Evolving patterns of macrolide and fluoroquinolone resistance in Mycoplasma genitalium: an updated systematic review and meta-analysis.

Background Over the past 5 years, since publication of the initial review, studies have provided additional data on macrolide and fluoroquinolone resistance in Mycoplasma genitalium, including data from regions previously lacking this information. We aimed to provide contemporary estimates of macrolide and fluoroquinolone resistance in M genitalium to inform national, regional, and global treatment guidelines.Methods This is an update of a previous systematic review and meta-analysis, which was performed up to Jan 7, 2019. In this update, we searched PubMed, Embase, and MEDLINE from Jan 1, 2018, to April 18, 2023, for published studies reporting macrolide, fluoroquinolone, or dual-class (macrolide and fluoroquinolone) resistance in M genitalium. Data were combined with the previous meta-analysis to examine resistance prevalence in M genitalium samples collected up to and including 2021. Random-effects meta-analyses were used to calculate summary estimates of prevalence. Subgroup analyses by WHO region and four time periods (before 2012 to 2018-21) were performed. This study was registered with PROSPERO, number CRD42021273340.Findings 166 studies (59 from the previous search period reporting data from M genitalium samples collected between 2003 and 2017, and 107 from the updated search period reporting data from M genitalium samples collected between 2005 and 2021) were included: 157 reporting macrolide resistance (41 countries; 22 974 samples), 89 reporting fluoroquinolone resistance (35 countries; 14 165 samples), and 74 reporting dual-class resistance (34 countries; 11 070 samples). In 2018-21, the overall prevalence of macrolide, fluoroquinolone, and dual-class resistance were 33·3% (95% CI 27·2-39·7), 13·3% (10·0-17·0), and 6·5% (4·0-9·4), respectively. Over time, there was a slight, although not statistically significant, decline in macrolide resistance in the Western Pacific and the Americas, but there was an increase in macrolide resistance in the European region. Fluoroquinolone resistance was highest in the Western Pacific and increased in the European non-Nordic region. ParC S83I was the most common variant associated with fluoroquinolone resistance, increasing from 0% (95% CI <0·0001-0·30) before 2012 to 7·3% (4·7-10·3) in 2018-21; ptrend=0·055.Interpretation Macrolide and fluoroquinolone resistance in M genitalium requires ongoing international surveillance, use of resistance assays for optimal antibiotic stewardship, and novel treatment options.Funding Australian Research Council.