Declining efficacy of moxifloxacin for Mycoplasma genitalium infection: time for fluoroquinolone-resistance guided therapy?

BACKGROUND: We assessed trends in moxifloxacin-use and efficacy for MG over a decade at Melbourne Sexual Health Centre (MSHC). Specific Mycoplasma genitalium (MG) mutations, namely ParC-S83I, have been associated with moxifloxacin failure. In 2024 MSHC introduced ParC-S83 testing, recommending moxifloxacin for ParC-S83 wildtype infections and alternative regimens if the ParC-S83I mutation was detected. We present preliminary impacts of ParC-S83 testing on moxifloxacin-use and efficacy. METHODS: Clients with MG from 2015-2024 were treated with doxycycline preceding macrolide-resistance guided azithromycin or moxifloxacin. Clients with a test-of-cure 14-90 days after completing moxifloxacin who reported >50% adherence and no condomless sex prior to test-of-cure were eligible for efficacy analyses. Proportions with 95% confidence intervals (CIs) were calculated for moxifloxacin-use and efficacy, with trends assessed by logistic regression. Moxifloxacin-use and efficacy were compared in the 12-months before and after introduction of the ParC-S83 assay. RESULTS: From 2015-2024, 2,611/5,739 MG infections received moxifloxacin. Moxifloxacin-use increased from 6.7% (n=19/282; 95%CI:4.1-10.3%) in 2015 to 60.3% (n=482/800; 95%CI:56.8-63.7%) in 2023 (ptrend<0.0001). Efficacy analyses included 1,623 infections. Moxifloxacin-efficacy decreased from 100% (n=11/11) in 2015 to 79.3% (n=238/300, 95%CI:74.3-83.8%) in 2023 (ptrend=0.007). After introduction of the ParC-S83 assay, moxifloxacin-use decreased from 60.3% (n=482/800, 95%CI:56.8-63.7%) in 2023 to 49.2% (n=438/890, 95%CI:45.9-52.6%) in 2024 (p<0.0001) and cure increased from 79.3% (n=238/300, 95%CI:74.3-83.8%) in 2023 to 89.2% (n=116/130, 95%CI:82.6-94.0%, p=0.013) in ParC-S83 wildtype infections. CONCLUSIONS: Increasing moxifloxacin-use and declining efficacy reflects rising resistance in our region. Preliminary data suggests a ParC-S83 assay has the potential to improve moxifloxacin- use and cure in this setting.