マイコプラズマ・ジェニタリウムのgyrA変異とモキシフロキサシン治療失敗への寄与

gyrA Mutations in Mycoplasma genitalium and Their contribution to Moxifloxacin Failure: Time for the Next Generation of Resistance-Guided Therapy

Clin Infect Dis. 2023 Jun 15; 76(12): 2187–2195.

・現在、M.genitaliumのキノロン薬剤耐性寄与としてParC(S83I)が推奨

・411名のM.genitalium患者(メルボルン, 2019-2020,観察研究)を対象にParC(S83I)＋gyrAの変異解析と治療効果を調査。

・ParC+gyrA複合変異でモキシフロキサシンの治療失敗確率が増大。 (81.2% vs 45.8%, P=.047)

Background

Although 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 cooccurred with parC S83I variations. Treatment failure was higher in patients with parC S83I/gyrA dual SNPs when compared with infections with single S83I SNP alone from analysis of (1) 194 cases in this study (81.2% vs 45.8%, P = .047), and (2) pooled analysis of a larger population of 535 cases (80.6% vs 43.2%; P = .0027), indicating a strong additive effect.

Conclusions

Compared with parC S83I SNP alone, M. genitalium infections with dual mutations affecting parC/gyrA had twice the likelihood of failing moxifloxacin. Although antimicrobial resistance 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.