Treatment recommendations are based on the National guideline on the diagnosis and treatment of gonorrhoea in adults, published by the British Association for Sexual Health and HIV (BASHH) [BASHH, 2005b], a primary care guideline [RCGP and BASHH, 2006], and a European guideline [Bignell, 2009].

Treatment with antibiotics

• For ethical reasons, the efficacy of antibiotics for gonorrhoea has not been established compared with placebo. However, historical evidence suggests that left untreated, Neisseria gonorrhoeae will cause prolonged infectivity and symptoms over several weeks, with a risk of chronic complications [Handsfield and Sparling, 2005].
• Good evidence from several comparative randomized controlled trials (RCTs) supports the use of antibiotics in the treatment of gonorrhoea. Historically, cephalosporins, fluoroquinolones, and macrolides have produced microbiological cure rates in excess of 95% in these trials [Moran and Levine, 1995].

Choice of antibiotics

• Since the introduction of sulphonamides in the 1930s, there has been growing evidence of gonococcal resistance to antibiotics [Workowski et al, 2008]. Therefore, antibiotic recommendations are mainly based on current gonococcal sensitivity to antibiotics, rather than historical evidence of their efficacy from RCTs [Tyson, 2005].
• Cephalosporins are recommended first line because N. gonorrhoeae is currently sensitive to this drug class [HPA, 2010a]. Cefixime and ceftriaxone are third-generation cephalosporins that have shown evidence of a cure rate greater than 95% in RCTs (the accepted level of effectiveness) [Moran and Levine, 1995].
• The use of cefixime for the treatment of gonorrhoea is off-label [ABPI Medicines Compendium, 2008a], but one RCT showed it to be effective at a single oral dose of 400 mg (cure rate 96%, 95% CI 94 to 98) [Handsfield, 1991].
• Ceftriaxone is less convenient than cefixime but was shown to give a 100% cure rate in one trial of people with uncomplicated infection [Zajdowicz et al, 1983], and in one trial which included people with pharyngeal infection [Christophersen et al, 1989].
• Confirmed therapeutic failure to cefixime is rare, and is undocumented for ceftriaxone in England and Wales [HPA, 2010a]. However, in 2009, 1.2% of gonococcal isolates demonstrated reduced susceptibility to cefixime, and 0.3% to ceftriaxone.
• For treatment of pharyngeal gonorrhoea, BASHH recommends ceftriaxone first line [BASHH, 2005b]. However, because ceftriaxone is not usually readily available in primary care, some experts recommend an alternative 3-day regimen of cefixime on the basis of pharmacokinetic principles [Horner, Personal Communication, 2009]. This is reasonable, as a test of cure is always recommended for pharyngeal gonorrhoea (see Follow-up).
• Ciprofloxacin and ofloxacin are fluoroquinolones that are recommended if cephalosporins are contraindicated, most commonly because of documented beta-lactam allergy (allergy to penicillins, cephalosporins, and associated antibiotics). Between 1% and 10% of people with penicillin allergy are thought to have cross-sensitivity to cephalosporins [Workowski et al, 2008].
• Good evidence from RCTs indicates that fluoroquinolones have been effective in the treatment of gonorrhoea [Bignell, 1996]. However, evidence from surveillance data indicates that there is endemic resistance of gonorrhoeal isolates to ciprofloxacin, with a prevalence of around 35% [HPA, 2010a]. Therefore, it is important that the sensitivity of the infection is known before treatment with a fluoroquinolone is prescribed.
• The manufacturers of ciprofloxacin (Ciproxin^®) and ofloxacin (Taravid^®) state that fluoroquinolones should be avoided in people with tendonitis or epilepsy [ABPI Medicines Compendium, 2008b; ABPI Medicines Compendium, 2009]. However, the adverse effects of fluoroquinolones are not likely to be significant, as they are given as a single dose for the treatment of gonorrhoea.

Antibiotics not recommended for confirmed gonorrhoea

• Ampicillin combined with probenecid is recommended as an alternative regimen by BASHH, provided that bacterial sensitivity is known [BASHH, 2005b], but this is an impractical option in primary care because of the limited availability of probenecid [BNF 57, 2009]. Likewise, spectinomycin is recommended for empirical treatment but is not widely available in primary care in the UK.
• Other cephalosporins are options but have not been as extensively studied as ceftriaxone, and they do not offer any additional benefits [BASHH, 2005b].
• Azithromycin is not recommended by BASHH, despite having shown adequate efficacy in RCTs. The guideline development group state 'the emergence of azithromycin resistant N. gonorrhoeae has been reported and clinical efficacy does not always correlate with in vitro sensitivity testing'. In addition, there are concerns cited that high-dose azithromycin is associated with gastrointestinal intolerance [BASHH, 2005b].

Empirical treatment

• As it is not possible to accurately differentiate between infection with N. gonorrhoeae and Chlamydia trachomatis by clinical features alone, and the infections often coexist, empirical treatment aims to cover both organisms [RCGP and BASHH, 2006].
• Azithromycin and doxycycline have both been shown to be effective in the treatment of chlamydia by RCTs [Lau and Qureshi, 2002], and they are recommended by national guidelines for chlamydia [BASHH, 2006] and non-gonococcal urethritis [BASHH, 2007].