Macrolide Resistance and Azithromycin Failure in a Mycoplasma genitalium–Infected Cohort and Response of Azithromycin Failures to Alternative Antibiotic Regimens

Background. Our aim was to determine the efficacy of 1 g azithromycin and alternative antibiotic regimens in a prospective cohort of Mycoplasma genitalium–infected participants, and factors associated with azithromycin failure. Methods. Consecutive eligible M. genitalium–infected men and women attending the Melbourne Sexual Health Centre between July 2012 and June 2013 were treated with 1 g of azithromycin and retested by polymerase chain reaction (PCR) on days 14 and 28. Cure was defined as PCR negative on day 28. Cases failing azithromycin were treated with moxifloxacin, and those failing moxifloxacin were treated with pristinamycin. Pre- and posttreatment samples were assessed for macrolide resistance mutations (MRMs) by high-resolution melt analysis. Mycoplasma genitalium samples from cases failing moxifloxacin were sequenced for fluoroquinolone resistance mutations. Multi-variable analysis was used to examine associations with azithromycin failure. Results. Of 155 participants treated with 1 g azithromycin, 95 (61% [95% confidence interval {CI}, 53%–69%]) were cured. Pretreatment MRM was detected in 56 (36% [95% CI, 28%–43%]) participants, and strongly associated with treatment failure (87% [95% CI, 76%–94%]; adjusted odds ratio, 47.0 [95% CI, 17.1–129.0]). All 11 participants who had MRM detected in posttreatment samples failed azithromycin. Moxifloxacin was effective in 53(88% [95% CI, 78%–94%]) of 60 cases failing azithromycin; all failures had gyrA and parC mutations detected in pretreatment samples. Six of 7 patients failing moxifloxacin treatment received pristinamycin, and all were PCR negative 28 days after pristinamycin treatment. Conclusions. We report a high azithromycin failure rate (39%) in an M. genitalium–infected cohort in association with high levels of pretreatment macrolide resistance. Moxifloxacin failure occurred in 12% of patients who received moxifloxacin; all had pretreatment fluoroquinolone mutations detected. Pristinamycin was highly effective in treating macrolide- and quinolone-resistant strains.