Discussion

This is a case of confirmed genotypic macrolide and quinolone-resistant M. genitalium in a patient routinely attending a GUM clinic in UK. The patient was treated with multiple antibiotic regimens for non-gonococcal urethritis (NGU), likely doxycycline 100 mg bd for 7 days, azithromycin 1 g stat and a 5-day course, before presenting to the GUM clinic and being tested for M. genitalium. After failed quinolone therapy, microbiological and clinical cure was only achieved with pristinamycin.

Macrolide resistance in M. genitalium was first reported in Australia in 2008, and cases of quinolone resistance have appeared in publication since 2013.1–4 This rapid emergence of antimicrobial resistance is likely to continue with current antibiotic usage and suboptimal diagnostics. With rates of macrolide resistance as high as 40% in parts of the world,3 ,4 ,7 moxifloxacin may be used more commonly which could also cause an increase in the selection of quinolone-resistant variants also leaving limited treatment options. So far, it is likely that quinolone resistance is rare in England; small studies have shown isolates in symptomatic men and women harbouring mutations in both macrolide and fluoroquinolone resistance associated genes.3 ,5 ,8 Most cases of dual resistance have been observed in the Asia/Pacific region.1 ,4 ,6 We hypothesise that our patient's strain was transmitted from a sexual partner in South-East Asia where quinolone use is widespread although we cannot rule out the possibility that quinolone resistance arose de novo because of suboptimal adherence to moxifloxacin.

Pristinamycin, an oral antibiotic that was previously used to treat gram-positive organisms in osteoarticular infections, has also been shown to have high activity against macrolide and quinolone-resistant M. genitalium.9 In the UK, a 10-day course of pristinamycin currently costs £175, and treating large numbers of patients will be mostly unaffordable. Cost and the challenge of four times daily dosing preclude it from being used more commonly. Despite this, our patient tolerated it well and managed to complete the full course. Concurrent treatment with doxycycline was suggested on the basis of a recent in vitro study which showed better clearance of M. genitalium using this dual therapy regimen (Jensen, personal communication), although conventionally pristinamycin would be given alone.

Routine testing for AMR at the point of M. genitalium detection is recommended in European guidelines10 and would have avoided unnecessary antibiotics, reduced duration of infectivity, and led to less clinic visits and anxiety for the patient. However, without access to resistance testing, the benefits of giving moxifloxacin first-line should be weighed against the importance of safeguarding currently efficacious antibiotics for later use.

The true prevalence of M. genitalium and antimicrobial resistance in the UK remains unknown. Commerical assays to detect M. genitalium are imminently available, but only to some clinics. Although an increase in testing will go some way towards helping to addressing these unanswered questions, real and effective management of this organism on a larger scale will only be possible when access to antimicrobial resistance testing improves. Until then it is imperative that where testing is implemented, clinical pathways include assessment for clinical cure and repeat M. genitalium testing to ensure its eradication. Furthermore, every effort should be made to ensure that partners who may be at risk are tested and treated with the same regimen as the index patient.