Ofloxacin is a synthetic fluoroquinolone anti-infective agent.1, 2, 3, 5, 420, 442, 464, 634, 636
Ofloxacin is used for the treatment of lower respiratory tract infections, including acute exacerbations of chronic bronchitis or community-acquired pneumonia (CAP) caused by susceptible Haemophilus influenzae 1, 230, 232, 236, 239, 244, 251, 253, 259, 265, 272, 274, 413, 414, 420, 433 or Streptococcus pneumoniae .1, 230, 232, 239, 244, 251, 253, 259, 265, 272, 274, 414, 420, 433 Ofloxacin also has been used for the treatment of lower respiratory tract infections caused by susceptible Moraxella catarrhalis †, 236, 239, 244, 251, 272, 433 S. aureus †, 232, 236, 244, 265, 414, 420 viridans streptococci†, 484 Enterobacteriaceae†, 230, 232, 251, 259, 265, 414, 420, 484 or Ps. aeruginosa †.230, 232, 239, 259, 265, 268, 414, 420
Ofloxacin should be used for the treatment of acute bacterial exacerbations of chronic bronchitis only when there are no other treatment options. 1, 140, 145Because systemic fluoroquinolones, including ofloxacin, 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, 140, 145and because acute bacterial exacerbations of chronic bronchitis may be self-limiting in some patients, 1the risks of serious adverse reactions outweigh the benefits of fluoroquinolones for patients with these infections. 140, 145
In controlled studies in adults with lower respiratory tract infections, oral ofloxacin therapy was at least as effective as oral therapy with amoxicillin,253, 259, 265 co-trimoxazole,464 erythromycin,253, 265, 272 cefazolin,259 or doxycycline,229 and more effective than cefaclor.259 For most susceptible bacteria, ofloxacin therapy resulted in clinical and bacteriologic cure rates of 60-100% in adults with lower respiratory tract infections.229, 230, 232, 244, 259, 270, 272, 414, 417, 420, 464 However, ofloxacin, like most fluoroquinolones, is less effective in the treatment of S. pneumoniae or Ps. aeruginosa infections;244, 272, 413, 420, 433 the bacteriologic cure rates in adults with infections caused by these bacteria were 55-79%.230, 232, 268, 417, 420
Skin and Skin Structure Infections
Ofloxacin is used for the treatment of mild to moderate skin and skin structure infections caused by susceptible S. aureus (oxacillin-susceptible [methicillin-susceptible] strains),1, 255, 420, 462 S. epidermidis †, 420 S. pyogenes (group A β-hemolytic streptococci; GAS),1 or P. mirabilis . 1 However, the increasing emergence of strains of staphylococci resistant to fluoroquinolones limits the usefulness of the drugs in the treatment of these infections.40, 133, 134, 413, 426, 506, 519, 520, 521, 522, 539, 541 Ofloxacin also has been effective when used in the treatment of skin and skin structure infections caused by other susceptible gram-negative bacteria, including E. coli †255 or Ps. aeruginosa †.255 The drug has been effective when used in the treatment of cellulitis, subcutaneous abscesses, surgical wound infections, furunculosis, and folliculitis, and has been used effectively for the treatment of skin and skin structure infections in patients with diabetes mellitus.255, 420 Oral ofloxacin resulted in a clinical and bacteriologic cure rate of 76-96% in adults with skin and skin structure infections.417, 420, 464
Urinary Tract Infections and Prostatitis
Uncomplicated Urinary Tract Infections
Ofloxacin is used for the treatment of uncomplicated urinary tract infections (UTIs) (cystitis) caused by susceptible gram-negative bacteria, including Citrobacter diversus ,1, 288, 425 C. freundii †, 490 Enterobacter aerogenes ,1, 288 E. cloacae †, 490 Escherichia coli ,1, 277, 278, 280, 282, 288, 423, 478, 490 Klebsiella pneumoniae ,1, 280, 288, 490 Morganella morganii †, 280 Proteus mirabilis ,1, 277, 278, 280, 288, 423, 490 or Pseudomonas aeruginosa .1, 280, 288, 478
The drug also has been effective in a limited number of adults when used orally for the treatment of uncomplicated UTIs caused by susceptible gram-positive bacteria, including Staphylococcus aureus †, 282, 288, 423, 490 S. epidermidis †, 277, 278, 423, 490 S. saprophyticus †, 277, 282, 423, 478 Enterococcus faecalis (formerly Streptococcus faecalis )†, 277, 278, 288, 490 viridans streptococci†, 490 or Streptococcus agalactiae † (group B streptococci; GBS).278 However, because of concerns about emergence of resistant strains of certain gram-positive bacteria (e.g., staphylococci) secondary to widespread use of fluoroquinolones, such use should be selective.40, 133, 134, 406, 506, 519, 520, 521, 522, 539, 541
Ofloxacin should be used for the treatment of uncomplicated UTIs only when there are no other treatment options. 1, 140, 145Because systemic fluoroquinolones, including ofloxacin, 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, 140, 145and because uncomplicated UTIs may be self-limiting in some patients, 1the risks of serious adverse reactions outweigh the benefits of fluoroquinolones for patients with uncomplicated UTIs. 140, 145
In the treatment of uncomplicated UTIs in adults, the bacteriologic cure rate reported with 3-7 days of oral ofloxacin therapy has been 81-100%.282, 284, 288, 413, 414, 417, 420, 423, 464, 478 In several controlled studies in men and women with uncomplicated UTIs, 3-7 days of oral ofloxacin therapy was as effective as 7 days of oral co-trimoxazole therapy.282, 413, 414, 420, 423, 464 Although a single 100- or 400-mg oral dose† of ofloxacin has been effective in some adults for the treatment of acute cystitis caused by susceptible organisms,278, 280, 284, 288, 414, 420, 464, 478 efficacy of a single dose of the drug for the treatment of these infections has not been established.413, 478 In one controlled study, a single 400-mg oral dose of ofloxacin was less effective for the treatment of acute cystitis in women than 3 days of oral ofloxacin therapy (200 mg once daily) or 7 days of oral co-trimoxazole therapy;478 in another controlled study in adults with uncomplicated UTIs, a single 100-mg oral dose of ofloxacin was as effective as a 3-day regimen (100 mg twice daily) of the drug.278
Complicated Urinary Tract Infections
Ofloxacin is used for the treatment of pyelonephritis and other complicated UTIs caused by susceptible gram-negative bacteria, including C. diversus ,1, 285 C. freundii †, 285 Enterobacter †, 285 E. coli ,1, 279, 281, 285 K. pneumoniae ,1, 285 M. morganii †, 285 P. mirabilis ,1, 285 P. rettgeri †, 285 or Ps. aeruginosa .1, 279, 281, 285
As with other anti-infectives, ofloxacin is more effective in the treatment of uncomplicated UTIs than in complicated infections.420 In adults with complicated UTIs caused by susceptible organisms, the bacteriologic cure rate reported for 7-10 days of oral ofloxacin therapy has been 63-100%.281, 285, 413, 414, 420, 464 In controlled studies in adults with complicated UTIs, oral ofloxacin therapy was as effective as therapy with oral co-trimoxazole285, 464 and slightly more effective than therapy with oral carbenicillin indanyl sodium.285 In controlled studies in adults with complicated UTIs, 7 days of oral ofloxacin (100 mg twice daily) was as effective as 7 days of oral ciprofloxacin (250 mg twice daily).281 Oral ofloxacin has been used effectively in renal transplant recipients for the treatment of complicated UTIs.490
Ofloxacin is used in men for the treatment of recurrent UTIs and chronic prostatitis caused by susceptible E. coli .1, 284, 285, 286, 288
Oral ofloxacin therapy given for 6 weeks or longer reportedly has resulted in a bacteriologic cure of 79-100% in men with prostatitis.284, 285
Oral ofloxacin has been used for the treatment of shigellosis† caused by susceptible Shigella .477
Infections caused by S. sonnei usually are self-limited (48-72 hours), and mild cases may not require treatment with anti-infectives.292 However, because there is some evidence that anti-infectives may shorten the duration of diarrhea and the period of fecal excretion of Shigella , anti-infective treatment generally is recommended in addition to fluid and electrolyte replacement in patients with severe shigellosis, dysentery, or underlying immunosuppression.292, 440 An empiric treatment regimen can be used initially, 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 ofloxacin has been used for the short-term treatment of travelers' diarrhea† and has been used for the prevention of travelers' diarrhea† in adults traveling for relatively short periods of time to high-risk areas.557, 588
Travelers' diarrhea caused by bacteria may be self-limited and often resolves within 3-7 days without anti-infective treatment.305, 525, 527, 588, 589, 612 The US Centers for Disease Control and Prevention (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, 527, 588, 589, 612 Since bacteria are the most common cause of travelers' diarrhea (80-90% of cases), an anti-infective directed against enteric bacterial pathogens usually is used.525 Fluoroquinolones (e.g., ciprofloxacin, levofloxacin) generally have been considered the anti-infectives of choice for empiric treatment, including self-treatment, of travelers' diarrhea in adults;305, 525, 557, 590, 612 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 anti-infective prophylaxis to prevent travelers' diarrhea in most individuals traveling to areas of risk.305, 524, 525, 527, 529 However, anti-infective prophylaxis may be considered for short-term travelers who are high-risk individuals (e.g., human immunodeficiency virus [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
Oral ofloxacin has been used in conjunction with other drugs for the treatment of infections caused by Helicobacter pylori †.406, 594, 595, 596, 643
Multiple-drug regimens that include ofloxacin, azithromycin, omeprazole, and a bismuth salt or ofloxacin, tetracycline, metronidazole, omeprazole, and a bismuth salt have effectively eradicated H. pylori in some patients with infections that failed to respond to other treatment regimens.594, 595, 596 Levofloxacin usually is the fluoroquinolone included in multiple-drug regimens used for first- or second-line and salvage therapy of H. pylori infections.235 Data are limited regarding the prevalence of fluoroquinolone-resistant H. pylori in the US;235 the possible impact of such resistance on the efficacy of fluoroquinolone-containing regimens used for the treatment of H. pylori infection is not known.235
Oral ofloxacin has been recommended as an alternative for postexposure prophylaxis following suspected or confirmed exposure to aerosolized Bacillus anthracis spores (inhalational anthrax)† and for treatment of inhalational anthrax†.668
CDC, American Academy of Pediatrics (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, 673, 683, 686 Other oral fluoroquinolones (levofloxacin, moxifloxacin, ofloxacin) are alternatives for postexposure prophylaxis when ciprofloxacin or doxycycline cannot be used.668, 671, 673
Some experts suggest that oral ciprofloxacin or other oral fluoroquinolones (levofloxacin, moxifloxacin, ofloxacin) can be considered for the treatment of inhalational anthrax† when a parenteral regimen is not available.668, 683 Although a multiple-drug parenteral regimen should be used for the treatment of inhalational anthrax that occurs as the result of exposure to anthrax spores in the context of biologic warfare or bioterrorism,668, 671, 673, 683 use of these parenteral regimens may not be possible if large numbers of individuals require treatment in a mass casualty setting and it may be necessary to use an oral regimen.668, 683
For additional information on postexposure prophylaxis and treatment of anthrax, see Uses: Anthrax in Ciprofloxacin 8:12.18.
Ofloxacin has been used in conjunction with other anti-infectives for the treatment of brucellosis† caused by Brucella melitensis .561, 562, 772 Some experts recommend a multiple-drug regimen that includes a tetracycline (doxycycline) and streptomycin (or gentamicin) or a regimen that includes a tetracycline (doxycycline) and rifampin for the treatment of brucellosis;197, 683, 772 alternative regimens include co-trimoxazole with or without gentamicin or rifampin; ciprofloxacin (or ofloxacin) and rifampin; or chloramphenicol with or without streptomycin.197, 683, 772 Monotherapy with any drug usually is associated with a high relapse rate and is not recommended.683, 772
In one study in patients with brucellosis caused by B. melitensis , 6 weeks of a regimen of ofloxacin (400 mg once daily) given in conjunction with rifampin (600 mg once daily) was as effective as a regimen of doxycycline (200 mg once daily) given in conjunction with rifampin (600 mg once daily).561 The mean time to defervescence was 5.1 days for patients receiving doxycycline and rifampin and 6.3 days for those receiving ofloxacin and rifampin; the relapse rate 1 year after the drugs were discontinued was about 3% in both groups.561
Ofloxacin is used for the treatment of urethral and cervical infections caused by Chlamydia trachomatis 1, 344 and is considered an alternative for the treatment of these infections.344 A bacteriologic cure rate of 67-100% has been reported in men and women who received a 7-10 day regimen of oral ofloxacin (200- or 300-mg twice daily) for the treatment of urogenital chlamydial infections.124, 287, 299, 301, 307, 309, 311, 436, 447, 449 In several controlled studies, a 7-day regimen of oral ofloxacin (300 mg twice daily) is at least as effective as a 7-day regimen of oral doxycycline (100 mg twice daily) for the treatment of these infections.301, 309, 447, 488
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
Ofloxacin is considered an alternative for the treatment of acute epididymitis† that may involve C. trachomatis .297, 344 (See Uses: Gonorrhea and Associated Infections.)
Gonorrhea and Associated Infections
Although ofloxacin was used in the past for the treatment of uncomplicated gonorrhea caused by susceptible Neisseria gonorrhoeae ,1, 131, 289, 290, 291, 294, 296, 300, 413, 447, 448, 486, 487, 488, 498 quinolone-resistant N. gonorrhoeae (QRNG) is widely disseminated throughout the world, including in the US.114, 116, 344, 578, 580, 581, 583, 584, 585, 857 (See Resistance: Resistance in Neisseria gonorrhoeae.) 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
Ofloxacin is considered an alternative for the treatment of acute PID.344 (See Uses: Pelvic Inflammatory Disease.)
Ofloxacin is considered an alternative 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-resistant N. gonorrhoeae (QRNG), see Uses: Gonorrhea and Associated Infections in Ciprofloxacin 8:12.18.
Treatment of Active Tuberculosis
Ofloxacin has been used in multiple-drug regimens for the treatment of active tuberculosis† caused by Mycobacterium tuberculosis .94, 456, 545, 564
Although the potential role of fluoroquinolones and the optimal length of therapy have not been fully defined, the American Thoracic Society (ATS), CDC, Infectious Diseases Society of America (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
The most recent ATS, CDC, and IDSA recommendations for the treatment of tuberculosis should be consulted for more specific information.218
Ofloxacin is used as an alternative in multiple-drug therapy (MDT) for treatment of multibacillary leprosy† (Hansen's disease);215, 216 the drug also is used as a component of a single-dose MDT regimen that has been used for treatment of single-lesion paucibacillary leprosy†.211, 212, 217
The World Health Organization (WHO) and US National Hansen's Disease Program (NHDP) recommend that MDT regimens that include rifampin be used for the treatment of all forms of leprosy.215, 216 MDT can rapidly kill M. leprae and render patients noninfectious after only a few days of treatment;216 however, clearance of dead M. leprae from the body may take several years.216 MDT regimens recommended by NHDP for US patients differ from those recommended by WHO.215, 216, 217
For treatment of multibacillary leprosy (i.e., 6 or more lesions or skin smear positive) in adults, WHO recommends a 12-month MDT regimen of dapsone (once daily), rifampin (once monthly), and clofazimine (once daily and once monthly).215, 217 For treatment of paucibacillary leprosy (i.e., 1-5 lesions) in adults, WHO recommends a 6-month MDT regimen of dapsone (once daily) and rifampin (once monthly).215, 217 A single-dose rifampin-based MDT regimen that includes a single dose of rifampin, a single dose of ofloxacin, and a single dose of minocycline (ROM) has been used for treatment of paucibacillary leprosy in patients with only a single lesion (i.e., single-lesion paucibacillary leprosy).211, 212, 217
For US patients, NHDP recommends more prolonged treatment.216 NHDP recommends that adults with multibacillary leprosy (i.e., those who are skin smear positive and/or have a biopsy indicating more advanced disease) receive a 24-month MDT regimen of dapsone (once daily), rifampin (once daily), and clofazimine (once daily); NHDP recommends that adults with paucibacillary leprosy (i.e., those who are skin smear negative without evidence of more advanced disease on biopsy) receive a 12-month MDT regimen of dapsone (once daily) and rifampin (once daily).216 Clofazimine is no longer commercially available in the US, but may be obtained from NHDP under an investigational new drug (IND) protocol for treatment of leprosy.216 (See Clofazimine 8:16.92.) Data indicate that leprosy is rare in the US (total of approximately 6500 living patients, about 3300 requiring active medical management), although about 150-200 new cases are reported each year.216
Both WHO and NHDP recommend ofloxacin as an alternative that can be used instead of clofazimine in MDT regimens in adults who will not accept or cannot tolerate clofazimine.215, 216
Treatment of leprosy is complicated and should be undertaken in consultation with a specialist familiar with the disease.216 In the US, clinicians should contact NHDP at 800-642-2477 on weekdays from 9:00 a.m. to 5:30 p.m. Eastern Standard Time or via email at [email protected] for assistance with diagnosis or treatment of leprosy or assistance obtaining clofazimine for treatment of leprosy.216
Mycobacterium fortuitum Infections
Oral ofloxacin has been effective when used alone or in conjunction with amikacin for the treatment of postoperative sternotomy wound or soft tissue infections caused by M. fortuitum †.256, 317, 332, 333, 479 The drug also has been used effectively in a few patients for the treatment of M. fortuitum pulmonary104, 332, 479 or urinary tract infections.489
Although optimum regimens have not been identified, ATS and IDSA recommend that M. fortuitum pulmonary infections be treated with a regimen consisting of at least 2 anti-infectives selected based on results of in vitro susceptibility testing and tolerability (e.g., amikacin, ciprofloxacin or ofloxacin, a sulfonamide, cefoxitin, imipenem, doxycycline).675
Ofloxacin is used in adults for the treatment of nongonococcal urethritis (NGU).1, 124, 287, 299, 300, 301, 307, 308, 309, 311, 344, 436, 447, 449, 450, 503 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 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
Ofloxacin has been used in the treatment of acute pelvic inflammatory disease (PID) caused by susceptible C. trachomatis .1, 344 Ofloxacin is considered an alternative for the treatment of 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
For further information on the treatment of PID, see Uses: Pelvic Inflammatory Disease in the Cephalosporins General Statement 8:12.06.
Fluoroquinolones (e.g., ciprofloxacin, levofloxacin, moxifloxacin, ofloxacin) have been suggested as alternatives for the treatment of plague† caused by Yersinia pestis and also have been recommended for postexposure prophylaxis† following a high risk exposure to Y. pestis , including exposure in the context of biologic warfare or bioterrorism.683, 688 The recommendation for use of fluoroquinolones for treatment or prophylaxis of plague is based on results of in vitro and animal testing.683, 688 Although human studies are not available, results of in vitro studies indicate that ofloxacin is active against Y. pestis and the drug has been effective for the treatment of murine plague infections.624, 625, 627
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 (drug of choice for plague meningitis), or co-trimoxazole (may be less effective than other alternatives).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 (e.g., ciprofloxacin, levofloxacin, moxifloxacin, ofloxacin) may be substituted when the patient's condition improves or if 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., the 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 (e.g., ciprofloxacin, levofloxacin, moxifloxacin, ofloxacin).683, 688
For additional information on use of fluoroquinolones for treatment or prophylaxis of plague, see Uses: Plague in Ciprofloxacin 8:12.18.
Ofloxacin has been used in a limited number of patients for the treatment of various rickettsial infections†, 325, 326, 460, 560 including Mediterranean spotted fever† (boutonneuse fever) caused by Rickettsia conorii .326 CDC and other clinicians state that doxycycline is the drug of choice for the treatment of all tickborne rickettsial diseases.197, 500 Although some fluoroquinolones have in vitro activity against Rickettsiae500 and some clinicians have suggested that fluoroquinolones (e.g., ciprofloxacin, ofloxacin) may be considered alternatives for the treatment of some rickettsial infections (e.g., Rocky Mountain spotted fever caused by R. rickettsii ) when doxycycline cannot be used,197, 560 CDC states that fluoroquinolones are not recommended for the treatment of Rocky Mountain spotted fever.500
Ofloxacin has been used in a few patients for the treatment of acute Q fever pneumonia caused by Coxiella burnetii †;560 the drug produced apyrexia and clinical improvement within the first 2-4 days.560 However, Q fever pneumonia usually resolves within 15 days without treatment, and clinical evaluation of the efficacy of anti-infective regimens in the treatment of acute infections is difficult.560 Ofloxacin may be effective for the treatment of Q fever endocarditis†, 325, 560 and has been used in conjunction with doxycycline for the long-term treatment of Q fever endocarditis.460, 560 However, in one limited study in patients with confirmed C. burnetii infection and chronic endocarditis, a regimen of doxycycline and ofloxacin was associated with a higher relapse rate than a regimen of doxycycline and hydroxychloroquine.460
Oral ofloxacin has been used for the treatment of typhoid fever† (enteric fever) caused by susceptible Salmonella enterica serovar Typhi, including chloramphenicol-resistant strains.318, 320, 331, 429, 481, 492 Although fluoroquinolones have been recommended for empiric treatment of Salmonella enteric fever in adults, resistance to fluoroquinolones has been reported in more than 80% of such infections in travelers to South and Southeast Asia and treatment failures will occur.525
For use of ofloxacin in the topical treatment of ophthalmic infections caused by susceptible organisms, see Ofloxacin 52:04.12.
Ofloxacin is administered orally.1, 417, 427, 464 Although ofloxacin also has been administered IV,175, 425, 437, 438, 439, 462 a parenteral preparation of the drug is no longer commercially available in the US.
While presence of food in the GI tract can decrease the rate and/or extent of absorption of ofloxacin,156, 176, 189, 420, 464, 649, 650, 651 this is not usually considered clinically important and the manufacturer states that the drug can be given without regard to meals.1, 156, 189, 464 Milk and yogurt do not appear to affect GI absorption of ofloxacin.649, 650 (See Pharmacokinetics: Absorption.)
To minimize the possibility of interference with the GI absorption of ofloxacin, patients should be instructed not to ingest antacids containing calcium, magnesium, or aluminum, sucralfate, metal cations such as iron or zinc (including multivitamin preparations containing zinc), or buffered didanosine preparations concomitantly with or within 2 hours of an ofloxacin dose.1 (See Drug Interactions.)
Patients receiving ofloxacin should be well hydrated and should be instructed to drink fluids liberally.1 (See Cautions: Precautions and Contraindications.)
The usual adult oral dosage of ofloxacin is 200-400 mg every 12 hours.1
If ofloxacin is used for the treatment of acute exacerbations of chronic bronchitis, the usual adult dosage is 400 mg every 12 hours given for 10 days.1 (See Uses: Respiratory Tract Infections.)
For the treatment of community-acquired pneumonia (CAP), the usual adult dosage of oral ofloxacin is 400 mg every 12 hours given for 10 days.1
Skin and Skin Structure Infections
For the treatment of uncomplicated skin and skin structure infections, the usual adult dosage of oral ofloxacin is 400 mg every 12 hours given for 10 days.1, 255, 271, 464
Urinary Tract Infections and Prostatitis
If ofloxacin is used for the treatment of uncomplicated urinary tract infections (UTIs), the usual adult dosage is 200 mg every 12 hours.1, 282, 285, 286 Although 3 days of ofloxacin therapy may be adequate for cystitis caused by susceptible Escherichia coli or Klebsiella pneumoniae , 7 days of therapy usually is required for the treatment of cystitis caused by other susceptible organisms.1 Various other oral dosage regimens have been used in the treatment of uncomplicated UTIs, including 100-mg doses given twice daily or 100- or 200-mg doses given once daily†; however, efficacy of these regimens has not been definitely established.275, 277, 278, 417, 420, 464 (See Uncomplicated Urinary Tract Infections under Uses: Urinary Tract Infections and Prostatitis.)
For the treatment of complicated UTIs caused by susceptible organisms, the usual adult dosage of oral ofloxacin is 200 mg every 12 hours for 10 days.1, 288 Some clinicians suggest that an oral dosage of 400 mg twice daily may be necessary for some complicated UTIs.420, 464
The usual adult dosage of oral ofloxacin for the treatment of prostatitis caused by E. coli is 300 mg every 12 hours1 given for 6 weeks1, 285 or longer.284, 285
For the treatment of travelers' diarrhea†, ofloxacin has been given in a dosage of 300 mg twice daily.557 If anti-infectives are used in patients with travelers' diarrhea, a treatment duration of 1-3 days is recommended.305, 557
Although the use of anti-infectives for prophylaxis of travelers' diarrhea† generally is discouraged (see Travelers' Diarrhea under Uses: GI Infections), 305, 525, 557 if oral ofloxacin is used for such prophylaxis, some clinicians recommend a dosage of 300 mg once daily.588 If anti-infective prophylaxis is used in travelers, it should be given 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, 588
When used as a component of multiple-drug regimens for the treatment of infections caused by Helicobacter pylori †, oral ofloxacin has been given in a dosage of 200 mg twice daily for 7-14 days.406, 594, 595, 596
Postexposure Prophylaxis of Anthrax
If oral ofloxacin is used as an alternative for postexposure prophylaxis following suspected or confirmed exposure to aerosolized Bacillus anthracis spores (inhalational anthrax)† (see Uses: Anthrax), the US Working Group on Civilian Biodefense suggests that adults can receive a dosage of 400 mg twice daily.668
Anti-infective prophylaxis should be initiated as soon as possible following suspected or confirmed exposure to aerosolized B. anthracis .668, 673, 683
Because of possible persistence of B. anthracis spores in lung tissue following an aerosol exposure, the US Centers for Disease Control and Prevention (CDC) and other experts recommend that anti-infective prophylaxis be continued for 60 days following a confirmed exposure.668, 673, 683
If oral ofloxacin is used as an alternative for treatment of inhalational anthrax† when a parenteral regimen is not available (see Uses: Anthrax), US Working Group on Civilian Biodefense suggests that adults can receive a dosage of 400 mg twice daily.668
Because of possible persistence of B. anthracis spores in lung tissue following an aerosol exposure, the total duration of anti-infective therapy of inhalational anthrax that occurs as the result of exposure to B. anthracis in the context of biologic warfare or bioterrorism should be 60 days.668, 683
For the treatment of brucellosis†, a 6-week regimen of oral ofloxacin in a dosage of 400 mg once daily in conjunction with oral rifampin (600 mg once daily) has been effective in some patients.561 Alternatively, an oral ofloxacin dosage of 400 mg twice daily for 6 weeks has been used in multiple-drug regimens for the treatment of brucellosis.772
For the treatment of urethritis and/or cervicitis caused by Chlamydia trachomatis or uncomplicated urethral, endocervical, or rectal† chlamydial infections, the usual adult dosage of oral ofloxacin is 300 mg twice daily for 7 days.1, 301, 307, 309, 344
Gonorrhea and Associated Infections
Although fluoroquinolones are no longer recommended for the treatment of gonorrhea or any associated infections that may involve Neisseria gonorrhoeae (see Uses: Gonorrhea and Associated Infections), the manufacturer recommends a single 400-mg oral dose of ofloxacin for the treatment of acute, uncomplicated urethral and cervical gonorrhea caused by susceptible N. gonorrhoeae .1
For the treatment of acute epididymitis† most likely caused by sexually transmitted enteric bacteria (e.g., E. coli ) and when N. gonorrhoeae has been ruled out, CDC recommends that oral ofloxacin be given in a dosage of 300 mg twice daily for 10 days.344
Ofloxacin should not be used alone for treatment of epididymitis unless N. gonorrhoeae has been ruled out.344 (See Uses: Gonorrhea and Associated Infections.)
For the treatment of multibacillary leprosy† in adults who will not accept or cannot tolerate clofazimine, the World Health Organization (WHO) recommends a regimen of oral ofloxacin (400 mg once daily), oral rifampin (600 mg once monthly), and oral dapsone (100 mg once daily) given for 12 months.215 For US patients with multibacillary leprosy who will not accept or cannot tolerate clofazimine, the National Hansen's Disease Program (NHDP) recommends that adults receive oral ofloxacin (400 mg once daily), oral rifampin (600 mg once daily), and oral dapsone (100 mg once daily) given for 24 months.216
For the treatment of single-lesion paucibacillary leprosy†, adults have received a single-dose multiple-drug regimen (ROM) that includes a single 600-mg dose of oral rifampin, a single 400-mg dose of oral ofloxacin, and a single 100-mg dose of oral minocycline.211, 212, 217
Mycobacterium fortuitum Infections
For the treatment of postoperative sternotomy wound or soft tissue infections caused by M. fortuitum †, ofloxacin has been given in a dosage of 300 mg once daily or 1.2 g daily in 3 or 4 divided doses for 3-6 months in conjunction with amikacin (usually 250 mg IM or IV twice daily for 4-8 weeks).256
For pulmonary infections, ATS and IDSA recommend that a regimen consisting of at least 2 anti-infectives be used (see Mycobacterium fortuitum Infections under Uses: Mycobacterial Infections) and that treatment be continued for at least 12 months after negative sputum cultures are attained.675 These experts also recommend that a regimen consisting of at least 2 anti-infectives be given for at least 4 months for the treatment of serious skin or soft tissue infections or for 6 months for bone infections.675
For the treatment of nongonococcal urethritis, the usual adult dosage of oral ofloxacin is 300 mg twice daily for 7 days.1, 301, 307, 309, 344, 447, 488 (See Uses: Nongonococcal Urethritis.)
For the treatment of acute pelvic inflammatory disease (PID), the manufacturer recommends an oral ofloxacin dosage of 400 mg every 12 hours given for 10-14 days.1
If oral ofloxacin is used as an alternative for the treatment of mild to moderately severe acute PID, CDC recommends a dosage of 400 mg twice daily for 14 days given in conjunction with oral metronidazole (500 mg twice daily for 14 days).344
Ofloxacin 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.)
For the treatment of Mediterranean spotted fever† (boutonneuse fever) caused by Rickettsia conorii , an oral ofloxacin dosage of 200 mg every 12 hours given for 7 days was effective in some patients.326
For the treatment of acute Q fever† pneumonia caused by Coxiella burnetii , ofloxacin has been given in a dosage of 600 mg daily for up to 16 days.560 For the treatment of Q fever endocarditis, ofloxacin has been given in a dosage of 200 mg 3 times daily in conjunction with oral doxycycline (100 mg twice daily); long-term treatment (at least 4 years) may be required.460
For the treatment of typhoid fever† (enteric fever) caused by susceptible Salmonella , oral ofloxacin has been given to adults in a dosage of 200-400 mg every 12 hours for 7-14 days.318, 320, 331, 429, 481, 492 (See Uses: Typhoid Fever.)
Dosage in Renal and Hepatic Impairment
Modification of usual dosage of ofloxacin generally is unnecessary in patients with creatinine clearances greater than 50 mL/minute.1 In patients with creatinine clearances of 50 mL/minute or less, doses and/or frequency of administration of ofloxacin should be modified in response to the degree of renal impairment.1, 182, 220, 223, 224, 225
The manufacturer recommends that adults with creatinine clearances of 50 mL/minute or less receive an initial ofloxacin dose equal to the usually recommended dose and that subsequent dosage be modified according to creatinine clearance.1 Adults with creatinine clearances of 20-50 mL/minute should receive the usual oral dose of ofloxacin every 24 hours and those with creatinine clearances less than 20 mL/minute should receive half the usually recommended oral dose every 24 hours.1
For adults undergoing hemodialysis, some clinicians recommend that a 200-mg loading dose of oral ofloxacin be given followed by 100-mg oral doses once daily.222, 431 For most patients, additional supplemental doses of the drug are unnecessary following each hemodialysis procedure;222, 223 however, some clinicians suggest that a single 100-mg supplemental oral dose of the drug be given after the first hemodialysis procedure.222
Because excretion of ofloxacin may be reduced in patients with severe hepatic impairment (e.g., cirrhosis with or without ascites), the maximum ofloxacin dosage in these patients is 400 mg daily.1
Adverse effects reported with ofloxacin are similar to those reported with other fluoroquinolone anti-infectives (e.g., ciprofloxacin).337, 340, 413, 414, 428, 464 Adverse effects have been reported in 2-12% of patients receiving ofloxacin,1, 230, 232, 264, 340, 341, 343, 414, 420, 428, 464 and have been severe enough to require discontinuance in 1-4% of patients.1, 230, 264, 340 The most frequent adverse effects of the drug involve the GI tract or CNS.1, 230, 232, 239, 250, 274, 282, 340, 341, 343, 413, 414, 420, 421, 423, 447, 464, 493
Systemic fluoroquinolones, including ofloxacin, have been associated with disabling and potentially irreversible serious adverse reactions (e.g., tendinitis and tendon rupture, peripheral neuropathy, CNS effects) that can occur together in the same patient.1, 140, 145 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 (See Cautions: Precautions and Contraindications.)
Systemic fluoroquinolones, including ofloxacin, are associated with an increased risk of tendinitis and tendon rupture in all age groups.1, 676, 851
The risk of developing fluoroquinolone-associated tendinitis and tendon rupture is increased in older adults (usually those older than 60 years of age), individuals receiving concomitant corticosteroids, and kidney, heart, or lung transplant recipients.1 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 However, tendinitis and tendon rupture have been reported in patients receiving fluoroquinolones who did not have any risk factors for such adverse reactions.1
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 Tendinitis or tendon rupture can occur within hours or days after ofloxacin is initiated or as long as several months after completion of therapy and can occur bilaterally.1
Ofloxacin should be discontinued immediately if pain, swelling, inflammation, or rupture of a tendon occurs.1 (See Cautions: Precautions and Contraindications.)
Systemic fluoroquinolones, including ofloxacin, have been associated with an increased risk of peripheral neuropathy.1
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 ofloxacin.1, 130 Symptoms may occur soon after initiation of ofloxacin and, in some patients, may be irreversible.1, 130
Ofloxacin 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, 130 (See Cautions: Precautions and Contraindications.)
Systemic fluoroquinolones, including ofloxacin, have been associated with an increased risk of psychiatric adverse effects, including toxic psychosis,1 hallucinations,1 agitation,1 delirium,1, 171 confusion,1 disorientation,1, 171 disturbances in attention,1, 171 nervousness,1, 171 restlessness,1 and memory impairment.1, 171 These adverse effects may occur after the first dose.1
Systemic fluoroquinolones have been associated with an increased risk of convulsions (seizures), increased intracranial pressure (pseudotumor cerebri), lightheadedness, and tremors.1
Headache,1, 185, 253, 277, 307, 340, 341, 343, 363, 414, 420, 447, 464 insomnia,1, 185, 253, 255, 340, 343, 363, 414, 447, 464 and dizziness1, 185, 232, 253, 277, 340, 343, 363, 414, 420, 464 are the most frequently reported adverse CNS effects of ofloxacin. These effects have been reported in 1-9% of patients receiving the drug,1, 232, 340, 343 generally become apparent during the first few days of therapy, and frequently subside during continued therapy with the drug.185, 340, 341, 343, 428 Fatigue,1 somnolence,1 sleep disorders,1, 341, 420 and nervousness1, 493 have been reported in 1-3%1 and asthenia,1 malaise,1 anxiety,1, 363 cognitive changes,1 depression,1, 363 dream abnormality,1, 363 euphoria,1 hallucinations,1, 341, 343, 363, 420 agitation,363 confusion,363 ataxia,363 tremor,363 paresthesia,1, 253, 343, 363 seizures,1, 355 myasthenia,341 syncope,1 and vertigo1, 277, 363 have been reported in less than 1% of patients receiving ofloxacin. Increased intracranial pressure, toxic psychosis, paranoia, and suicidal ideation or acts also have been reported.1 In most reported cases, hallucinations or psychotic reactions generally began within the first 3 days of therapy;343, 363, 364 these reactions subsided when the drug was discontinued.343, 363, 364
Some adverse nervous system effects of ofloxacin may be related to the fact that the drug, like other fluoroquinolones, is an γ-aminobutyric acid (GABA) inhibitor.336, 363, 366, 388, 409, 410, 411, 427, 428, 435 However, further study is needed to elucidate the mechanism(s) of these adverse CNS effects during fluoroquinolone therapy.341, 343, 366, 388, 427, 428 In addition, while it also has been suggested that some CNS stimulant effects reported in patients receiving fluoroquinolones may result from quinolone-induced alterations in caffeine pharmacokinetics,537, 547, 548 ofloxacin is less likely than many other fluoroquinolones to induce such pharmacokinetic alterations.191, 367, 368, 378, 379, 384, 386, 387, 389, 392, 394, 396, 397, 427 (See Drug Interactions: Xanthine Derivatives.)
If psychiatric or other CNS effects occur during ofloxacin therapy, the drug should be discontinued immediately and appropriate measures instituted.1 (See Cautions: Precautions and Contraindications.)
Exacerbation of Myasthenia Gravis
Fluoroquinolones, including ofloxacin, have neuromuscular blocking activity and may exacerbate muscle weakness in individuals with myasthenia gravis.1 Use of fluoroquinolones in myasthenia gravis patients has resulted in requirements for ventilatory support and in death.1 (See Cautions: Precautions and Contraindications.)
Dermatologic and Sensitivity Reactions
Rash1, 239, 253, 271, 273, 277, 281, 335, 340, 341, 343, 360, 464, 493 and pruritus1, 274, 277, 341, 464, 493 have been reported in 1-3% and eosinophilia,1, 232, 253, 262, 421 angioedema,1 urticaria,1 and vasculitis1, 360 have been reported in up to 1% of patients receiving ofloxacin. Although a causal relationship was not definitely established, fatal vasculitis occurred in at least one patient receiving ofloxacin.360 Fever,1, 464 chills,1 and diaphoresis1 have been reported in less than 3% of patients receiving the drug.1
Although most hypersensitivity reactions to ofloxacin are mild cutaneous reactions, serious and occasionally fatal hypersensitivity and/or anaphylactic reactions, sometimes occurring following the first dose, have been reported in patients receiving the drug.1, 343, 414, 439 Severe hypersensitivity reactions, characterized by rash, fever, jaundice, and hepatic necrosis with a fatal outcome,1 also have been reported with other fluoroquinolones.1, 413, 423, 505
Some hypersensitivity reactions reported in patients receiving fluoroquinolones, including ofloxacin, have been accompanied by cardiovascular collapse, hypotension or shock, seizures, loss of consciousness, tingling, angioedema (including tongue, laryngeal, pharyngeal, or facial edema), airway obstruction (including bronchospasm, shortness of breath, and acute respiratory distress), dyspnea, urticaria, pruritus, and other serious skin reactions.1, 414, 420, 439
Other serious and sometimes fatal adverse reactions that have been reported with fluoroquinolones, including ofloxacin, and that may or may not be related to hypersensitivity reactions include one of more of the following: fever, rash or severe dermatologic reaction (e.g., toxic epidermal necrolysis, Stevens-Johnson syndrome); vasculitis, arthralgia, myalgia, serum sickness; allergic pneumonitis; interstitial nephritis, acute renal insufficiency or failure; hepatitis, jaundice, acute hepatic necrosis or failure; anemia (including hemolytic and aplastic anemia), thrombocytopenia (including thrombotic thrombocytopenic purpura), leukopenia, agranulocytosis, pancytopenia, and/or other hematologic abnormalities.1
Ofloxacin should be discontinued immediately at the first appearance of rash, jaundice, or any other sign of hypersensitivity.1 Appropriate therapy (e.g., epinephrine, corticosteroids, maintenance of an adequate airway, oxygen, IV fluids, antihistamines, maintenance of blood pressure) should be initiated as indicated.1
Because of a high percentage of false-positive results, skin testing with ofloxacin has not been useful in evaluating hypersensitivity to the drug and is not recommended.341, 343
Moderate to severe photosensitivity/phototoxicity reactions have been reported in patients receiving fluoroquinolones, including ofloxacin.1, 262, 335, 428, 491
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
Although studies using topical ofloxacin in guinea pigs have not revealed evidence of phototoxicity, photoallergenicity, or contact allergy,339 in vitro studies indicate the drug is phototoxic.362
Ofloxacin should be discontinued if photosensitivity or phototoxicity (sunburn-like reaction, skin eruption) occurs.1 (See Cautions: Precautions and Contraindications.)
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 The cause for this increased risk has not been identified.1, 172
If a patient reports adverse effects suggestive of aortic aneurysm or dissection, fluoroquinolone treatment should be discontinued immediately.172 (See Cautions: Precautions and Contraindications.)
Systemic fluoroquinolones, including ofloxacin, have been associated with alterations in blood glucose concentrations, including symptomatic hypoglycemia and hyperglycemia.1, 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, 171
Severe cases of hypoglycemia resulting in coma or death have been reported with some systemic fluoroquinolones.1, 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
If a hypoglycemic reaction occurs, ofloxacin should be discontinued and appropriate therapy initiated immediately.1 (See Cautions: Precautions and Contraindications.)
Nausea1, 232, 253, 255, 271, 273, 277, 301, 340, 341, 414, 420, 464, 493 has been reported in 3-10%1, 232, 340 and diarrhea,1, 253, 262, 301, 340, 341, 420, 464, 493 vomiting,1, 232, 253, 271, 273, 277, 301, 340, 414, 420 abdominal pain/discomfort,1, 229, 253, 262, 277, 340, 341, 420, 464, 493 abdominal cramps,1 flatulence,1, 253 constipation,1 dyspepsia,1 heartburn,232, 414, 420 dry mouth,1 dysgeusia,1, 340 decreased appetite,1 and anorexia420, 464 have been reported in 5% or less of patients receiving ofloxacin.1, 232, 340 Adverse GI effects generally are mild and transient and only rarely require discontinuance of ofloxacin.340, 421
Ofloxacin therapy has only a minimal effect on normal salivary flora.494 Following oral administration of a single 400-mg dose of ofloxacin, total bacterial counts of Branhamella in saliva were reduced and did not return to pretreatment levels until 4 weeks after the dose;494 total bacterial counts of salivary streptococci, micrococci, and corynebacteria were unaffected by the drug.494
Ofloxacin exerts a selective effect on normal bowel flora.185, 349, 350, 351, 354, 355 Total bacterial counts of normal anaerobic fecal flora generally are unaffected during or following ofloxacin therapy.185, 349, 350, 354, 355, 494 However, ofloxacin therapy generally markedly reduces or completely eradicates normal fecal Enterobacteriaceae within 2-6 days185, 282, 349, 350, 351, 354, 355, 494 and may reduce, but not eliminate, total bacterial counts of fecal aerobic gram-positive bacteria (e.g., Streptococcus faecalis ).349, 350, 351 Total bacterial counts of normal fecal flora generally return to pretreatment levels within 1-4 weeks following discontinuance of ofloxacin.185, 350, 354, 355, 494 In studies evaluating the effects of ofloxacin on physiological and/or biochemical intestinal characteristics that depend on intestinal flora, the drug had no discernible effect on conversion of cholesterol to coprostanol, conversion of bilirubin to urobilinogen, breakdown of mucin, inactivation of tryptic activity, formation of short chain fatty acids, or presence of β-aspartylglycine.345, 346, 348, 355
C. difficile-associated Diarrhea and Colitis
Treatment with anti-infectives alters normal colon flora and may permit overgrowth of Clostridioides difficile (formerly known as Clostridium difficile ).1, 302, 303, 304, 674
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 in patients receiving fluoroquinolones, including ofloxacin, and may range in severity from mild diarrhea to fatal colitis.1, 302, 303, 304, 341, 343, 350, 351, 352, 353, 355C. difficile produces toxins A and B which contribute to development of CDAD;1, 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 (See Superinfection/C. difficile-associated Diarrhea and Colitis under Cautions: Precautions and Contraindications.)
When fluoroquinolones were first marketed, there appeared to be a relative lack of association between use of the drugs and CDAD and the risk of CDAD appeared to be lower than that reported with some other anti-infectives.341, 343, 352, 353 However, there now is some evidence that increasing use of the drugs may have resulted in emergence of C. difficile that are more resistant and/or more virulent than previous strains.659, 660, 661, 662, 664, 665
In women receiving ofloxacin, external genital pruritus,1, 340 candidal301, 307 vaginitis,1, 301, 307, 340 and vaginal discharge1 have been reported in 1-6%1 and burning,1 irritation,1 pain and rash of the genitalia,1 dysmenorrhea,1 menorrhagia,1 and metrorrhagia1 have been reported in less than 1%.1
Ofloxacin does not appear to be nephrotoxic.342, 356, 361, 446 Increased serum creatinine1, 341, 343, 414 and BUN1, 232 concentrations have been reported only rarely343 and dysuria,1 urinary retention,1 increased urinary frequency,1 and elevated urinary pH340 have been reported in less than 1% of patients receiving the drug.1 Glucosuria,1 proteinuria,1 hematuria,1, 341 and pyuria,1 have been reported in at least 1% of patients receiving the drug.1 Although crystalluria and cylindruria have not been reported to date with ofloxacin,340, 361 these adverse effects have been reported rarely in patients receiving some other fluoroquinolones (e.g., ciprofloxacin),2, 361, 413, 417 generally occurring in patients with alkaline urine who received high dosages of the drugs; these effects were not associated with renal toxicity.340, 413 Crystalluria, sometimes associated with nephropathy, has occurred in animals receiving other fluoroquinolones (e.g., ciprofloxacin) but has not been observed to date in animal studies using ofloxacin.1, 339, 342
Fluoroquinolones, including ofloxacin, cause arthropathies (arthrosis) in immature animals of various species.1, 339, 342, 359, 413, 417, 420, 421, 428, 446, 464 In various studies in immature animals, oral ofloxacin has caused blisters and/or erosions in articular cartilage and increased synovial fluid and lesion formation of diarthric joints;339, 342, 359, 420, 464 in one study in immature rats, adverse effects were detected as soon as 5 hours after a single 1- or 3-g/kg oral dose of the drug.359 The severity of these adverse effects appears to be species-specific, being more evident in dogs than in rats, rabbits, or mice, and also appears to depend on the age of the animal and dosage and duration of therapy.337, 339, 359, 428, 446 Morphologic changes observed in animals with quinolone-induced arthropathies include erosions in joint cartilage accompanied by noninflammatory, cell-free effusions of the joint space; the cartilage is incapable of regeneration and may serve as a site for the development of arthropathy deformans.359, 446 Although arthropathies have been detected in adult dogs receiving some quinolones (e.g., pefloxacin [not commercially available in the US]),428, 446 there has been no evidence of arthropathies in fully mature dogs or rats when ofloxacin was given in doses up to 5 times the usual human dosage.1, 420 (See Cautions: Pediatric Precautions.)
Chest or trunk pain has been reported in 1-3%1 and transient337 arthralgia,1, 262, 341, 343, 420 myalgia,1, 341, 343, 420 or pain in the extremities1 or body as a whole1 have been reported in less than 1% of patients receiving ofloxacin.1
Transient, mild increases in serum concentrations of AST (SGOT)1, 229, 232, 262, 271, 301, 343, 414, 421, 447 and/or ALT (SGPT)1, 229, 232, 262, 271, 340, 343, 414, 421, 447 have been reported in 1-2%232, 340, 414 and increased serum concentrations of alkaline phosphatase,1, 232 LDH,253 bilirubin,307 and γ-glutamyltransferase (γ-glutamyl transpeptidase, GGT, GGTP)343, 414 have been reported in less than 1% of patients receiving ofloxacin.232, 343
Severe hepatotoxicity, including acute hepatitis and fatalities, has been reported in patients receiving ofloxacin.1 In some cases, substantial elevations in serum liver enzyme concentrations and other manifestations of hepatitis resolved following discontinuance of the drug.537, 553
Eosinophilia,1, 232, 253, 301, 340, 420 lymphocytopenia,1 lymphocytosis,1, 340 leukocytosis,1, 253, 340 neutropenia,1 neutrophilia,1 thrombocytosis,1 thrombocytopenia,1 leukopenia,1 anemia,1 and elevated erythrocyte sedimentation rate (ESR)1 have been reported in at least 1% of patients receiving ofloxacin;1, 340 however, it is not clear in all cases whether these effects were caused by the drug or underlying conditions of the patients.1
Prolonged QT interval leading to ventricular arrhythmias, including torsades de pointes, has been reported with some fluoroquinolones, including ofloxacin.1 Geriatric patients may be at increased risk for drug-associated effects on the QT interval.1 (See Cautions: Geriatric Precautions.)
Edema,1, 420 hypertension,1, 343 hypotension,1 palpitations,1 tachycardia,343 vasodilation,1 and cardiac arrest1 have been reported in less than 1% of patients receiving ofloxacin.
Rupture or dissection of aortic aneurysms has been reported in patients receiving systemic fluoroquinolones.172 (See Cautions: Aortic Aneurysm and Dissection.)
Transient visual disturbances,1, 343 including diplopia or changes in visual acuity or color perception,343 have been reported in 1-3% of patients receiving ofloxacin.1 Photophobia has been reported in less than 1% of patients receiving the drug.1, 464 Although ophthalmologic abnormalities, including cataracts and multiple punctate lenticular opacities, have been reported with some other quinolones (e.g., pefloxacin [not commercially available in the US]) in both multiple-dose studies in humans and long-term, high dosage studies in animals, there has been no evidence of ofloxacin-induced ocular toxicity in humans or in animal studies.1, 337, 339, 342, 428, 464 Although the clinical importance in unclear, in vitro studies using rabbit corneal epithelial cultures indicate that topical ofloxacin at concentrations exceeding 0.05 mg/mL delayed corneal epithelial wound healing.496
Cough,1 respiratory arrest,1 rhinorrhea,1 thirst,1 and weight loss1 have been reported in less than 1% of patients receiving ofloxacin.1
Decreased hearing acuity1 and tinnitus1, 253 have been reported in less than 1% of patients receiving ofloxacin.
Precautions and Contraindications
Ofloxacin is contraindicated in patients with a history of hypersensitivity to the drug or to other quinolones.1
Systemic fluoroquinolones, including ofloxacin, have been associated with disabling and potentially irreversible serious adverse reactions (e.g., tendinitis and tendon rupture, peripheral neuropathy, CNS effects) that can occur together in the same patient.1, 140, 145 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 Patients receiving ofloxacin should be informed about these serious adverse reactions and advised to immediately discontinue ofloxacin and contact a clinician if they experience any signs or symptoms of serious adverse effects (e.g., unusual joint or tendon pain, muscle weakness, a “pins and needles” tingling or pricking sensation, numbness of the arms or legs, confusion, hallucinations) while taking the drug.1, 140, 145 Systemic fluoroquinolones, including ofloxacin, should be avoided in patients who have experienced any of the serious adverse reactions associated with fluoroquinolones.1, 140, 145
Because fluoroquinolones, including ofloxacin, are associated with an increased risk of tendinitis and tendon rupture in all age groups (see Cautions: Tendinitis and Tendon Rupture), patients receiving ofloxacin should be informed of this potentially irreversible adverse effect and the drug should be discontinued immediately if pain, swelling, inflammation, or rupture of a tendon occurs.1, 676, 851 The risk of developing fluoroquinolone-associated tendinitis and tendon rupture is increased in adults older than 60 years of age, patients receiving concomitant corticosteroids, and kidney, heart, or lung transplant recipients.1 (See Cautions: Geriatric Precautions and see Drug Interactions: Corticosteroids.) Patients should be advised to rest and refrain from exercise at the first sign of tendinitis or tendon rupture (e.g., pain, swelling, or inflammation of a tendon or weakness or inability to use a joint) and advised to immediately discontinue the drug and contact a clinician.1, 676, 851 Systemic fluoroquinolones, including ofloxacin, should be avoided in patients who have a history of tendon disorders or have experienced tendinitis or tendon rupture.1
Because fluoroquinolones, including ofloxacin, are associated with an increased risk of peripheral neuropathy (see Cautions: Peripheral Neuropathy), ofloxacin 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, 130 Patients receiving ofloxacin should be advised that peripheral neuropathies have been reported in patients receiving systemic fluoroquinolones, including ofloxacin, and that symptoms may occur soon after initiation of the drug and, in some patients, may be irreversible.1, 130 Patients should be advised of the importance of immediately discontinuing the drug and contacting a clinician if such symptoms occur.1, 130 Systemic fluoroquinolones, including ofloxacin, should be avoided in patients who have experienced peripheral neuropathy.1
Because fluoroquinolones, including ofloxacin, have been associated with an increased risk of adverse CNS effects (see Cautions: CNS Effects), 1, 171 ofloxacin should be used with caution in patients with known or suspected CNS disorders (e.g., severe cerebral arteriosclerosis, epilepsy) or other risk factors (e.g., certain drugs, renal impairment) that predispose to seizures or lower the seizure threshold.1 Patients should be informed that seizures have been reported in patients receiving ofloxacin and advised to inform their clinician of any history of seizures before initiating therapy with the drug.1 Patients receiving ofloxacin should be advised to notify their clinician if persistent headache (with or without blurred vision) occurs.1 Patients also should be cautioned not to operate a motor vehicle or machinery or engage in activities requiring mental alertness and coordination until they experience how the drug affects them.1 Systemic fluoroquinolones, including ofloxacin, should be avoided in patients who have experienced CNS effects associated with fluoroquinolones.1
Ofloxacin should be avoided in patients with myasthenia gravis since fluoroquinolones, including ofloxacin, may exacerbate myasthenia gravis symptoms.1 Patients should be advised to immediately contact their clinician if they have any worsening muscle weakness or breathing problems.1
Because an increased risk of aortic aneurysm and dissection has been reported with systemic fluoroquinolones, ofloxacin should not be used in patients who have an aortic aneurysm or are at increased risk for an aortic aneurysm unless there are no other treatment options.1, 172 This includes geriatric patients and patients with peripheral atherosclerotic vascular disease, hypertension, or certain genetic conditions (e.g., Marfan syndrome, Ehlers-Danlos syndrome).172 Patients should be informed that systemic fluoroquinolones may increase the risk of aortic aneurysm and dissection and advised of the importance of informing their clinician of any history of aneurysms, blockages or hardening of the arteries, high blood pressure, or genetic conditions such as Marfan syndrome or Ehlers-Danlos syndrome.172 Patients receiving ofloxacin should be advised to seek immediate medical treatment if they experience sudden, severe, and constant pain in the stomach, chest, or back.1, 172
Blood glucose concentrations should be carefully monitored when systemic fluoroquinolones, including ofloxacin, are used in patients with diabetes mellitus receiving antidiabetic agents.1, 171 Patients should be informed that hypoglycemia has been reported when systemic fluoroquinolones were used in some patients receiving antidiabetic agents.171 Patients with diabetes mellitus receiving oral antidiabetic agents or insulin should be advised to discontinue ofloxacin and contact a clinician if they experience hypoglycemia or symptoms of hypoglycemia.171 Appropriate therapy should be initiated immediately.1
Because severe hepatotoxicity, including acute hepatitis and fatalities, has been reported in patients receiving ofloxacin, the drug should be discontinued immediately if any sign or symptom of hepatitis (e.g., anorexia, jaundice, dark urine, pruritus, tender abdomen) occurs.1 Patients should be advised to contact a clinician if any sign or symptom of hepatotoxicity (e.g., loss of appetite, nausea, vomiting, fever, weakness, tiredness, right upper quadrant tenderness, itching, yellowing of skin or eyes, light colored bowel movements, dark colored urine) occurs.1
Use of ofloxacin should be avoided in patients with a history of QT interval prolongation, 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 (See Drug Interactions.) The risk of drug-associated effects on the QT interval may be increased in geriatric patients.1 (See Cautions: Geriatric Precautions.)
Ofloxacin, like other quinolones, can cause serious, potentially fatal hypersensitivity reactions, occasionally following the initial dose.1, 343, 414, 439 (See Cautions: Dermatologic and Sensitivity Reactions.) Patients receiving ofloxacin should be advised of this possibility and instructed to immediately discontinue the drug and contact a clinician at the first sign of rash, urticaria, or other skin reactions, jaundice, or any other sign of hypersensitivity such as rapid heartbeat, difficulty in swallowing or breathing, or any swelling indicative of angioedema (e.g., swelling of the lips, tongue, face; tightness of the throat; hoarseness).1 Serious anaphylactic reactions require immediate emergency treatment with epinephrine and other resuscitation measures (e.g., oxygen, IV fluids, IV antihistamines, corticosteroids, pressor amines, airway management such as intubation) as indicated.1
Because photosensitivity/phototoxicity reactions have been reported following exposure to direct sunlight in patients receiving fluoroquinolones, including ofloxacin,1, 337, 413, 446 patients receiving ofloxacin should be cautioned to avoid excessive exposure to direct sunlight or artificial UV light (sunlamps, solariums) while receiving the drug.1, 428 Ofloxacin should be discontinued if photosensitivity or phototoxicity (sunburn-like reaction, skin eruption) occurs.1
Selection and Use of Anti-infectives
Ofloxacin should be used for the treatment of acute bacterial exacerbations of chronic bronchitis or uncomplicated urinary tract infections only when no other treatment options are available.1, 140, 145 Because ofloxacin, 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 ofloxacin for patients with these infections.140, 145
To reduce development of drug-resistant bacteria and maintain effectiveness of ofloxacin and other antibacterials, the drug should be used only for the treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.1 When selecting or modifying anti-infective therapy, results of culture and in vitro susceptibility testing should be used.1 In the absence of such data, local epidemiology and susceptibility patterns should be considered when selecting anti-infectives for empiric therapy.1
Patients should be advised that antibacterials (including ofloxacin) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).1 Patients also should be advised about the importance of completing the full course of therapy, even if feeling better after a few days, and that skipping doses or not completing therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with ofloxacin or other antibacterials in the future.1
Superinfection/C. difficile-associated Diarrhea and Colitis
As with other anti-infectives, use of ofloxacin may result in emergence and overgrowth of nonsusceptible bacteria or fungi, especially enterococci or Candida .420, 439 Resistant strains of some organisms (e.g., Pseudomonas aeruginosa , staphylococci) have developed during ofloxacin therapy.126, 177, 417, 439, 445 Careful monitoring of the patient and periodic in vitro susceptibility tests are essential.4, 471
Because CDAD has been reported with the use of nearly all anti-infectives, including ofloxacin, it should be considered in the differential diagnosis in patients who develop diarrhea during or after ofloxacin therapy.1, 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, 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, 302, 303, 304
Patients should be advised that diarrhea is a common problem caused by anti-infectives and usually ends when the drug is discontinued; however, it is important to contact a clinician if watery and bloody stools (with or without stomach cramps and fever) occur during or as late as 2 months or longer after the last dose.1
Other Precautions and Contraindications
Renal, hepatic, and hematologic systems should be evaluated periodically during prolonged ofloxacin therapy.1
Crystalluria, cylindruria, and hematuria have been reported with some other fluoroquinolones (e.g., ciprofloxacin).1, 2, 413 Although crystalluria is not expected to occur under usual conditions with the usual recommended dosages of ofloxacin, patients should be instructed to drink sufficient quantities of fluids to ensure proper hydration and adequate urinary output during therapy with the drug.1, 446
Ofloxacin should be used with caution in patients with impaired renal or hepatic function since elimination of the drug may be reduced in these patients.1 When ofloxacin is used in patients with known or suspected renal or hepatic impairment, the patient should be monitored carefully and appropriate laboratory studies should be performed prior to and during therapy with the drug.1
Doses and/or frequency of administration of ofloxacin should be decreased in patients with creatinine clearances of 50 mL/minute or less.1 (See Dosage and Administration: Dosage in Renal and Hepatic Impairment.)
Safety and efficacy of ofloxacin have not been established in children younger than 18 years of age.1 Because ofloxacin, like most other fluoroquinolones, causes arthropathy (arthrosis) in immature animals of several species, some clinicians state that the drug should not be used in children younger than 16-18 years of age.2, 413, 419, 420, 421, 428, 446 Other clinicians suggest that ofloxacin may be used cautiously in adolescents if skeletal growth is complete and suggest that the potential benefits of therapy with the drug may outweigh the possible risks in certain children 9-18 years of age with serious infections (e.g., cystic fibrosis patients) when the causative organism is resistant to other available anti-infectives.264, 327, 337, 417, 428
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.292, 293 For information regarding when fluoroquinolones may be a preferred option in children, see Cautions: Pediatric Precautions in Ciprofloxacin 8:12.18.
In immature rats, oral ofloxacin in dosages 5-16 times the usual human oral dosage increased the incidence and severity of osteochondrosis; the lesions were still present and had not regressed 13 weeks after the drug was discontinued.1 Ofloxacin and most other fluoroquinolones (e.g., ciprofloxacin,) have caused erosions of the cartilage in weight-bearing joints and other signs of arthropathies (arthrosis) in immature animals of various species.1, 339, 342, 359, 413, 417, 420, 421, 428, 446, 464 (See Cautions: Musculoskeletal Effects.)
When the total number of patients studied in phase II/III clinical studies of ofloxacin is considered, 14.2 % (688 patients) were 65 years of age or older, while 5.2% (252 patients) were 75 years of age and older.1 Ofloxacin generally is well tolerated in geriatric patients;1, 246, 269, 485, 495 the frequency and severity of adverse effects reported in patients older than 65 years of age generally are similar to those reported in younger adults.1, 269, 340, 485, 495
Pharmacokinetic parameters in geriatric patients receiving ofloxacin generally are similar to those in younger adults.1 Results of pharmacokinetic studies in geriatric individuals 65-81 years of age indicate that the rate of absorption, volume of distribution, and route of elimination of ofloxacin in geriatric individuals are similar to those reported in younger adults.1 However, mean peak plasma concentrations of ofloxacin are 9-21% higher and the plasma elimination half-life more prolonged in geriatric individuals compared with younger adults.1 (See Pharmacokinetics.) The slower elimination of ofloxacin in geriatric individuals presumably is secondary to reduced renal function and clearance observed in geriatric individuals.1 Because ofloxacin is excreted by the kidneys and geriatric individuals are more likely to have decreased renal function than younger individuals, dosage adjustment may be necessary in geriatric patients with renal impairment as recommended for all patients with renal impairment.1 Dosage of ofloxacin does not need to be modified in geriatric patients with creatinine clearances greater than 50 mL/minute.1, 187, 269 (See Dosage and Administration: Dosage in Renal and Hepatic Impairment.)
The risk of fluoroquinolone-associated tendon disorders, including tendon rupture, is increased in geriatric adults older than 60 years of age.1, 676, 851 This risk is further increased in those receiving concomitant corticosteroids.1, 676, 851 (See Cautions: Precautions and Contraindications.) Ofloxacin should be used with caution in geriatric adults, especially those receiving concomitant corticosteroids.
The risk of QT interval prolongation, 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 (See Cautions: Cardiovascular Effects.)
The risk of fluoroquinolone-associated aortic aneurysm and dissection may be increased in geriatric patients.1 (See Cautions: Aortic Aneurysm and Dissection.)
Mutagenicity and Carcinogenicity
Ofloxacin was not mutagenic in the Ames microbial ( Salmonella ) mutagen test or in in vitro and in vivo cytogenic assays, including the sister chromatid exchange (Chinese hamster and human cell lines) assay, unscheduled DNA repair assay using human fibroblasts, dominant lethal assay, or mouse micronucleus assay.1, 342 When ofloxacin was tested in the in vitro rat hepatocyte DNA repair assay, mouse lymphoma assay, and Rec-assay for DNA repair, results were positive,1, 339, 342, 369 which may indicate a potential for primary DNA damage.339, 342, 369 However, other more sensitive tests, such as the V-79 mammalian cell assay, have not shown evidence of mutagenicity.342
Studies have not been performed to date to evaluate the carcinogenic potential of ofloxacin.1, 428
Pregnancy, Fertility, and Lactation
There are no adequate and controlled studies to date using ofloxacin in pregnant women.1 Since the drug, like most other fluoroquinolones, causes arthropathy in immature animals, ofloxacin should not be used in pregnant women unless the potential benefits justify the possible risks to the fetus.1
Reproduction studies in rats and rabbits using oral347 ofloxacin in dosages up to 810 and 160 mg/kg daily, respectively, have not revealed evidence of teratogenicity.1, 347 However, fetotoxicity (decreased fetal body weight and increased fetal mortality) did occur in rats and rabbits347 receiving oral ofloxacin dosages equivalent to 50 and 10 times the usual human dosage, respectively.1, 347 In rats receiving ofloxacin dosages of 810 mg/kg daily (more than 50 times the maximum human dosage), retardation in the degree of ossification and minor skeletal variations such as cervical ribs and shortened or absent 13th ribs occurred.347 Perinatal and postnatal studies in rats using oral dosages up to 360 mg/kg daily revealed a decrease in food intake during gestation and an increase in food and water intake during lactation, but did not reveal evidence of adverse effects on late fetal development, labor, delivery, lactation, neonatal viability, or growth of the offspring.1, 347
Studies in male and female rats using ofloxacin doses up to 360 mg/kg indicate that the drug does not have an appreciable effect on fertility or reproductive performance.342, 347 Although administration of high dosages of some other quinolones (e.g., norfloxacin [no longer commercially available in the US]) has been associated with impaired spermatogenesis and/or testicular damage (atrophy in rats and dogs) in chronic (for 3 months or longer) toxicity studies,342, 428, 446 similar studies using ofloxacin have not revealed evidence of these adverse effects.342, 428
Ofloxacin is distributed into milk.1 Because of the potential for serious adverse effects of ofloxacin in nursing infants, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.1
Drugs That Prolong QT Interval
Ofloxacin, like some other fluoroquinolones, can prolong the QT interval and should be avoided in patients receiving class IA (e.g., quinidine, procainamide) or class III (e.g., amiodarone, sotalol) antiarrhythmic agents.1
Antacids containing magnesium, aluminum, or calcium may decrease absorption of oral quinolones resulting in decreased serum and urine concentrations of the anti-infectives.1, 189, 367, 404, 405, 414, 420, 427, 464 The extent of this interaction appears to vary depending on the specific quinolone and antacid involved.367, 427, 536 In patients receiving ofloxacin and an antacid concomitantly, peak serum ofloxacin concentrations may be decreased by 20-77% and areas under the plasma concentration-time curve (AUCs) decreased by 60-70%.189, 405, 420 The mechanism of this interaction has not been fully elucidated to date, but magnesium and aluminum ions may bind to and form insoluble complexes with quinolones.1, 189, 367, 405, 413, 414, 427, 536 To minimize the possibility of an interaction, patients should be instructed not to ingest antacids concomitantly with or within 2 hours of an ofloxacin dose.1, 404, 414, 427, 536
Concomitant use of antiarrhythmic agents may increase the risk of QT interval prolongation during ofloxacin therapy.1 Concomitant use of class IA (e.g., quinidine, procainamide) or class III (e.g., amiodarone, sotalol) antiarrhythmic agents should be avoided.1
The antibacterial activities of ofloxacin and aminoglycosides (e.g., amikacin, gentamicin, tobramycin) may be additive or partially synergistic in vitro against susceptible strains of Pseudomonas aeruginosa or Escherichia coli .371, 373, 375 However, synergism between the drugs appears to be unpredictable, and indifference or antagonism has been reported more frequently.375
In vitro, the combination of ofloxacin and aminosalicylic acid, ethambutol, ethionamide, isoniazid, kanamycin, rifampin, or streptomycin is neither synergistic nor antagonistic against Mycobacterium tuberculosis .93 Although the clinical importance has not been determined, ofloxacin used in conjunction with ethambutol results in a synergistic effect in vitro against M. avium complex (MAC).377
Adverse neurologic effects, including insomnia and seizures, have been reported in a few patients with multidrug-resistant pulmonary tuberculosis† who received concomitant oral ofloxacin (600 or 800 mg once daily) and cycloserine (500 or 750 mg once daily or a 2-dose regimen of 500 mg in the morning and 250 mg in the evening).565 Some clinicians suggest that, pending accumulation of additional information on this possible drug interaction, ofloxacin and cycloserine should be used concomitantly with caution.565
In vitro, the combination of ofloxacin and rifampin generally is indifferent or antagonistic against S. aureus .374
An additive or synergistic effect has occurred in vitro against some strains of Staphylococcus epidermidis and methicillin-resistant Staphylococcus aureus (MRSA; also known as oxacillin-resistant S. aureus or ORSA) when ofloxacin was used concomitantly with oxacillin; this combination generally was indifferent against ORSA.372 Synergism was demonstrated more readily at 30°C than at 35°C and did not appear to depend on the ofloxacin susceptibility of the organisms since it occurred in some cases even when the strain was resistant to ofloxacin alone.372 The clinical importance of this in vitro effect is unclear since many strains of staphylococci, principally ORSA, are resistant to ofloxacin.539
Indifference generally occurred in vitro when ofloxacin was used in combination with ampicillin or nafcillin against Enterobacteriaceae or Ps. aeruginosa .12
In vitro, the combination of ofloxacin and cefotaxime was neither synergistic nor antagonistic against Enterobacteriaceae, including Klebsiella pneumoniae and E. coli that were slightly susceptible or resistant to cefotaxime.472
Ofloxacin used in conjunction with imipenem has been additive or synergistic in vitro against some strains of staphylococci, streptococci, Ps. aeruginosa , and Enterobacteriaceae; however, synergism appears to be unpredictable and this combination may be indifferent or antagonistic against these organisms.370
Buffered didanosine preparations (pediatric oral solution admixed with antacid) may interfere with oral absorption of ofloxacin.1 To minimize the possibility of interaction, patients should be instructed not to ingest buffered didanosine preparations concomitantly with or within 2 hours of an ofloxacin dose.1
In vitro studies using ofloxacin and zidovudine indicate that the antiviral agent does not antagonize ofloxacin's antibacterial activity against susceptible S. aureus , S. epidermidis , E. coli , Salmonella typhimurium , or Ps. aeruginosa .451 Although the clinical importance in unclear, the combination of ofloxacin and zidovudine resulted in a slightly additive antibacterial effect in vitro against E. coli and S. typhimurium .451
In one in vitro study, the combination of ofloxacin and bismuth subcitrate was not synergistic against Helicobacter pylori .407
In vitro, the antibacterial activity of ofloxacin and metronidazole is additive or indifferent against anaerobic bacteria; neither synergism nor antagonism occurs with this combination.540
Alterations in blood glucose concentrations resulting in hypoglycemia have been reported in diabetic patients receiving ofloxacin and concomitant antidiabetic agents (e.g., insulin, glyburide).1 If ofloxacin is used in a diabetic patient receiving insulin or an oral antidiabetic agent, blood glucose and concentrations should be monitored carefully.1 Ofloxacin should be discontinued immediately and a clinician consulted if a hypoglycemic reaction occurs.1
Cimetidine, Ranitidine, and Sucralfate
Concomitant administration of cimetidine reportedly may interfere with the elimination of some quinolones resulting in prolonged serum half-lives and AUCs of the drugs.1 It is not known if this occurs with ofloxacin.1
Concomitant administration of ranitidine does not appear to alter oral absorption of ofloxacin.420, 427, 464
Concomitant administration of sucralfate reportedly may interfere with GI absorption of ofloxacin,1, 592 and some clinicians state that concomitant use of ofloxacin with sucralfate is not recommended.592 If concomitant use of ofloxacin and sucralfate is necessary, the manufacturer and some clinicians recommend that patients be instructed not to ingest sucralfate concomitantly with or within 2 hours of an ofloxacin dose.1, 592
Concomitant use of corticosteroids increases the risk of severe tendon disorders (e.g., tendinitis, tendon rupture), especially in geriatric patients older than 60 years of age.1, 676, 851 (See Cautions: Tendinitis and Tendon Rupture.)
In some patients stabilized on warfarin, prolongation of the prothrombin time occurred following initiation of ofloxacin therapy.367, 403, 427, 593 Concomitant administration of some other quinolones (e.g., ciprofloxacin) in patients receiving coumarin anticoagulants also has resulted in increased prothrombin times.1, 367, 403, 427, 452 The mechanism of this interaction has not been determined to date; these drugs may displace the anticoagulants from serum albumin binding sites or may suppress vitamin K production by intestinal bacteria.403 Ofloxacin should be administered with caution in patients receiving a coumarin anticoagulant,367, 403, 593 and prothrombin times should be monitored in patients receiving concomitant therapy.1, 367, 427, 593
Concomitant use of some quinolones in patients receiving cyclosporine reportedly may result in increased cyclosporine serum concentrations.1 It is not known if this occurs with ofloxacin.1
Iron, Multivitamins, and Mineral Supplements
Oral multivitamin and mineral supplements containing divalent or trivalent cations such as iron or zinc may decrease oral absorption of ofloxacin resulting in decreased serum concentrations of the quinolone; therefore, these multivitamins and/or mineral supplements should not be ingested concomitantly with or within 2 hours of an ofloxacin dose.1, 367, 427, 536
In a crossover study, concomitant administration of a single dose of oral ferrous sulfate complex and ofloxacin decreased the AUC of the anti-infective by 36%.427
Nonsteroidal Anti-inflammatory Agents
Concomitant administration of a fluoroquinolone (i.e., ofloxacin) and fenbufen (a nonsteroidal anti-inflammatory agent [NSAIA]) reportedly resulted in an increased incidence of seizures.1, 366, 415, 427 Concomitant use of a fluoroquinolone with an NSAIA could increase the risk of CNS stimulation (e.g., seizures).1, 415, 427 Animal studies using other fluoroquinolones suggest that the risk may vary depending on the specific NSAIA.670
Studies using other fluoroquinolones (e.g., ciprofloxacin) indicate that concomitant administration of probenecid interferes with renal tubular secretion of the drugs.1, 556 The effect of concomitant administration of probenecid and ofloxacin has not been studied to date.1, 556
Concomitant administration of some fluoroquinolone anti-infectives (e.g., ciprofloxacin, ofloxacin) in patients receiving theophylline has resulted in higher and prolonged serum theophylline concentrations and may increase the risk of theophylline-related adverse effects.1, 181, 189, 191, 365, 366, 367, 368, 378, 379, 380, 382, 383, 384, 385, 386, 387, 389, 391, 392, 393, 394, 395, 396, 397, 416, 427, 464 The extent of this interaction varies considerably among the commercially available fluoroquinolones; the effect is less pronounced with ofloxacin than with ciprofloxacin.191, 367, 368, 378, 379, 384, 386, 387, 389, 392, 393, 394, 396, 397, 427 While it has been suggested that the 4-oxo metabolites of these quinolones may inhibit metabolism of theophylline in the liver, and there is some evidence that the degree to which the various quinolones are metabolized to 4-oxo metabolites may correlate with the extent of alteration in theophylline pharmacokinetics when the drugs are administered concomitantly,191, 365, 367, 379, 392, 393, 396, 427 the potential contribution, if any, of the 4-oxo metabolites to this interaction has not been fully elucidated. In addition, other evidence indicates that, while formation of these metabolites may correlate with inhibition of theophylline metabolism, the 4-oxo metabolites themselves are not responsible for the observed effect.365, 367, 427, 539
In some controlled studies in patients receiving ofloxacin and theophylline concomitantly, the pharmacokinetics of theophylline were not altered substantially;378, 379, 381, 384, 386, 390, 392, 393, 394, 397 in other studies, serum theophylline concentrations were increased by 9-10%,380, 414, 464 the AUC of the drug increased by 10-13%,380, 464 and theophylline clearance decreased by 0-16%.181, 365, 367, 380, 395, 414, 464 Concomitant theophylline does not affect the pharmacokinetics of ofloxacin.420
Although the risk of serious adverse effects resulting from theophylline toxicity appears to be low when usual dosages of ofloxacin are used, most studies to date evaluating concomitant therapy have been done in healthy adults;365, 378, 381, 384, 389, 392, 393, 394 experience with concomitant use of the drugs in patients considered at higher risk for adverse effects (e.g., geriatric patients with chronic obstructive pulmonary disease, patients with impaired renal or hepatic function) is limited.379, 365 Therefore, the manufacturer and some clinicians recommend that plasma theophylline concentrations be monitored and the patient observed for manifestations of theophylline toxicity whenever ofloxacin is given concomitantly; appropriate theophylline dosage adjustments should be made if needed.1, 365
Although some quinolones (e.g., ciprofloxacin) have been reported to alter the pharmacokinetics of caffeine,189, 365, 366, 367, 416, 427 results of several studies in healthy adults indicate that ofloxacin does not have a clinically important effect on the elimination half-life, total body clearance, or volume of distribution of caffeine.1, 189, 365, 366, 398, 399, 400, 401, 402, 427, 454 Therefore, although precautions relating to caffeine intake may be necessary in patients receiving these other quinolones, these precautions do not appear to be necessary in patients receiving ofloxacin.398
Some quinolones, including ofloxacin, may cause false-positive results for opiates when commercially available immunoassay kits for urine screening are used.1 It may be necessary to confirm positive opiate screening test results using more specific methods.1
The oral LD50 of ofloxacin is 3.6-5.5 g/kg in mice and rats and exceeds 200 mg/kg in dogs.339 The IV LD50 of the drug is 208-276 mg/kg in mice and rats and exceeds 70 mg/kg in dogs.339
In animals receiving oral ofloxacin, acute toxicity is manifested as ptosis, hypoactivity, sedation, prostration, hypopnea, dyspnea, and seizures.339 Limited information is available on the acute toxicity of ofloxacin in humans.1, 410, 550 Overdosage of ofloxacin would be expected to produce manifestations that principally are extensions of the adverse reactions reported with the drug, and may include nausea, vomiting, seizures, vertigo, dysgeusia, and psychosis.410, 550
A 23-year-old woman who inadvertently received approximately 3 g of ofloxacin IV over 45 minutes (a parenteral preparation is no longer commercially available in the US) developed drowsiness, nausea, hot and cold flashes, facial flushing and edema, slurred speech, dizziness, and disorientation during the infusion; all manifestations except dizziness, which was exacerbated on standing, and nausea resolved within 1 hour after discontinuance of the infusion, with the latter effects resolving several hours later.1, 550 Serum ofloxacin concentration 15 minutes after completion of the infusion in this woman was approximately 40 mcg/mL.1, 550 In a 14-year-old who ingested an unknown quantity of ofloxacin along with therapeutic doses of diphenhydramine and chlormezanone (no longer commercially available in the US), confusion, delirium, agitation, hallucinations, extreme mydriasis, and dry and warm skin occurred within a few hours; plasma concentrations of ofloxacin 12 hours after ingestion were 15 mcg/mL.410 Although activated charcoal was administered and forced diuresis was initiated, symptoms persisted for the next several days until IV physostigmine salicylate was given.410 It was suggested that the anticholinergic and psychotic manifestations observed in this patient may have resulted from a drug interaction between ofloxacin and diphenhydramine and/or chlormezanone.410
If acute overdosage of ofloxacin occurs, the stomach should be emptied by inducing emesis or by gastric lavage.1 Supportive and symptomatic treatment should be initiated, and the patient should be observed carefully; adequate hydration should be maintained.1 Because ofloxacin is not efficiently removed by hemodialysis or peritoneal dialysis, these procedures should not be relied on to enhance elimination of the drug from the body.1
Ofloxacin usually is bactericidal in action.1, 3, 14, 147, 148, 152, 466 Like other fluoroquinolone anti-infectives, ofloxacin420 inhibits DNA synthesis in susceptible organisms via inhibition of the enzymatic activities of 2 members of the DNA topoisomerase class of enzymes, DNA gyrase and topoisomerase IV.1, 632, 633, 634, 635, 636 DNA gyrase and topoisomerase IV have distinct essential roles in bacterial DNA replication.1, 632, 633, 634, 635, 636 DNA gyrase, a type II DNA topoisomerase, was the first identified quinolone target; DNA gyrase is a tetramer composed of 2 GyrA and 2 GyrB subunits.632, 633, 634, 635, 636 DNA gyrase introduces negative superhelical twists in DNA, an activity important for initiation of DNA replication.634, 636 DNA gyrase also facilitates DNA replication by removing positive super helical twists.634, 636 Topoisomerase IV, another type II DNA topoisomerase, is composed of 2 ParC and 2 ParE subunits.632, 633, 634, 635, 636 DNA gyrase and topoisomerase IV are structurally related; ParC is homologous to GyrA and ParE is homologous to GyrB.632, 633, 634, 635, 636 Topoisomerase IV acts at the terminal states of DNA replication by allowing for separation of interlinked daughter chromosomes so that segregation into daughter cells can occur.632, 633, 634, 635, 636 Fluoroquinolones inhibit these topoisomerase enzymes by stabilizing either the DNA-DNA gyrase complex or the DNA-topoismerase IV complex; these stabilized complexes block movement of the DNA replication fork and thereby inhibit DNA replication resulting in cell death.632, 633, 634, 635, 636
Although all fluoroquinolones generally are active against both DNA gyrase and topoisomerase IV, the drugs differ in their relative activities against these enzymes.632, 633, 634, 635, 636 For many gram-negative bacteria, DNA gyrase is the primary quinolone target and for many gram-positive bacteria, topoisomerase IV is the primary target. The other enzyme is the secondary target in both cases.632, 633, 634, 635, 636 However, there are exceptions to this pattern.632, 633, 634, 635, 636 For certain bacteria (e.g., Streptococcus pneumoniae ), the principal target depends on the specific fluoroquinolone.632, 635
The mechanism by which ofloxacin's inhibition of DNA gyrase or topoisomerase IV results in death in susceptible organisms has not been fully determined.3, 152, 162, 417, 466, 632, 633, 634, 635, 636 Unlike β-lactam anti-infectives, which are most active against susceptible bacteria when they are in the logarithmic phase of growth, studies using Escherichia coli and Pseudomonas aeruginosa indicate that ofloxacin can be bactericidal during both logarithmic and stationary phases of growth.148, 417 In vitro studies indicate that ofloxacin concentrations that approximate the minimum inhibitory concentration (MIC) of the drug induce filamentation in susceptible organisms and lysis; high concentrations of the drug result in enlarged or elongated cells that may not be extensively filamented and may not lyse.148, 417, 466 Although the bactericidal effect of some fluoroquinolones evidently requires competent RNA and protein synthesis in the bacterial cell, and concurrent use of anti-infectives that affect protein synthesis (e.g., chloramphenicol, tetracyclines) or RNA synthesis (e.g., rifampin) inhibit the in vitro bactericidal activity of these drugs, the bactericidal effect of ofloxacin, like that of ciprofloxacin, is only partially reduced in the presence of these anti-infectives.149, 152, 161, 417, 420, 443 This suggests that ofloxacin, like ciprofloxacin, has an additional mechanism of action that is independent of RNA and protein synthesis.152, 161, 417, 420, 443
For most susceptible organisms, the minimum bactericidal concentration (MBC) of ofloxacin is 1-4 times higher than the MIC.3, 14, 35, 153, 417, 420, 464
Mammalian cells contain type II topoisomerase similar to that contained in bacteria.138, 147, 153, 161, 163, 164, 336, 417, 441, 634 At concentrations attained during therapy, quinolones do not appear to appreciably affect the mammalian enzyme.138, 153, 161, 163, 417, 421, 634
Results of in vitro studies indicate that exposure of some plasmid-containing bacteria (e.g., E. coli ) to ofloxacin or other fluoroquinolones may result in loss of plasmid DNA.149, 153, 420 This effect is unpredictable and depends on the specific plasmid and concentration of drug.149 It is unclear whether this effect is related to inhibition of DNA gyrase or some other mechanism of action of the drugs.417, 420
In vitro studies, particularly those involving in vitro susceptibility tests, indicate that the antibacterial activity of ofloxacin, like that of ciprofloxacin, is decreased in the presence of urine, especially acidic urine.12, 14, 42, 153, 413, 417, 420, 421, 464 The clinical importance of this in vitro effect has not been determined to date; however, because ofloxacin concentrations attained in urine are usually substantially higher than ofloxacin MICs for most urinary tract pathogens, the effect probably is not clinically important.413
Ofloxacin has a spectrum of activity similar to that of some other fluoroquinolones (e.g., ciprofloxacin).3, 9, 10, 12, 15, 23, 24, 32, 119, 173, 189, 413, 414, 417, 418, 419, 420, 421, 442, 464, 469 In vitro on a weight basis, the activity of ofloxacin against susceptible gram-positive bacteria is approximately equal to that of ciprofloxacin.6, 9, 10, 12, 32, 189, 414, 417, 419, 420, 421, 464 The activity of ofloxacin against susceptible gram-negative bacteria is slightly less than that of ciprofloxacin.9, 12, 15, 23, 32, 35, 118, 189, 414, 417, 420, 421, 469
Ofloxacin is active in vitro against many gram-positive aerobic bacteria, including penicillinase-producing, nonpenicillinase-producing, and some oxacillin-resistant staphylococci (previously known as methicillin-resistant staphylococci).1, 3, 9, 12, 413, 414, 417, 420, 464 Ofloxacin is active in vitro against most gram-negative aerobic bacteria, including Enterobacteriaceae and Pseudomonas aeruginosa .1, 3, 9, 12, 413, 414, 417, 418, 420, 464 Like other fluoroquinolones, ofloxacin generally is less active against gram-positive than gram-negative bacteria.3, 9, 12, 413, 414, 417, 418, 421 Ofloxacin has some activity in vitro against obligately anaerobic bacteria, but most of these organisms, including Bacteroides fragilis , are considered resistant to the drug.1, 3, 9, 12, 413, 417, 420, 421, 464, 540 The drug also has some activity in vitro against Chlamydia ,1, 3, 413, 417, 420, 421, 464 Mycoplasma ,1, 3, 413, 417, 420, 464 Mycobacterium ,3, 98, 99, 100, 103, 104, 105, 107, 108, 109, 413, 414, 417, 420, 421, 464, 468 Plasmodium ,101, 102, 413 and Rickettsia .413 Ofloxacin is inactive against fungi.413, 464
Gram-positive Aerobic Bacteria
Ofloxacin is active in vitro against most strains of Staphylococcus aureus ,1, 3, 6, 12, 13, 14, 15, 16, 17, 19, 21, 22, 23, 25, 26, 27, 28, 32, 33, 34, 74, 504 S. epidermidis ,1, 6, 12, 13, 15, 16, 17, 19, 21, 22, 23, 25, 26, 27, 28, 32, 33, 34 and S. saprophyticus .1, 15, 28, 33, 34 The drug is active against both penicillinase-producing and nonpenicillinase-producing staphylococci and also is active in vitro against some oxacillin-resistant S. aureus (ORSA).1, 12, 16, 17, 18, 19, 21, 22, 25, 26, 27, 28, 33, 34, 39, 420, 464 However, S. aureus , including ORSA, that are resistant to ofloxacin and other fluoroquinolones have been reported with increasing frequency.106, 123, 125, 133, 506, 519, 520, 521, 522 (See: Resistance.)
Ofloxacin is less active in vitro on a weight basis against streptococci than against staphylococci.420, 464 Streptococcus pneumoniae ,3, 8, 17, 21, 22, 23, 25, 26, 27, 28, 33, 34, 38, 193, 467, 504 S. pyogenes (group A β-hemolytic streptococci; GAS),3, 6, 12, 14, 16, 17, 21, 22, 23, 25, 26, 27, 28, 33, 34 and group B streptococci ( S. agalactiae ; GBS),3, 12, 14, 17, 21, 22, 23, 26, 27, 32, 33, 34, 504 viridans streptococci (e.g., S. mitis ),3, 6, 21, 25, 26, 27, 29 Groups C, F, and G streptococci,14, 21, 22, 23, 25, 26, 27 and nonenterococcal group D streptococci (e.g., S. bovis )9, 13 generally are inhibited in vitro by ofloxacin concentrations of 4 mcg/mL or less. Ofloxacin is equally active against both penicillin-susceptible and -resistant strains of S. pneumoniae .38, 193 Ofloxacin is active in vitro against some strains of enterococci, including Enterococcus faecalis (formerly S. faecalis ).3, 6, 15, 16, 17, 19, 21, 22, 23, 25, 26, 27, 28, 29, 32, 33, 34, 132, 504
Table 1 includes MIC50s (minimum inhibitory concentrations of the drug at which 50% of strains tested are inhibited) and MIC90s (minimum inhibitory concentrations of the drug at which 90% of strains tested are inhibited) of ofloxacin reported for gram-positive aerobic cocci:
Organism | MIC50 (mcg/mL) | MIC90 (mcg/mL) |
|---|---|---|
Staphylococcus aureus | 0.2-0.5 | 0.2-1.63, 6, 12, 13, 14, 15, 16, 17, 19, 21, 22, 23, 25, 26, 27, 28, 32, 33, 34, 40, 74, 504 |
S. epidermidis | 0.2-0.5 | 0.125-16, 12, 13, 15, 16, 17, 19, 21, 22, 23, 25, 26, 27, 28, 32, 33, 34 |
S. saprophyticus | 0.5-2 | |
Oxacillin-resistant S. aureus | 0.25-2 | 0.25-412, 16, 17, 18, 19, 21, 22, 25, 26, 27, 28, 33, 34, 39, 40 |
Streptococcus pneumoniae | 1-3.1 | |
Group A streptococci | 1-2 | |
Group B streptococci | 1-4 | |
Groups C, F, and G streptococci | 1-2 | |
Viridans streptococci | 1-2 | |
Nonenterococcal group D streptococci | 1.2-2 | |
Enterococci | 0.8-4 | 1.6-6.33, 6, 15, 16, 17, 19, 21, 22, 23, 25, 26, 27, 28, 29, 32, 33, 34, 132, 504 |
Ofloxacin is active against Bacillus anthracis in vitro. 621, 630, 631 In several in vitro studies, B. anthracis isolates had ofloxacin MICs of 0.03-0.25 mcg/mL.621, 630, 631 Anti-infectives are active against the germinated form of B. anthracis , but are not active against the organism when it is still in the spore form.682 Strains of B. anthracis with naturally occurring resistance to fluoroquinolones have not been reported to date.682 However, reduced susceptibility to ofloxacin (fourfold increase in MICs from baseline) was produced in vitro following sequential subculture of the Sterne strain of B. anthracis in subinhibitory concentrations of the fluoroquinolone.630
Ofloxacin is active in vitro against Corynebacterium .21, 25, 26, 32, 62, 66 The MIC90 of the drug reported for C. diphtheria ,32 JK strains of Corynebacterium ,21, 25, 26 Corynebacterium D2,62, 66 and C. jeikeium 66 is 0.5-1 mcg/mL.
Ofloxacin is active in vitro against Listeria monocytogenes , and the MIC90 of the drug reported for this organism is 1-8 mcg/mL.21, 22, 25, 26, 27, 32, 34, 37, 420
Although some strains of Nocardia asteroides are inhibited in vitro by ofloxacin concentrations of 4-8 mcg/mL, this organism generally is considered resistant to the drug.32, 35, 63, 420, 504
Gram-negative Aerobic Bacteria
Ofloxacin is active in vitro against some strains of penicillinase- and nonpenicillinase-producing Neisseria gonorrhoeae 1, 3, 6, 12, 17, 19, 20, 21, 22, 23, 26, 28, 33, 34, 41, 44, 54, 420, 559 and N. gonorrhoeae with chromosomally mediated resistance to penicillin (CMRNG) or plasmid-mediated tetracycline resistance (TRNG).559 The MIC90 of ofloxacin is 0.007-0.1 mcg/mL for most penicillinase- or nonpenicillinase-producing N. gonorrhoeae ,3, 6, 12, 17, 19, 20, 21, 22, 23, 26, 28, 33, 34, 41, 44, 54 CMRNG, and TRNG.559 However, N. gonorrhoeae with decreased susceptibility to fluoroquinolones (quinolone-resistant N. gonorrhoeae ; QRNG) have been reported with increasing frequency.344, 578, 580, 581, 583, 584, 585, 642, 857 To date, most strains of N. gonorrhoeae with reduced susceptibility have ofloxacin MICs of 0.13-0.5 mcg/mL; however, strains with ofloxacin MICs of 2 mcg/mL also have been reported.578, 584, 585 (See Resistance: Resistance in Neisseria gonorrhoeae.)
Ofloxacin is active in vitro against N. meningitidis ,17, 27, 32, 34, 420, 504 and the MIC90 of the drug for this organisms usually is 0.015-0.03 mcg/mL.17, 27, 32, 34, 504
Ofloxacin is active in vitro against β-lactamase- and non-β-lactamase-producing Haemophilus influenzae ,1, 3, 6, 12, 17, 19, 21, 23, 26, 27, 28, 32, 33, 34, 52, 420, 467, 504 and the MIC90 of the drug for these organisms is 0.02-0.13.17, 19, 34, 467 H. parainfluenzae generally are inhibited in vitro by ofloxacin concentrations of 0.25 mcg/mL.12, 52 The MIC90 of ofloxacin for H. ducreyi is 0.03-2 mcg/mL.20, 32, 35, 60, 135, 420 Ofloxacin is active against β-lactamase-producing H. ducreyi and is active against strains resistant to tetracycline, ampicillin, and sulfamethoxazole.135
Ofloxacin is active in vitro against both β-lactamase- and non-β-lactamase-producing strains of Moraxella catarrhalis (formerly Branhamella catarrhalis ), and the MIC90 of the drug reported for this organism is 0.06-1 mcg/mL.12, 17, 19, 21, 22, 23, 25, 26, 27, 34, 59, 420
Ofloxacin is active in vitro against most clinically important Enterobacteriaceae.420 With the exception of Providencia and Serratia , the MIC90 of ofloxacin for Enterobacteriaceae generally is 2.5 mcg/mL or less.12, 16, 32, 414, 420, 421 Ofloxacin is active against some Enterobacteriaceae resistant to aminoglycosides and/or β-lactam antibiotics.120
Table 2 includes MIC50s and MIC90s of ofloxacin reported for Enterobacteriaceae:
Organism | MIC50 (mcg/mL) | MIC90 (mcg/mL) |
|---|---|---|
Citrobacter spp. | 0.03-0.1 | |
C. diversus | 0.03-0.13 | |
C. freundii | 0.06-0.4 | |
Enterobacter spp. | 0.03-0.1 | |
E. aerogenes | 0.06-0.13 | |
E. agglomerans | 0.06-0.2 | |
E. cloacae | 0.05-0.13 | 0.25-3.13, 6, 12, 13, 16, 17, 19, 21, 22, 23, 24, 26, 27, 28, 34 |
Escherichia coli | 0.015-0.06 | 0.05-0.23, 6, 9, 12, 13, 14, 15, 16, 17, 19, 21, 22, 24, 26, 27, 28, 32, 33, 34 |
Hafnia alvei | 0.03-0.125 | |
Klebsiella spp. | 0.03-0.125 | |
K. oxytoca | 0.06-0.25 | |
K. pneumoniae | 0.06-0.25 | |
Morganella morganii | 0.03-0.15 | 0.06-0.53, 12, 13, 14, 15, 16, 17, 21, 22, 23, 25, 26, 27, 28, 33, 34 |
Proteus mirabilis | 0.06-0.3 | 0.12-0.53, 6, 9, 12, 13, 14, 15, 16, 17, 19, 21, 22, 23, 25, 26, 27, 28, 33, 34 |
P. vulgaris | 0.03-0.125 | 0.06-1.63, 12, 13, 14, 15, 16, 17, 21, 22, 23, 25, 26, 27, 28, 33, 34 |
Providencia rettgeri | 0.12-1 | 0.5-83, 12, 13, 14, 15, 16, 17, 21, 22, 23, 25, 26, 27, 28, 33, 34 |
P. stuartii | 0.12-1 | 0.25-6.253, 12, 13, 15, 16, 17, 21, 22, 23, 25, 26, 27, 28, 33, 34 |
Serratia spp. | 0.25-0.3 | |
S. marcescens | 0.25-1.6 | |
Salmonella spp. | 0.04-0.13 | 0.06-0.253, 9, 12, 13, 14, 16, 21, 22, 26, 27, 32, 34, 44, 320, 504 |
S. enteritidis | 0.06 | 0.12525 |
S. typhi | 0.03 | |
Shigella spp. | 0.03-0.125 | 0.03-0.253, 12, 13, 16, 21, 22, 25, 26, 27, 32, 34, 44, 49, 504 |
Yersinia enterocolitica | 0.06-0.125 |
Ofloxacin is active in vitro against most strains of Ps. aeruginosa 1, 3, 6, 9, 12, 13, 14, 15, 16, 17, 19, 21, 23, 25, 26, 27, 32, 33, 34, 75, 420, 469, 504 and also has some activity against other Pseudomonas .3, 6, 12, 13, 17, 19, 21, 25, 26, 27, 37, 50, 75 The MIC50 and MIC90 of ofloxacin for Ps. aeruginosa are 0.25-3.2 and 1-6.3 mcg/mL, respectively.3, 6, 9, 12, 13, 14, 15, 16, 17, 19, 21, 23, 25, 26, 27, 32, 33, 34, 75, 469, 504 The MIC90 of the drug for Ps. acidovorans ,12, 17, 75 Ps. fluorescens ,12, 17, 37, 75 and Ps. putida 17 is 0.4-1.6 mcg/mL and the MIC90 for Xanthomonas maltophilia ( Ps. maltophilia ) is 1.6-8 mcg/mL.3, 6, 12, 13, 19, 21, 26, 27, 37, 75 Although some strains of Burkholderia cepacia (formerly Ps. cepacia ),12, 17, 21, 25, 27, 34, 37, 75, 464 Brevundimonas diminuta (formerly Ps. diminuta ,75 Ps. paucimobilis ,75 and B. pseudomallei (formerly Ps. pseudomallei )50, 324 are inhibited by ofloxacin concentrations of 8 mcg/mL or less, many of these organisms require concentrations of 16-32 mcg/mL for in vitro inhibition and are considered resistant to the drug.12, 21, 25, 27, 34, 37, 50, 58, 75
Ofloxacin is active in vitro against Vibrio cholerae 34, 44, 420, 504 and V. parahaemolyticus ,44, 504 and the MIC90 of the drug reported for these organisms is 0.008-0.13 mcg/mL.
Other Gram-negative Aerobic Bacteria
The MIC90 of ofloxacin for Acinetobacter lwoffi ( A. calcoaceticus subsp. lwoffi )34, 37, 75, 420 and A. baumannii ( A. calcoaceticus subsp. anitratus )13, 21, 22, 25, 34, 37, 75, 79, 420, 469 is 0.25-2 mcg/mL.
Aeromonas hydrophila ,3, 12, 16, 21, 22, 25, 26, 27, 32, 34, 44, 46, 420, 470, 504A. caviae ,470 and A. sobria 470 generally are inhibited in vitro by ofloxacin concentrations of 0.03-0.1 mcg/mL. The MIC90 of ofloxacin reported for Plesiomonas shigelloides is 0.015-0.06 mcg/mL.9, 44, 504 Alcaligenes xylosoxidans ( Achromobacter xylosoxidans )12, 72, 75 and Alcaligenes faecalis 28, 75 may require ofloxacin concentrations of 1.6-32 mcg/mL for in vitro inhibition.
Ofloxacin is active in vitro against some strains of Campylobacter fetus subsp. jejuni , and the MIC90 of the drug for this organism is 0.25-1.25 mcg/mL.19, 32, 34, 44, 46, 61, 504 The MIC90 of ofloxacin reported for Helicobacter pylori is 0.25 mcg/mL.473 However, emergence of strains of Campylobacter resistant to fluoroquinolones has been reported in areas with widespread use of the drugs.128, 524, 530, 531 (See Resistance.)
Bordetella pertussis 35, 65, 68, 73 and B. parapertussis 68, 73 generally are inhibited by ofloxacin concentrations of 0.03-0.125 mcg/mL. B. bronchiseptica may be inhibited by ofloxacin concentrations of 1.6-8 mcg/mL.12, 73
The MIC90 of ofloxacin reported for Brucella melitensis ,67, 89, 561 B. abortus ,67 and Flavobacterium 6, 74, 75 is 0.5-4 mcg/mL, and the MIC90 reported for Pasteurella multocida 74 and Eikenella corrodens 37, 48, 74 is 0.03-0.125 mcg/mL.
Ofloxacin has in vitro activity against Francisella tularensis .623
Ofloxacin has in vitro activity against Yersinia pestis .624, 625, 627 In a study evaluating in vitro susceptibility of 100 Y. pestis isolates obtained from plague patients in Africa, all isolates were inhibited by ofloxacin concentrations of 0.12 mcg/mL or less.624 In another study, isolates obtained from plague patients, rats, or fleas from Vietnam were inhibited by ofloxacin concentrations of 0.03-0.25 mcg/mL.625 Ofloxacin also has been shown to have in vivo activity against Y. pestis in murine plague infections.626, 627 However, mutant strains of Y. pestis resistant to fluoroquinolones (e.g., ciprofloxacin) have been selected in vitro.507, 508
Some strains of Gardnerella vaginalis (formerly Haemophilus vaginalis ) are inhibited in vitro by ofloxacin concentrations of 1-2 mcg/mL; other strains require concentrations of 16-32 mcg/mL for in vitro inhibition and are considered resistant to the drug.3, 20, 23, 32, 35, 420, 464, 504
Ofloxacin is active in vitro against Legionella pneumophila ,1, 3, 27, 32, 92, 97, 420 L. bozemanii ,92, 97, 457 L. dumoffii ,92, 97, 457 L. gormanii ,92, 97, 457 L. jordanis ,92, 97, 457 L. longbeachae ,92, 97, 457 L. micdadei (the Pittsburgh pneumonia agent),92, 97, 457 and L. wadsworthii ,97, 457 and the MIC of the drug reported for these organisms is 0.03-0.25 mcg/mL.92, 97, 457
Ofloxacin has some activity against gram-positive and -negative anaerobic bacteria;1, 420, 464, 540 however, high concentrations of the drug generally are required for in vitro inhibition and most of these organisms are considered resistant to the drug.464, 540 The MIC90 of ofloxacin for Peptococcus 3, 23, 26, 28, 464, 540 and Peptostreptococcus 3, 21, 23, 26, 32, 74, 464, 540 is 2-8 mcg/mL. Some strains of Clostridium perfringens 1, 6, 22, 27, 32, 34, 70, 464, 540 and C. welchii 420, 504 may be inhibited in vitro by ofloxacin concentrations of 0.5-1 mcg/mL, but most clostridia require ofloxacin concentrations of 8 mcg/mL or greater for in vitro inhibition and are considered resistant to the drug.22, 27, 32, 34, 69, 71, 420, 464
The MIC90 of ofloxacin reported for Bacteroides fragilis is 2-8 mcg/mL.3, 6, 9, 21, 22, 23, 25, 26, 27, 28, 32, 33, 34, 71, 113, 420, 464, 504 Ofloxacin concentrations of 0.02-2 mcg/mL may inhibit some strains of Prevotella melaninogenica 23, 32, 74, 420, 464, 504 and B. ureolyticus .23 The MIC90 of ofloxacin for B. distasonis , B. ovatus , B. thetaiotaomicron , B. uniformis , and B. vulgatus is 8-32 mcg/mL, and these organisms are considered resistant to the drug.540 Some strains of Eubacterium ,12, 464, 540 Fusobacterium ,6, 23, 32, 74, 420, 464, 504, 540 and Veillonella 464 may be inhibited in vitro by ofloxacin concentrations of 0.5-4 mcg/mL.
Ofloxacin is active in vitro against Chlamydia trachomatis , C. pneumoniae ,569 and C. psittaci ,569 and these organisms generally are inhibited in vitro by concentrations of 0.5-4 mcg/mL.32, 34, 45, 82, 83, 84, 85, 86, 88, 90, 569 The minimum lethal concentration (MLC) of ofloxacin reported for C. trachomatis is similar to the MIC and ranges from 0.5-8 mcg/mL.45, 83, 86, 88, 90 Both urogenital and ocular isolates of C. trachomatis are inhibited in vitro by ofloxacin.86, 90
Ofloxacin also is active in vitro against Mycoplasma hominis ,1, 32, 87 M. pneumoniae ,1, 3, 91, 420, 464, 568 and Ureaplasma urealyticum .1, 3, 20, 32, 34, 45, 87, 420, 464 The MIC90 of ofloxacin reported for M. hominis and M. pneumoniae is 1-2 mcg/mL87, 91, 420, 464, 568 and the MIC90 for U. urealyticum is 1.6-8 mcg/mL.34, 45, 87, 420, 464, 474
Ofloxacin is active in vitro against some Mycobacterium .93, 94, 95, 96, 98, 99, 100, 103, 104, 105, 107, 108, 109, 420, 464, 468 In vitro on a weight basis, ofloxacin is slightly less active than ciprofloxacin or levofloxacin against these organisms.96, 98, 100, 104, 644 The MIC90 of ofloxacin for M. tuberculosis 93, 94, 96, 98, 99, 100, 105, 108, 644, 667 and M. kansasii 98, 99 is 0.6-2.4 mcg/mL. The MIC90 for M. bovis ,99, 104 M. fortuitum ,98, 104, 256, 332, 333 M. gordonae ,104 and M. xenopi 98, 99, 104 is 0.03-2.5 mcg/mL. The MIC90 of the drug for M. avium complex generally is 2-16 mcg/mL;96, 98, 99, 104 ofloxacin concentrations greater than 8 mcg/mL are required for in vitro inhibition of M. chelonae 104, 107 and M. scrofulaceum .104
Ofloxacin is active in vitro against M. leprae 95, 109 and is bactericidal in vivo against M. leprae in mouse footpad studies.95, 459
Although the clinical importance in unclear, ofloxacin has some activity in vitro against Plasmodium falciparum .101, 102 Results of in vitro tests indicate that ofloxacin is active against both chloroquine-susceptible and -resistant P. falciparum , but is less active against these organisms than ciprofloxacin.101, 102
Ofloxacin has some activity in vitro against Rickettsia conorii , the causative organism of Mediterranean spotted fever,80 and Coxiella burnetii , the causative organism of Q fever.76, 78, 80
Although the clinical importance has not been determined, ofloxacin has some activity against the Lister strain of vaccinia virus in vitro in mammalian cell cultures and in vivo in mice.455 In similar tests, the drug had only weak antiviral effects against herpes simplex virus (HSV) and no appreciable effects against influenza virus.455
Ofloxacin has some activity against Trypanosoma cruzi , the causative organism of Chagas' disease.142 The drug is inactive against Treponema pallidum .1 Ofloxacin also is inactive against Trichomonas vaginalis .526
Resistance to ofloxacin can be produced easily in vitro in some strains of Enterobacteriaceae, Pseudomonas aeruginosa , streptococci, and Staphylococcus aureus , including methicillin-resistant Staphylococcus aureus (MRSA; also known as oxacillin-resistant S. aureus or ORSA), by serial passage in the presence of increasing concentrations of the drug.3, 4, 12, 39, 40, 111, 121, 126, 132, 420, 445, 464, 471 Ofloxacin resistance resulting from spontaneous mutation occurs only rarely in vitro (i.e., with a frequency of 10-11 to 10-9).1, 3, 4, 12, 14, 25, 121, 413, 420, 445, 552 Spontaneous mutation occurs in a single step and results in low-level resistance to the drug.127, 413, 420
Resistant strains of Ps. aeruginosa have emerged rarely during therapy with the drug, especially in patients with cystic fibrosis;126, 177, 417, 445 in some cases, the development of resistance was not associated with clinical failure of ofloxacin therapy.126, 127 Resistant strains of Escherichia coli also have emerged rarely during therapy with the drug.445 Although the clinical importance is unclear, ofloxacin-resistant strains of Ps. aeruginosa 125, 126, 127, 132 and Bacteroides fragilis 113 have been reported with increasing frequency since the drug was introduced.
Strains of S. aureus , especially ORSA resistant to fluoroquinolones, have been reported with increasing frequency.106, 123, 125, 133, 506, 519, 520, 521, 522 Emergence of fluoroquinolone resistance in staphylococci has been alarmingly rapid.506, 520 In one hospital in Georgia, high-level resistance to ciprofloxacin (MIC90 64 mcg/mL or greater) was apparent within 3 months of availability of the drug and increased from a baseline of 0% to 79% of ORSA isolates over a 1-year period; such resistance also increased to 14% of isolates in oxacillin-susceptible strains over the same period.520 In some countries (e.g., Israel, France, Canada), approximately 30-90% of clinical isolates of ORSA reportedly are resistant to fluoroquinolones; less than 10% of oxacillin-susceptible strains in these countries are resistant to the drugs.133, 506 Results of resistance surveys indicate that fluoroquinolone resistance has emerged in multiple strains of ORSA; however, at some institutions, resistance occurred principally in a single ORSA strain which was then nosocomially transmitted to other patients.125, 133, 539
Rapid emergence of resistance to fluoroquinolones in Campylobacter also has been reported and appears to be associated with widespread use or prolonged therapy with the drugs.128, 524, 530, 531 In several patients with chronic active gastritis and duodenal ulcers, MICs of ofloxacin for H. pylori (formerly C. pylori ) increased from 0.25-1 mcg/mL prior to ofloxacin therapy to 16-32 mcg/mL after 4 weeks of therapy.128 Over a 10- to 12-year period in Finland, fluoroquinolone-resistant strains of C. jejuni and C. coli increased from 0-4% to 9-11%.524 A similar increase was observed over a 7-year period in Campylobacter isolates obtained from poultry and humans in the Netherlands; this increase in resistance was attributed to use of enrofloxacin in the poultry industry.530 In the US, fluoroquinolone-resistant isolates of Campylobacter have been obtained from raw turkey or chicken products in the retail market.434
Resistance in Neisseria gonorrhoeae
Neisseria gonorrhoeae with decreased susceptibility to ofloxacin and other fluoroquinolones (quinolone-resistant N. gonorrhoeae ; QRNG) are widely disseminated throughout the world, including in the US.344, 578, 580, 581, 583, 584, 585, 642, 857N. gonorrhoeae with decreased susceptibility to one fluoroquinolone also have decreased susceptibility to other fluoroquinolones (e.g., ciprofloxacin, ofloxacin), but may be susceptible to ceftriaxone, cefixime, and spectinomycin (currently not commercially available in the US).578, 581, 584
Ofloxacin-resistant strains of Mycobacterium tuberculosis have been reported.93, 94, 126, 620, 644, 648 Resistance has developed in initially susceptible M. tuberculosis in some patients with pulmonary tuberculosis receiving ofloxacin in conjunction with antituberculosis agents.93, 94, 126 Some multidrug-resistant strains of M. tuberculosis (i.e., strains resistant to rifampin and isoniazid) also are resistant to ofloxacin or other fluoroquinolones.644 Extensively drug-resistant tuberculosis (XDR tuberculosis) caused by strains 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) has been reported with increasing frequency.645, 646
Some strains of M. kansasii are resistant to ofloxacin.666
Mechanisms of Fluoroquinolone Resistance
The mechanism(s) of resistance to fluoroquinolones, including ofloxacin, has not been fully elucidated but appears to involve mutations in the target DNA type II topoisomerase enzymes and mutations that result in alterations in membrane permeability and/or efflux pumps.3, 113, 115, 121, 123, 126, 127, 132, 134, 420, 497, 632, 634, 635, 636
Resistance to fluoroquinolones generally occurs as a result of mutational amino acid substitutions in the subunits (i.e., Gyr A, Gyr B, Par C, Par E) of the more sensitive (i.e., the primary target) topoisomerase enzyme (i.e., DNA gyrase or topoisomerase IV).632, 633, 634, 635, 636 Mutations in the primary target precede those in the secondary target, in a stepwise selection for resistance; mutations in both targets produce high level resistance.632, 633, 634, 635, 636 A single mutational event in the more sensitive primary target can result in an increase in the MIC of the drug.632, 633, 634, 635, 636 If the altered primary-target enzyme remains more sensitive to the quinolone than does the secondary target, the altered primary target will continue to determine the MIC.632, 633, 634, 635, 636 If the altered primary target becomes less sensitive than the secondary target, the MIC will be determined by the inhibitory activity of the quinolone against the secondary target.632, 633, 634, 635, 636 If both DNA gyrase and topoisomerase IV are equally sensitive to the quinolone, a single mutational alteration in either enzyme will not result in an increase in MIC.632, 633, 634, 635, 636
Resistance to ofloxacin in gram-negative organisms (e.g., Enterobacteriaceae, Ps. aeruginosa ) appears to result from mutations that alter the A subunits.113, 117, 121, 123, 126, 127, 132, 136, 137, 420, 444, 445, 497, 632, 633, 634, 635, 636 Resistance in some gram-negative organisms also may be related to alterations in outer-membrane porin proteins and/or other factors that affect permeability of the organism to the drug.113, 115, 117, 123, 126, 127, 132, 136, 420, 445 The mechanism of resistance in gram-positive bacteria has not been studied as extensively, but results of in vitro studies using S. aureus indicate that resistance to fluoroquinolones in some gram-positive bacteria also results from alterations in one of the subunits of topoisomerase IV and DNA gyrase.123, 129, 134, 520, 566, 632, 633, 634, 635, 636 In addition, resistance in some S. aureus appears to be related to the nor A gene located in the D fragment of the organism's chromosome.197 The nor A gene apparently encodes a hydrophobic membrane protein that results in decreased membrane permeability by hydrophilic quinolones such as ofloxacin.123, 129 A third possible mechanism of resistance in S. aureus also has been suggested and appears to be related to mutations(s) in the flq locus of the A fragment of the chromosome; further study is needed to determine whether mutation(s) in this fragment alters a second topoisomerase or another gene controlling supercoiling or whether it affects permeability.123 Although further study is needed, it appears that S. aureus can have either low-level or high-level resistance to fluoroquinolones that results from one or more alterations in topoisomerase IV and DNA gyrase.133, 134, 520 Current evidence suggests that resistance to ofloxacin or other fluoroquinolones in either gram-negative or -positive bacteria is chromosomally rather than plasmid mediated.3, 121, 126, 127, 132, 417, 420, 445, 464, 520, 542, 632
Cross-resistance can occurs between ofloxacin and other fluoroquinolones.118, 414, 418, 420, 421, 441
Cross-resistance generally does not occur between ofloxacin and other anti-infectives,3, 126, 421, 445, 464 including aminoglycosides, β-lactam antibiotics, sulfonamides (including co-trimoxazole), macrolides, and tetracyclines.421 However, rare strains of Enterobacteriaceae and Ps. aeruginosa resistant to fluoroquinolones also are resistant to aminoglycosides, β-lactam antibiotics, chloramphenicol, trimethoprim, and/or tetracyclines.112, 126, 445 Resistance in these organisms appears to be related to alterations in outer-membrane porin proteins.112, 445 Rarely, strains of E. coli or Ps. aeruginosa that were originally susceptible to fluoroquinolones and resistant to aminoglycosides and β-lactam antibiotics developed resistance to fluoroquinolones and reverted to being susceptible to aminoglycosides and β-lactams.112, 117 It has been suggested that this may occur because exposure of some plasmid-containing bacteria to ofloxacin and other fluoroquinolones can result in loss of plasmid DNA in these organisms.112, 417, 420 (See Mechanism of Action.) In addition, fluoroquinolone-resistant ORSA frequently also are resistant to aminoglycosides.506
In studies described in the Pharmacokinetics section, body fluid and tissue concentrations of ofloxacin were measured with either a high-pressure liquid chromatographic (HPLC) assay154, 156, 169, 175, 178, 187, 192, 194, 208, 221, 224, 476 or a microbiologic assay.77, 154, 156, 176, 178, 183, 186, 195, 196, 201, 208, 209, 476 HPLC assays presumably would be more specific for ofloxacin than microbiologic assays since the latter method measures the antibacterial activity of the parent drug as well as its microbiologically active metabolite(s).221, 224 However, controlled studies comparing results obtained using HPLC and microbiologic assays indicate that these methods provide essentially equivalent results for serum, urine, and CSF ofloxacin concentrations and pharmacokinetic parameters determined using these concentrations.154, 156, 178, 208 This apparently occurs because ofloxacin is not extensively metabolized and only low concentrations of active ofloxacin metabolite(s) are attained in serum or urine.154, 156, 178
The pharmacokinetics of ofloxacin after oral administration are best described by a 2-compartment open model.154, 156 There is some evidence that disposition of the commercially available racemic mixture of ofloxacin (see Chemistry and Stability: Chemistry) is stereoselective principally as a result of differences in renal excretion of the enantiomers; however, such differences appear to be small.535
Ofloxacin is rapidly and almost completely absorbed from the GI tract following oral administration.1, 154, 156, 175, 183, 188, 194, 464 The drug does not undergo appreciable first-pass metabolism.175
Although presence of food in the GI tract can decrease the rate and/or extent of absorption of ofloxacin to some extent,1, 156, 176, 189, 420, 464, 649, 650, 651 this effect is not usually considered clinically important.1, 156, 189, 464, 649 In an open, randomized, cross-over study in healthy adult men receiving a single 300-mg oral dose of ofloxacin with or without a standard breakfast, maximum serum concentrations and area under the concentration-time curves (AUCs) were slightly lower when the dose was given with food, but the time to peak serum concentrations, terminal elimination half-life, and urinary concentrations of the drug did not differ substantially between fasted and nonfasting conditions.156 When a 400-mg ofloxacin tablet was crushed and mixed with 120 mL of enteral premixed liquid (Ensure) and swallowed, the AUC was 10% lower and peak plasma concentrations were 36% lower compared with results attained when the tablet was crushed and mixed with water before swallowing.651 Milk and yogurt do not appear to affect GI absorption of ofloxacin.649, 650
Antacids may decrease the oral bioavailability of ofloxacin.1, 404, 405, 414, 420, 427 (See Drug Interactions: Antacids.)
The oral bioavailability of ofloxacin is 85-100% in healthy, fasting adults,1, 169, 175, 188, 189, 210 and peak serum concentrations of the drug generally are attained within 0.5-2 hours.1, 154, 169, 175, 176, 178, 185, 194, 420, 464 In patients with normal renal and hepatic function, peak serum concentrations and AUCs increase in proportion to the dose over the oral dosage range of 100-600 mg1, 154, 175, 176, 420 and generally are unaffected by age.1
Following oral administration of a single 100-, 200-, 300-, or 400-mg dose of ofloxacin in healthy, fasting adults, peak serum concentrations average 1-1.3, 1.5-2.7, 2.4-4.6, or 2.9-5.6 mcg/mL, respectively.1, 154, 175, 176, 178, 185, 194, 420, 464 Some accumulation occurs following multiple doses.185, 188, 464 Steady-state serum concentrations of ofloxacin are achieved after 4 doses of the drug and are approximately 40% higher than concentrations achieved following single oral doses.1
Pharmacokinetic parameters in geriatric patients receiving ofloxacin generally are similar to those in younger adults.1 Although results of pharmacokinetic studies in geriatric individuals 65-81 years of age indicate that the rate of absorption, volume of distribution, and route of excretion in geriatric individuals are similar to those in younger adults,1 peak serum concentrations are slightly higher (9-21% higher) and half-life more prolonged in geriatric patients than in younger adults.1, 187, 189, 420, 464 There also is evidence that peak plasma concentration are higher in geriatric women than geriatric men (114% higher following single doses or 54% higher following multiple doses).1
Following oral administration of usual dosage of ofloxacin in patients with cystic fibrosis, peak serum concentrations and AUCs are similar to those reported in healthy adults.189
Ofloxacin is widely distributed into body tissues and fluids following oral administration.1, 181, 183, 189 In healthy adults, the apparent volume of distribution of ofloxacin averages 1-2.5 L/kg.169, 175, 189, 192, 194, 220, 223, 225, 464 Impaired renal function does not appear to affect the volume of distribution of ofloxacin;220, 223, 226 the apparent volume of distribution of the drug averages 1.1-2 L/kg in patients with impaired renal function, including those with severe renal failure undergoing hemodialysis.220, 223, 225, 431
Ofloxacin is distributed into bone,183, 214, 432 cartilage,432 bile,77, 160, 183 skin,1 sputum,1, 183, 189, 195, 214, 430 bronchial secretions,189, 196, 206, 214, 230 pleural effusions,534 tonsils,203 saliva,185, 186, 192 gingival mucosa,186 nasal secretions,183 aqueous humor,159, 214 tears,183 sweat,183 lung,1, 183, 189, 205, 219, 228, 430 blister fluid,1, 183, 189, 192, 226 pancreatic fluid,160, 201 ascitic fluid,168 peritoneal fluid,225, 458 gynecologic tissue,183, 189 vaginal fluid,200 cervix,1 ovary,1 semen,453 prostatic fluid,1, 181, 183, 198, 202, 214 and prostatic tissue.1, 181, 183, 198, 202, 214 For most of these tissues and fluids, ofloxacin concentrations are approximately 0.5-1.7 times concurrent serum concentrations.1, 183, 185, 186, 189, 195, 196, 198, 201, 202, 204, 206, 534 Ofloxacin is concentrated within neutrophils, achieving concentrations in these cells that may be up to 8 times greater than extracellular concentrations.214, 430
In cholecystectomy patients who received oral ofloxacin in a dosage of 200 mg every 12 hours, concentrations of the drug in samples obtained during surgery (6 hours after the 7th dose) ranged from 1.7-9.9 mcg/g in gallbladder wall, 2.1-79.2 mcg/mL in gallbladder bile, and 3.2-19.6 mcg/mL in common duct bile; concomitant serum concentrations ranged from 1-4.2 mcg/mL.77
Following a single 400-mg oral dose of ofloxacin in geriatric men 65-81 years of age, prostatic fluid concentrations ranged from 2.5-5.6 mcg/mL and prostatic adenoma tissue concentrations ranged from 2.4-5.6 mcg/g.198
Ofloxacin is distributed into CSF following oral administration.189, 199, 203, 208, 214, 475, 476 Peak concentrations of ofloxacin in CSF generally are attained within 2-6 hours and exhibit considerable interindividual variation, depending in part on the degree of meningeal inflammation.207, 208, 475, 476 Peak CSF concentrations may be 28-87% of concurrent serum concentrations.189, 207, 214, 464, 475, 476 In adults with meningitis, a single 300-mg oral dose of ofloxacin resulted in CSF concentrations ranging from 0.1-2.8 or 0.1-2.2 mcg/mL in samples obtained 3 or 6 hours, respectively, after the dose.203
Ofloxacin is 20-32% bound to serum proteins.1, 169, 175, 210, 420
Ofloxacin crosses the placenta and is distributed into cord blood and amniotic fluid.209, 420 The drug is distributed into milk following oral administration.209, 213, 420 In one study in lactating women who received 400-mg oral doses of ofloxacin every 12 hours, drug concentrations averaged 0.29-2.4 mcg/mL in milk and 0.26-2.5 mcg/mL in serum 2-12 hours after a dose; the drug still was detectable in milk 24 hours after a dose.209
In healthy adults with normal renal function, the elimination half-life of ofloxacin in the distribution phase (t½α) averages 0.5-0.6 hours and the elimination half-life in the terminal phase (t½β) averages 4-8 hours.154, 169, 175, 176, 178, 185, 194, 420, 464, 535 In healthy geriatric adults 64-86 years of age with renal function normal for their age, half-life of the drug averages 6.4-8.5 hours.1, 187 The slower elimination of ofloxacin in geriatric individuals presumably is due to reduced renal function and clearance observed in geriatric individuals.1
In adults with impaired renal function, serum concentrations of ofloxacin are higher and the half-life prolonged.1, 174, 181, 182, 189, 220, 221, 222, 223, 224, 225, 226, 227, 420, 431, 458, 464 In adults with creatinine clearances of 10-50 mL/minute, half-life of the drug averages 16.4 hours (range: 11-33.5 hours); in adults with creatinine clearances less than 10 mL/minute, half-life averages 21.7 hours (range: 16.9-28.4 hours).190 In patients with end-stage renal failure, half-life of the drug may range from 25-48 hours.227 Further study is needed to determine whether hepatic impairment effects the pharmacokinetics of ofloxacin.464 In one study in cirrhotic adults with ascites and creatinine clearances of 47-123 mL/minute who received a single 200-mg oral dose of ofloxacin, peak serum concentrations of the drug averaged 3.6 mcg/mL and half-life averaged 11.6 hours; however, these alterations in pharmacokinetics appeared to result from renal (tubular) rather than hepatic effects.168
Less than 10% of a single dose of ofloxacin is metabolized;182, 188, 191 approximately 3-6% of the dose is metabolized to desmethyl ofloxacin and 1-5% is metabolized to ofloxacin N -oxide.169, 175, 182, 190, 191 Desmethyl ofloxacin is microbiologically active, but is less active against susceptible organisms than is ofloxacin; ofloxacin N -oxide has only minimal antibacterial activity.221 Ofloxacin and its metabolites are excreted in both urine and feces.1, 175, 185 Following a single 100- to 600-mg oral dose of ofloxacin, 65-90% of the dose is excreted unchanged in urine within 48 hours;1, 154, 169, 175, 178, 210 less than 5% of the dose is excreted in urine as metabolites.1, 175, 210 Approximately 4-8% of the dose is excreted in feces.1, 169 Following oral administration of a single 200-mg oral dose of ofloxacin, urine concentrations average 220 mcg/mL in urine collected over 0-6 hours after the dose; concentrations in urine collected over 12-24 hours after the dose average 34 mcg/mL.1 In healthy adults receiving 200-mg oral doses of ofloxacin every 12 hours, fecal concentrations of the drug have been reported to average 38-44 mcg/g (range: 30-65 mcg/g).345, 346, 348 However, other limited data suggest that this dosage produces fecal concentrations of approximately 300 mcg/g.538, 544
Renal clearance of ofloxacin averages 133-200 mL/minute in adults with normal renal function.169, 420
Small amounts of ofloxacin and desmethyl ofloxacin are removed by hemodialysis.1, 189, 190, 222, 223, 224, 225, 227, 431 The amount of drug removed during hemodialysis depends on several factors (e.g., type of coil used, dialysis flow rate).222, 224 In patients with end-stage renal disease undergoing hemodialysis, the serum half-life of ofloxacin averages 8-12 hours during hemodialysis and 13-48 hours between dialysis sessions.222, 223, 227, 431 Approximately 10-21% of a single 100- or 200-mg oral dose of ofloxacin is removed by hemodialysis,182, 189, 190, 222, 431 and approximately 10% of a single 200-mg oral dose is removed by peritoneal dialysis.189, 190 In a study in patients with end-stage renal failure who were maintained on continuous ambulatory peritoneal dialysis (CAPD), less than 2% of a 400-mg oral dose of ofloxacin was removed by the procedure.458
Ofloxacin is a fluoroquinolone anti-infective agent.2, 3, 5, 420, 442, 464, 634, 636 Like all other commercially available fluoroquinolones, ofloxacin contains a fluorine at the C-6 position of the quinolone nucleus.3, 5, 181, 417, 420, 441, 442 Like some other fluoroquinolones (ciprofloxacin, levofloxacin), ofloxacin contains a piperazinyl group at position 7 of the quinolone nucleus.3, 5, 173, 181, 417, 420, 441, 442 The piperazinyl group in ofloxacin results in antipseudomonal activity.5, 417, 441 The piperazinyl group contained in ofloxacin is methylated, unlike the piperazinyl group contained in ciprofloxacin, and this may contribute to the greater oral bioavailability of ofloxacin compared with that of these other fluoroquinolones.5 Ofloxacin also contains an oxazine ring linking the nitrogen at position 1 and the carbon at position 8 of the quinolone nucleus.3, 182, 420, 464 This fused ring results in increased activity against gram-positive and anaerobic bacteria and also contributes to ofloxacin's low degree of in vivo metabolism.2, 5, 189, 191 The methyl group at the C-3 position in the oxazine ring results in the formation of isoenantiomers; ofloxacin occurs as a racemic mixture of the two isomers.158, 420, 441, 535 The S -(-)isomer is 8-128 times as active against susceptible gram-positive and gram-negative organisms as the R -(+)isomer and approximately twice as active as racemic ofloxacin.5, 28, 138, 144, 158
Ofloxacin occurs as an off-white to pale yellow crystalline powder.1 At room temperature, ofloxacin is soluble in aqueous solutions with pH 2-5, sparingly to slightly soluble (4 mg/mL) in aqueous solutions with pH 7, and freely soluble in aqueous solutions with pH greater than 9.1 The pKas of the drug are 5.74 and 7.9.541
Ofloxacin tablets should be stored at 20-25°C in tight, light-resistant containers.1
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 | Tablets, film-coated | 200 mg* | Ofloxacin Tablets | |
300 mg* | Ofloxacin Tablets | |||
400 mg* | Ofloxacin Tablets |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
1. Larken Laboratories Inc. Ofloxacin tablets prescribing information. Canton, MS; 2019 May.
2. Hooper DC, Wolfson JS. The fluoroquinolones: pharmacology, clinical uses, and toxicities in humans. Antimicrob Agents Chemother . 1985; 28:716-21. [PubMed 2936302][PubMedCentral]
3. Wolfson JS, Hooper DC. The fluoroquinolones: structures, mechanisms of action and resistance, and spectra of activity in vitro. Antimicrob Agents Chemother . 1985; 28:581-6. [PubMed 3000292][PubMedCentral]
4. Felmingham D, Foxall P, O'Hare MD et al. Resistance studies with ofloxacin. J Antimicrob Chemother . 1988; 22(Suppl C):27-34. [PubMed 3182460]
5. Neu HC. Chemical evolution of the fluoroquinolone antimicrobial agents. Am J Med . 1989; 87(Suppl 6C):2-9S. [PubMed 2500854]
6. Sato K, Matsuura Y, Inoue M et al. In vitro and in vivo activity of DL-8280, a new oxine derivative. Antimicrob Agents Chemother . 1982; 22:548-53. [PubMed 6960805][PubMedCentral]
8. Shah PM, Schafer V, Hubener T et al. Bactericidal activity of ofloxacin versus roxithromycin in the treatment of Streptococcus pneumoniae . Drugs . 1987; 34(Suppl 1):9-13. [PubMed 3481332]
9. Van Caekenberghe DL, Pattyn SR. In vitro activity of ciprofloxacin compared with those of other new fluorinated piperazinyl-substituted quinoline derivatives. Antimicrob Agents Chemother . 1984; 25:518-21. [PubMed 6732221][PubMedCentral]
10. Bauernfeind A, Ullmann U. In-vitro activity of enoxacin, ofloxacin, norfloxacin and nalidixic acid. J Antimicrob Chemother . 1984; 14(Suppl C): 33-7. [PubMed 6238931]
12. Kumada T, Neu HC. In-vitro activity of ofloxacin, a quinolone carboxylic acid compared to other quinolones and other antimicrobial agents. J Antimicrob Chemother . 1985; 16:563-74. [PubMed 3865923]
13. Neu HC. The in-vitro activity of EN 272, a quinolone-7-carboxylic acid, in comparison with other quinolones. J Antimicrob Chemother . 1985; 16:43-8. [PubMed 3862659]
14. Chantot JF, Bryskier A. Antibacterial activity of ofloxacin and other 4-quinolone derivatives: in-vitro and in-vivo comparison. J Antimicrob Chemother . 1985; 16:475-84. [PubMed 3864775]
15. Digranes A, Dibb WL, Benonisen E. In vitro activities of ciprofloxacin, ofloxacin, norfloxacin and rosoxacin compared with cinoxacin and trimethoprim. Chemotherapy . 1985; 31:466-71. [PubMed 2934234]
16. Aldridge KE, Schiro DD, Sanders CV. Pefloxacin (RB 1589): an in vitro comparison with other oral antimicrobial agents and imipenem. Curr Ther Res . 1986; 40:1103-13.
17. Barry AL, Thornsberry C, Jones RN. In vitro evaluation of A-56619 and A-56620, two new quinolones. Antimicrob Agents Chemother . 1986; 29:40-3. [PubMed 2942099][PubMedCentral]
18. Smith SM. In vitro comparison of A-56619, A-56620, amifloxacin, ciprofloxacin, enoxacin, norfloxacin, and ofloxacin against methicillin-resistant Staphylococcus aureus . Antimicrob Agents Chemother . 1986; 29:325-6. [PubMed 2940966][PubMedCentral]
19. Hirai K, Aoyama H, Hosaka M et al. In vitro and in vivo antibacterial activity of AM-833, a new quinolone derivative. Antimicrob Agents Chemother . 1986; 29:1059-66. [PubMed 2942103][PubMedCentral]
20. Liebowitz LD, Saunders J, Fehler G et al. In vitro activity of A-56619 (difloxacin), A-56620, and other new quinolone antimicrobial agents against genital pathogens. Antimicrob Agents Chemother . 1986; 30:948-50. [PubMed 3101590][PubMedCentral]
21. Mandell W, Neu HC. In vitro activity of CI-934, a new quinolone, compared with that of other quinolones and other antimicrobial agents. Antimicrob Agents Chemother . 1986; 29:852-7. [PubMed 3729343][PubMedCentral]
22. Chin NX, Brittain DC, Neu HC. In vitro activity of Ro 23-6240, a new fluorinated 4-quinolone. Antimicrob Agents Chemother . 1986; 29:675-80. [PubMed 3085584][PubMedCentral]
23. King A, Phillips I. The comparative in-vitro activity of eight newer quinolones and nalidixic acid. J Antimicrob Chemother . 1986; 28(Suppl D): 1-20.
24. Willems FT. Quinolones in vitro. Pharm Weekbl [Sci] . 1986; 8:26-8. [PubMed 3960690]
25. Hirschhorn L, Neu HC. In vitro activity of two new aryl-fluoroquinolone antimicrobial agents, difloxacin (A-56619) and A-56620 compared to that of other antimicrobial agents. Chemotherapy . 1987; 33:28-39. [PubMed 3549179]
26. Espinoza AM, Chin NX, Novelli A et al. Comparative in vitro activity of a new fluorinated 4-quinolone, T-3262 (A-60969). Antimicrob Agents Chemother . 1988; 32:663-70. [PubMed 3293524][PubMedCentral]
27. Chin NX, Novelli A, Neu HC. In vitro activity of lomefloxacin (SC-47111; NY-198), a difluoroquinolone 3-carboxylic acid, compared with those of other quinolones. Antimicrob Agents Chemother . 1988; 32:656-62. [PubMed 3164987][PubMedCentral]
28. 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.
29. Etienne J, Coulet M, Brun Y et al. Susceptibilities of streptococcal strains associated with infective endocarditis to nine antibiotics. Chemotherapy . 1988; 34:113-6. [PubMed 3391051]
32. Gruneberg RN, Felmingham D, O'Hare MD et al. The comparative in-vitro activity of ofloxacin. J Antimicrob Chemother . 1988; 22(Suppl C):9-19. [PubMed 3182468]
33. Digranes A, Dibb WL. In vitro activities of A-56619 (difloxacin) and A-56620, two aryl fluoroquinolones. Chemotherapy . 1988; 34:298-307. [PubMed 3208547]
34. Fung-Tomc J, Desiderio JV, Tsai YH et al. In vitro and in vivo antibacterial activities of BMY 40062, a new fluoronaphthyridone. Antimicrob Agents Chemother . 1989; 33:906-14. [PubMed 2764541][PubMedCentral]
35. Fuchs PC. In vitro antimicrobial activity and susceptibility testing of ofloxacin. Am J Med . 1989; 87(Suppl 6C):10s-13s. [PubMed 2690614]
37. Osato MS, Jensen HG, Trousdale MD et al. The comparative in vitro activity of ofloxacin and selected ophthalmic antimicrobial agents against ocular bacterial isolates. Am J Ophthalmol . 1989; 108:380-6. [PubMed 2519514]
38. Appelbaum PC, Spangler SK, Crotty E et al. Susceptibility of penicillin-sensitive and -resistant strains of Streptococcus pneumoniae to new antimicrobial agents, including daptomycin, teicoplanin, cefpodoxime and quinolones. J Antimicrob Chemother . 1989; 23:509-16. [PubMed 2545656]
39. Kojima T, Inoue M, Mitsuhashi S. In vitro activity of AT-4140 against quinolone- and methicillin-resistant Staphylococcus aureus . Antimicrob Agents Chemother . 1990; 34:1123-7. [PubMed 2393270][PubMedCentral]
40. Maple PA, Hamilton-Miller JM, Brumfitt W. Differing activities of quinolones against ciprofloxacin-susceptible and ciprofloxacin-resistant, methicillin-resistant Staphylococcus aureus . Antimicrob Agents Chemother . 1991; 35:345-50. [PubMed 1827242][PubMedCentral]
41. Peeters M, Van Dyck E, Piot P. In vitro activities of the spectinomycin analog U-63366 and four quinolone derivatives against Neisseria gonorrhoeae . Antimicrob Agents Chemother . 1984; 26:608-9. [PubMed 6240224][PubMedCentral]
42. Zeiler HJ. Influence of pH and human urine on the antibacterial activity of ciprofloxacin, norfloxacin and ofloxacin. Drugs Exp Clin Res . 1985; 11:335-8. [PubMed 2941261]
44. O'Hare MD, Felmingham D, Ridgway GL et al. The comparative in vitro activity of twelve 4-quinolone antimicrobials against enteric pathogens. Drugs Exp Clin Res . 1985; 11:253-7. [PubMed 2941257]
45. Aznar J, Caballero MC, Loxano MC et al. Activities of new quinoline derivatives against genital pathogens. Antimicrob Agents Chemother . 1985; 27:76-8. [PubMed 3920959][PubMedCentral]
46. Goossens H, De Mol P, Coignau H et al. Comparative in vitro activities of aztreonam, ciprofloxacin, norfloxacin, ofloxacin, HR 810 (a new cephalosporin), RU28965 (a new macrolide), and other agents against enteropathogens. Antimicrob Agents Chemother . 1985; 27:388-92. [PubMed 3158276][PubMedCentral]
48. Goldstein EJ, Citron DM, Vagvolgyi AE et al. Susceptibility of Eikenella corrodens to newer and older quinolones. Antimicrob Agents Chemother . 1986; 30:172-3. [PubMed 3530124][PubMedCentral]
49. Ling J, Kam KM, Lam AW et al. Susceptibilities of Hong Kong isolates of multiply resistant Shigella spp. to 25 antimicrobial agents, including ampicillin plus sulbactam and new 4-quinolones. Antimicrob Agents Chemother . 1988; 32:20-3. [PubMed 3348608][PubMedCentral]
50. Winton MD, Everett ED, Dolan SA. Activities of five new fluoroquinolones against Pseudomonas pseudomallei . Antimicrob Agents Chemother . 1988; 32:928-9. [PubMed 3415212][PubMedCentral]
52. Quentin R, Koubaa N, Cattier B et al. In vitro activities of five new quinolones against 88 genital and neonatal Haemophilus isolates. Antimicrob Agents Chemother . 1988; 32:147-9. [PubMed 3258143][PubMedCentral]
54. Lefevre JC, Tempesta MC, Gaubert E et al. In vitro activity of six quinolone derivatives against Neisseria gonorrhoeae . Chemotherapy . 1988; 34:315-7. [PubMed 2850138]
58. Kuman A, Wofford-McQueen R, Gordon RC. In vitro activity of multiple antimicrobial combinations against Pseudomonas cepacia isolates. Chemotherapy . 1989; 35:246-53. [PubMed 2766866]
59. Laurans G, Suermondt G, Denamur E et al. In vitro studies of quinolones against Branhamella catarrhalis . Rev Infect Dis . 1989; 11(Suppl 5):s927.
60. Dangor Y, Ballard RC, Miller SD et al. Antimicrobial susceptibility of Haemophilus ducreyi . Antimicrob Agents Chemother . 1990; 34:1303-7. [PubMed 2201248][PubMedCentral]
61. Van der Auwera P, Scorneaux B. In vitro susceptibility of Campylobacter jejuni to 27 antimicrobial agents and various combinations of β-lactams with clavulanic acid or sulbactam. Antimicrob Agents Chemother . 1985; 28:37-40. [PubMed 2994557][PubMedCentral]
62. Fernandex-Roblas R, Prieto S, Santamaria M et al. Activity of nine antimicrobial agents against Corynebacterium group D2 strains isolated from clinical specimens and skin. Antimicrob Agents Chemother . 1987; 31:821-2. [PubMed 3606082][PubMedCentral]
63. Gombert ME, Aulicino TM, DuBouchet L et al. Susceptibility of Nocardia asteroides to new quinolones and β-lactams. Antimicrob Agents Chemother . 1987; 31:2013-4. [PubMed 3326528][PubMedCentral]
65. Hagedorn HJ, Kraminer-Hagedorn A, Diekmann U. In vitro activity of quinolones against Bordetella pertussis . Rev Infect Dis . 1989; 11(Suppl 5):s931.
66. Fernandex-Roblas R, Jimenez-Arriero M, Romero M et al. In vitro activity of quinolones and other agents against problematic gram-positive pathogens. Rev Infect Dis . 1989; 11(Suppl 5):S931.
67. Garcia-Rodriguez JA, Garcia Sanchez JE, Trujillano I. Lack of effective bactericidal activity of new quinolones against Brucella spp. Antimicrob Agents Chemother . 1991; 35:756-9. [PubMed 2069383][PubMedCentral]
68. Hoppe JE, Simon CG. In vitro susceptibilities of Bordetella pertussis and Bordetella parapertussis to seven fluoroquinolones. Antimicrob Agents Chemother . 1990; 34:2287-8. [PubMed 2073123][PubMedCentral]
69. Delmee M, Avesani V. Comparative in vitro activity of seven quinolones against clinical isolates of Clostridium difficile . Antimicrob Agents Chemother . 1986; 29:374-5. [PubMed 2940968][PubMedCentral]
70. Traub WH, Karthein J, Spohr M. Susceptibility of Clostridium perfringens type A to 23 antimicrobial drugs. Chemotherapy . 1986; 32:439-45. [PubMed 2875853]
71. Edlund C, Nord CE. Comparative in vitro activities of ciprofloxacin, enoxacin, norfloxacin, ofloxacin and pefloxacin against Bacteroides fragilis and Clostridium difficile . Scand J Infect Dis . 1986; 18:149-51. [PubMed 2939556]
72. Glupczynski Y, Hansen W, Freney J et al. In vitro susceptibility of Alcaligenes denitrificans subsp xylosoxidans to 24 antimicrobial agents. Antimicrob Agents Chemother . 1988; 32:276-8. [PubMed 3163242][PubMedCentral]
73. Kurzynski TA, Boehm DM, Rott-Petri JA et al. Antimicrobial susceptibilities of Bordetella species isolated in a multicenter pertussis surveillance project. Antimicrob Agents Chemother . 1988; 32:137-40. [PubMed 2894817][PubMedCentral]
74. Goldstein EJ, Citron DM. Comparative activities of cefuroxime, amoxicillin-clavulanic acid, ciprofloxacin, enoxacin, and ofloxacin against aerobic and anaerobic bacteria isolated from bite wounds. Antimicrob Agents Chemother . 1988; 32:1143-8. [PubMed 3190202][PubMedCentral]
75. Appelbaum PC, Spangler SK, Tamarree T. Susceptibility of 310 nonfermentative gram-negative bacteria to aztreonam, carumonam, ciprofloxacin, ofloxacin and fleroxacin. Chemotherapy . 1988; 34:40-5. [PubMed 3127127]
76. Raoult D, Yeaman MR, Baca OG. Susceptibility of Coxiella burnetii to pefloxacin and ofloxacin in ovo and in persistently infected L929 cells. Antimicrob Agents Chemother . 1989; 33:621-3. [PubMed 2751278][PubMedCentral]
77. Kazmierczak A, Pechinot A, Duez JM et al. Biliary tract excretion of ofloxacin in man. Drugs . 1987; 34(Suppl 1):39-43. [PubMed 3481327]
78. Yeaman MR, Roman MJ, Baca OG. Antibiotic susceptibilities of two Coxiella burnetii isolates implicated in distinct clinical syndromes. Antimicrob Agents Chemother . 1989; 33:105207.
79. Kropec A, Daschner F. In vitro activity of fleroxacin and 6 other antimicrobials against Acinetobacter anitratus. Chemotherapy . 1989; 35:360-2. [PubMed 2507235]
80. Raoult D, Yeaman M, Baca O. Susceptibility of Rickettsia and Coxiella burnetii to quinolones. Rev Infect Dis . 1989; 11(Suppl 5):s986.
82. Moller BR, Evans R, Kaspersen P et al. Activity of ofloxacin against Chlamydia trachomatis . Drugs . 1987; 34(Suppl 1):181-2. [PubMed 3481321]
83. Bailey JM, Heppleston C, Richmond SJ. Comparison of the in vitro activities of ofloxacin and tetracycline against Chlamydia trachomatis as assessed by indirect immunofluorescence. Antimicrob Agents Chemother . 1984; 26:13-6. [PubMed 6383207][PubMedCentral]
84. Bianchi A, Scieux C, Salmeron CM et al. Rapid determination of MICs of 15 antichlamydial agents by using an enzyme immunoassay (chlamydiazyme). Antimicrob Agents Chemother . 1988; 32:1350-3. [PubMed 3058019][PubMedCentral]
85. Ehret JM, Judson FN. Susceptibility testing of Chlamydia trachomatis : from eggs to monoclonal antibodies. Antimicrob Agents Chemother . 1988; 32:1295-9. [PubMed 3058015][PubMedCentral]
86. Nagayama A, Nakao T, Taen H. In vitro activities of ofloxacin and four other new quinoline-carboxylic acids against Chlamydia trachomatis . Antimicrob Agents Chemother . 1988; 32:1735-7. [PubMed 3150916][PubMedCentral]
87. Kenny GE, Hooton TM, Roberts MC et al. Susceptibilities of genital mycoplasmas to the newer quinolones as determined by the agar dilution method. Antimicrob Agents Chemother . 1989; 33:103-7. [PubMed 2712541][PubMedCentral]
88. Schachter J, Moncada JV. In vitro activity of ofloxacin against Chlamydia trachomatis . Am J Med . 1989; 87(Suppl 6C):14s-16s. [PubMed 2690615]
89. Garcia-Rodriguez JA, Garcia Sanchez JE, Trujillano I et al. In vitro activity of new quinolones against Brucella melitensis . Rev Infect Dis . 1989; 11(Suppl 5):s992-3.
90. Borsum T, Dannevig L, Storvold G et al. Chlamydia trachomatis : in vitro susceptibility of genital and ocular isolates to some quinolones, amoxicillin and azithromycin. Chemotherapy . 1990; 36:407-15. [PubMed 1963393]
91. Osada Y, Ogawa H. Antimycoplasmal activity of ofloxacin (DL-8280). Antimicrob Agents Chemother . 1983; 23:509-11. [PubMed 6573869][PubMedCentral]
92. Ruckdeschel G, Ehret W, Ahl A. Susceptibility of Legionella sppl to quinolone derivatives and related organic acids. Eur J Clin Microbiol . 1984; 3:373. [PubMed 6489330]
93. Tsukamura M. In vitro antituberculosis activity of a new antibacterial substance ofloxacin (DL8280). Am Rev Respir Dis . 1985; 131:348-51. [PubMed 3919625]
94. Tsukamura M, Nakamura E, Yoshii S et al. Therapeutic effect of a new antibacterial substance ofloxacin (DL8280) on pulmonary tuberculosis. Am Rev Respir Dis . 1985; 131:352-6. [PubMed 3856412]
95. Saito H, Tomioka H, Nagashima K. In vitro and in vivo activities of ofloxacin against Mycobacterium leprae infection induced in mice. Int J Leprosy . 1986; 54:560-2.
96. Fenlon CH, Cynamon MH. Comparative in vitro activities of ciprofloxacin and other 4-quinolones against Mycobacterium tuberculosis and Mycobacterium intracellulare . Antimicrob Agents Chemother . 1986; 29:386-8. [PubMed 2940969][PubMedCentral]
97. Saito A, Koga H, Shigeno H et al. The antimicrobial activity of ciprofloxacin against Legionella species and the treatment of experimental Legionella pneumonia in guinea pigs. J Antimicrob Chemother . 1986; 18:251-60. [PubMed 3759736]
98. Young LS, Berlin OG, Inderlied CB. Activity of ciprofloxacin and other fluorinated quinolones against mycobacteria. Am J Med . 1987; 82(Suppl 4A):23-6. [PubMed 3107379]
99. Davies S, Sparham PD, Spencer RC. Comparative in-vitro activity of five fluoroquinolones against mycobacteria. J Antimicrob Chemother . 1987; 19:605-9. [PubMed 3112094]
100. Heifets LB. Bacteriostatic and bactericidal activity of ciprofloxacin and ofloxacin against Mycobacterium tuberculosis and Mycobacterium avium complex. Tubercle . 1987; 68:267-76. [PubMed 3138801]
101. Divo AA, Sartorelli AC, Patton CL et al. Activity of fluoroquinolone antibiotics against Plasmodium falciparum in vitro. Antimicrob Agents Chemother . 1988; 32:1182-6. [PubMed 2847647][PubMedCentral]
102. Midgley JM, Keter DW, Phillipson JD et al. Quinolones and multiresistant Plasmodium falciparum . Lancet . 1988; 2:281. [PubMed 2899268]
103. Crowle AJ, Elkins N, May MH. Effectiveness of ofloxacin against Mycobacterium tuberculosis and Mycobacterium avium , and rifampin against M. tuberculosis in cultured human macrophages. Am Rev Respir Dis . 1988; 137:1141-6. [PubMed 3143278]
104. Leysen DC, Haemers A, Pattyn SR. Mycobacteria and the new quinolones. Antimicrob Agents Chemother . 1989; 33:1-5. [PubMed 2540705][PubMedCentral]
105. Gorzynski EA, Gutman SI, Allen W. Comparative antimycobacterial activities of difloxacin, temafloxacin, enoxacin, pefloxacin, reference fluoroquinolones, and a new macrolide, clarithromycin. Antimicrob Agents Chemother . 1989; 33:591-2. [PubMed 2524998][PubMedCentral]
106. Shalit I, Berger SA, Gorea A et al. Widespread quinolone resistance among methicillin-resistant Staphylococcus aureus isolates in a general hospital. Antimicrob Agents Chemother . 1989; 33:593-4. [PubMed 2729953][PubMedCentral]
107. Cooper JF, Lichtenstein MJ, Graham BS et al. Mycobacterium chelonae : a cause of nodular skin lesions with a proclivity for renal transplant recipients. Am J Med . 1989; 86:173-7. [PubMed 2643868]
108. Chen CH, Shih JF, Lindholm-Levy PJ et al. Minimal inhibitory concentrations of rifabutin, ciprofloxacin, and ofloxacin against Mycobacterium tuberculosis isolated before treatment of patients in Taiwan. Am Rev Respir Dis . 1989; 140:987-9. [PubMed 2552883]
109. Franzblau SG, White KE. Comparative in vitro activities of 20 fluoroquinolones against Mycobacterium leprae . Antimicrob Agents Chemother . 1990; 34:229-31. [PubMed 2183714][PubMedCentral]
111. Piddock LJ, Wise R. The selection and frequency of streptococci with decreased susceptibility to ofloxacin compared with other quinolones. J Antimicrob Chemother . 1988; 22(Suppl C):45-51. [PubMed 3182461]
112. Lewin CS, Smith JT, Hamilton-Miller JM et al. Gain of antibiotic sensitivity accompanying emergence of clinical ciprofloxacin resistance. Lancet . 1988; 1:1462-3. [PubMed 2898615]
113. Kato N, Miyauchi M, Muto Y et al. Emergence of fluoroquinolone resistance in Bacteroides fragilis accompanied by resistance to β-lactam antibiotics. Antimicrob Agents Chemother . 1988; 32:1437-8. [PubMed 2848446][PubMedCentral]
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]
115. Taylor DE, Courvalin P. Mechanisms of antibiotic resistance in Campylobacter species. Antimicrob Agents Chemother . 1988; 32:1107-12. [PubMed 3056250][PubMedCentral]
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. Hirai K, Suzue S, Irikura T et al. Mutations producing resistance to norfloxacin in Pseudomonas aeruginosa . Antimicrob Agents Chemother . 1987; 31:582-6. [PubMed 3111356][PubMedCentral]
118. Cullmann W, Stieglitz M, Baars B et al. Comparative evaluation of recently developed quinolone compounds—with a note on the frequency of resistant mutants. Chemotherapy . 1985; 31:19-28. [PubMed 3156025]
119. Smith JT. Mutational resistance to 4-quinolone antibacterial agents. Eur J Clin Microbiol . 1984; 3:347-50. [PubMed 6237904]
120. Neu HC. Current mechanisms of resistance to antimicrobial agents in microorganisms causing infection in the patient at risk for infection. Am J Med . 1984; :11-27.
121. Crumplin GC, Odell M. Development of resistance to ofloxacin. Drugs . 1987; 34(Suppl 1):1-8. [PubMed 3325254]
123. Ubukata K, Itoh-Yamashita N, Konno M. Cloning and expression of the norA gene for fluoroquinolone resistance in Staphylococcus aureus . Antimicrob Agents Chemother . 1989; 33:1535-9. [PubMed 2817852][PubMedCentral]
124. Argenziano G. Ofloxacin, a new quinolone derivative, in the treatment of Chlamydia trachomatis and Staphylococcus aureus urethritis. Curr Ther Res . 1989; 46:993-1001.
125. Wiedemann B, Zuhlsdorf MT. Brief report: resistance development to fluoroquinolones in Europe. Am J Med . 1989; 87(Suppl 5A):9-11S.
126. Hooper DC, Wolfson JS. Bacterial resistance to the quinolone antimicrobial agents. Am J Med . 1989; 87(Suppl 6C):17-23S.
127. Wolfson JS, Hooper DC. Bacterial resistance to quinolones: mechanisms and clinical importance. Rev Infect Dis . 1989; 11(Suppl 5):s960-66.
128. Abb J. Resistance to fluoroquinolones in Campylobacter pylori . Rev Infect Dis . 1989; 11(Suppl 5):s1379.
129. Yoshida H, Bogaki M, Nakamura S et al. Nucleotide sequence and characterization of the Staphylococcus aureus norA gene, which confers resistance to quinolones. J Bacteriol . 1990; 172:6942-9. [PubMed 2174864][PubMedCentral]
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]
131. Tack KJ, Callery SV, Smith JA et al. Ofloxacin in the treatment of sexually transmitted diseases. Rev Infect Dis . 1989; 11(Suppl 5):S1282-3.
132. Kresken M, Wiedemann B. Development of resistance to nalidixic acid and the fluoroquinolones after the introduction of norfloxacin and ofloxacin. Antimicrob Agents Chemother . 1988; 32:1285-8. [PubMed 3142353][PubMedCentral]
133. Trucksis M, Hooper DC, Wolfson JS. Emerging resistance to fluoroquinolones in staphylococci: an alert. Ann Intern Med . 1991; 114:424-6. [PubMed 1992885]
134. Kaatz GW, Seo SM, Ruble CA. Mechanisms of fluoroquinolone resistance in Staphylococcus aureus . J Infect Dis . 1991; 163:1080-6. [PubMed 1850442]
135. Rutanarugsa A, Vorachit M, Polnikorn N et al. Drug resistance of Haemophilus ducreyi . Southeast Asian J Trop Med Public Health . 1990; 21:185-93. [PubMed 2237585]
136. Dechene M, Leying H, Cullmann W. Role of the outer membrane for quinolone resistance in enterobacteria. Chemotherapy . 1990; 36:13-23. [PubMed 2106416]
137. Masecar BL, Robillard NJ. Spontaneous quinolone resistance in Serratia marcescens due to a mutation in gyrA. Antimicrob Agents Chemother . 1991; 35:898-902. [PubMed 1649573][PubMedCentral]
138. Hoshino K, Sato K, Akahane K et al. Significance of the methyl group on the oxazine ring of ofloxacin derivatives in the inhibition of bacterial and mammalian type II topoisomerases. Antimicrob Agents Chemother . 1991; 35:309-12. [PubMed 1850968][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]
142. Gonzales-Perdomo M, Lisboa de Castro S, Mierelles MN et al. Typanosoma cruzi proliferation and differentiation are blocked by topoisomerase II inhibitors. Antimicrob Agents Chemother . 1990; 34:1707-14. [PubMed 2178335][PubMedCentral]
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]
144. Pascual A, Garcia I, Perea EJ. Uptake and intracellular activity of an optically active ofloxacin isomer in human neutrophils and tissue culture cells. Antimicrob Agents Chemother . 1990; 34:277-80. [PubMed 2327777][PubMedCentral]
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]
147. Sato K, Hoshino K, Une T et al. Inhibitory effects of ofloxacin on DNA gyrase of Escherichia coli and topoisomerase II of bovine calf thymus. Rev Infect Dis . 1989; 11(Suppl 5):S915-6.
148. Nishino T, Tanaka M, Ohtsuki M. Effect of ofloxacin on the ultrastructure of Escherichia coli and Pseudomonas aeruginosa in the logarithmic and stationary phases of growth. Rev Infect Dis . 1989; 11(Suppl 5):S914-5.
149. Hooper DC, Wolfson JS. Mode of action of the quinolone antimicrobial agents: review of recent information. Rev Infect Dis . 1989; 11(Suppl 5):S902-20.
152. Lewin CS, Smith JT. Bactericidal mechanisms of ofloxacin. J Antimicrob Chemother . 1988; 22(Suppl C):1-8. [PubMed 3053574]
153. Fernandes PB. Mode of action, and in vitro and in vivo activities of the fluoroquinolones. J Clin Pharmacol . 1988; 28:156-68. [PubMed 3283179]
154. Verho M, Malerczyk V, Dagrosa E et al. Dose linearity and other pharmacokinetics of ofloxacin: a new, broad-spectrum antimicrobial agent. Pharmatherapeutica . 1985; 4:376-82. [PubMed 3866256]
156. Verho M, Malerczyk V, Dagrosa E et al. The effect of food on the pharmacokinetics of ofloxacin. Curr Med Res Opin . 1986; 10:166-171. [PubMed 3460737]
158. Imamura M, Shibamura S, Hayakawa I et al. Inhibition of DNA gyrase by optically active ofloxacin. Antimicrob Agents Chemother . 1987; 31:325-7. [PubMed 3032098][PubMedCentral]
159. Bron A, Talon D, Estavoyer JM et al. Ocular distribution of the new quinolones. Rev Infect Dis . 1989; 11(Suppl 5):S1206-7.
160. Pederzoli P, Falconi M, Bassi C et al. Ofloxacin penetration into bile and pancreatic juice. J Antimicrob Chemother . 1989; 23:805-7. [PubMed 2759927]
161. Smith JT. The mode of action of 4-quinolones and possible mechanisms of resistance. J Antimicrob Chemother . 1986; 18(Suppl D):21-9. [PubMed 3542946]
162. Zweerink MM, Edison A. Inhibition of Micrococcus luteus DNA gyrase by norfloxacin and 10 other quinolone carboxylic acids. Antimicrob Agents Chemother . 1986; 29:598-601. [PubMed 3010848][PubMedCentral]
163. Smith JT. Wirkmechanismus der chinolone. Infection . 1986; 14(Suppl 1):S3-15.
164. Hussy P, Maass G, Tummler B et al. Effect of 4-quinolones and novobiocin on calf thymus DNA polymerase α primase complex, topoisomerases I and II, and growth of mammalian lymphoblasts. Antimicrob Agents Chemother . 1986; 29:1073-8. [PubMed 3015015] [PubMedCentral]
168. Silvain C, Bouquet S, Breux JP et al. Oral pharmacokinetics and ascitic fluid penetration of ofloxacin in cirrhosis. Eur J Clin Pharmacol . 1989; 37:261-5. [PubMed 2612541]
169. Lode H, Hoffken G, Prinzing C et al. Comparative pharmacokinetics of new quinolones. Drugs . 1987; 32(Suppl 1):21-5.
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]
173. Verbist L. Quinolones: pharmacology. Pharm Weekbl [Sci] . 1986; 8:22-5. [PubMed 3008075]
174. Vree TV, Wijnands WJ, Guelen PJ et al. Pharmacokinetics: metabolism and renal excretion of quinolones in man. Pharm Weekbl [Sci] . 1986; 8:29-34. [PubMed 3960691]
175. Lode H, Hoffken G, Olschewski P et al. Pharmacokinetics of ofloxacin after parenteral and oral administration. Antimicrob Agents Chemother . 1987; 31:1338-42. [PubMed 3479046][PubMedCentral]
176. Leroy A, Borsa F, Humbert G et al. The pharmacokinetics of ofloxacin in healthy adult male volunteers. Eur J Clin Pharmacol . 1987; 31:629-30. [PubMed 3470180]
177. Jensen T, Pedersen SS, Nielsen CH et al. The efficacy and safety of ciprofloxacin and ofloxacin in chronic Pseudomonas aeruginosa infection in cystic fibrosis. J Antimicrob Chemother . 1987; 20:585-94. [PubMed 3479420]
178. Malerczyk V, Verho M, Korn A et al. Relative bioavailability of ofloxacin tablets in comparison to oral solution. Curr Med Res Opin . 1987; 10:514-9. [PubMed 3479296]
179. Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing: Twenty-first informational supplement. CLSI document M100-S21. Wayne, PA; 2011.
181. Nix DE, Schentag JJ. The quinolones: an overview and comparative appraisal of their pharmacokinetics and pharmacodynamics. J Clin Pharmacol . 1988; 28:169-78. [PubMed 3283180]
182. Neuman M. Clinical pharmacokinetics of the newer antibacterial 4-quinolones. Clin Pharmacokinet . 1988; 14:96-121. [PubMed 3282749]
183. Wise R, Lockley MR. The pharmacokinetics of ofloxacin and a review of its tissue penetration. J Antimicrob Chemother . 1988; 22(Suppl C):59-64. [PubMed 3182463]
185. Leigh DA, Walsh B, Harris K et al. Pharmacokinetics of ofloxacin and the effect on the faecal flora of healthy volunteers. J Antimicrob Chemother . 1988; 22(Suppl C):115-25. [PubMed 3182453]
186. Bedeschi G, Beltrame M, Baldin C et al. Pharmacokinetics of a new oral antibacterial agent, ofloxacin, in dentistry and oral surgery. Int J Clin Pharmacol Ther Toxicol . 1988; 26:162-4. [PubMed 3165967]
187. Rademaker CM, Jones RW, Notarianni LJ et al. Pharmacokinetics of a single dose of ofloxacin in healthy elderly subjects using noncompartmental and compartmental models. Pharm Weekbl [Sci] . 1989; 11:224-8. [PubMed 2616254]
188. Lode H, Hoffken G, Borner K et al. Unique aspects of quinolone pharmacokinetics. Clin Pharmacokinet . 1989; 16(Suppl 1):1-4. [PubMed 2653691]
189. Wolfson JS, Hooper DC. Comparative pharmacokinetics of ofloxacin and ciprofloxacin. Am J Med . 1989; 87(Suppl 6C):31S-36S. [PubMed 2690617]
190. Flor S. Pharmacokinetics of ofloxacin. Am J Med . 1989; 87(Suppl 6C):24S-30S. [PubMed 2603892]
191. Outman WR, Nightingale CH. Metabolism and the fluoroquinolones. Am J Med . 1989; 87(Suppl 6C):37S-42S. [PubMed 2690618]
192. Warlich R, Korting HC, Schafer Korting M et al. Multiple-dose pharmacokinetics of ofloxacin in serum, saliva, and skin blister fluid of healthy volunteers. Antimicrob Agents Chemother . 1990; 34:78-81. [PubMed 2327762][PubMedCentral]
193. Mazzulli T, Simor AE, Jaeger R et al. Comparative in vitro activities of several new fluoroquinolones and β-lactam antimicrobial agents against community isolates of Streptococcus pneumoniae . Antimicrob Agents Chemother . 1990; 34:467-9. [PubMed 2334158][PubMedCentral]
194. Yuk JH, Nightingale CH, Quintiliani R et al. Bioavailability and pharmacokinetics of ofloxacin in healthy volunteers. Antimicrob Agents Chemother . 1991; 35:384-6. [PubMed 2024973][PubMedCentral]
195. Davies BI, Maesen FP, Geraedts WH et al. Penetration of ofloxacin from blood to sputum. Drugs . 1987; 34(Suppl 1):26-32. [PubMed 3481324]
196. Symonds J, Bone M, Turner A et al. Penetration of ofloxacin into bronchial secretions. Drugs . 1987; 34(Suppl 1):33-6. [PubMed 3481325]
197. Anon. Drugs for bacterial infections. Treat Guidel Med Lett . 2010; 8:43-52. [PubMed 20489679]
198. Naber KG, Adam D, Kees F. In vitro activity and concentrations in serum, urine, prostatic secretion and adenoma tissue of ofloxacin in urological patients. Drugs . 1987; 34(Suppl 1):44-50. [PubMed 3481328]
199. Anders CU, Hofeler H, Schmidt CG. Concentration of the quinolone ofloxacin in the cerebrospinal fluid. Am J Med . 1987; 83:1006. [PubMed 3479021]
200. Tartaglione TA, Johnson CR, Brust P et al. Pharmacodynamic evaluation of ofloxacin and trimethoprim-sulfamethoxazole in vaginal fluid of women treated for acute cystitis. Antimicrob Agents Chemother . 1988; 32:1640-3. [PubMed 3075434][PubMedCentral]
201. Brattstrom C, Malmborg AS, Tyden G. Penetration of ciprofloxacin and ofloxacin into human allograft pancreatic juice. J Antimicrob Chemother . 1988; 22:213-9. [PubMed 3053553]
202. Flor S, Madsen PO, Tack K et al. Prostatic tissue and fluid levels of ofloxacin following oral administration of 300 mg tablets. Clin Pharmacol Ther . 1988; 43:123. [PubMed 3338233]
203. Drancourt M, Gallais H, Raoult D et al. Ofloxacin penetration into cerobrospinal fluid. J Antimicrob Chemother . 1988; 22:263-5. [PubMed 3182421]
204. Van Landuyt HW, Gordts B, D'Hondt G. Pharmacokinetic evaluation of ofloxacin in serum and tonsils. J Antimicrob Chemother . 1988; 22(Suppl C):81-3.
205. Wijnands WJ, Vree TB, Baars AM et al. The penetration of ofloxacin into lung tissue. J Antimicrob Chemother . 1988; 22(Suppl C):85-9. [PubMed 3182467]
206. Symonds J, Javaid A, Bone M et al. The penetration of ofloxacin into bronchial secretions. J Antimicrob Chemother . 1988; 22(Suppl C):91-5. [PubMed 3182469]
207. Pioget JC, Wolff M, Singlas E et al. Diffusion of ofloxacin into cerebrospinal fluid of patients with purulent meningitis or ventriculitis. Antimicrob Agents Chemother . 1989; 33:933-6. [PubMed 2764544][PubMedCentral]
208. Bitar N, Claes R, Van der Auwera P. Concentrations of ofloxacin in serum and cerebrospinal fluid of patients without meningitis receiving the drug intravenously and orally. Antimicrob Agents Chemother . 1989; 33:1686-90. [PubMed 2589841][PubMedCentral]
209. Giamarellou H, Kolokythas E, Petrikkos G et al. Pharmacokinetics of three newer quinolones in pregnant and lactating women. Am J Med . 1989; 87(Suppl 5A):49S-51S. [PubMed 2589384]
210. Sorgel F, Jaehde U, Naber K et al. Pharmacokinetic disposition of quinolones in human body fluids and tissues. Clin Pharmacokinet . 1989; 16(Suppl 1):5-24. [PubMed 2653696]
211. Deshmukh AR, Dhurat RS, Jerajani HR et al. A comparative clinico-pathological study of single dose ROM in paucibacillary leprosy patients with 1-3 skin lesions. Indian J Lepr . 2003 Jul-Sep; 75:209-17.
212. Single-lesion Multicentre Trial Group. Efficacy of single-dose multidrug therapy for the treatment of single-lesion paucibacillary leprosy. Indian J Leprosy . 1997; 69:121-9.
213. Muth P, Marx T, Sorgel F. Penetration of ofloxacin into maternal milk. Rev Infect Dis . 1989; 11(Suppl 5):S1079-80. [PubMed 2549606]
214. Gerding DN, Hitt JA. Tissue penetration of the new quinolones in humans. Rev Infect Dis . 1989; 11(Suppl 5):S1046-56. [PubMed 2672243]
215. World Health Organization. WHO Expert Committee on leprosy: eighth report. WHO Technical Report Series No. 968. Geneva: World Health Organization; 2012. [Web]
216. National Hansen's Disease (Leprosy) Program. From the US Department of Health and Human Services Health Resources and Services Administration (HRSA) website. Accessed 2015 Aug 3. [Web]
217. World Health Organization. WHO recommended multidrug therapy (MDT) regimens. From the WHO website. Accessed 2015 Aug 2. [Web]
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; :.
219. Serour F, Dan M, Gorea A et al. Penetration of ofloxacin into human lung tissue following a single oral dose of 200 milligrams. Antimicrob Agents Chemother . 1991; 35:380-1. [PubMed 2024972][PubMedCentral]
220. Hoffler D, Koeppe P. Pharmacokinetics of ofloxacin in healthy subjects and patients with impaired renal function. Drugs . 1987; 34(Suppl 1):51-5. [PubMed 3125032]
221. White LO, MacGowan AP, Lovering AM et al. A preliminary report on the pharmacokinetics of ofloxacin, desmethyl ofloxacin and ofloxacin N-oxide in patients with chronic renal failure. Drugs . 1987; 34(Suppl 1):56-61. [PubMed 3481329]
222. Dorfler A, Schultz W, Burkhardt F et al. Pharmacokinetics of ofloxacin in patients on haemodialysis treatment. Drugs . 1987; 34(Suppl 1):62-70. [PubMed 3481330]
223. Fillastre JP, Leroy A, Humbert G. Ofloxacin pharmacokinetics in renal failure. Antimicrob Agents Chemother . 1987; 31:156-60. [PubMed 3471179][PubMedCentral]
224. White LO, MacGowan AP, Mackay IG et al. The pharmacokinetics of ofloxacin, desmethyl ofloxacin and ofloxacin N-oxide in haemodialysis patients with end stage renal failure. J Antimicrob Chemother . 1988; 22(Suppl C):65-72. [PubMed 3182464]
225. Tsubakihara Y, Itoh T, Kitamura E et al. Pharmacokinetics of ofloxacin in patients with severe chronic renal failure. Rev Infect Dis . 1989; 11(Suppl 5):S1006-7.
226. Navarro AS, Lanao JM, Recio MM et al. Effect of renal impairment on distribution of ofloxacin. Antimicrob Agents Chemother . 1990; 34:455-9. [PubMed 2334157][PubMedCentral]
227. Janknegt R. Pharmacokinetics of antimicrobial agents in organ function impairment: a review. Pharm Weekbl [Sci] . 1990; 12:121-7. [PubMed 2277757]
228. Couraud L, Fourtillan JB, Saux MC et al. Diffusion of ofloxacin into human lung tissue. Drugs . 1987; 34(Suppl 1):37-8. [PubMed 3481326]
229. Harazim H, Wimmer J, Mittermayer HP. An open randomised comparison of ofloxacin and doxycycline in lower respiratory tract infections. Drugs . 1987; 34(Suppl 1):71-3. [PubMed 3481331]
230. Grassi C, Gialdroni Grassi G, Mangiarotti P. Clinical efficacy of ofloxacin in lower respiratory tract infections: a multicenter study. Drugs . 1987; 34(Suppl 1):80-2. [PubMed 3325260]
231. World Health Organization. Treatment of tuberculosis guidelines. 4th ed. World Health Organization; 2010. From WHO website. [Web]
232. Saito A, Katsu M, Saito A et al. Ofloxacin in respiratory tract infection: a review of the results of clinical trials in Japan. Drugs . 1987; 34(Suppl 1):83-9. [PubMed 3325261]
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. Hanninen P. Ofloxacin in lower respiratory tract infections. Drugs . 1987; 34(Suppl 1):179-80. [PubMed 3481320]
237. Hoiby N. Clinical uses of nalidixic acid analogues: the fluoroquinolones. Eur J Clin Microbiol . 1986; 5:138-40. [PubMed 3013628]
238. Maesen FP, Davies BI. Branhamella catarrhalis respiratory infections in the Netherlands. Drugs . 1986; 31(Suppl 3):83-6. [PubMed 3732084]
239. Davies BI, Maesen FP, Teengs JP et al. The quinolones in chronic bronchitis. Pharm Weekbl [Sci] . 1986; 8:53-9. [PubMed 3960693]
241. Mouton RP. The place of quinolones in antibacterial therapy in hospitals. Pharm Weekbl [Sci] . 1986; 8:72-8. [PubMed 3960694]
243. Neu HC. Clinical use of the quinolones. Lancet . 1987; 2:1319-22. [PubMed 2890913]
244. Jitta NM, Sumajow A. Effect of oral ofloxacin on acute exacerbations of chronic bronchitis. Curr Ther Res . 1987; 42:39-43.
246. Gantz NM. Quinolones: their uses in geriatric infections. Geriatrics . 1988; 43:41-7. [PubMed 3335336]
250. Chan MK, Chau PY, Chan WW. Oral treatment of peritonitis in CAPD patients with two dosage regimens of ofloxacin. J Antimicrob Chemother . 1988; 22:371-5. [PubMed 3182430]
251. Moorhouse EC, Clarke PC. Efficacy of ofloxacin in the treatment of lower respiratory tract infections in general practice. J Antimicrob Chemother . 1988; 22(Suppl C):135-8. [PubMed 3182455]
253. Stocks JM, Wallace RJ, Griffith DE et al. Ofloxacin in community-acquired lower respiratory infections: a comparison with amoxicillin or erythromycin. Am J Med . 1989; 87(Suppl 6C):52S-56S. [PubMed 2690620]
255. Gentry LO, Rodriguez-Gomez G, Zeluff BJ et al. A comparative evaluation of oral ofloxacin versus intravenous cefotaxime therapy for serious skin and skin structure infections. Am J Med . 1989; 87(Suppl 6C):57-60S. [PubMed 2472743]
256. Combination of ofloxacin and amikacin in the treatment of sternotomy wound infection. Chest . 1989; 95:1051-5. (IDIS 255399)
259. Thys JP, Jacobs F, Motte S. Quinolones in the treatment of lower respiratory tract infections. Rev Infect Dis . 1989; 11(Suppl 5):S1212-9. [PubMed 2672250]
262. Peyramond D, Biron F, Tigaud S et al. Treatment of bacterial osteomyelitis with ofloxacin. Rev Infect Dis . 1989; 11(Suppl 5):S1269-70.
263. Ketterl R, Beckurts T, Stubinger B et al. Ofloxacin for prevention of and therapy for bone and joint infections. Rev Infect Dis . 1989; 11(Suppl 5):S1264-5.
264. Grenier B. Use of the new quinolones in cystic fibrosis. Rev Infect Dis . 1989; 11(Suppl 5):S1245-51. [PubMed 2672252]
265. Lam WK, Chau PY, So SY et al. Ofloxacin compared with amoxycillin in treating infective exacerbations in bronchiectasis. Resp Med . 1989; 83:299-303.
266. Chan MK, Chau PY, CHan WW. Oral treatment of peritonitis in CAPD patients with ofloxacin. Nephrol Dial Transplant . 1988; 2:194-7.
268. Meek JC, Maesen FP, Davies BI. A prospective study of ofloxacin in acute exacerbations of chronic respiratory disease associated with Pseudomonas aeruginosa . J Antimicrob Chemother . 1989; 24:447-53. [PubMed 2808196]
269. Yoshikawa TT. Antimicrobial therapy for the elderly patient. JAGS . 1990; 38:1353-72.
270. Guay DR. Oral fluoroquinolone versus mono- or combination parenteral therapy in the management of bacterial infections: a critical appraisal. DICP . 1990; 24:11-8. [PubMed 2405585]
271. Kanellakopoulou K, Giamarellou H. Clinical experience with parenteral and oral ofloxacin in severe infections. Scand J Infect Dis . 1990; 68:64-9.
272. Ball P. Overview of experience with ofloxacin in respiratory tract infection. Scand J Infect Dis . 1990; 68:56-63.
273. Lode H, Wiley E, Olschewski P et al. Prospective randomized clinical trials of new quinolones versus β-lactam antibiotics in lower respiratory tract infections. Scand J Infect Dis . 1990; 68:50-5.
274. Punakivi L, Keistinen T, Backman R et al. Oral ofloxacin once daily and doxycycline in the treatment of acute exacerbations of chronic bronchitis. Scand J Infect Dis . 1990; 68:41-5.
275. Kromann-Andersen B, Nielsen KK. Ofloxacin in urinary tract infections. Scand J Infect Dis . 1990; 68:35-40.
276. World Health Organization. WHO treatment guidelines for drug-resistant tuberculosis: 2016 update. From WHO website. [Web]
277. Block MJ, Walstad RA, Bjertnaes A et al. Ofloxacin versus trimethoprim-sulphamethoxazole in acute cystitis. Drugs . 1987; 34(Suppl 1):100-6. [PubMed 3501750]
278. Ludwig G, Pauthner H. Clinical experience with ofloxacin in upper and lower urinary tract infections: a comparison with co-trimoxazole and nitrofurantoin. Drugs . 1987; 34(Suppl 1):95-9. [PubMed 3501751]
279. Rugendorff EW. Open randomised comparison of ofloxacin and norfloxacin in the treatment of complicated urinary tract infections. Drugs . 1987; 34(Suppl 1):91-4. [PubMed 3481333]
280. Raz R, Genesin J, Gonen E et al. Single low-dose ofloxacin for the treatment of uncomplicated urinary tract infection in young women. J Antimicrob Chemother . 1988; 22:945-9. [PubMed 3243742]
281. Kromann-Andersen B, Sommer P, Pers C et al. Ofloxacin compared with ciprofloxacin in the treatment of complicated lower urinary tract infections. J Antimicrob Chemother . 1988; 22(Suppl C):143-7. [PubMed 3182457]
282. Hooton TM, Latham RH, Wong ES et al. Ofloxacin versus trimethoprim-sulfamethoxazole for treatment of acute cystitis. Antimicrob Agents Chemother . 1989; 33:1308-12. [PubMed 2802557][PubMedCentral]
283. Hooper DC, Wolfson JS. Treatment of genitourinary tract infections with fluoroquinolones: clinical efficacy in genital infections and adverse effects. Antimicrob Agents Chemother . 1989; 33:1662-7. [PubMed 2686546][PubMedCentral]
284. Wolfson JS, Hooper DC. Treatment of genitourinary tract infections with fluoroquinolones: activity in vitro, pharmacokinetics, and clinical efficacy in urinary tract infections and prostatitis. Antimicrob Agents Chemother . 1989; 33:1655-61. [PubMed 2686545][PubMedCentral]
285. Cox CE. Ofloxacin in the management of complicated urinary tract infections, including prostatitis. Am J Med . 1989; 87(Suppl 6C):61S-8S. [PubMed 2690622]
286. Naber KG. Use of quinolones in urinary tract infections and prostatitis. Rev Infect Dis . 1989; 11(Suppl 5):S1321-32. [PubMed 2672257]
287. Ekwere PD. Ofloxacin and genitourinary infections: an open noncomparative evaluation. Curr Ther Res . 1991; 49:99-105.
288. Corrado ML. Worldwide clinical experience with ofloxacin in urologic cases. Urology . 1991; 37(Suppl):28-32. [PubMed 2003342]
289. Aznar J, Prados R, Herrera A et al. Single doses of ofloxacin in uncomplicated gonorrhoea. Drugs . 1987; 34(Suppl 1):107-10. [PubMed 3325255]
290. Black JR, Long JM, Zwickl BE et al. Multicenter randomized study of single-dose ofloxacin versus amoxicillin-probenecid for treatment of uncomplicated gonococcal infection. Antimicrob Agents Chemother . 1989; 33:167-70. [PubMed 2719459][PubMedCentral]
291. Abeyemi-Doro FA, Rotowa NA, Bakare RA et al. Clinical evaluation of ofloxacin as single-dose therapy for uncomplicated gonococcal urethritis in men. Curr Ther Res . 1989; 46:303-7.
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]
294. Black JR, Handsfield HH, Hook EW. Single-dose ofloxacin vs. amoxicillin plus probenecid for treatment of uncomplicated gonococcal infection. Rev Infect Dis . 1989; 11(Suppl 5):S1313-4. [PubMed 2682964]
296. Covino JM, Cummings M, Smith B et al. Comparison of ofloxacin and ceftriaxone in the treatment of uncomplicated gonorrhea caused by penicillinse-producing and non-penicillinase-producing strains. Antimicrob Agents Chemother . 1990; 34:148-9. [PubMed 2109573][PubMedCentral]
297. Weidner W, Schiefer HG, Garbe CH et al. Acute nongonococcal epididymitis: aetiological and therapeutic aspects. Drugs . 1987; 34(Suppl 1):111-7. [PubMed 3481311]
299. Nayagam AT, Ridgway GL, Oriel JD. Efficacy of ofloxacin in the treatment of non-gonococcal urethritis in men and genital infections caused by Chlamydia trachomatis in men and women. J Antimicrob Chemother . 1988; 22(Suppl C):155-8. [PubMed 3182459]
300. Richmond SJ, Bhattacharyya MN, Maiti H et al. The efficacy of ofloxacin against infection caused by Neisseria gonorrhoeae and Chlamydia trachomatis . J Antimicrob Chemother . 1988; 22(Suppl C):149-53. [PubMed 3182458]
301. Batteiger BE, Jones RB, White A. Efficacy and safety of ofloxacin in the treatment of nongonococcal sexually transmitted disease. Am J Med . 1989; 87(Suppl 6C):75-7S.
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]
307. Stein GE, Saravolatz LD. Randomized clinical study of ofloxacin and doxycycline in the treatment of nongonococcal urethritis and cervicitis. Rev Infect Dis . 1989; 11(Suppl 5):S1277. [PubMed 2772464]
308. Oriel JD. Use of quinolones in chlamydial infection. Rev Infect Dis . 1989; 11(Suppl 5):S1273-6. [PubMed 2672254]
309. Mogabgab WJ, Homes B, Murray M et al. Randomized comparison of ofloxacin and doxycycline for Chlamydia and Ureaplasma urethritis and cervicitis. Chemotherapy . 1990; 36:70-6. [PubMed 2307026]
311. Moller MR, Hermann B, Ibsen HH et al. Occurrence of Ureaplasma urealyticus and Mycoplasma hominis in non-gonococcal urethritis before and after treatment in a double-blind trial of ofloxacin versus erythromycin. Scand J Infect Dis . 1990; 68(Suppl):31-4.
317. Yew WW, Kwan SY, Ma WK et al. Ofloxacin therapy of Mycobacterium fortuitum infection: further experience. J Antimicrob Chemother . 1990; 25:880-1. [PubMed 2373673]
318. Wang F, Gu XJ, Zhang MF et al. Treatment of typhoid fever with ofloxacin. Rev Infect Dis . 1989; 11(Suppl 5):S1192.
320. Asperilla MO, Smego RA, Scott LK. Quinolone antibiotics in the treatment of Salmonella infections. Clin Infect Dis . 1990; 12:873-89.
321. Hoogkamp-Korstanje JA. The possible role of quinolones in yersiniosis. Drugs . 1987; 34(Suppl 1):134-8. [PubMed 3436262]
324. Leelarasamee A, Bovornkitti S. Meliodosis: review and update. Rev Infect Dis . 1989; 11:413-25. [PubMed 2665001]
325. Raffi F. Q-fever endocarditis. Lancet . 1989; 2:1336-7. [PubMed 2574284]
326. Lecour H, Ferreira I, Cordeiro J et al. Ofloxacin in the treatment of booutonneuse fever. Rev Infect Dis . 1989; 11(Suppl 5):S994-5.
327. Fontaine O. Antibiotics in the management of shigellosis in children: what role for the quinolones? Rev Infect Dis . 1989; 11(Suppl 5):S1145-50.
329. Rodriguez-Noriega E, Andrade-Villanueva J, Amaya-Tapia G. Quinolones in the treatment of salmonella carriers. Rev Infect Dis . 1989; 11(Suppl 5):S1179-86. [PubMed 2672248]
331. Wang F, Gu XJ, Zhang MF et al. Treatment of typhoid fever with ofloxacin. J Antimicrob Chemother . 1989; 23:785-8. [PubMed 2759925]
332. Ichiyama S, Tsukamura M. Ofloxacin and the treatment of pulmonary disease due to Mycobacterium fortuitum . Chest . 1987; 92:1110-2. [PubMed 3479304]
333. Yew WW, Kwan SY, Ma WK et al. Single daily-dose ofloxacin monotherapy for Mycobacterium fortuitum sternotomy infection. Chest . 1989; 96:1150-2. [PubMed 2805845]
335. Davey PG. Post-marketing surveillance of the quinolones: a view from Great Britain. Rev Infect Dis . 1989; 11(Suppl 5):S1402-7. [PubMed 2672260]
336. Forsgren A, Bredberg A, Riesbeck K. New quinolones: in vitro effects as a potential source of clinical toxicity. Rev Infect Dis . 1989; 11(Suppl 5):S1382-9. [PubMed 2549607]
337. Ball P. Long-term use of quinolones and their safety. Rev Infect Dis . 1989; 11(Suppl 5):S1365-9. [PubMed 2672258]
339. Davis GJ, McKenzie ME. Toxicologic evaluation of ofloxacin. Am J Med . 1989; 87(Suppl 6C):43S-46S. [PubMed 2690619]
340. Tack KJ, Smith JA. The safety profile of ofloxacin. Am J Med . 1989; 87(Suppl 6C):78S-81S. [PubMed 2690623]
341. Jungst G, Mohr R. Overview of postmarketing experience with ofloxacin in Germany. J Antimicrob Chemother . 1988; 22(Suppl C):167-75. [PubMed 3053577]
342. Mayer DG. Overview of toxicological studies. Drugs . 1987; 34(Suppl 1):150-3. [PubMed 3325258]
343. Jungst G, Mohr R. Side effects of ofloxacin in clinical trials and in postmarketing surveillance. Drugs . 1987; 34(Suppl 1):144-9. [PubMed 3325257]
344. Workowski KA, Bolan GA. Sexually Transmitted Diseases Treatment Guidelines, 2015. MMWR Recomm Rep . 2015; 64(RR-03):1-137. [PubMed 26042815]
345. Midtvedt T. Influence of ofloxacin on the faecal flora. Drugs . 1987; 34(Suppl 1):154-8. [PubMed 3481316]
346. Saxerholt H, Carlstedt-Duke B, Hoverstad T et al. Influence of antibiotics on the faecal excretion of bile pigments in healthy subjects. Scand J Gastroenterol . 1986; 21:991-6. [PubMed 3775264]
347. Takayama S, Watanabe T, Akiyama Y et al. Reproductive toxicity of ofloxacin. Arzneimittelforschung . 1986; 36:1244-8. [PubMed 3465327]
348. Hoverstad T, Carlstedt-Duke B, Lingaas E et al. Influence of oral intake of seven different antibiotics on faecal short-chain fatty acid excretion in healthy subjects. Scand J Gastroenterol . 1986; 21:997-1003. [PubMed 3775265]
349. Pecquet S, Andremont A, Tancrede C. Effect of oral ofloxacin on fecal bacteria in human volunteers. Antimicrob Agents Chemother . 1987; 31:124-5. [PubMed 3471178][PubMedCentral]
350. Shah PM, Enzensberger R, Glogau O et al. Influence of oral ciprofloxacin or ofloxacin on the fecal flora of healthy volunteers. Am J Med . 1987; 82(Suppl 4A):333-5. [PubMed 3101497]
351. Van Saene HK, Lemmens SE, Van Saene JJ. Gut decontamination by oral ofloxacin and ciprofloxacin in healthy volunteers. J Antimicrob Chemother . 1988; 22(Suppl C):127-34. [PubMed 3182454]
352. Dan M, Samra Z. Clostridium difficile colitis associated with ofloxacin therapy. Am J Med . 1989; 87:479. [PubMed 2801739]
353. Chew SL, Daelemans R, Lins RL. Ciprofloxacin and pseudomembranous colitis. Lancet . 1990; 336:1509-10. [PubMed 1979116]
354. Brismar BO, Edlund C, Malmborg AS et al. Ecological impact of antimicrobial prophylaxis on intestinal microflora in patients undergoing colorectal surgery. Scand J Infect Dis . 1990; 70(Suppl):25-30.
355. Midtvedt T. The influence of quinolones on the faecal flora. Scand J Infect Dis . 1990; 68(Suppl):14-8.
356. Verho M, Dagrosa EE, Usinger P et al. Renal tolerance of ofloxacin, a new gyrase inhibitor. Pharmatherapeutica . 1985; 4:306-13. [PubMed 2866542]
359. Kato M, Onodera T. Morphological investigation of cavity formation in articular cartilage induced by ofloxacin in rats. Fund Appl Toxicol . 1988; 11:110-9.
360. Pace JL, Gatt P. Fatal vasculitis associated with ofloxacin. BMJ . 1989; 299:658-9. [PubMed 2508853][PubMedCentral]
361. Bergan T, Rohwedder R, Thorsteinsson SB. Significance of crystalluria caused by quinolones. Rev Infect Dis . 1989; 11(Suppl 5):S1395-6.
362. Johnson BE, Walker EM, Ferguson J. Quinolone-induced photosensitivity. Rev Infect Dis . 1989; 11(Suppl 5):S1396-7.
363. Zaudig M, von Bose M, Weber MM et al. Psychotoxic effects of ofloxacin. Pharmacopsychiat . 1989; 22:11-5.
364. Zaudig M, von Bose M. Ofloxacin-induced psychosis. Br J Psychiat . 1987; 151:563-4.
365. Edwards DJ, Bowles SK, Svensson CK et al. Inhibition of drug metabolism by quinolone antibiotics. Clin Pharmacokinet . 1988; 15:194-204. [PubMed 3052987]
366. Davey PG. Overview of drug interactions with the quinolones. J Antimicrob Chemother . 1988; 2(Suppl C):97-107.
367. Polk RE. Drug-drug interactions with ciprofloxacin and other fluoroquinolones. Am J Med . 1989; 87(Suppl 5A):76S-81S. [PubMed 2686430]
368. Wijnands GJ, Vree TB, Janssen TJ et al. Drug-drug interactions affecting fluoroquinolones. Am J Med . 1989; 87(Suppl 6C):47S-51S. [PubMed 2603893]
369. McQueen CA, Williams GM. Effects of quinolone antibiotics in tests for genotoxicity. Am J Med . 1987; 82(Suppl 4A):94-6.
370. Kern W, Gulden H, Vanek E et al. In vitro antibacterial activity of imipenem in combination with newer quinolone derivatives. Chemotherapy . 1988; 34:117-26. [PubMed 3164670]
371. Traub WH, Spohr M, Bauer D. Pseudomonas aeruginosa: in vitro susceptibility to antimicrobial drugs, single and combined, with and without defibrinated human blood. Chemotherapy . 1988; 34:284-97. [PubMed 3145172]
372. Rohner P, Herter C, Auckenthaler R et al. Synergistic effect of quinolones and oxacillin on methacillin-resistant Staphylococcus species. Antimicrob Agents Chemother . 1989; 33:2037-41. [PubMed 2619272][PubMedCentral]
373. Lewin CS, Smith JT. Interactions of the 4-quinolones with other antibacterials. J Med Microbiol . 1989; 29:221-7. [PubMed 2664184]
374. Neu HC. Synergy of fluoroquinolones with other antimicrobial agents. Rev Infect Dis . 1989; 11(Suppl 5):S1025-34. [PubMed 2505355]
375. Madhavan T, Price J, Fitzsimons B et al. In vitro evaluation of the antimicrobial effect of norfloxacin and ofloxacin in combination with aminoglycosides. Rev Infect Dis . 1989; 11(Suppl 5):S1041-2.
377. Hoffner SE, Kratz M, Olsson-Liljequist B et al. In-vitro synergistic activity between ethambutol and fluorinated quinolones against Mycobacterium avium complex. J Antimicrob Chemother . 1989; 24:317-24. [PubMed 2808189]
378. Wijnands WJ, Vree TB, Baars AM et al. Steady-state kinetics of the quinolone derivatives ofloxacin, enoxacin, ciprofloxacin and pefloxacin during maintenance treatment with theophylline. Drugs . 1987; 34(Suppl 1):159-69. [PubMed 3481317]
379. Wijnands WJ, Bree TB, Van Herwaarden CL. The influence of quinolone derivatives on theophylline clearance. Br J Clin Pharmacol . 1986; 22:677-83. [PubMed 3567014][PubMedCentral]
380. Gregoire SL, Grasela TH, Freer JP et al. Inhibition of theophylline clearance by coadministered ofloxacin without alteration of theophylline effects. Antimicrob Agents Chemother . 1987; 31:375-8. [PubMed 3472488][PubMedCentral]
381. Sano M, Yamamoto I, Ueda J et al. Comparative pharmacokinetics of theophylline following two fluoroquinolones co-administration. Eur J Clin Pharmacol . 1987; 32:431-2. [PubMed 3475207]
382. Thomson AH, Thomson GD, Hepburn M et al. A clinically significant interaction between ciprofloxacin and theophylline. Eur J Clin Pharmacol . 1987; 33:435-6. [PubMed 3443151]
383. Raoof S, Wollschlager C, Khan FA. Ciprofloxacin increases serum levels of theophylline. Am J Med . 1987; 82(Suppl 4A):115-8. [PubMed 3578320]
384. Niki Y, Soejima R, Kawane H et al. New synthetic quinolone antibacterial agents and serum concentration of theophylline. Chest . 1987; 92:663-9. [PubMed 3477409]
385. Rybak MJ, Bowles SK, Chandrasekar PH et al. Increased theophylline concentrations secondary to ciprofloxacin. Drug Intell Clin Pharm . 1987; 21:879-81. [PubMed 3678060]
386. Wijnands GJ, Vree TB, Van Herwaarden CL. Comment: potential theophylline toxicity with enoxacin. Drug Intell Clin Pharm . 1987; 21:383. [PubMed 3471434]
387. Schwartz J, Jauregui L, Lettieri J et al. Impact of ciprofloxacin on theophylline clearance and steady-state concentrations in serum. Antimicrob Agents Chemother . 1988; 32:75-7. [PubMed 3348614][PubMedCentral]
388. Segev S, Rhavi M, Rubinstein E. Quinolones, theophylline, and diclofenac interactions with γ-aminobutyric acid receptor. Antimicrob Agents Chemother . 1988; 32:1624-6. [PubMed 2855295][PubMedCentral]
389. Ho G, Tierney MG, Dales RE. Evaluation of the effect of norfloxacin on the pharmacokinetics of theophylline. Clin Pharmacol Ther . 1988; 44:35-8. [PubMed 3391003]
390. Al-Turk WA, Shaheen OM, Othman S et al. Effect of ofloxacin on the pharmacokinetics of a single intravenous theophylline dose. Ther Drug Monit . 1988; 10:160-3. [PubMed 3164150]
391. Bem JL, Mann RD. Danger of interaction between ciprofloxacin and theophylline. BMJ . 1988; 296:1131. [PubMed 3132238][PubMedCentral]
392. Sano M, Kawakatsu K, Ohkita C et al. Effects of enoxacin, ofloxacin and norfloxacin on theophylline disposition in humans. Eur J Clin Pharmacol . 1988; 35:161-5. [PubMed 3191935]
393. Wijands WJ, Janssen TJ, Guelen PJ et al. The influence of ofloxacin and enoxacin on the metabolic pathways of theophylline in healthy volunteers. Pharm Weekbl [Sci] . 1988; 10:272-6. [PubMed 3211700]
394. Wijnands WJ, Vree TB. Interaction between the fluoroquinolones and the bronchodilator theophylline. J Antimicrob Chemother . 1988; 22(Suppl C):109-14. [PubMed 3053575]
395. Sano M, Kawakatsu K, Yamamoto I et al. Inhibitory effect of enoxacin, ofloxacin and norfloxacin on renal excretion of theophylline in humans. Eur J Clin Pharmacol . 1989; 36:323-4. [PubMed 2744074]
396. Sarkar M, Polk RE, Guzelian PS et al. In vitro effect of fluoroquinolones on theophylline metabolism in human liver microsomes. Antimicrob Agents Chemother . 1990; 34:594-9. [PubMed 2344166][PubMedCentral]
397. Parent M, LeBel M. Meta-analysis of quinolone-theophylline interactions. DICP . 1991; 25:191-4. [PubMed 1647570]
398. Staib AH, Stille W, Dietlein G et al. Interaction between quinolones and caffeine. Drugs . 1987; 34(Suppl 1):170-4. [PubMed 3481318]
399. Staib AH, Harder S, Mieke S et al. Gyrase-inhibitors impair caffeine elimination in man. Meth Find Exptl Clin Pharmacol . 1987; 9:193-8.
400. Harder S, Staib AH, Beer C et al. 4-Quinolones inhibit biotransformation of caffeine. Eur J Clin Pharmacol . 1988; 35:651-6. [PubMed 2853056]
401. Harder S, Fuhr U, Staib AH. Ciprofloxacin-caffeine: a drug interaction established using in vivo and in vitro investigations. Am J Med . 1989; 87(Suppl 5A):89S-91S. [PubMed 2589393]
402. Barnett G, Segura J, de la Torre R et al. Pharmacokinetic determination of relative potency of quinolone inhibition of caffeine disposition. Eur J Clin Pharmacol . 1990; 39:63-9. [PubMed 2177401]
403. Leor J, Matetzki S. Ofloxacin and warfarin. Ann Intern Med . 1988; 109:761. [PubMed 3190063]
404. Flor S, Guay DR, Opsahl JA et al. Effects of magnesium-aluminum hydroxide and calcium carbonate antacids on bioavailability of ofloxacin. Antimicrob Agents Chemother . 1900; 34:2436-8.
405. Maesen FP, Davies BI, Geraedts WH et al. Ofloxacin and antacids. J Antimicrob Chemother . 1987; 19:848-50. [PubMed 3475268]
406. Bayerdorffer E, Simon TH, Bastlein CH et al. Bismuth/ofloxacin combination for duodenal ulcer. Lancet . 1987; 2:1467.
407. Van Caekenberghe DL, Breyssens J. In vitro synergistic activity between bismuth subcitrate and various antimicrobial agents against Campylobacter pyloridis ( C. pylori ). Antimicrob Agents Chemother . 1987; 31:1429-30. [PubMed 3674850][PubMedCentral]
409. Halliwell RF, Lambert JJ, Davey PG. Actions of quinolones and nonsteroidal antiinflammatory drugs on γ-aminobutyric acid currents of rat dorsal root ganglion neurons. Rev Infect Dis . 1989; 11(Suppl 1):S1398-9. [PubMed 2672260]
410. Koppel C, Hopfe T, Menzel J. Central anticholinergic syndrome after ofloxacin overdose and therapeutic doses of diphenhydramine and chlormezanone. J Toxicol Clin Toxicol . 1990; 28:249-53. [PubMed 2398523]
411. Akahane K, Sekiguchi M, Une T et al. Structure-epileptogenicity relationship of quinolones with special reference to their interaction with γ-aminobutyric acid receptor sites. Antimicrob Agents Chemother . 1989; 33:1704-8. [PubMed 2556076][PubMedCentral]
413. Hooper DC, Wolfson JS. Fluoroquinolone antimicrobial agents. N Engl J Med . 1991; 324:384-94. [PubMed 1987461]
414. Smythe MA, Rybak MJ. Ofloxacin: a review. DICP . 1989; 23:839-46. [PubMed 2688325]
415. Jaber LA, Bailey EM, Rybak MJ. Enoxacin: a new fluoroquinolone. Clin Pharm . 1989; 8:97-107. [PubMed 2645085]
416. Henwood JM, Monk JP. Enoxacin: a review of its antibacterial activity, pharmacokinetic properties and therapeutic use. Drugs . 1988; 36:32-66. [PubMed 3063494]
417. Paton JH, Reeves DS. Fluoroquinolone antibiotics: microbiology, pharmacokinetics and clinical uses. Drugs . 1988; 36:193-228. [PubMed 3053126]
418. Andersen RC, Goldstein EJ. The introduction of the quinolones: a new class of anti-infectives. Hosp Formul . 1987; 22:36-47.
419. Walker RC, Wright AJ. The quinolones. Mayo Clin Proc . 1987; 62:1007-12. [PubMed 3312850]
420. Monk JP, Campoli-Richards DM. Ofloxacin: a review of its antibacterial activity, pharmacokinetic properties and therapeutic use. Drugs . 1987; 33:346-91. [PubMed 3297617]
421. Janknegt R. Fluorinated quinolones: a review of their mode of action, antimicrobial activity, pharmacokinetics and clinical efficacy. Pharm Weekbl [Sci] . 1986; 8:1-21. [PubMed 3515312]
423. Basista MP. Randomized study to evaluate efficacy and safety of ofloxacin vs. trimethoprim and sulfamethoxazole in treatment of uncomplicated urinary tract infection. Urology . 1991; 37:21-7. [PubMed 2003341]
424. Aagaard J, Madsen PO. Bacterial prostatitis: new methods of treatment. Urology . 1991; 37:4-8. [PubMed 2003343]
425. Cox CE. Parenteral ofloxacin in treatment of pyelonephritis. Urology . 1991; 37:16-20. [PubMed 2003340]
426. VanLanduyt HW, Magerman K, Gordts B. The importance of the quinolones in antibacterial therapy. J Antimicrob Chemother . 1990; 26(Suppl D):1-6. [PubMed 2286584]
427. Janknegt R. Drug interactions with quinolones. J Antimicrob Chemother . 1990; 26(Suppl D):7-25. [PubMed 2286594]
428. Stahlmann R. Safety profile of the quinolones. J Antimicrob Chemother . 1990; 26(Suppl D):31-44. [PubMed 2286589]
429. Lang R, Lishner M, Segev S et al. Ofloxacin and the gastrointestinal tract: a potential role in the treatment of bacterial enteritis. J Antimicrob Chemother . 1990; 26(Suppl D):45-53. [PubMed 2286590]
430. Perea EJ. Ofloxacin concentrations in tissues involved in respiratory tract infections. J Antimicrob Chemother . 1990; 26(Suppl D):55-60. [PubMed 2286591]
431. Kampf D, Borner K, Pustelnik A. Pharmacokinetics of ofloxacin and adequacy of maintenance dose for patients on haemodialysis. J Antimicrob Chemother . 1990; 26(Suppl D):61-8. [PubMed 2286592]
432. Meissner A, Borner K, Koeppe P. Concentrations of ofloxacin in human bone and in cartilage. J Antimicrob Chemother . 1990; 26(Suppl D):69-74. [PubMed 2286593]
433. Rademaker CM, Sips AP, Beumer HM et al. A double-blind comparison of low-dose ofloxacin and amoxycillin/clavulanic acid in acute exacerbations of chronic bronchitis. J Antimicrob Chemother . 1990; 26(Suppl D):75-81. [PubMed 2286595]
434. Ge B, White DG, McDermott PF et al. Antimicrobial-resistant Campylobacter species from retain raw meats. Appl Environ Microbiol . 2003;69:3005-7. [PubMed 12732579][PubMedCentral]
435. Unseld E, Ziegler G, Gemeinhardt A et al. Possible interaction of fluoroquinolones with the benzodiazepine-GABAa-receptor complex. Br J Clin Pharmacol . 1990; 30:63-70. [PubMed 2167717][PubMedCentral]
436. Kitchen VS, Donegan C, Ward H et al. Comparison of ofloxacin with doxycycline in the treatment of non-gonococcal urethritis and cervical chlamydial infection. J Antimicrob Chemother . 1990; 26(Suppl D):99-105. [PubMed 2286598]
437. Mouton Y, Leroy O, Beuscart C et al. Efficacy of intravenous ofloxacin: a French multicentre trial in 185 patients. J Antimicrob Chemother . 1990; 26(Suppl D):115-20. [PubMed 2286586]
438. Regamey C, Steinbach-Lebbin C. Severe infection treated with intravenous ofloxacin: a prospective clinical multicentre Swiss study. J Antimicrob Chemother . 1990; 26(Suppl D):107-14. [PubMed 2286585]
439. Granger W, Presterl E, Walzl B et al. Intravenous ofloxacin in severe infections. J Antimicrob Chemother . 1990; 26(Suppl D):123-35. [PubMed 2286587]
440. Panel on Opportunistic Infections 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]
441. Crumplin GC. Aspects of chemistry in the development of the 4-quinolone antibacterial agents. Rev Infect Dis . 1988; 10(Suppl 1):S2-9. [PubMed 3279494]
442. Bryskier A, Chantoto JF, Veyssier P. Classification of structure-activity relation of new pyridone β-carboxylic derivatives. Rev Infect Dis . 1988; 10(Suppl 1):S10.
443. Hooper DC, Wolfson JS. Mode of action of the quinolone antimicrobial agents. Rev Infect Dis . 1988; 10(Suppl 1):S14-20. [PubMed 2831608]
444. Inoue Y, Sato K, Fujii T et al. Resistance mechanism of Pseudomonas aeruginosa against quinolones. Rev Infect Dis . 1988; 10(Suppl 1):S22.
445. Neu HC. Bacterial resistance to fluoroquinolones. Rev Infect Dis . 1988; 10(Suppl 1):S57-63. [PubMed 3279500]
446. Christ W, Lehnert T, Ulbrich B. Specific toxicologic aspects of the quinolones. Rev Infect Dis . 1988; 10(Suppl 1):S141-6. [PubMed 3279489]
447. Boslego JW, Hicks CB, Greenup R et al. A prospective randomized trial of ofloxacin vs. doxycycline in the treatment of uncomplicated male urethritis. Sex Transm Dis . 1987; 5:186-91.
448. Rajakumar MK, Ngeow YF, Khor BS et al. Ofloxacin, a new quinolone for the treatment of gonorrhea. Sex Transm Dis . 1988; 16:25-6.
449. Ibsen HH, Moller BR, Halkier-Sorensen L et al. Treatment of nongonococcal urethritis: comparison of ofloxacin and erythromycin. Sex Transm Dis . 1988; 16:32-5.
450. Perea EJ, Aznar J, Herrera A et al. Clinical efficacy of new quinolones for therapy of nongonococcal urethritis. Sex Transm Dis . 1988; 16:7-10.
451. Lewin CS, Allen RA, Amyes SG. Antibacterial activity of fluoroquinolones in combination with zidovudine. J Med Microbiol . 1990; 33:127-31. [PubMed 2121991]
452. Linville D, Emory C, Graves L. Ciprofloxacin and warfarin interaction. Am J Med . 1991; 90:765. [PubMed 2042696]
453. Berger SA, Yavetz H, Paz G et al. Concentration of ofloxacin and ciprofloxacin in human semen following a single oral dose. J Urol . 1990; 144:683-4. [PubMed 2388328]
454. Stille W, Harder S, Mieke S et al. Decrease of caffeine elimination in man during co-administration of 4-quinolones. J Antimicrob Chemother . 1987; 20:729-34. [PubMed 3480885]
455. Ikeda S, Yazawa M, Nishimura C. Antiviral activity and inhibition of topoisomerase by ofloxacin, a new quinolone derivative. Antiviral Res . 1987; 8:103-13. [PubMed 2827566]
456. Alegre J, Fernandex de Sevilla T, Falco V et al. Ofloxacin in miliary tuberculosis. Eur Respir J . 1990; 3:238-9. [PubMed 2311746]
457. Saito A, Sawatari K, Fukuda Y et al. Susceptibility of Legionella pneumophila to ofloxacin in vitro and in experimental Legionella pneumonia in guinea pigs. Antimicrob Agents Chemother . 1985; 28:15-20. [PubMed 3862361][PubMedCentral]
458. Chan MK, Chau PY, Chan WW. Ofloxacin pharmacokinetics in patients on continuous ambulatory peritoneal dialysis. Clin Nephrol . 1987; 28:277-80. [PubMed 3481692]
459. Pattyn SR. Activity of ofloxacin and pefloxacin against Mycobacterium leprae in mice. Antimicrob Agents Chemother . 1987; 31:671-2. [PubMed 3475035][PubMedCentral]
460. Raoult D, Houpikian P, Dupont HT et al. Treatment of Q fever endocarditis: comparison of 2 regimens containing doxycycline and ofloxacin or hydrochloroquine. Arch Intern Med . 1999; 159:167-73. [PubMed 9927100]
462. Lentino JR, Augustinsky JB, Weber TM et al. Therapy of serious skin and soft tissue infections with ofloxacin administered by intravenous and oral route. Chemotherapy . 1991; 37:70-6. [PubMed 2013245]
464. Drew RH, Gallis HA. Ofloxacin: its pharmacology, pharmacokinetics, and potential for clinical application. Pharmacotherapy . 1988; 8:35-46. [PubMed 3287354]
466. Vincent S, Glauner B, Gutmann L. Lytic effect of two fluoroquinolones, ofloxacin and pefloxacin, on Escherichia coli W7 and its consequences on peptidoglycan composition. Antimicrob Agents Chemother . 1991; 35:1381-5. [PubMed 1929297][PubMedCentral]
467. Ridgway GL, O'Hare MD, Gelmingham D et al. The comparative activity of twelve 4-quinolone antimicrobials against Haemophilus influenzae and Streptococcus pneumoniae . Drugs Exp Clin Res . 1985; 11:259-62. [PubMed 2941258]
468. Yew WW, Kwan SY, Keung Ma W et al. Minimal bactericidal and inhibitory concentrations of ofloxacin on Mycobacterium fortuitum at pH 7 and 5: therapeutic implications. Tubercle . 1990; 71:205-8. [PubMed 2238127]
469. Chiaradia V, Pascoli L, Mucignat G et al. Ofloxacin: in vitro activity against recently isolated gram-negative bacterial strains. J Chemother . 1989; 1:80-5. [PubMed 2543801]
470. Burgos A, Quindos G, Martinez R et al. In vitro susceptibility of Aeromonas caviae , Aeromonas hydrophila and Aeromonas sobria to fifteen antibacterial agents. Eur J Clin Microbiol Infect Dis . 1990; 9:413-7. [PubMed 2387294]
471. Lopez-Brea M, Alarcon T. Isolation of fluoroquinolone-resistant Escherichia coli and Klebsiella pneumoniae from an infected Hickman catheter. Eur J Clin Microbiol Infect Dis . 1990; 9:345-7. [PubMed 2197092]
472. Weber P, Boussougant Y, Farinotti R et al. Serum bactericidal activity against Enterobacteriaceae producing broad-spectrum beta-lactamases in volunteers administered ofloxacin and cefotaxime, alone or combined. Eur J Clin Microbiol Infect Dis . 1989; 8:524-6. [PubMed 2504593]
473. McNulty CA, Dent JC. Susceptibility of clinical isolates of Campylobacter pylori to twenty-one antimicrobial agents. Eur J Clin Microbiol Infect Dis . 1988; 7:566-9. [PubMed 3141174]
474. Krausse R, Ullmann U. Comparative in vitro activity of fleroxacin (RO 23-6240) against Ureaplasma urealyticum and Mycoplasma hominis . Eur J Clin Microbiol Infect Dis . 1988; 7:67-9. [PubMed 3132382]
475. Stubner G, Weinrich W, Brands U. Study of the cerebrospinal fluid penetrability of ofloxacin. Infection . 1986; 14(Suppl 4):S250-3. [PubMed 3469155]
476. Stahl JP, Croize J, Lefebvre A et al. Diffusion of ofloxacin into the cerebrospinal fluid in patients with bacterial meningitis. Infection . 1986; 14(Suppl 4):S254-5.
477. Guerrant RL, Gilder TV, Steiner TS et al. Practice guidelines for the management of infectious diarrhea. Clin Infect Dis . 2001; 32:331-50. [PubMed 11170940]
478. Hooton TM, Johnson C, Winter C et al. Single-dose and three-day regimens of ofloxacin versus trimethoprim-sulfamethoxazole for acute cystitis in women. Antimicrob Agents Chemother . 1991; 35:1479-83. [PubMed 1929311][PubMedCentral]
479. Yew WW, Kwan SY, Wong PC et al. Ofloxacin and imipenem in the treatment of Mycobacterium fortuitum and Mycobacterium chelonae lung infections. Tubercle . 1990. 71:131-3.
481. Sabbour MS, Osman LM. Experience with ofloxacin in enteric fever. J Chemother . 1990; 2:113-5. [PubMed 2113941]
484. Bariffi F, Giacomelli P, Sanduzzi A et al. A comparative study of ofloxacin versus cefazolin in lower respiratory tract infections. Int J Clin Pharm Res . 1987; 7:199-201.
485. Bruck K, Blomer R. Efficacy and safety of ofloxacin in elderly patients. Int J Clin Pharm Res . 1987; 7:195-8.
486. Chan AS, Tang KC, Fung KK et al. Single dose ofloxacin in treatment of uncomplicated gonorrhoea. Infection . 1986; 14(Suppl 4):S314-5. [PubMed 3546155]
487. Ariyarit C, Panikabutra K, Chitwarakorn C et al. Efficacy of ofloxacin in uncomplicated gonorrhoea. Infection . 14(Suppl 4):S311-3.
488. Judson FN, Beals BS, Tack KJ. Clinical Experience with ofloxacin in sexually transmitted disease. Infection . 1986; 14(Suppl 4):S309-10.
489. Oren B, Raz R, Hass H. Urinary mycobacterium fortuitum infection. Infection . 1990; 18:105-6. [PubMed 2332244]
490. Vogt P, Schorn T, Frei U. Ofloxacin in the treatment of urinary tract infection in renal transplant recipients. Infection . 1988; 16:175-7. [PubMed 3042627]
491. Dellamonica P, Bernard E, Etesse H et al. Evaluation of pefloxacin, ofloxacin, and ciprofloxacin in the treatment of thirty-nine cases of chronic osteomyelitis. Eur J Clin Microbiol Dis . 1989; 8:1024-30.
492. Yousaf M, Sadick A. Ofloxacin in the treatment of typhoid fever unresponsive to chloramphenicol. Clin Ther . 1990; 12:44-7. [PubMed 2328527]
493. Blomer R, Bruch K, Krauss H et al. Safety of ofloxacin - adverse drug reactions reported during phase-II studies in Europe and in Japan. Infection . 1986; 14(Suppl 4):S332-3. [PubMed 2950061]
494. Edlund C, Kager L, Malmborg AS et al. Effect of ofloxacin on oral and gastrointestinal microflora in patients undergoing gastric surgery. Eur J Clin Microbiol Infect Dis . 1988; 7:135-43. [PubMed 3134200]
495. Fostini R, Girelli M, Vedove D et al. Safety profile of ofloxacin in elderly patients. Drugs Exp Clin Res . 1988; 14:393-5. [PubMed 3063474]
496. Nelson JD, Silverman V, Lima PH et al. Corneal epithelial wound healing: a tissue culture assay on the effect of antibiotics. Curr Eye Res . 1989; 9:277-85.
497. Yoshida H, Bogaki M, Nakamura M et al. Quinolone resistance-determining region in the DNA gyrase gyrB gene of Escherichia coli . Antimicrob Agents Chemother . 1991; 35:1647-50. [PubMed 1656869][PubMedCentral]
498. Smith BL, Cummings MC, Covino JM et al. Evaluation of ofloxacin in the treatment of uncomplicated gonorrhea. Sex Trans Dis . 1991; 18:18-20.
500. Biggs HM, Behravesh CB, Bradley KK et al. Diagnosis and Management of Tickborne Rickettsial Diseases: Rocky Mountain Spotted Fever and Other Spotted Fever Group Rickettsioses, Ehrlichioses, and Anaplasmosis - United States. MMWR Recomm Rep . 2016; 65:1-44. [PubMed 27172113]
503. Blomer R, Bruch K, Klose U. Ofloxacin in the treatment of gonococcal and chlamydial urethritis. Clin Ther . 1988; 10:263-5. [PubMed 2978862]
504. Felmingham D, O'Hare MD, Robbins MJ et al. Comparative in vitro studies with 4-quinolone antimicrobials. Drugs Exp Clin Res . 1985; 11:317-29. [PubMed 2941259]
505. Peters B, Pinching AJ. Fatal anaphylaxis associated with ciprofloxacin in a patient with AIDS related complex. BMJ . 1989; 298:605. [PubMed 2495139][PubMedCentral]
506. Harnett N, Brown S, Krishnan C. Emergence of quinolone resistance among clinical isolates of methicillin-resistant Staphylococcus aureus in Ontario, Canada. Antimicrob Agents Chemother . 1991; 115:1911-3.
507. Ryzhko IV, Shcherbaniuk AT, Samokhodkina ED et al. Virulence of rifampicin and quinolone resistant mutants of strains of plague microbe with Fra+ and Fra- phenotypes. Antibiot Khimioter . 1994; 39:32-6. [PubMed 7826172]
508. Lindler LE, Fan W, Jahna N. Detection of ciprofloxacin-resistant Yersinia pestis by fluorogenic PCR using the lightcycler. J Clin Microbiol . 2001; 39:3649-55. [PubMed 11574586][PubMedCentral]
519. Peterson LR, Quick JN, Jensen B et al. Emergence of ciprofloxacin resistance in nosocomial methicillin-resistant Staphylococcus aureus isolates: resistance during ciprofloxacin plus rifampin therapy for methicillin-resistant S. aureus colonization. Arch Intern Med . 1990; 150:2151-5. [PubMed 2222100]
520. Blumberg HM, Rimland D, Carroll DJ et al. Rapid development of ciprofloxacin resistance in methicillin-susceptible and -resistant Staphylococcus aureus . J Infect Dis . 1991; 163:1279-85. [PubMed 2037793]
521. Raviglione MC, Boyle JF, Mariuz P et al. Ciprofloxacin-resistant methicillin-resistant Staphylococcus aureus in an acute-care hospital. Antimicrob Agents Chemother . 1990; 34:2050-4. [PubMed 2073096][PubMedCentral]
522. Daum TE, Shaberg DR, Terpenning MS et al. Increasing resistance of Staphylococcus aureus to ciprofloxacin. Antimicrob Agents Chemother . 1990; 34:1862-3. [PubMed 2285306][PubMedCentral]
524. Rautelin H, Renkonen OV, Kosunen TU. Emergence of fluoroquinolone resistance in Campylobacter jejuni and Campylobacter coli in subjects from Finland. Antimicrob Agents Chemother . 1992; 35:2065-9.
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]
526. Morris JT, Beckius M, McAllister CK. Quinolones lack efficacy for treatment of trichomoniasis. J Infect Dis . 1991; 164:624-5. [PubMed 1651363]
527. National Institutes of Health Office of Medical Applications of Research. Consensus conference: travelers' diarrhea. JAMA . 1985; 253:2700-4. [PubMed 2985834]
529. Pavia AT, Tauxe RV. Travel to the Soviet Union: is diarrhea a risk? JAMA . 1987; 260:224-5.
530. Endtz HP, Ruijs GJ, van Klingeren B et al. Quinolone resistance in campylobacter isolated from man and poultry following the introduction of fluoroquinolones in veterinary medicine. J Antimicrob Chemother . 1991; 27:199-208. [PubMed 2055811]
531. Reina J, Alomar P. Fluoroquinolone-resistance in thermophilic Campylobacter spp isolated from stools of Spanish patients. Lancet . 1990; 336:186. [PubMed 1973508]
534. Yew WW, Lee J, Chan CY et al. Ofloxacin penetration in tuberculous pleural effusion. Antimicrob Agents Chemother . 1991; 35:2159-60. [PubMed 1759841][PubMedCentral]
535. Okazaki O, Kojima C, Hakusui H et al. Enantioselective disposition of ofloxacin in humans. Antimicrob Agents Chemother . 1991; 35:2106-9. [PubMed 1759834][PubMedCentral]
536. Martinez-Cabarga M, Sanchez-Navarro A, Colino-Gandarillas CI et al. Effects of two cations on gastrointestinal absorption of ofloxacin. Antimicrob Agents Chemother . 1991; 35:2102-5. [PubMed 1759833][PubMedCentral]
537. Reviewers' comments (personal observations) on ciprofloxacin.
538. Wolfson JS, Hooper DC. Comparative pharmacokinetics of ofloxacin and ciprofloxacin. Am J Med . 1989; 87(Suppl 6C):31-6S.
539. Reviewer's comments (personal observations).
540. Goldstein EJ, Citron DM. Susceptibility of anaerobic bacteria isolated from intra-abdominal infections to ofloxacin and interaction of ofloxacin and metronidazole. Antimicrob Agents Chemother . 1991; 35:2447-9. [PubMed 1804024][PubMedCentral]
541. McNeil Pharmaceutical, Springhouse, PA: Personal communication.
542. Courvalin P. Plasmid-mediated 4-quinolone resistance: a real or apparent absence? Antimicrob Agents Chemother . 1990; 34:681-4.
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. Pequet S, Andremont A, Tancrède C. Effect of oral ofloxacin on fecal bacteria in human volunteers. Antimicrob Agents Chemother . 1987; 31:124-5. [PubMed 3471178][PubMedCentral]
545. Yew WW, Kwan SY, Ma WK et al. In-vitro activity of ofloxacin against Mycobacterium tuberculosis and its clinical efficacy in multiply resistant pulmonary tuberculosis. J Antimicrob Chemother . 1990; 26:227-36. [PubMed 2120177]
546. Khuri-Bulos N, Shaker K. Relapse of brucellosis following ofloxacin therapy. Infection . 1991; 22:302-3.
547. Healy DP, Polk RE, Kanawati L et al. Interaction between oral ciprofloxacin and caffeine in normal volunteers. Antimicrob Agents Chemother . 1989; 33:474-8. [PubMed 2729942][PubMedCentral]
548. Harder S, Staib AH, Beer C et al. 4-Quinolones inhibit biotransformation of caffeine. Eur J Clin Pharmacol . 1988; 35:651-5. [PubMed 2853056]
549. Carmargo EE, Sostre S, Sazdot B. Global and regional cerebral metabolic rate of 2[18F]fluoro-2-deoxy-d-glucose in the presence of ofloxacin, a gamma-aminobutyric acid A receptor antagonist. Antimicrob Agents Chemother . 1991; 35:648-52. [PubMed 1648886][PubMedCentral]
550. Kohler RB, Arkins N, Tack KJ. Accidental overdose of intravenous ofloxacin with benign outcome. Antimicrob Agents Chemother . 1991; 35:1239-40. [PubMed 1929271][PubMedCentral]
552. Forstall GJ, Knapp CC, Washington JA. Activity of new quinolones against ciprofloxacin-resistant staphylococci. Antimicrob Agents Chemother . 1991; 35:1679-81. [PubMed 1656873][PubMedCentral]
553. Blum A. Ofloxacin-induced acute severe hepatitis. South Med J . Letter.
554. 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]
556. Lamp KC, Bailey EM, Rybak MJ. Ofloxacin clinical pharmacokinetics. Clin Pharmacokinet . 1992; 22:32-46. [PubMed 1559306]
557. DuPont HL, Ericsson CD, Mathewson JJ et al. Five versus three days of ofloxacin therapy for traveler's diarrhea: a placebo-controlled study. Antimicrob Agents Chemother . 1992; 36:87-91. [PubMed 1590705][PubMedCentral]
559. Zenilman JM, Neumann T, Patton M et al. Antibacterial activities of OPC-17116, ofloxacin, and ciprofloxacin against 200 isolates of Neisseria gonorrhoeae . Antimicrob Agents Chemother . 1993; 37:2244-6. [PubMed 8257153][PubMedCentral]
560. Raoult D. Treatment of Q fever. Antimicrob Agents Chemother . 1993; 37:1733-6. [PubMed 8239576][PubMedCentral]
561. Akova M, Uzun O, Akalin HE et al. Quinolones in the treatment of human brucellosis: comparative trial of ofloxacin-rifampin versus doxycycline-rifampin. Antimicrob Agents Chemother . 1993; 37:1831-4. [PubMed 8239591][PubMedCentral]
562. Karabay O, Sencan I, Kayas D et al. Ofloxacin plus rifampicin versus doxycycline plus rifampicin in the treatment of brucellosis: a randomized clinical trial [ISRCTN11871179]. BMC Infect Dis . 2004; 4:18. [PubMed 15214959][PubMedCentral]
564. Kohno S, Koga H, Kaku M et al. Prospective comparative study of ofloxacin or ethambutol for the treatment of pulmonary tuberculosis. Chest . 1992; 102:1815-8. [PubMed 1446494]
565. Yew WW, Wong CF, Wong PC et al. Adverse neurological reactions in patients with multidrug-resistant pulmonary tuberculosis after coadministration of cycloserine and ofloxacin. Clin Infect Dis . 1993; 17:289-90. [PubMed 8399889]
566. Trucksis M, Wolfson JS, Hooper DC. A novel locus conferring fluoroquinolone resistance in Staphylococcus aureus . J Bacteriol . 1991; 173:5854-60. [PubMed 1653224][PubMedCentral]
568. Bebear C, Dupon M, Renaudin H et al. Potential improvements in therapeutic options for mycoplasmal respiratory infections. Clin Infect Dis . 1993; 17(Suppl 1):S202-7.
569. Kimura M, Kishimoto T, Niki Y et. In vitro and in vivo antichlamydial activities of newly developed quinolone antimicrobial agents. Antimicrob Agents Chemother . 1993; 37:801-3. [PubMed 8494377][PubMedCentral]
578. Centers for Disease Control and Prevention. Decreased susceptibility of Neisseria gonorrhoeae to fluoroquinolone—Ohio and Hawaii, 1992-1994. MMWR Morb Mortal Wkly Rep . 1994; 43:325-7. [PubMed 8164636]
580. Tapsall JW, Schultz TR, Lovett R et al. Failure of 500 mg ciprofloxacin therapy in male urethral gonorrhoea. Med J Aust . 1992; 156:143. [PubMed 1736071]
581. Bogaerts J, Tello WM, Akingeneye J et al. Effectiveness of norfloxacin and ofloxacin for treatment of gonorrhoea and decrease of in vitro susceptibility to quinolones over time in Rwanda. Genitourin Med . 1993; 69:196-200. [PubMed 8335312][PubMedCentral]
583. Turner A, Jephcott AE, Gough KR. Laboratory detection of ciprofloxacin resistant Neisseria gonorrhoeae. J Clin Pathol . 1991; 44:169-70. [PubMed 1907618][PubMedCentral]
584. 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]
585. 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]
586. Bartlett JG. Antibiotic-associated diarrhea. Clin Infect Dis . 1992; 573-81.
588. DuPont HL, Ericsson CK. Prevention and treatment of traveler's diarrhea. N Engl J Med . 1993; 328:1821-7. [PubMed 8502272]
589. DuPont. Travellers' diarrhoea: which antimicrobial? Drugs . 1993; 45:910-7.
590. Adachi JA, Ostrosky-Zeichner L, DuPont HL et al. Empirical antimicrobial therapy for travelers' diarrhea. Clin Infect Dis . 2000; 31:1079-83. [PubMed 11049792]
592. Lehto P, Kivistö KT. Effect of sucralfate on absorption of norfloxacin and ofloxacin. Antimicrob Agents Chemother . 1994; 38:248-51. [PubMed 8192452][PubMedCentral]
593. Baciewicz Am, Ashar BH, Locke TW. Interaction of ofloxacin and warfarin. Ann Intern Med . 1993; 119:1223. [PubMed 8239258]
594. Minakari M, Davarpanah Jazi AH, Shavakhi A et al. A randomized controlled trial: efficacy and safety of azithromycin, ofloxacin, bismuth, and omeprazole compared with amoxicillin, clarithromycin, bismuth, and omeprazole as second-line therapy in patients with Helicobacter pylori infection. Helicobacter . 2010; 15:154-9. [PubMed 20402818]
595. Fakheri H, Bari Z, Aarabi M et al. Helicobacter pylori eradication in West Asia: a review. World J Gastroenterol . 2014; 20:10355-67. [PubMed 25132752][PubMedCentral]
596. Mansour-Ghanaei F, Joukar F, Naghipour MR et al. Seven-day quintuple regimen as a rescue therapy for Helicobacter pylori eradication. World J Gastroenterol . 2015; 21:661-6. [PubMed 25593496][PubMedCentral]
612. Caeiro JP, DuPont HL. Management of travelers' diarrhoea. Drugs . 1998; 56:73-81. [PubMed 9664200]
620. 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]
621. Doganay M, Aydin N. Antimicrobial susceptibility of Bacillus anthracis . Scand J Infect Dis . 1991; 23:333-5. [PubMed 1909051]
623. Syrjala H, Schildt R, Raisainen S. In vitro susceptibility of Francisella tularensis to fluoroquinolones and treatment of tularemia with norfloxacin and ciprofloxacin. Eur J Clin Microbiol Infect Dis . 1991; 10:68-70. [PubMed 1864276]
624. 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]
625. Smith MD, Vinh DX, Nguyen TT et al. In vitro antimicrobial susceptibilities of strains of Yersinia pestis . Antimicrob Agents Chemother . 1995; 39:2153-4. [PubMed 8540736][PubMedCentral]
626. Bonacorsi SP, Scavizzi MR, Guiyoule A et al. Assessment of a fluoroquinolone, three beta-lactams, two aminoglycosides, and a cycline in treatment of murine Yersinia pestis infection. Antimicrob Agents Chemother . 1994; 38:481-6. [PubMed 8203841][PubMedCentral]
627. Byrne WR, Welkos SL, Pitt ML et al. Antibiotic treatment of experimental pneumonic plague in mice. Antimicrob Agents Chemother . 1998; 42:675-81. [PubMed 9517950][PubMedCentral]
630. Choe CH, Bouhaouala SS, Brook I et al. In vitro development of resistance to ofloxacin and doxycycline in Bacilluls anthracis Sterne. Antimicrob Agents Chemother . 2000; 44:1766. [PubMed 10896651][PubMedCentral]
631. Cavallo JD, Ramisse F, Giradet M et al. Antibiotic susceptibilities of 96 isolates of Bacillus anthracis isolated in France between 1994 and 2000. Antimicrob Agents Chemother . 2002; 46:2307-9. [PubMed 12069996][PubMedCentral]
632. Bearden DT, Danziger LH. Mechanism of action of and resistance to quinolones. Pharmacotherapy . 2001; 21:224S-32S. [PubMed 11642689]
633. Hooper DC. Mode of action of fluoroquinolones. Drugs . 1999; 58(Supple 2):6-10. [PubMed 10553698]
634. Hooper DC. Quinolones. In: Mandell GL, Bennett JE, Dolin R eds. Mandell, Douglas and Bennett's principles and practice of infectious diseases. 5th ed. Philadelphia: Churchill Livingstone; 2000:406-7.
635. Zhanel GG, Ennis K, Vercaigene L et al. A critical review of the fluoroquinolones: focus on respiratory tract infections. Drugs . 2002; 62:13-59. [PubMed 11790155]
636. Hooper DC. Mechanisms of action and resistance of older and newer fluoroquinolones. Clin Infect Dis . 2000; 31(Supple 2):S24-8. [PubMed 10984324][PubMedCentral]
642. 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.
643. Bosques-Padilla FJ, Garza-Gonzalex E, Calderon-Lozano IE et al. Open, randomized multicenter comparative trial of rabeprazole, ofloxacin and amoxicillin therapy for helicobacter pylori eradication: 7 vs. 14 day treatment. Helicobacter . 2004; 9:417-21. [PubMed 15361080]
644. Huang TS, Kunin CM, Lee SS et al. Trends in fluoroquinolone resistance of Mycobacterium tuberculosis complex in Taiwanese medical centre: 1995-2003. J Antimicrob Chemother . 2005; 56:1058-62. [PubMed 16204341]
645. World Health Organization. Extensively drug-resistant tuberculosis (XDR-TB): recommendations for prevention and control. Wkly Epidemiol Rec . 2006; 45:430-2.
646. 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]
648. Shi R, Zhang J, Li C et al. Emergence of ofloxacin resistance in Mycobacterium tuberculosis clinical isolates from China as determined by gyrA mutation analysis using denaturing high-pressure liquid chromatography and DNA sequencing. J Clin Microbiol . 2006; 44:4566-8. [PubMed 17035499][PubMedCentral]
649. Dudley MN, Marchbanks CR, Flor SC et al. The effect of food or milk on the absorption kinetics of ofloxacin. Eur J Clin Pharmacol . 1991; 41:569-71. [PubMed 1815968]
650. Neuvonen PJ, Kivisto KT. Milk and yoghurt do not impair the absorption of ofloxacin. Br J Clin Pharmacol . 1992; 33:346-8. [PubMed 1576061][PubMedCentral]
651. Mueller BA, Brierton DG, Abel SR et al. Effect of enteral feeding with ensure on oral bioavailabilities of ofloxacin and ciprofloxacin. Antimicrob Agents Chemother . 1994; 38:2101-5. [PubMed 7811026][PubMedCentral]
659. 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]
660. 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]
661. 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]
662. Bartlett JG, Peri TM. The new Clostridium difficile -what does it mean? N Engl J Med . 2005; 353:2503-5.
664. 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]
665. 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.
666. Shitrit D, Baum GL, Priess R et al. Pulmonary Mycobacterium kansasii infection in Israel, 1999-2004: clinical features, drug susceptibility, and outcome. Chest . 2006; 129:771-6. [PubMed 16537880]
667. 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.
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]
670. 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]
671. Bradley JS, Peacock G, Krug SE et al. Pediatric anthrax clinical management. Pediatrics . 2014; 133:e1411-36. [PubMed 24777226]
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]
674. 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]
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]
676. 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]
682. Centers for Disease Control and Prevention. Update: investigation of anthrax associated with intentional exposure and interim public health guidelines, October 2001. MMWR Morb Mortal Wkly Rep . 2001; 50:889-93. [PubMed 11686472]
683. US Army Medical Research Institute of Infectious Disease. USAMRIID's medical management of biologic casualties handbook. 7th ed. USAMRIID: Fort Detrick, MD; 2011 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]
772. Pappas G, Akritidis N, Bosilkovski M et al. Brucellosis. N Engl J Med . 2005; 352:2325-36. [PubMed 15930423]
851. US Food and Drug Administration. FDA news. FDA requests boxed warnings on fluoroquinolone antimicrobial drugs. From FDA website. Accessed 2008 Sept 8. [Web]
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]