Declining Efficacy of Moxifloxacin for Mycoplasma genitalium Infection: Time for Fluoroquinolone Resistance-Guided Therapy?

Abstract

We assessed trends in moxifloxacin use and efficacy for Mycoplasma genitalium over a decade at Melbourne Sexual Health Centre (MSHC). Specific M. genitalium mutations, namely ParC-S83I, have been associated with moxifloxacin failure. In 2024 MSHC introduced ParC-S83 testing, recommending moxifloxacin for ParC-S83 wild type infections and alternative regimens if the ParC-S83I mutation was detected. We present preliminary impacts of ParC-S83 testing on moxifloxacin use and efficacy. Clients with M. genitalium from 2015 to 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% 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. From 2015 to 2024, 2611 of 5739 M. genitalium 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 < .0001). Efficacy analyses included 1623 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 = .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 < .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 = .013) in ParC-S83 wild type infections. Increasing moxifloxacin use and declining efficacy reflects rising resistance in our region. Preliminary data suggest a ParC-S83 assay has the potential to improve moxifloxacin use and cure in this setting.