Background: Our previous meta-analysis of data to the end of 2017 found global macrolide, fluoroquinolone, and dual-class resistance in Mycoplasma genitalium had reached 51.4%, 9.3%, and 4.0%, respectively; prevalence was highest in the Western-Pacific. We updated this review to estimate current global antimicrobial resistance prevalence, including trends in specific ParC amino acid changes in M. genitalium.
Methods: PubMed, Embase, and MEDLINE were searched for studies reporting macrolide and fluoroquinolone resistance-associated mutations in M. genitalium positive samples published between 7 January 2019 and 1 February 2022, the period since our original meta-analysis. Data were extracted by year of sample collection (< 2012, 2012–2014, 2015–2017, 2018–2020) and geographic region. The frequency of each ParC amino acid change (S83I/R/C/N and D87N/Y) was also extracted. Pooled prevalence estimates (95% confidence intervals [CI]) were calculated using random-effects models. Results: Overall, 139 studies (59 from the previous review and 80 new studies from this update), were eligible for inclusion. Compared with 2015–2017, global macrolide resistance was stable at 44.8% (95% CI: 37.3–52.4%) in 2018–2020, although in Europe, prevalence continued to increase (Figure 1A). Global fluoroquinolone resistance rose from 10.5% (7.0–14.5%) in 2015–2017 to 17.0% (11.2–23.5%) in 2018–2020, and prevalence was highest in the Western-Pacific (Figure 1B). Global dual-class resistance also increased from 5.3% (2.7–8.5%) in 2015–2017 to 9.7% (3.5–18.1%) in 2018–2020, also highest in the Western-Pacific (Figure 1C). For individual ParC amino acid changes, only S83I increased in prevalence from 0.0% (0.0–0.4%) before 2012 to 9.3% (4.7–14.9%) in 2018–2020 (p-trend=0.069).
Conclusion: Macrolide resistance levels appear to have stabilised in some regions. Plausible explanations include reduced use of single-dose azithromycin as first-line therapy and the uptake of resistance-guided therapy for M. genitalium. The continuing rise in the prevalence of fluoroquinolone and dual-class resistance mutations highlights the urgent need for new management strategies including, reducing unnecessary testing, diagnostic assays that detect fluoroquinolone resistance markers and novel treatment alternatives. The steady increase in the ParC S83I mutation supports emerging evidence of its contribution to fluoroquinolone failure suggesting it may be a useful target for next-generation resistance assays.
