Mycoplasma genitalium: the next sexually transmitted superbug?BMJ 2018; 363 doi: https://doi.org/10.1136/bmj.k4376 (Published 29 October 2018) Cite this as: BMJ 2018;363:k4376
The publication of national treatment guidelines does not usually generate headlines in national newspapers. However, the recent release of draft management guidelines for Mycoplasma genitalium infection was accompanied by high profile media coverage suggesting that it is the next sexually transmitted “superbug.”1 So what are the facts behind these headlines, and how concerned should we be?
First isolated in 1981, M genitalium is the smallest known self replicating bacterium,2 but its natural course of infection and importance for public health remain poorly understood. Most infections are probably asymptomatic and have no adverse health outcomes.34 Nonetheless, evidence that M genitalium is associated with serious genitourinary and reproductive health morbidity is accumulating.
In men, an unequivocal association exists with non-gonococcal urethritis, and it is detected in up to 40% of men with persistent and recurrent urethritis.5 There is some evidence of associations with balanoposthitis6 but no clear association with prostatitis or epididymitis.78 A study among men who have sex with men found no association with symptoms of proctitis and rectal infection.9 In women, a recent meta-analysis found significant associations with a range of clinical syndromes and adverse reproductive health outcomes, including cervicitis, postcoital bleeding, pelvic inflammatory disease, preterm birth, and spontaneous abortion, and a weak association with infertility.10
Data on population prevalence are sparse, but a meta-analysis of six studies suggested that the prevalence of M genitalium infection ranged from 1.3% to 3.9% and was higher in countries with a low development index.11 In Britain, a probability sample survey estimated a prevalence of around 1.3% in the sexually active British population aged 16-44 years.4 In common with many other sexually transmitted infections (STIs), M genitalium infection rates can be considerably higher in men who have sex with men, sex workers, and people attending STI clinics,11 but those infected tend to be older than people with other STIs such as chlamydia; 91% of infected men and 67% of infected women are aged 25 to 44.4
The main concern is M genitalium’s increasing resistance to azithromycin and moxifloxacin, the recommended first and second line treatments in Europe, North America, and Australia, especially in the Asia-Pacific region.1213 For example, single nucleotide polymorphisms in region V of the 23S rRNA gene, which confer macrolide resistance, were found in over 60% of M genitalium specimens from people attending STI clinics in Australia in 2015.14 Furthermore, selective pressure can lead to the emergence of macrolide resistance after exposure to suboptimal levels of drug.15 Mutations in the ParC gene (possibly modified by mutations in GyrA), which confer fluoroquinolone resistance, are also becoming increasingly common.13
Importantly, resistance markers are highly correlated with treatment failure, especially when the organism load is high.121617 A recent meta-analysis showed the pooled efficacy of a 1 g single dose of azithromycin has declined from 85% in studies conducted before 2009 to 67% in later studies.12 About 9-12% of M genitalium infections may have dual resistance mutations and are therefore unlikely to be effectively treated with azithromycin or moxifloxacin.1316 Treatment options in those who do not respond to first and second line therapy are limited and include extended courses of doxycycline (effective in up to 30% of cases) and pristinamycin, which is not easily available in the UK. Management of such cases will usually require specialist advice from sexual health clinicians and microbiologists.
Such high levels of antimicrobial resistance and treatment failure present challenges not only for managing individual patients but for developing an appropriate public health response. Although nucleic acid amplification tests for M genitalium are available, including in multiplex kits testing for Chlamydia trachomatis and Neisseria gonorrhoeae, routine screening for asymptomatic M genitalium infection is not recommended, even in higher risk populations attending STI clinics.3 Detection of an infection that may not cause harm and may be difficult to cure in people without symptoms could lead to distress, unnecessary treatment, and the selection and spread of resistance.
However, diagnosis and treatment of C trachomatis and N gonorrhoeae in asymptomatic people attending STI clinics is routine. If these people have undiagnosed coinfections with M genitalium, the organism may be exposed to suboptimal macrolide concentrations, potentially selecting macrolide resistance.
The draft UK guideline for M genitalium takes a pragmatic view, recommending testing in all men with symptomatic urethritis, women with pelvic inflammatory disease, and their current sexual partners (regardless of symptoms) to reduce the risk of reinfection. Even such limited testing may present practical and financial challenges to service providers and commissioners. But we need to improve the evidence base on the natural course of M genitalium infection and develop treatment regimens that support a cost effective public health response to minimise associated harms. Diagnosis of antimicrobial resistance mutations at point of care could also better guide treatment decisions for M genitalium and other sexually transmitted organisms.18
This article was updated on 29 October to correct the corresponding author’s email address.
Competing interests: We have read and understood BMJ policy on declaration of interests and have no relevant interests to declare.
Provenance and peer review: Commissioned; not externally peer reviewed.