Single-dose oral cefixime versus amoxicillin plus probenecid for the treatment of uncomplicated gonorrhea in men

Abstract

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...

Treatment of uncomplicated gonococcal urethritis by double-dosing of 200mg cefixime at a 6-h interval

“…17 In Japan, where the efficacy of oral regimens with fluoroquinolone and cephalosporin is failing, 11,18 the emergence of resistance to ceftriaxone and specinomycin in clinical strains of N. gonorrhoeae, which would be disastrous for the treatment of gonococcal infections, must be prevented. At the same time, because oral regimens are clinically more convenient for the treatment of gonococcal urethritis, new oral regimens, including a single-dose regimen with an increased dose of cefixime; for example, a single dose of 800 mg cefixime or more, 9,[19][20][21][22] must be developed.…”

Efficacy and Safety of Injectable and Oral Antibiotics in Treating Gonorrhea: A Systematic Review and Network Meta-Analysis

“…Nineteen of these studies reported adverse reactions in 569 patients and the safety of 11 drugs was assessed [27][28][29][30][31][32][33][34][36][37][38][39][40][41][44][45][46]49,50]. Similarly, 19 studies focused on oral monotherapy [51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66][67][68][69][70]. These studies of oral drugs involved 3782 patients, and compared the efficacy of 11 antibiotics.…”

Activity of cefixime against Neisseria gonorrhoeae

“…Cefixime eradicated also 75% (6/8) [25] to 93% (14/15) [19] of pharyngeal gonococcal infections. The number of documented-treated rectal infections is quite low, but so far, 100% eradication of Neisseria gonorrhoea from the rectum was achieved [19.25].…”

“…Treatment of uncomplicated gonorrhoea with a single oral dose of 800 mg cefixime achieved cure rates of 98% (86/88) [19] to 99% (96/97) [25]. A single oral dose of 400 mg cefixime resulted in cure rates ranging from 96%; (89/93) [19] to 98% (118/121) [16], and even reducing the dose to 200 mg cefixime seemed to be effective, with a cure rate of 95%' (93/98) [18].…”

“…It might be possible that an incubating primary syphilitic infection, simultaneously acquired with gonorrhoea, will also be treated simultaneously with a single oral dose of cefixime. Like all cephalosporins, cefixime is not active against Chlamydia trachomatis and Ureaplasma urealyticum [17,25]. To prevent post gonococca I urethritis, cefixime treatment should be followed by a regimen effective against C trachomatis.…”