Background There has been a rapid increase in the resistance of Mycoplasma genitalium to first line (azithromycin) and second line (fluoroquinolone) therapy, particularly in the Asia-Pacific region. While mutations conferring resistance to azithromycin are well established, this is not the case for fluoroquinolones. We aimed to define mutations associated with fluoroquinolone failure to inform next generation resistance assays.
Methods Samples from patients undergoing resistance-guided therapy with either moxifloxacin (Apr-2017–Jun-2018, 202 cases: 21 moxifloxacin failures) or sitafloxacin (Jun-2016–May-2017, 125 cases:12 sitafloxacin failures) were sequenced for key regions of parC and gyrA genes. Chi-square or Fisher’s exact tests were used to examine prevalence of each mutation and treatment outcome.
Results In an interim analysis the most common parC mutations were G248T (amino acid change S83I; 16%), G259A (D87N; 4%), G248A (S83N; 1%) and mutations effecting S83R (1%). G248T (S83I) mutation was more common among patients that failed moxifloxacin [15/21 failures (71%) vs 11/181 cures (6%), p<0.001] and sitafloxacin [6/12 failures (50%) vs 19/113 cures (17%), p=0.0063]. Notably, sitafloxacin cured a higher proportion of infections carrying the S83I mutation than moxifloxacin (76% vs 42%; p=0.015). ParC D87N was not associated with failure of moxifloxacin [1/21 failures (5%) vs 11/181 cures (6%)]. The most common gyrA mutations were G285A (M95I; 5%) and G295T (D99Y; 1%). An infection with an S83I mutation was more likely to fail treatment when combined with a gyrA mutation (M95I or D99N) (4/6 sitafloxacin failures with parC S83I also had gyrA mutation, compared to 1/16 cures; p=0.0093), suggesting an additive effect.
Conclusion This study provides compelling evidence that parC G248T (S83I) mutations contribute to failure of moxifloxacin and sitafloxacin used for macrolide-resistant M. genitalium. These data will inform the development of quinolone resistance assays needed to ensure optimal selection of antimicrobials in M. genitalium.
Disclosure No significant relationships.
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.