Comparative double-blind study of 200- and 400-mg enoxacin given orally in the treatment of acute uncomplicated urethral gonorrhea in males

Abstract

In a double-blind randomized study, 155 male patients with uncomplicated urethral gonorrhea were given 200 mg (one capsule with 200 mg and one capsule with placebo; n = 77) or 400 mg (two capsules with 200 mg; n = 78) of enoxacin orally. The cure rates in the 200-and 400-mg treatment groups were 90 and 92%, respectively. The enoxacin MIC for the isolated Neisseria gonorrhoeae strains ranged from 0.015 to 0.12 ,ug/ml.Postgonococcal urethritis was diagnosed in 29 (42%) patients in the 200-mg treatment group and 19 (26%) patients in the 400-mg treatment group. Side effects (nausea, headache, and vomiting) occurred in 2 (3%) of the 77 patients in the 200-mg treatment group and in 3 (4%) of the 78 patients in the 400-mg treatment group.The increasing resistance of Neisseria gonorrhoeae to penicillins and tetracycline calls for new therapeutic agents. The 4-quinolone group has yielded some derivatives that are active against N. gonorrhoeae and can be given orally. Cure rates of up to 100% have been reported in previous studies with ciprofloxacin in the treatment of uncomplicated urogenital gonorrhea in males (12) and with enoxacin in the treatment of uncomplicated urogenital gonorrhea in females (4, 13). In vitro studies have shown that enoxacin, one of the new quinolone agents, is effective against N. gonorrhoeae with MICs of 0.03 to 0.25 ,ug/ml (8). Our double-blind randomized study involved clinical evaluation of the treatment of uncomplicated urethral gonorrhea in males with a single oral dose of either 200 or 400 mg of enoxacin. MATERIALS AND METHODSPatient population. All patients were men attending the outpatient clinic for sexually transmitted diseases at the University Hospital Rotterdam-Dijkzigt. Patients who were under 18, had disseminated gonococcal infections, had solitary rectal or pharyngeal gonococcal infections, had syphilis, liver, or kidney diseases, had allergies to quinolones, and were recently treated with enoxacin or on theophylline medication were excluded. This was a double-blind study. A randomization list ensured that patients received a single oral dose of either 400 mg of enoxacin in two 200-mg capsules or 200 mg of enoxacin in one 200-mg capsule and one placebo capsule. The capsules were taken with water under the supervision of a nurse. The patients were advised to abstain from sexual contacts throughout the follow-up period.All subjects gave oral informed consent before they were enrolled, and the study was approved by the committee for the protection of human subjects at the University Hospital Rotterdam-Dijkzigt.Venereological study. A standard history was taken, and all patients underwent the following tests before and after * Corresponding author.therapy. Gram stains were made of the discharge, and samples for Chlamydia trachomatis and N. gonorrhoeae cultures were taken from the urethra. N. gonorrhoeae culture samples were taken from the pharynx (and from the rectum in homosexual men), and the sediment of 10 to 15 ml of the first-voided urine was collected. Blood was drawn for Vener...

Proposed criteria for interpretation of susceptibilities of strains of Neisseria gonorrhoeae to ciprofloxacin, ofloxacin, enoxacin, lomefloxacin, and norfloxacin

“…Recently, however, the failure of gonococcal infections to respond to CDC-recommended doses of fluoroquinolones has been reported (5,20,23). The failure of an infection to respond to enoxacin was reported in 1987 (23).…”

“…The failure of an infection to respond to enoxacin was reported in 1987 (23). Recently, strains of N. gonorrhoeae exhibiting decreased susceptibilities to ciprofloxacin and ofloxacin have also been reported from Asia (4,17), the United Kingdom (9,11), North America (13,14), and Spain (1).…”

High Prevalence of High-Level Ciprofloxacin Resistance in Neisseria gonorrhoeae in Tel Aviv, Israel: Correlation with Response to Therapy

“…More recently, however, the incidence of gonorrhea has been increasing and was up to 13 reported cases per 100,000 population in 2001 (10). The documentation of a case of gonococcal urethritis with clinical and laboratory failure of ciprofloxacin therapy (9) prompted a study of the antimicrobial susceptibilities of N. gonorrhoeae isolates in the Tel Aviv area of Israel.Gonococcal strains with reduced in vitro susceptibilities to fluoroquinolones (MIC of ciprofloxacin, 0.125 to 0.5 g/ml) were first described in the mid-1980s (5) and since then have been identified in the Far East (7,8,20), Australia (21, 22), Africa (3), Europe (12,13,23), and the United States (4). Fluoroquinolone-resistant N. gonorrhoeae (ciprofloxacin MICs, Ն1 g/ml) emerged during the early 1990s and became well established in several Asian countries (16).…”

“…Gonococcal strains with reduced in vitro susceptibilities to fluoroquinolones (MIC of ciprofloxacin, 0.125 to 0.5 g/ml) were first described in the mid-1980s (5) and since then have been identified in the Far East (7,8,20), Australia (21,22), Africa (3), Europe (12,13,23), and the United States (4). Fluoroquinolone-resistant N. gonorrhoeae (ciprofloxacin MICs, Ն1 g/ml) emerged during the early 1990s and became well established in several Asian countries (16).…”

Persistence of Neisseria gonorrhoeae strains with decreased susceptibilities to ciprofloxacin and ofloxacin in Cleveland, Ohio, from 1992 through 1993

“…CDC currently recommends that broad-spectrum cephalosporins or selected quinolones be used as primary therapies for uncomplicated gonorrhea (2). Clinically significant resistance to enoxacin (16), associated with a demonstrated increase in resistance to quinolones in N. gonorrhoeae, has been confirmed. Clinically significant resistance to ciprofloxacin has been suggested for isolates for which MICs of ciprofloxacin are 0.125 to 0.25 p,g/ml and which have been treated with 250 mg of ciprofloxacin (6).…”