The parC mutation G248T (S83I), and concurrent gyrA mutations, are associated with moxifloxacin and sitafloxacin treatment failure for Mycoplasma genitalium

Abstract

Abstract Background The basis of fluoroquinolone treatment failure for Mycoplasma genitalium is poorly understood. Methods To identify mutations associated with failure we sequenced key regions of the M. genitalium parC and gyrA genes for patients undergoing sequential therapy with doxycycline-moxifloxacin (201 patients, including 21 failures) or doxycycline-sitafloxacin (126 patients, including 13 failures). Results The parC G248T/S83I mutation was more common among patients who failed sequential doxycycline-moxifloxacin (present in 76.2% of failures vs 7.8% cures, p<0.001) and doxycycline-sitafloxacin (50% failures vs 16.8% cures, p = 0.014). Doxycycline-sitafloxacin was more efficacious than doxycycline-moxifloxacin against infections carrying the ParC S83I mutation. Infections with a ParC S83I were more likely to fail treatment with a concurrent gyrA mutation (M95I or D99N) (for doxycycline- moxifloxacin group p = 0.067, for doxycycline-sitafloxacin group p = 0.0093), suggesting an additive effect. Conclusions This study indicates that parC G248T/S83I mutations contribute to failure of moxifloxacin and sitafloxacin, and will inform the development of quinolone resistance assays needed to ensure optimal selection of antimicrobials for M. genitalium.