BackgroundAntimicrobial resistance in Mycoplasma genitalium is rising globally with resultant clinical treatment failure. We investigated the prevalence of mutations in the macrolide and fluoroquinolone resistance-determining regions of M. genitalium in Johannesburg, South Africa, and ascertained their association with HIV serostatus.MethodsStored M. genitalium positive specimens, collected from STI and HIV patients enrolled in the Gauteng STI National Microbiological Surveillance programme (2007–2014) and a large HIV outpatient clinic-based study (2007) in Johannesburg, were tested for antimicrobial resistance.ResultsWe determined the prevalence of 23S rRNA gene mutations conferring macrolide resistance and mutations in the quinolone resistance-determining regions (QRDR) of the gyrA and parC genes in 266 M. genitalium positive DNA extracts. No macrolide resistance-associated mutations were detected in any of the specimens analysed. QRDR mutations with known M. genitalium-associated fluoroquinolone resistance were not detected in gyrA, however, one specimen (0.4%) contained a D87Y amino acid alteration in parC, which has been linked to fluoroquinolone treatment failure. The most common parC amino acid change detected, of unknown clinical significance, was P62S (18.8%). We found no significant association between QRDR mutations in M. genitalium and HIV-infection.ConclusionsOngoing antimicrobial resistance surveillance in M. genitalium is essential, as macrolide resistance may emerge given the recent incorporation of azithromycin into the 2015 South African national STI syndromic management guidelines.

The human immunodeficiency virus seroprevalence in Mycoplasma genitalium –infected females was significantly higher than in uninfected females, regardless of the presence or absence of other sexually transmitted infection pathogens.

A low prevalence of macrolide resistance–associated mutations in Mycoplasma genitalium strains obtained from genital discharge specimens was observed in South Africa over a 4-year surveillance period.

Treponema pallidum macrolide resistance and clinical treatment failure have emerged rapidly within communities where macrolides have been used as convenient, oral therapeutic alternatives to benzathine penicillin G for syphilis, or for other clinical indications. Macrolides are not included in the South African syndromic management guidelines for genital ulcer disease; however, in 2015, a 1 gram dose of azithromycin was incorporated into treatment algorithms for genital discharge. We determined the prevalence of 23S rRNA macrolide resistance-associated point mutations in 135 T. pallidum -positive surveillance specimens from Botswana, Zimbabwe and South Africa between 2008 and 2018. Additionally, we investigated the association between macrolide resistance, T. pallidum strain type and HIV co-infection. A significant increase in the prevalence of the A2058G macrolide resistance-associated point mutation was observed in specimens collected after 2015. There was a high level of molecular heterogeneity among T. pallidum strains circulating in the study communities, with strain type 14d/f being the most predominant in South Africa. Fourteen novel strain types, derived from three new tpr -gene restriction fragment length polymorphism patterns and seven new tp0548 -gene sequence types, were identified. There was an association between A2058G-associated macrolide resistance and T. pallidum strain types 14d/f and 14d/g, but no association between T. pallidum macrolide resistance and HIV co-infection. The majority of T. pallidum strains, as well as strains containing the A2058G mutation, belonged to the SS14-like clade. This is the first study to extensively detail the molecular epidemiology and emergence of macrolide resistance in T. pallidum in southern Africa.