gyrA mutations in Mycoplasma genitalium and their contribution to moxifloxacin failure: time for the next generation of resistance-guided therapy

alexandrossfakianakis shared this article with you from Inoreader gyrA mutations in Mycoplasma genitalium and their contribution to moxifloxacin failure: time for the next generation of resistance-guided therapy via Clinical Infectious Diseases Advance Access Abstract Background While single nucleotide polymorphisms (SNPs) in Mycoplasma genitalium parC contribute to fluoroquinolone treatment failure, data are limited for the homologous gene, gyrA. This study investigated the prevalence of gyrA SNPs, and their contribution to fluoroquinolone failure. Methods Samples from 411 patients (male and female) undergoing treatment for M. genitalium infection (Melbourne Sexual Health Centre, March 2019–February 2020) were analyzed by Sanger sequencing (gyrA and parC). For patients treated with moxifloxacin (n=194), the association between SNPs and microbiologic treatment outcome was analyzed. Results The most common parC SNP was G248T/S83I (21.1% of samples), followed by D87N (2.3%). The most common gyrA SNP was G285A/M95I (7.1%). Dual parC/gyrA SNPs were found in 8.6% of cases. One third of infections harboring parC G248T/S83I SNP had a concurrent SNP in gyrA conferring M95I. SNPs in gyrA co-occurred with parC S83I variations. Treatment failure was higher in patients with parC S83I/gyrA dual SNPs, when compared to infections with single S83I SNP alone from analysis of (i) 194 cases in this study (81.2% vs 45.8%, p=0.047), and (ii) pooled analysis of a larger population of 535 cases (80.6% vs 43.2%; p=0.0027), indicating a strong additive ef fect. Conclusions Compared to parC S83I SNP alone, M. genitalium infections with dual mutations affecting parC/gyrA had twice the likelihood of failing moxifloxacin. While AMR varies by region globally, these data indicate that gyrA should be considered as a target for future resistance assays in Australasia. We propose a strategy for the next generation of resistance-guided therapy incorporating parC and gyrA testing. View on Web

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