New fluoroquinolones have generally been well tolerated. In a double-blind evaluation of oral fleroxacin, using 400, 600, or 800 mg once daily for 7 days in an ambulatory setting for treatment of uncomplicated genital infections, we encountered unexpectedly high rates of adverse reactions. The objective of this analysis was to determine whether any factors in addition to dose could be found to account for our observations. Adverse Fluoroquinolones have generally been considered to be relatively safe antimicrobial agents (7, 9). The most frequently reported adverse reactions were gastrointestinal (2.9 to 5.6%), central nervous system (0.9 to 1.7%), and skin (0.4 to 2.2%) reactions, with overall rates of adverse reactions of 4 to 8% (7). Reactions were reversible, not dose dependent, and similar among different fluoroquinolones (7).Our own experience with norfloxacin in a sexually transmitted disease clinic setting was very favorable (3). However, not all quinolones have been well tolerated, and adverse reactions have prevented marketing of some (8,12). In a double-blind clinical trial of fleroxacin, using 400, 600, and 800 mg once daily for 7 days, adverse reactions were dose related, frequent at higher doses, and often reported by the patient as being severe. Especially frequent or troublesome were insomnia, bad dreams or nightmares, and photosensitivity reactions resulting in desquamation. Consequently, in this study we attempted to ascertain what factors might have accounted for our observations. MATERIALS AND METHODSStudy population and protocol. Men and women 18 years of age and older who presented to the Vancouver and Calgary Sexually Transmitted Disease Clinics were eligible for the study. Entrance criteria and study design are described in our companion paper (4). At the initial visit, individuals completed a detailed questionnaire about symptoms, sexual history, prior use of antimicrobial agents, use of other medications (prescribed, over the counter, and recreational), and exclusion criteria. After the initial evaluation, all were then given medication to be taken with or immediately after meals at a similar time each day. All took * Corresponding author.four identical tablets daily, of which two, three, or four contained active medication. Thus, they received 400, 600, or 800 mg daily for 7 days. The patients and the investigators were blind as to the regimen received.Subjects were specifically warned not to use antacids.They were also warned that caffeine might interact unfavorably with fleroxacin. In the last two-thirds of the study, they were urged to avoid sun exposure or else to take more precautions than usual, including use of sunscreens, long sleeves, and hats.

In this randomized study, a single 800-mg oral dose of cefixime cured 96 of 97 men with uncomplicated gonococcal urethritis, compared with 44 cures of 46 men who received standard therapy with amoxicillin (3 g) plus probenecid (1 g). Both regimens were ineffective against coexistent infection with Chiamydia trachomatis and Ureaplasma urealyticum. Cefixime was well tolerated, and all side effects were mild and self-limited.Cefixime is a novel oral cephalosporin with ,-lactamase stability and in vitro activity similar to that of many of the broad-spectrum cephalosporins (5, 6). Previous studies have revealed that Neisseria gonorrhoeae is highly susceptible to cefixime in vitro (2,5,6). MICs for 90% of isolates of penicillin-susceptible strains as well as for those strains demonstrating penicillinase production and chromosomally mediated resistance have been 0.05 ,ug/ml. Furthermore, it has been shown that a single 400-mg oral dose of cefixime in healthy volunteers results in mean levels in serum of 3.85 ,ug/ml at 4.3 h (peak) and 1.13 ,ug/ml at 12 h following administration (4). Thus, we wished to compare the clinical efficacy and tolerability of a single dose of cefixime (in this case, 800 mg) with those of an established regimen, namely amoxicillin and probenecid, in the treatment of uncomplicated gonorrhea in men.Males aged 18 years and older with positive cultures for N. gonorrhoeae from any site or with gram-negative intracellular diplococci from endourethral or rectal swabs were eligible for study. Patients receiving antimicrobial therapy in the preceding 2 weeks were excluded from the study, as were persons with a history of hypersensitivity to penicillins or cephalosporins and those with serious underlying disorders. All participants provided informed, written consent.At the initial visit, all patients were questioned about symptoms, prior medications, and sexual history and underwent examination of the external genitalia. Endourethral swabs for Gram stain and culture for N. gonorrhoeae, Chlamydia trachomatis, and Ureaplasma urealyticum were collected. Pharyngeal swabs for N. gonorrhoeae culture were obtained from all patients, but rectal swabs were performed only on homosexual and bisexual men. Patients were then randomized in a 2:1 ratio to receive either cefixime (800 mg in four 200-mg capsules) as a single oral dose (without probenecid) or amoxicillin (3.0 g) and probenecid (1.0 g) orally. All men were provided with a diary card to record subsequent side effects, symptoms, and sexual contact, if any. * Corresponding author. Patients were requested to return for follow-up 6 to 9 days after treatment, and men whose cultures were initially C. trachomatis positive and those with persistent symptoms or signs of infection following therapy were encouraged to return 3 and 6 weeks posttreatment. At each follow-up, patients were questioned about side effects, symptoms, and sexual activity. Physical examination was repeated, as were swabs for endourethral Gram stain and N. gonorrhoeae, C. trachomatis, and U. ure...

Men and women with suspected or proven genital infections caused by Chiamydia trachomatis were enrolled in a double-blind study to evaluate the efficacy and tolerability of fleroxacin. Patients received either 400, 600, or 800 mg once daily for 7 days and were monitored approximately 2, 4, and 7 weeks after initiation of therapy. In men monitored for at least 6 weeks or until failure of the therapy, fleroxacin failed to eradicate C. trachoniahis in three of eight on the 400-mg regimen, in one of four on the 600-mg regimen, and in four of seven on the 800-mg regimen. All

Norfloxacin has some activity in vitro against Chiamydia trachomatis and Ureaplasma urealyticum, although not at levels attainable in serum. In this study, norfloxacin was administered (400 mg orally twice daily for 10 days) to men with acute nongonococcal urethritis. Of 25 men from whom C. trachomatis was initially isolated, 21 had the organism reisolated at the first follow-up visit posttreatment, and there were minimal changes in the number of inclusion-forming units in culture. Ultimately, all but 1 of the 22 men from whom C. trachomatis was initially isolated and who were monitored became clinical failures within 42 ± 7 days posttreatment. The clinical outcome was significantly better for men from whom U. urealyticum was initially isolated but from whom C. trachomatis was not isolated. Of 27 men, 17 became and stayed culture negative for U. urealyticum at follow-ups, and clinically, 15 no longer had nongonococcal urethritis. Of these 15, all 12 monitored until at least 42 ± 7 days posttreatment remained improved. Of 26 men from whom neither C. trachomatis nor U. urealyticum was initially isolated, 18 improved and all 15 who were monitored until at least 42 ± 7 days posttreatment remained improved. Thus, although norfloxacin attains high levels in urine and has good tissue penetration, it had essentially no activity against chlamydial urethritis in men. It had better, but incomplete, activity against U. urealyticum. For quinolones to show promise in vivo against C. trachomatis, either the MICs will need to be much lower or the levels attained in serum will have to be much higher.The search for an antimicrobial agent active against the major bacterial genital pathogens continues. Norfloxacin at 600 mg orally, with the same dose repeated 4 h later, was highly effective in vivo against penicillin-susceptible and -resistant Neisseria gonorrhoeae (4). The in vivo activity of norfloxacin against Chlamydia trachomatis and genital mycoplasmas is not known. In vitro, the MICs of norfloxacin against C. trachomatis (1, 5, 6, 8, 9, 13) and Ureaplasma urealyticum (1) have been 8 to 64 ,ug/ml. These levels exceed those attainable in serum, but because norfloxacin has good tissue penetration, urinary levels exceed the MICs, and in vitro results do not always accurately predict in vivo efficacy, a recent review concluded that norfloxacin should be evaluated for activity in nongonococcal urethritis (7). In this study, norfloxacin (400 mg orally twice daily for 10 days) was administered to men with acute nongonococcal urethritis and its clinical and microbiological efficacy was evaluated. compounds, and subsequently had a negative urethral culture for N. gonorrhoeae. MATERIALS AND METHODSProtocol. Men were administered a standard questionnaire, and a genital exam which included stripping the urethra from the base to the meatus at least three times was performed to detect urethral discharge and other abnormalities. A calcium alginate endourethral swab was then inserted 3 to 4 cm into the urethra for culture for C. trachomatis....

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