Prevalence of mutations associated with resistance to macrolides and fluoroquinolones in Mycoplasma genitalium: a systematic review and meta-analysis - 22/10/20

Doi : 10.1016/S1473-3099(20)30154-7

Dorothy A Machalek, PhD ^a,^b,^c,⁎ , Yusha Tao, MPH ^e,^f,^g, Hannah Shilling, GradDip ^a,ⁱ, Jørgen S Jensen, ProfMD ^j, Magnus Unemo, PhD ^k, Gerald Murray, PhD ^a,^d,ⁱ, Eric P F Chow, PhD ^e,^f, Nicola Low, ProfMD ^l, Suzanne M Garland, ProfMD ^a,^d,ⁱ, Lenka A Vodstrcil, PhD ^e,^f, Christopher K Fairley, ProfPhD ^e,^f, Jane S Hocking, ProfPhD ^c, Lei Zhang, PhD ^e,^f,^g,^h,^m,^{^{†
Joint senior authors}}, Catriona S Bradshaw, PhD ^c,^e,^f,^{^{†
Joint senior authors}}

^a Centre for Women’s Infectious Diseases, The Royal Women’s Hospital, Parkville, VIC, Australia

^b The Kirby Institute, University of New South Wales, Kensington, Sydney, NSW, Australia

^c Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Parkville, VIC, Australia

^d Department of Obstetrics and Gynaecology, University of Melbourne, Parkville, VIC, Australia

^e Melbourne Sexual Health Centre, Alfred Health, Melbourne, VIC, Australia

^f Central Clinical School, Monash University, Melbourne, VIC, Australia

^g China–Australia Joint Research Center for Infectious Diseases, School of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an, China

^h Department of Epidemiology and Biostatistics, School of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an, China

ⁱ Molecular Microbiology Research Group, Murdoch Children’s Research Institute, Parkville, VIC, Australia

^j Research Unit for Reproductive Microbiology, Statens Serum Institut, Copenhagen, Denmark

^k WHO Collaborating Centre for Gonorrhoea and Other STIs, Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden

^l Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland

^m Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, China

^* Correspondence to: Dr Dorothy Machalek, Centre for Women’s Infectious Diseases, The Royal Women’s Hospital, Parkville, VIC 3052, Australia Centre for Women’s Infectious Diseases The Royal Women’s Hospital Parkville VIC 3052 Australia

Summary

Background

Mycoplasma genitalium is now recognised as an important bacterial sexually transmitted infection. We summarised data from studies of mutations associated with macrolide and fluoroquinolone resistance in M genitalium to establish the prevalence of resistance. We also investigated temporal trends in resistance and aimed to establish the association between resistance and geographical location.

Methods

In this systematic review and meta-analysis, we searched PubMed, Embase, and MEDLINE for studies that included data for the prevalence of mutations associated with macrolide and fluoroquinolone resistance in M genitalium published in any language up to Jan 7, 2019. We defined prevalence as the proportion of M genitalium samples positive for key mutations associated with azithromycin resistance (23S rRNA gene, position 2058 or 2059) or moxifloxacin resistance (S83R, S83I, D87N, or D87Y in parC), or both, among all M genitalium samples that were successfully characterised. We used random-effects meta-analyses to calculate summary estimates of prevalence. Subgroup and meta-regression analyses by WHO region and time period were done. This study was registered with PROSPERO, number CRD42016050370.

Results

Overall, 59 studies from 21 countries met the inclusion criteria for our study: 57 studies of macrolide resistance (8966 samples), 25 of fluoroquinolone resistance (4003 samples), and 22 of dual resistance to macrolides and fluoroquinolones (3280 samples). The summary prevalence of mutations associated with macrolide resistance among M genitalium samples was 35·5% (95% CI 28·8–42·5); prevalence increased from 10·0% (95% CI 2·6–20·1%) before 2010, to 51·4% (40·3–62·4%) in 2016–17 (p<0·0001). Prevalence of mutations associated with macrolide resistance was significantly greater in samples in the WHO Western Pacific and Americas regions than in those from the WHO European region. The overall prevalence of mutations associated with fluoroquinolone resistance in M genitalium samples was 7·7% (95% CI 4·5–11·4%). Prevalence did not change significantly over time, but was significantly higher in the Western Pacific region than in the European region. Overall, the prevalence of both mutations associated with macrolide resistance and those associated with fluoroquinolone resistance among M genitalium samples was 2·8% (1·3–4·7%). The prevalence of dual resistance did not change significantly over time, and did not vary significantly by geographical region.

Interpretation

Global surveillance and measures to optimise the efficacy of treatments—including resistance-guided strategies, new antimicrobials, and antimicrobial combination approaches—are urgently needed to ensure cure in a high proportion of M genitalium infections and to prevent further spread of resistant strains.

Funding

Australian National Health and Medical Research Council.

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Vol 20 - N° 11

P. 1302-1314 - novembre 2020 Retour au numéro

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Prevalence of mutations associated with resistance to macrolides and fluoroquinolones in Mycoplasma genitalium: a systematic review and meta-analysis - 22/10/20

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