Randomized controlled trials (RCTs) have found single-dose antibiotics to be effective in the treatment of uncomplicated genital gonorrhoea, although they are less effective in the treatment of pharyngeal gonorrhoea. Cephalosporins, fluoroquinolones, and macrolides have historically all produced microbiological cure rates in excess of 95%, but recent issues with bacterial resistance have meant that third-generation cephalosporins (cefixime or ceftriaxone) are recommended first line.

Overall effectiveness of antibiotics

• A systematic review (search date: 1981 to 1993) investigated the effectiveness of single-dose antibiotics in men and women with confirmed gonorrhoea infection [Moran and Levine, 1995]. In total, 24,383 trial participants receiving 30 different antibiotic regimens (21 antibiotic drugs) were analysed. The main outcome reported was microbiological cure.
• Most of the antibiotics were highly effective, with an overall cure rate of 96.7%.
• Antibiotics that were effective included cephalosporins, fluoroquinolones, and macrolides (penicillin drugs were not studied, or these trials predated the literature search).
• Antibiotics were at least 95% effective for the treatment of gonorrhoea of the male and female urethra, male and female rectum, and cervix. For example, the cure rate for male urethritis was 96.4% (95% CI 96.0 to 96.7).
• Antibiotics were less effective in the treatment of pharyngeal gonorrhoea, with a 79.2% cure rate in men (95% CI 73.3 to 85.2) and 83.6% in women (95% CI 78.9 to 88.4).
• The investigators found a good correlation between the cure rate and the minimum inhibitory concentration required to inhibit the growth of 90% of organisms (MIC₉₀, calculated from studies in vitro). The authors commented that, ideally, a drug should achieve a plasma concentration of four times its MIC₉₀ for a minimum of 10 hours to be considered fully effective.
• The authors concluded that ceftriaxone, cefixime, ciprofloxacin, or ofloxacin was the preferred treatment for people with uncomplicated gonorrhoea. Fluoroquinolones are no longer suitable for empirical treatment because of problems with resistance. See Resistance to antibiotics for more information.

Effectiveness of ceftriaxone and cefixime

• CKS identified three comparative RCTs that investigated the effectiveness of intramuscular ceftriaxone and oral cefixime (third-generation cephalosporin antibiotics recommended first line by UK national guidelines [BASHH, 2005b]).
• One study randomized 128 men with confirmed gonococcal urethritis to receive either ceftriaxone 250 mg or cefoxitin 2 g (both delivered intramuscularly) [Zajdowicz et al, 1983]. Both drugs were highly effective at curing the infection, with ceftriaxone having a 100% success rate and cefoxitin having a 99% success rate (one person with penicillin-resistant gonorrhoea relapsed).
• One study in 393 people with uncomplicated and/or pharyngeal gonorrhoea randomized them to receive a single 250 mg dose of ceftriaxone or pivampicillin (1.2 grams with probenecid, unavailable in the UK) [Christophersen et al, 1989]. Ceftriaxone was found to have a 100% cure rate for both sites of infection (70 people had pharyngeal infection).
• One study randomized 209 men and 124 women with uncomplicated gonorrhoea to receive one of three interventions: oral cefixime 400 mg or 800 mg, or intramuscular ceftriaxone 250 mg [Handsfield, 1991].
• The overall microbiological cure rates were similar in men and women: 96% (95% CI 94 to 98) for cefixime 400 mg, 98% (95% CI 95 to 100) for cefixime 800 mg, and 98% (95% CI 95 to 100) for ceftriaxone.
• However, only 91% of people presenting with pharyngeal gonorrhoea were successfully treated, and about 50% of people who presented with coexisting chlamydia had persistent chlamydial infection.