O04.4 Mycoplasma genitalium parC and gyrA mutations associated with moxifloxacin and sitafloxacin treatment failure. (14th July 2019)

• Record Type: Journal Article
• Authors: Murray, Gerald; Bradshaw, Catriona; Bodiyabadu, Kaveesha; Danielewski, Jennifer; Birnie, Josh; Tan, Litty; Mokany, Elisa; Read, Tim; Machalek, Dorothy; Fairley, Christopher; Garland, Suzanne
• Is Part Of: Sexually transmitted infections. Volume 95(2019)Supplement 1
• Page Start: A45
• Page End: A46
• Publication Date: 2019-07-14
• Subjects: Treatment failure -- Mycoplasma genitalium; Sexually transmitted diseases -- Periodicals; HIV infections -- Periodicals; 616.951005
• DOI: 10.1136/sextrans-2019-sti.125
• Languages: English
• ISSNs: 1368-4973

Abstract

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.