Macrolide and fluoroquinolone resistance-associated mutations in Mycoplasma genitalium in Johannesburg, South Africa, 2007\u20132014

Etienne E. Muller,Ranmini S. Kularatne,David A. Lewis,Mahlape P. Mahlangu

doi:10.1186/s12879-019-3797-6

Abstract

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.

Highlights

Antimicrobial resistance in Mycoplasma genitalium is rising globally with resultant clinical treatment failure
We evaluated the prevalence of macrolide and fluoroquinolone resistance in stored M. genitalium positive specimens at the National Institute for Communicable Diseases (NICD), South Africa
* NMS National Microbiological Surveillance study, people living with HIV/AIDS (PLWHA) People living with human immunodeficiency virus (HIV)/Acquired immune deficiency syndrome (AIDS) study # Percentage of genital discharge specimens that initially tested positive for M. genitalium § Percentage of stored Deoxyribonucleic acid (DNA) specimens that tested M. genitalium positive after confirmatory testing in this study to the quinolone resistance-determining region (QRDR) of the E. coli DNA gyrase genes and the topoisomerase IV genes in M. genitalium were analysed

Summary

Introduction

Antimicrobial 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. The current STI Management Guidelines (2015) for South Africa include the use of 1 g azithromycin (a macrolide), orally, as a single dose for the treatment of male urethritis syndrome (MUS) and vaginal discharge syndrome (VDS) [8]. Moxifloxacin, a fluoroquinolone, is often recommended as a second-line treatment in cases of azithromycin treatment failure; reports of moxifoxacin treatment failure, have been described, especially in the Asia-Pacific region, and are associated with point mutations in the quinolone resistance-determining region (QRDR) of the DNA gyrase (gyrA) and the topoisomerase IV (parC) genes [10, 17,18,19,20,21]. The genetic characterisation of M. genitalium strains from South Africa is important for studies of antimicrobial resistance, which in turn enables the development of effective treatment algorithms for syndromic management of patients with genital discharge

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