What is the appropriate therapy for asymptomatic gonorrhoea in men who have sex with men?

Dear Editor,

Guidelines from Europe and the United States advocate screening sexually active men who have sex with men (MSM) from three- to 12-monthly for gonorrhoea and chlamydia.^1,2 No specific mention is made of appropriate eradication therapy but it is generally assumed that this should be the same dual therapy (ceftriaxone/azithromycin) advocated for symptomatic infection. The rationale for dual therapy in symptomatic gonorrhea is to prevent the emergence of resistance. ³ We propose that concerns around long-term residual ecological antimicrobial resistance lead to a reconsideration of this approach in asymptomatic cases of gonorrhoea detected in MSM screening programmes.

It is increasingly appreciated that antibiotic usage can have a profound impact on the composition of the recipient’s microbiome and resistome. Typically, antibiotic usage is associated with an increase in the prevalence of resistance-associated genes. A number of studies have found that the impact of macrolides endures the longest. In two studies, the use of macrolides was associated with a large increase (three to five orders of magnitude) in prevalence of the erm (macrolide-resistance) genes. This increase persisted for the duration of the studies (two and four years).^4,5 This effect has been found in the pharyngeal and the colonic microbiomes.^4,6 In another study, azithromycin was found to have the most enduring effect. ⁶

Screening programmes typically detect gonorrhoea in 3–10% of MSM attending sexual health services,^7,8 which means that treatment of asymptomatic N. gonorrhoeae may put more antibiotic pressure on the MSM resistome than the treatment of symptomatic gonorrhoea. We were unable to find any direct evidence that screening programmes reduce the prevalence of N. gonorrhoeae in MSM. This makes it all the more important to ensure they do as little harm as possible – particularly in terms of their effects on the resistome. Given that detection of gonorrhoea is a marker of connection to a high-risk section of the sexual network, individuals screening positive are likely to have a higher than average risk of becoming reinfected with gonorrhoea and other sexually transmitted infections. ⁹ If their initial gonorrhoea was treated with the current protocol that includes azithromycin then there is a risk that if they are re-infected within four years that macrolide resistance mechanisms will be relatively widespread in their microbiome. As such, there is a risk of the new gonorrhoea infection acquiring these resistance mechanisms. This transfer of antibiotic resistance genes from indigenous microbes to newly arriving N. gonorrhoeae is thought to have been important in the genesis of gonococcal cephalosporin resistance ¹⁰ and in other examples of rapid acquisition of antibiotic resistance. ¹¹ Given the risks of gonorrhoea evolving to become untreatable, even if this risk is small it is not trivial. ¹⁰

We still do not understand why gonococcal resistance to quinolones and cephalosporins first emerged in MSM. ¹² One study that investigated explanatory factors found that a higher antibiotic usage in the prior 60 days to be a risk factor. ¹² Studies are needed to assess the longer-term ecological level role that antibiotic prescriptions could be playing in this regard. An alternative approach to therapy of asymptomatic gonorrhoea would include single therapy with intramuscular ceftriaxone, which is successful in gonococcal eradication in over 95% of rectal, urethral and pharyngeal cases. ¹³ If combination therapy is required then other agents that do not have such an enduring effect on the resistome (such as gentamicin) could be used. Prospective randomised studies should be conducted to compare the efficacy of these strategies on gonococcal clearance as well as their long-term impact on the recipient’s microbiome and resistome.