MYCOPLASMA GENITALIUM parC AND gyrA MUTATIONS ASSOCIATED WITH MOXIFLOXACIN AND SITAFLOXACIN TREATMENT FAILURE

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 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.