 Mean plasma half-life of levofloxacin following a 500-mg dose given as a tablet is 27 hours in those with creatinine clearances of 20-49 mL/minute and 35 hours in those with creatinine clearances less than 20 mL/minute.1, 8
Levofloxacin is a fluoroquinolone anti-infective agent.1, 2, 8, 3, 4 Like other commercially available fluoroquinolones, levofloxacin contains a fluorine at the C-6 position of the quinolone nucleus.3, 4 Like some other fluoroquinolones (ciprofloxacin, ofloxacin), levofloxacin contains a piperazinyl group at C-7.4 The piperazinyl group in levofloxacin results in increased activity against gram-negative bacteria.4 Levofloxacin is the levorotatory isomer of ofloxacin and is 8-128 times as active against susceptible gram-positive and gram-negative bacteria as the dextrorotatory isomer and approximately twice as active as racemic ofloxacin.5, 12
Like other fluoroquinolone anti-infectives, levofloxacin inhibits DNA synthesis in susceptible organisms via inhibition of type II DNA topoisomerases (DNA gyrase, topoisomerase IV).1, 2, 4, 8, 39 In susceptible S. pneumoniae , levofloxacin principally targets topoisomerase IV.4, 39
Levofloxacin is more active in vitro against gram-positive bacteria (including Streptococcus pneumoniae ) and anaerobes than some other currently available fluoroquinolones (e.g., ciprofloxacin, ofloxacin),3, 13, 14, 15, 16, 17 but is less active in vitro than ciprofloxacin against Pseudomonas aeruginosa .3, 14, 17
Levofloxacin is active in vitro and in clinical infections against Staphylococcus aureus (methicillin-susceptible [oxacillin-susceptible] strains only), S. epidermidis (oxacillin-susceptible strains only), S. saprophyticus , S. pneumoniae (including multidrug-resistant strains [MDRSP]), S. pyogenes (group A β-hemolytic streptococci, GAS), and Enterococcus faecalis (many strains only moderately susceptible).1, 2, 3, 8 The drug also is active in vitro against some other gram-positive bacteria, including S. haemolyticus , S. agalactiae (group B streptococci, GBS), groups C, G, and F streptococci, S. milleri , and viridans streptococci.1, 3 Levofloxacin is active against Bacillus anthracis in vitro and in a primate infection model.1, 2, 8, 93
Levofloxacin is active in vitro and in clinical infections against Haemophilus influenzae , H. parainfluenzae , Klebsiella pneumoniae , Moraxella catarrhalis , Enterobacter cloacae , Escherichia coli , Proteus mirabilis , Serratia marcescens , Ps. aeruginosa (some may develop resistance during therapy), and Legionella pneumophila .1, 2, 8, 3 The drug also is active in vitro against some other gram-negative bacteria, including Acinetobacter , Bordetella pertussis , Citrobacter koseri , C. freundii , E. aerogenes , E. sakazakii , K. oxytoca , Morganella morganii , Pantoea agglomerans , Proteus vulgaris , Providencia , and Ps. fluorescens .1, 2, 8 Levofloxacin is active against Yersinia pestis in vitro and in a primate infection model.1, 2, 8
Although levofloxacin has in vitro activity against Helicobacter pylori ,241 resistance to the drug can occur and the prevalence of levofloxacin-resistant strains may be high in some geographic areas.235, 239, 240
Levofloxacin also is active against some other organisms, including Chlamydophila pneumoniae (formerly Chlamydia pneumoniae ),1, 3 Mycoplasma pneumoniae , and Clostridium perfringens .1, 2, 3, 8
Levofloxacin is active in vitro against some mycobacteria, including Mycobacterium tuberculosis ,40, 41, 73, 75, 111 and M. fortuitum .42 Although levofloxacin is active against some strains of M. tuberculosis resistant to isoniazid and/or rifampin,40, 75 levofloxacin-resistant M. tuberculosis have been reported and some multidrug-resistant M. tuberculosis (i.e., strains resistant to rifampin and isoniazid) also are resistant to levofloxacin or other fluoroquinolones.70, 71, 72, 74, 75 Extensively drug-resistant tuberculosis (XDR tuberculosis) is caused by strains that are resistant to rifampin and isoniazid (multiple-drug resistant strains) and also resistant to a fluoroquinolone and at least one parenteral second-line antimycobacterial (capreomycin, kanamycin, amikacin).71, 72
Resistance to fluoroquinolones can occur as the result of mutations in defined regions of DNA gyrase or topoisomerase IV (i.e., quinolone-resistance determining regions [QRDRs]) or altered efflux.1, 2, 8
Cross-resistance can occur between levofloxacin and other fluoroquinolones,1, 2, 8, 45 but some bacteria resistant to other fluoroquinolones may be susceptible to levofloxacin.1, 8
Advise patients to read the manufacturer's patient information (medication guide) prior to initiating levofloxacin therapy and each time the prescription is refilled.1, 2, 8
Advise patients that antibacterials (including levofloxacin) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).1, 2, 8
Importance of completing full course of therapy, even if feeling better after a few days.1, 2, 8
Advise patients that skipping doses or not completing the full course of therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with levofloxacin or other antibacterials in the future.1, 2, 8
Advise patients that the oral solution should be taken 1 hour before or 2 hours after meals;8 tablets may be taken without regard to meals.1
Levofloxacin should be taken at the same time each day and with liberal amounts of fluids.1, 8
Importance of taking oral levofloxacin at least 2 hours before or 2 hours after aluminum- or magnesium-containing antacids, metal cations (e.g., iron), sucralfate, multivitamins containing iron or zinc, or buffered didanosine (pediatric oral solution prepared admixed with antacid).1, 8
Inform patients that systemic fluoroquinolones, including levofloxacin, have been associated with disabling and potentially irreversible serious adverse reactions (e.g., tendinitis and tendon rupture, peripheral neuropathy, CNS effects) that may occur together in the same patient.1, 2, 8, 140, 145 Advise patients to immediately discontinue levofloxacin 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, 2, 8, 140, 145 Advise patients to talk with a clinician if they have any questions or concerns.1, 2, 8, 140, 145
Inform patients that systemic fluoroquinolones, including levofloxacin, are associated with an increased risk of tendinitis and tendon rupture in all age groups and that this risk is increased in adults older than 60 years of age, individuals receiving corticosteroids, and kidney, heart, or lung transplant recipients.1, 2, 8 Symptoms may be irreversible.1, 2, 8 Importance of resting and refraining 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 importance of immediately discontinuing the drug and contacting a clinician.1, 2, 8 (See Tendinitis and Tendon Rupture under Warnings/Precautions: Warnings, in Cautions.)
Inform patients that peripheral neuropathies have been reported in patients receiving systemic fluoroquinolones, including levofloxacin, and that symptoms may occur soon after initiation of the drug and may be irreversible.1, 2, 8 Importance of immediately discontinuing levofloxacin and contacting a clinician if symptoms of peripheral neuropathy (e.g., pain, burning, tingling, numbness, and/or weakness) occur.1, 2, 8
Inform patients that systemic fluoroquinolones, including levofloxacin, have been associated with CNS effects (e.g., convulsions, dizziness, lightheadedness, increased intracranial pressure).1, 2, 8 Importance of informing clinician of any history of convulsions before initiating therapy with the drug.1 Importance of contacting a clinician if persistent headache with or without blurred vision occurs.1, 2, 8
Advise patients that levofloxacin may cause dizziness and lightheadedness;1, 2, 8 caution patients that they should not engage in activities requiring mental alertness and motor coordination (e.g., driving a vehicle, operating machinery) until the effects of the drug on the individual are known.1, 2, 8
Advise patients that systemic fluoroquinolones, including levofloxacin, may worsen myasthenia gravis symptoms;1, 2, 8 importance of informing clinician of any history of myasthenia gravis.1 Importance of immediately contacting a clinician if any symptoms of muscle weakness, including respiratory difficulties, occur.1, 2, 8
Inform patients that levofloxacin may be associated with hypersensitivity reactions (including anaphylactic reactions), even after the first dose.1, 2, 8 Importance of immediately discontinuing levofloxacin and contacting a clinician at first sign of rash or any symptom of hypersensitivity (e.g., hives, other skin reaction, rapid heartbeat, difficulty swallowing or breathing, throat tightness, hoarseness, swelling of lips, tongue, or face).1, 2, 8
Inform patients that photosensitivity/phototoxicity reactions have been reported following exposure to sun or UV light in patients receiving fluoroquinolones.1, 2, 8 Importance of avoiding or minimizing exposure to sunlight or artificial UV light (e.g., tanning beds, UVA/UVB treatment) and using protective measures (e.g., wearing loose-fitting clothes, sunscreen) if outdoors during levofloxacin therapy.1, 2, 8 Importance of discontinuing levofloxacin and contacting a clinician if a sunburn-like reaction or skin eruption occurs.1, 2, 8
Importance of informing clinician of personal or family history of QT interval prolongation or proarrhythmic conditions (e.g., hypokalemia, bradycardia, recent myocardial ischemia) and of concurrent therapy with any drugs that may affect QT interval (e.g., class IA [quinidine, procainamide] or class III [e.g., amiodarone, sotalol] antiarrhythmic agents).1, 2, 8 Importance of contacting a clinician if symptoms of prolonged QT interval (e.g., prolonged heart palpitations, loss of consciousness) occur.1, 2, 8
Inform patients that systemic fluoroquinolones may increase the risk of aortic aneurysm and dissection;172 importance of informing 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 Advise patients to seek immediate medical treatment if they experience sudden, severe, and constant pain in the stomach, chest, or back.1, 2, 8, 172
Inform patients that hypoglycemia has been reported when systemic fluoroquinolones were used in some patients receiving antidiabetic agents.171 Advise patients with diabetes mellitus receiving an oral antidiabetic agent or insulin to discontinue levofloxacin and contact a clinician if they experience hypoglycemia or symptoms of hypoglycemia.1, 2, 8
Inform patients that severe hepatotoxicity (including acute hepatitis and fatal events) has been reported in patients receiving levofloxacin.1, 2, 8 Importance of immediately discontinuing levofloxacin and informing clinician if any signs or symptoms of liver injury (e.g., loss of appetite, nausea, vomiting, fever, weakness, tiredness, right upper quadrant tenderness, itching, yellowing of the skin and eyes, light colored bowel movements, dark colored urine) occur.1, 2, 8
Advise patients that diarrhea is a common problem caused by anti-infectives and usually ends when the drug is discontinued.1, 2, 8 Importance of contacting 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, 2, 8
If considering levofloxacin for a pediatric patient (see Pediatric Use under Warnings/Precautions: Specific Populations, in Cautions), importance of parent informing clinician if the child has a history of joint-related problems.1, 2, 8 Importance of parent contacting a clinician if the child develops any joint-related problems during or following levofloxacin therapy.1, 2, 8
Advise patients receiving levofloxacin for inhalational anthrax (postexposure) or for treatment or prophylaxis of plague that human efficacy studies have not been performed for ethical and feasibility reasons and that use in these conditions is based on animal efficacy studies.1, 2, 8
Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs (e.g., drugs that may affect QT interval, antidiabetic agents, warfarin), as well as any concomitant illnesses.1, 2, 8
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1, 2, 8
Importance of advising patients of other important precautionary information.1, 2, 8 (See Cautions.)
Additional Information
Overview® (see Users Guide). For additional information on this drug until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Solution | 125 mg/5 mL* | levoFLOXacin Solution | |
Tablets, film-coated | 250 mg (of anhydrous levofloxacin)* | Levaquin® | Janssen | |
levoFLOXacin Tablets | ||||
500 mg (of anhydrous levofloxacin)* | Levaquin® | Janssen | ||
levoFLOXacin Tablets | ||||
750 mg (of anhydrous levofloxacin)* | Levaquin® | Janssen | ||
levoFLOXacin Tablets | ||||
Parenteral | For injection, concentrate, for IV infusion | equivalent to levofloxacin 25 mg/mL (500 mg)* | levoFLOXacin Concentrate, for IV Infusion |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | Injection, for IV infusion | equivalent to levofloxacin 5 mg/mL (250, 500, or 750 mg) in 5% Dextrose* | levoFLOXacin in Dextrose Injection |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
1. Janssen Pharmaceuticals Inc. Levaquin® (levofloxacin) tablets, film coated prescribing information. Titusville, NJ; 2019 May.
2. Baxter Healthcare Corporation. Levofloxacin injection, solution prescribing information. Deerfield, IL; 2019 Mar.
3. Davis R, Bryson HM. Levofloxacin: a review of its antibacterial activity, pharmacokinetics and therapeutic efficacy. Drugs . 1994; 47:677-700. [PubMed 7516863]
4. Zhanel GC, Ennis K, Vercaigne L et al. A critical review of the fluoroquinolones: focus on respiratory tract infections. Drugs . 2002. 62:13-59.
5. Fish DN, Chow AT. The clinical pharmacokinetics of levofloxacin. Clin Pharmacokinet . 1997; 32:101-19. [PubMed 9068926]
6. Williams NA, Bornstein M, Johnson K. Stability of levofloxacin in intravenous solutions in polyvinyl chloride bags. Am J Health-Syst Pharm . 1996; 53:2309-13. [PubMed 8893070]
7. Shiba K, Sakai O, Shimada J et al. Effects of antacids, ferrous sulfate, and ranitidine on absorption of DR-3355 in humans. Antimicrob Agents Chemother . 1992; 36:2270-4. [PubMed 1444308][PubMedCentral]
8. Hi-Tech Pharmacal Co., Inc. Levofloxacin oral solution prescribing information. Amityville, NY; 2019 Mar.
9. Christ W, Lehnert T, Ulbrich B. Specific toxicologic aspects of the quinolones. Rev Infect Dis . 1988; 10(Suppl 1):S141-6. [PubMed 3279489]
10. Reviewer's comments (personal observations) on ciprofloxacin 8:12.18.
12. Une T, Fujimoto T, Sato K et al. In vitro activity of DR-3355, an optically active ofloxacin. Antimicrob Agents Chemother . 1988; 32:1336-40. [PubMed 3195996][PubMedCentral]
13. Plouffe JF and the Franklin County Pneumonia Study Group. Levofloxacin in vitro activity against bacteremic isolates of Streptococcus pneumoniae . Diagn Microbiol Infect Dis . 1996; 25:43-5. [PubMed 8831044]
14. Goa KL, Bryson HM, Markham A. Sparfloxacin: a review of its antibacterial activity, pharmacokinetic properties, clinical efficacy and tolerability in lower respiratory tract infections. Drugs . 1997; 53:700-25. [PubMed 9098667]
15. Hecht DW, Wexler HM. In vitro susceptibility of anaerobes to quinolones in the United States. Clin Infect Dis . 1996; 23(Suppl 1):S2-8.
16. Eliopoulos GM. In vitro activity of fluoroquinolones against gram-positive bacteria. Drugs . 1995; 49(Suppl 2):48-57. [PubMed 8549407]
17. Hooper DC. Quinolones. In: Mandell GL, Bennett JE, Dolin R eds. Mandell, Douglas and Bennett's principles and practice of infectious diseases. 4th ed. New York: Churchill Livingstone; 1995:366-7.
18. Adeglass J, DeAbate AC, McElvaine P et al. Comparison of the effectiveness of levofloxacin and amoxicillin-clavulanate for the treatment of acute sinusitis in adults. Otolaryngol Head Neck Surg . 1999; 120:320-7. [PubMed 10064632]
19. DeAbate CA, Russell M, McElvaine P et al. Safety and efficacy of oral levofloxacin versus cefuroxime axetil in acute bacterial exacerbation of chronic bronchitis. Respir Care . 1997; 42:206-13.
20. Habib MP, Gentry LO, Rodriguez-Gomez G et al. A multicenter, randomized study comparing the efficacy and safety of oral levofloxacin vs cefaclor in the treatment of acute bacterial exacerbations of chronic bronchitis. Proceedings of ICAAC New Orleans 1996. Abstract L002.
21. File TM Jr, Segreti J, Dunbar L et al. A multicenter, randomized study comparing the efficacy and safety of intravenous and/or oral levofloxacin vs ceftriaxone and/or cefuroxime axetil in the treatment of adults with community-acquired pneumonia. Antimicrob Agents Chemother . 1997; 41:1965-72. [PubMed 9303395][PubMedCentral]
23. Nicodemo AC, Robledo JA, Jasovich A et al. A multicenter, double-blind, randomized study comparing the efficacy and safety of oral levofloxacin versus ciprofloxacin in the treatment of uncomplicated skin and skin structure infections. Int J Clin Pract . 1998; 52:69-74. [PubMed 9624783]
24. Richard GA, Klimberg IN, Fowler CL et al. Levofloxacin versus ciprofloxacin versus lomefloxacin in acute pyelonephritis. Urology . 1998; 52:51-5. [PubMed 9671870]
25. Richard GA, Childs S, Fowler C et al. A comparison of levofloxacin (LVFX) and ciprofloxacin (cipro) for the treatment of complicated urinary tract infections (cUTI). Clin Infect Dis . 1996; 23:914.
27. Nichols R, Smith J, Gentry LO et al. Multicenter, open-label, active-controlled, randomized comparison of levofloxacin (LVFX) QD vs. ciprofloxacin (CIP) BID in 469 adults with mild-to-moderate skin and skin structure infections. Clin Infect Dis . 1996; 23:913.
32. Heffelfinger JD, Dowell SF, Jorgensen JH et al. Management of community-acquired pneumonia in the era of pneumococcal resistance: a report from the drug-resistance streptococcus pneumoniae therapeutic working group. Arch Intern Med . 2000; 160:1399-1408. [PubMed 10826451]
37. Morganroth J, DiMarco JP, Anzueto A et al. A randomized trial comparing the cardiac rhythm safety of moxifloxacin vs levofloxacin in elderly patients hospitalized with community-acquired pneumonia. Chest . 2005; 128:3398-406. [PubMed 16304291]
38. Bishai W. Current issues on resistance, treatment guidelines, and the appropriate use of fluoroquinolones for respiratory tract infections. Clin Ther . 2002; 24:838-50. [PubMed 12117077]
39. Bearden DT, Danziger LH. Mechanism of action of and resistance to quinolones. Pharmacotherapy . 2001; 21:224S-32S. [PubMed 11642689]
40. Tomioka H, Sato K, Akaki T et al. Comparative in vitro antimicrobial activities of the newly synthesized quinolone HSR-903, sitafloxacin (DU-6859s), gatifloxacin (AM-1155), and levofloxacin against Mycobacterium tuberculosis and Mycobacterium avium complex. Antimicrob Agents Chemother . 1999; 43:3001-4. [PubMed 10582897][PubMedCentral]
41. Alvirez-Freites EJ, Carter JL, Cynamon MH. In vitro and in vivo activities of gatifloxacin against Mycobacterium tuberculosis . 2002; 46:1022-5.
42. Yang SC, Hsueh PR, Lai HC et al. High prevalence of antimicrobial resistance in rapidly growing mycobacteria in Taiwan. Antimicrob Agents Chemother . 2003; 47:1958-62. [PubMed 12760874][PubMedCentral]
44. Zhanel GG, Palatnick L, Nichol KA et al. Antimicrobial resistance in respiratory tract Streptococcus pneumoniae isolates: results of the Canadian respiratory organism susceptibility study, 1997 to 2002. Antimicrob Agents Chemother . 2003; 47:1867-74. [PubMed 12760860][PubMedCentral]
45. Kays MB, Smith DW, Wack ME et al. Levofloxacin treatment failure in a patient with fluoroquinolone-resistant Streptococcus pneumoniae pneumonia. Pharmacotherapy . 2002; 22:395-9. [PubMed 11898897]
46. Graham DR, Talan DA, Nichols RL et al. Once-daily, high-dose levofloxacin versus ticarcillin-clavulanate alone or followed by amoxicillin-clavulanate for complicated skin and skin-structure infections: a randomized, open-label trial. Clin Infect Dis . 2002; 35:381-9. [PubMed 12145720]
50. Frean JA, Arntzen L, Capper T et al. In vitro activities of 14 antibiotics against 100 human isolates of Yersinia pestis from a Southern African plague focus. Antimicrob Agents Chemother . 1996; 40:2646-7. [PubMed 8913481][PubMedCentral]
53. Centers for Disease Control and Prevention. Increases in fluoroquinolone-resistant Neisseria gonorrhoeae among men who have sex with men—United States, 2003, and revised recommendations for gonorrhea treatment, 2004. MMWR Morb Mortal Wkly Rep . 2004; 53:3235-8.
58. Graham DR, Talan DA, Nichols RL et al. Once-daily, high-dose levofloxacin versus ticarcillin-clavulanate alone or followed by amoxicillin-clavulanate for complicated skin and skin-structure infections: a randomized, open-label trial. Clin Infect Dis . 2002; 35:381-9. [PubMed 12145720]
64. Scotton PG, Pea F, Giobbia M et al. Cerebrospinal fluid penetration of levofloxacin in patients with spontaneous acute bacterial meningitis. Clin Infect Dis . 2001; 33:e109-11. [PubMed 11577376]
65. Pea F, Pavan F, Nascimben E et al. Levofloxacin disposition in cerebrospinal fluid in patients with external ventriculostomy. Antimicrob Agents Chemother . 2003; 47:3104-8. [PubMed 14506016][PubMedCentral]
66. Scotton PG, Tonon E, Giobbia M et al. Rhodococcus equi nosocomial meningitis cured by levofloxacin and shunt removal. Clin Infect Dis . 2000; 30:223-4. [PubMed 10619769]
67. Nau R, Schmidt T, Kaye K et al. Quinolone antibiotics in therapy of experimental pneumococcal meningitis in rabbits. Antimicrob Agents Chemother . 1995; 39:593-7. [PubMed 7793857][PubMedCentral]
68. Kuhn F, Cottagnoud M, Acosta F et al. Cefotaxime acts synergistically with levofloxacin in experimental meningitis due to penicillin-resistant pneumococci and prevents selection of levofloxacin-resistant mutants in vitro. Antimicrob Agents Chemother . 2003; 47:2487-91. [PubMed 12878509][PubMedCentral]
69. Cottagnoud P, Cottagnoud M, Acosta F et al. Meropenem prevents levofloxacin-induced resistance in penicillin-resistant pneumococci and acts synergistically with levofloxacin in experimental meningitis. Eur J Clin Microbiol Infect Dis . 2003; 22:656-62. [PubMed 14557920]
70. Granich RM, Oh P, Lewis B et al. Multidrug resistance among persons with tuberculosis in California, 1994-2003. JAMA . 2005; 293:2732-9. [PubMed 15941802]
71. World Health Organization. Extensively drug-resistant tuberculosis (XDR-TB): recommendations for prevention and control. Wkly Epidemiol Rec . 2006; 45:430-2.
72. Gandhi NR, Moll A, Sturm AW et al. Extensively drug-resistant tuberculosis as a cause of death in patients co-infected with tuberculosis and HIV in a rural area of South Africa. Lancet . 2006; 368:1575-80. [PubMed 17084757]
73. Johnson JL, Hadad DJ, Boom WH et al. Early and extended early bactericidal activity of levofloxacin, gatifloxacin and moxifloxacin in pulmonary tuberculosis. Int J Tuberc Lung Dis . 2006; 10:605-12. [PubMed 16776446]
74. Aubry A, Veziris N, Cambau E et al. Novel gyrase mutations in quinolone-resistant and -hypersusceptible clinical isolates of Mycobacterium tuberculosis : functional analysis of mutant enzymes. Antimicrob Agents Chemother . 2006; 50:104-12. [PubMed 16377674][PubMedCentral]
75. Huang TS, Kunin CM, Lee SS et al. Trends in fluoroquinolone resistance of Mycobacterium tuberculosis complex in a Taiwanese medical centre: 1995-2003. J Antimicrob Chemother . 2005; 56:1058-62. [PubMed 16204341]
76. Yew WW, Chan CK, Leung CC et al. Comparative roles of levofloxacin and ofloxacin in the treatment of multidrug-resistant tuberculosis. Chest . 2003; 124:1476-81. [PubMed 14555582]
77. Marra F, Marra CA, Moadebi S et al. Levofloxacin treatment of active tuberculosis and the risk of adverse events. Chest . 2005; 128:1406-13. [PubMed 16162736]
78. Ziganshina LE, Vizel AA, Squire SB. Fluoroquinolones for treating tuberculosis. Cochrane Database Syst Rev . 2005; Jul 20:CD004795.
79. El-Sadr WM, Perlman DC, Matts JP et al. Evaluation of an intensive intermittent-induction regimen and duration of short-course treatment for human immunodeficiency virus-related pulmonary tuberculosis. Clin Infect Dis . 1998; 26:1148-58.
80. Cahill JB, Bailey EM, Chien S et al. Levofloxacin secretion in breast milk: a case report. Pharmacotherapy ; 2005; 25:116-8.
81. Flatz L, Cottagnoud M, Kuhn F et al. Ceftriaxone acts synergistically with levofloxacin in experimental meningitis and reduces levofloxacin-induced resistance in penicillin-resistant pneumococci. J Antimicrob Chemother . 2004; 53:305-10. [PubMed 14729741]
82. Friedrich LV, Dougherty R. Fatal hypoglycemia associated with levofloxacin. Pharmacotherapy ; 2004; 24:1807-12.
83. Chien SC, Rogge MC, Williams RR et al. Absence of a pharmacokinetic interaction between digoxin and levofloxacin. J Clin Pharm Ther . 2002; 27:7-12. [PubMed 11846857]
84. Bauer LA, Black DJ, Lill JS et al. Levofloxacin and ciprofloxacin decrease procainamide and N-acetylprocainamide renal clearances. Antimicrob Agents Chemother . 2005; 49:1649-51. [PubMed 15793163][PubMedCentral]
85. Nykamp DL, Blackmon CL, Schmidt PE et al. QTc prolongation associated with combination therapy of levofloxacin, imipramine, and fluoxetine. Ann Pharmacother . 2005; 39:543-6. [PubMed 15687478]
86. Lee LJ, Hafkin B, Lee ID et al. Effects of food and sucralfate on a single oral dose of 500 milligrams of levofloxacin in healthy subjects. Antimicrob Agents Chemother . 1997; 41:2196-200. [PubMed 9333047][PubMedCentral]
87. Amsden GW, Whitaker AM, Johnson PW. Lack of bioequivalence of levofloxacin when coadministered with a mineral-fortified breakfast of juice and cereal. J Clin Pharmacol . 2003; 43:990-5. [PubMed 12971031]
88. Wallace AW, Victory JM, Amsden GW. Lack of bioequivalence when levofloxacin and calcium-fortified orange juice are coadministered to healthy volunteers. J Clin Pharmacol . 2003; 43:539-44. [PubMed 12751275]
89. Wright DH, Pietz SL, Konstantinides FN et al. Decreased in vitro fluoroquinolone concentrations after admixture with an enteral feeding formulation. J Parenter Enteral Nutr . 2000; 24:42-8.
90. Poole M, Anon J, Paglia M et al. A trial of high-dose, short-course levofloxacin for the treatment of acute bacterial sinusitis. Otolaryngol Head Neck Surg . 2006; 134:10-7. [PubMed 16399173]
91. Hori S, Kizu J, Kawamura M. Effects of anti-inflammatory drugs on convulsant activity of quinolones: a comparative study of drug interactions between quinolones and anti-inflammatory drugs. J Infect Chemother . 2003; 9:314-20. [PubMed 14691652]
92. Federico S, Carrano R, Capone D et al. Pharmacokinetic interaction between levofloxacin and ciclosporin or tacrolimus in kidney transplant recipients: ciclosporin, tacrolimus and levofloxacin in renal transplantation. Clin Pharmacokinet . 2006; 45:169-75. [PubMed 16485913]
93. Kao LM, Bush K, Barnewall R et al. Pharmacokinetic considerations and efficacy of levofloxacin in an inhalational anthrax (postexposure) rhesus monkey model. Antimicrob Agents Chemother . 2006; 50:3535-42. [PubMed 17065619][PubMedCentral]
94. Pai MP, Allen SE, Amsden GW. Altered steady state pharmacokinetics of levofloxacin in adult cystic fibrosis patients receiving calcium carbonate. J Cyst Fibros . 2006; 5:153-7. [PubMed 16481224]
95. Anzueto A, Niederman MS, Pearle J et al. Community-acquired pneumonia recovery in the elderly (CAPRIE): efficacy and safety of moxifloxacin therapy versus that of levofloxacin therapy. Clin Infect Dis . 2006; 42:73-81. [PubMed 16323095]
101. McDonald LC, Killgore GE, Thompson A et al. An epidemic, toxin gene-variant strain of Clostridium difficile . N Engl J Med . 2005; 353:2433-41. [PubMed 16322603]
102. Loo VG, Poirier L, Miller MA et al. A predominantly clonal multi-institutional outbreak of Clostridium difficile -associated diarrhea with high morbidity and mortality. N Engl J Med . 2005; 353:2442-9. [PubMed 16322602]
103. McDonald LC, Owings M, Jernigan DB. Clostridium difficile infection in patients discharged from US short-stay hospitals, 1996-2003. Emerg Infect Dis . 2006; 12:409-15. [PubMed 16704777][PubMedCentral]
104. Bartlett JG, Peri TM. The new Clostridium difficile -what does it mean? N Engl J Med . 2005; 353:2503-5.
105. Centers for Disease Control and Prevention. Severe Clostridium difficile -associated disease in populations previously at low risk-four states, 2005. MMWR Morb Mortal Wkly Rep . 2005; 54:1201-5. [PubMed 16319813]
106. Kazakova SV, Ware K, Baughman B et al. A hospital outbreak of diarrhea due to an emerging epidemic strains of Clostridium difficile . Arch Intern Med . 2006; 166:2518-24. [PubMed 17159019]
107. Dhalla IA, Mamdani MM, Simor AE et al. Are broad-spectrum fluoroquinolones more likely to cause Clostridium difficile -associated disease? Antimicrob Agents Chemother . 2006; 50:3216-9.
109. Knapp JS, Ohye R, Neal SW et al. Emerging in vitro resistance to quinolones in penicillinase-producing Neisseria gonorrhoeae strains in Hawaii. Antimicrob Agents Chemother . 1994; 38:2200-3. [PubMed 7811047][PubMedCentral]
110. Bradley JS, Jackson MA, Committee on Infectious Diseases et al. The use of systemic and topical fluoroquinolones. Pediatrics . 2011; 128:e1034-45.
111. Ruiz-Serrano MJ, Alcala L, Martinez L et al. In vitro activities of six fluoroquinolones against 250 clinical isolates of Mycobacterium tuberculosis susceptible or resistant to first-line antituberculosis drugs. Antimicrob Agents Chemother . 2000; 44:2567-8.
112. Kam KM, Yip CW, Cheung TL et al. Stepwise decrease in moxifloxacin susceptibility amongst clinical isolates of multidrug-resistant Mycobacterium tuberculosis : correlation with ofloxacin susceptibility. Microb Drug Resist . 2006; 12:7-11. [PubMed 16584301]
113. Shandil RK, Jayaram R, Kaur P et al. Moxifloxacin, ofloxacin, sparfloxacin, and ciprofloxacin against Mycobacterium tuberculosis : evaluation of in vitro and pharmacodynamic indices that best predict in vivo efficacy. Antimicrob Agents Chemother . 2007; 51:576-82. [PubMed 17145798]
114. . Update to CDC's sexually transmitted diseases treatment guidelines, 2006: fluoroquinolones no longer recommended for treatment of gonococcal infections. MMWR Morb Mortal Wkly Rep . 2007; 56:332-6. [PubMed 17431378]
116. Douglas JM Jr. Dear colleague letter: Fluoroquinolones are no longer recommended for the treatment of gonorrhea in the United States. Division of STD Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention, Department of Health & Human Services; 2007 April 12.
117. Ball P. Long-term use of quinolones and their safety. Rev Infect Dis . 1989; 11(Suppl 5):S1365-9. [PubMed 2672258]
118. Davis GJ, McKenzie ME. Toxicologic evaluation of ofloxacin. Am J Med . 1989; 87(Suppl 6C):43S-46S. [PubMed 2690619]
119. Mayer DG. Overview of toxicological studies. Drugs . 1987; 34(Suppl 1):150-3. [PubMed 3325258]
120. Kato M, Onodera T. Morphological investigation of cavity formation in articular cartilage induced by ofloxacin in rats. Fund Appl Toxicol . 1988; 11:110-9.
121. Hooper DC, Wolfson JS. Fluoroquinolone antimicrobial agents. N Engl J Med . 1991; 324:384-94. [PubMed 1987461]
122. Paton JH, Reeves DS. Fluoroquinolone antibiotics: microbiology, pharmacokinetics and clinical uses. Drugs . 1988; 36:193-228. [PubMed 3053126]
123. Maggiolo F, Caprioli S, Suter F. Risk/benefit analysis of quinolone use in children: the effect on diarthrodial joints. J Antimicrob Chemother . 1990; 26:469-71. [PubMed 2254219]
124. Pfister K, Mazur D, Vormann J et al. Diminished ciprofloxacin-induced chondrotoxicity by supplementation with magnesium and vitamin E in immature rats. Antimicrob Agents Chemother . 2007; 51:1022-7. [PubMed 17210779][PubMedCentral]
125. Stahlmann R. Safety profile of the quinolones. J Antimicrob Chemother . 1990; 26(Suppl D):31-44. [PubMed 2286589]
126. Christ W, Lehnert T, Ulbrich B. Specific toxicologic aspects of the quinolones. Rev Infect Dis . 1988; 10(Suppl 1):S141-6. [PubMed 3279489]
128. US Food and Drug Administration. FDA news. FDA requests boxed warnings on fluoroquinolone antimicrobial drugs. From FDA website. Accessed 2008 Sept 8. [Web]
129. US Food and Drug Administration. Information for healthcare professionals. FDA alert regarding fluoroquinolone antimicrobial drugs. 2008 Jul 8. From FDA website. Accessed 2008 Sept 8. [Web]
130. US Food and Drug Administration. FDA drug safety communication: FDA requires label changes to warn of risk for possibly permanent nerve damage from antibacterial fluoroquinolone drugs taken by mouth or by injection. 2013 Aug 15. From FDA website. [Web]
132. Knapp JS, Washington JA, Doyle LJ et al. Persistence of Neisseria gonorrhoeae strains with decreased susceptibility to ciprofloxacin and ofloxacin in Cleveland, Ohio, from 1992 through 1993. Antimicrob Agents Chemother . 1994; 38:2194-6. [PubMed 7811045][PubMedCentral]
140. US Food and Drug Administration. FDA drug safety communication: FDA advises restricting fluoroquinolone antibiotic use for certain uncomplicated infections; warns about disabling side effects that can occur together. Silver Spring, MD; 2016 May 12. From FDA website. [Web]
143. Gupta K, Hooton TM, Naber KG et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis . 2011; 52:e103-20. Updates may be available at IDSA website at www.idsociety.org. [PubMed 21292654]
145. US Food and Drug Administration. FDA drug safety communication: FDA updates warnings for oral and injectable fluoroquinolone antibiotics due to disabling side effects. Silver Spring, MD; 2016 Jul 26. From FDA website. [Web]
171. US Food and Drug Administration. FDA drug safety communication: FDA reinforces safety information about serious low blood sugar levels and mental health side effects with fluoroquinolone antibiotics; requires label changes. Silver Spring, MD; 2018 Jul 10. From FDA website. [Web]
172. US Food and Drug Administration. FDA drug safety communication: FDA warns about increased risk of ruptures or tears in the aorta blood vessel with fluoroquinolone antibiotics in certain patients. Silver Spring, MD; 2018 Dec 20. From FDA website. [Web]
197. Anon. Drugs for bacterial infections. Treat Guidel Med Lett . 2010; 8:43-52. [PubMed 20489679]
218. Nahid P, Dorman SE, Alipanah N et al. Official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America Clinical Practice Guidelines: Treatment of Drug-Susceptible Tuberculosis. Clin Infect Dis . 2016; :.
231. World Health Organization. Treatment of tuberculosis guidelines. 4th ed. World Health Organization; 2010. From WHO website. [Web]
235. Chey WD, Leontiadis GI, Howden CW et al. ACG Clinical Guideline: Treatment of Helicobacter pylori Infection. Am J Gastroenterol . 2017; 112:212-239. [PubMed 28071659]
236. Sebghatollahi V, Soheilipour M, Khodadoostan M et al. Levofloxacin-containing versus Clarithromycin-containing Therapy for Helicobacter pylori Eradication: A Prospective Randomized Controlled Clinical Trial. Adv Biomed Res . 2018; 7:55. [PubMed 29657940]
237. Hsu PI, Tsai FW, Kao SS et al. Ten-Day Quadruple Therapy Comprising Proton Pump Inhibitor, Bismuth, Tetracycline, and Levofloxacin is More Effective than Standard Levofloxacin Triple Therapy in the Second-Line Treatment of Helicobacter pylori Infection: A Randomized Controlled Trial. Am J Gastroenterol . 2017; 112:1374-1381. [PubMed 28719592]
239. Zerbetto De Palma G, Mendiondo N, Wonaga A et al. Occurrence of Mutations in the Antimicrobial Target Genes Related to Levofloxacin, Clarithromycin, and Amoxicillin Resistance in Helicobacter pylori Isolates from Buenos Aires City. Microb Drug Resist . 2017; 23:351-358. [PubMed 27391421]
240. Shao Y, Lu R, Yang Y et al. Antibiotic resistance of Helicobacter pylori to 16 antibiotics in clinical patients. J Clin Lab Anal . 2018; 32:e22339. [PubMed 28984385]
241. Cheng A, Sheng WH, Liou JM et al. Comparative in vitro antimicrobial susceptibility and synergistic activity of antimicrobial combinations against Helicobacter pylori isolates in Taiwan. J Microbiol Immunol Infect . 2015; 48:72-9. [PubMed 23036269]
276. World Health Organization. WHO treatment guidelines for drug-resistant tuberculosis: 2016 update. From WHO website. [Web]
292. American Academy of Pediatrics. Red Book: 2018-2021 Report of the Committee on Infectious Diseases. 31st ed. Itasca, IL: American Academy of Pediatrics; 2018.
293. Jackson MA, Schutze GE, Committee on Infectious Diseases. The Use of Systemic and Topical Fluoroquinolones. Pediatrics . 2016; 138 [PubMed 27940800]
302. McDonald LC, Gerding DN, Johnson S et al. Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis . 2018; 66:987-994. [PubMed 29562266]
303. Fekety R for the American College of Gastroenterology Practice Parameters Committee. Guidelines for the diagnosis and management of Clostridium difficile -associated diarrhea and colitis. Am J Gastroenterol . 1997; 92:739-50. [PubMed 9149180]
304. American Society of Health-System Pharmacists Commission on Therapeutics. ASHP therapeutic position statement on the preferential use of metronidazole for the treatment of Clostridium difficile -associated disease. Am J Health-Syst Pharm . 1998; 55:1407-11. [PubMed 9659970]
305. Anon. Advice for travelers. Med Lett Drugs Ther . 2015; 57:52-8. [PubMed 25853663]
315. Kalil AC, Metersky ML, Klompas M et al. Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis . 2016; 63:e61-e111. [PubMed 27418577]
344. Workowski KA, Bolan GA. Sexually Transmitted Diseases Treatment Guidelines, 2015. MMWR Recomm Rep . 2015; 64(RR-03):1-137. [PubMed 26042815]
418. Tunkel AR, Hartman BJ, Kaplan SL et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis . 2004; 39:1267-84. Updates may be available at IDSA website at www.idsociety.org. [PubMed 15494903]
440. Panel on Opportunistic Infection in HIV-infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America (Accessed May 13, 2019). Updates may be available at HHS AIDS Information (AIDSinfo) website. [Web]
450. Baddour LM, Wilson WR, Bayer AS et al. Infective Endocarditis in Adults: Diagnosis, Antimicrobial Therapy, and Management of Complications: A Scientific Statement for Healthcare Professionals From the American Heart Association. Circulation . 2015; 132:1435-86. [PubMed 26373316]
512. Mandell LA, Wunderink RG, Anzueto A et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis . 2007; 44 Suppl 2:S27-72. Updates may be available at IDSA website at www.idsociety.org. [PubMed 17278083]
525. Centers for Disease Control and Prevention. CDC health information for international travel, 2018. Atlanta, GA: US Department of Health and Human Services. Updates may be available at CDC website. [Web]
543. Stevens DL, Bisno AL, Chambers HF et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the infectious diseases society of America. Clin Infect Dis . 2014; 59:147-59. Updates may be available at IDSA website at www.idsociety.org. [PubMed 24947530]
544. Lipsky BA, Berendt AR, Cornia PB et al. 2012 Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections. Clin Infect Dis . 2012; 54:e132-73. Updates may be available at IDSA website at www.idsociety.org.
599. Centers for Disease Control and Prevention. Additional options for preventive treatment for persons exposed to inhalational anthrax. MMWR Morb Mortal Wkly Rep . 2001; 50:1142.
668. Inglesby TV, O'Toole T, Henderson DA et al for the Working Group on Civilian Biodefense. Anthrax as a biological weapon, 2002: updated recommendations for management. JAMA . 2002; 287:2236-52. [PubMed 11980524]
671. Bradley JS, Peacock G, Krug SE et al. Pediatric anthrax clinical management. Pediatrics . 2014; 133:e1411-36. [PubMed 24777226]
672. Meaney-Delman D, Zotti ME, Creanga AA et al. Special considerations for prophylaxis for and treatment of anthrax in pregnant and postpartum women. Emerg Infect Dis . 2014; 20:e1-6. [PubMed 24457117]
673. Hendricks KA, Wright ME, Shadomy SV et al. Centers for disease control and prevention expert panel meetings on prevention and treatment of anthrax in adults. Emerg Infect Dis . 2014; 20 [PubMed 24447897]
675. Griffith DE, Aksamit T, Brown-Elliott BA et al. An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med . 2007; 175:367-416. [PubMed 17277290]
677. Caeiro JP, Dupont HL. Management of travelers' diarrhoea. Drugs . 1998; 56:73-81. [PubMed 9664200]
679. Adachi JA, Ostrosky-Zeichner L, DuPont HL et al. Empirical antimicrobial therapy for travelers' diarrhea. Clin Infect Dis . 2000; 31:1079-83. [PubMed 11049792]
681. Centers for Disease Control and Prevention. Diagnosis and management of foodborne illnesses: a primer for physicians. MMWR Recomm Rep . 2001; 50(RR-2):1-69.
683. US Army Medical Research Institute of Infectious Disease. USAMRIID's medical management of biologic casualties handbook. 8th ed. USAMRIID: Fort Detrick, MD; 2014 Sep.
686. Centers for Disease Control and Prevention. Update: investigation of bioterrorism-related anthrax and interim guidelines for exposure management and antimicrobial therapy, October 2001. MMWR Morb Mortal Wkly Rep . 2001; 50:909-19. [PubMed 11699843]
688. Inglesby TV, Dennis DT, Henderson DA et al for the Working Group on Civilian Biodefense. Plague as a biological weapon: medical and public health management. JAMA . 2000; 283:2281-90. [PubMed 10807389]
710. Jernigan JA, Stephens DS, Ashford DA and the Anthrax Bioterrorism Investigation Team. Bioterrorism-related inhalation anthrax: the first 10 cases reported in the United States. Emerg Infect Dis . 2001; 7:933-44. [PubMed 11747719][PubMedCentral]
767. Brookmeyer R, Johnson E, Bollinger R. Modeling the optimum duration of antibiotic prophylaxis in an anthrax outbreak. Proc Natl Acad Sci . 2003; 100:10129-32. [PubMed 12890865][PubMedCentral]
857. Kirkcaldy RD, Harvey A, Papp JR et al. Neisseria gonorrhoeae Antimicrobial Susceptibility Surveillance - The Gonococcal Isolate Surveillance Project, 27 Sites, United States, 2014. MMWR Surveill Summ . 2016; 65:1-19. [PubMed 27414503]