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O04.4 Mycoplasma genitalium parC and gyrA mutations associated with moxifloxacin and sitafloxacin treatment failure
  1. Gerald Murray1,
  2. Catriona Bradshaw2,
  3. Kaveesha Bodiyabadu1,
  4. Jennifer Danielewski1,
  5. Josh Birnie1,
  6. Litty Tan3,
  7. Elisa Mokany3,
  8. Tim Read4,
  9. Dorothy Machalek1,
  10. Christopher Fairley5,
  11. Suzanne Garland1
  1. 1The Royal Women’s Hospital, Centre For Women’s Infectious Disease Research, Parkville, Australia
  2. 2Alfred Health, Melbourne Sexual Health Centre, Carlton, Australia
  3. 3SpeeDx Pty Ltd., Sydney, Australia
  4. 4Monash University, Central Clinical School, Carlton, Australia
  5. 5Melbourne Sexual Health Centre, Melbourne, Australia

Abstract

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.

  • Treatment failure
  • Mycoplasma genitalium

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