Prevalence of Mycoplasma Genitalium Macrolide and Fluoroquinolone Antibiotic Resistance Markers in Women Enrolled in a Multi-Center Clinical Study

Background: This study evaluated the prevalence of Mycoplasma genitalium (Mgen) 23s rRNA, gyrA, and parC mutations possibly associated with macrolide and fluoroquinolone antibiotic resistance, among female urogenital specimens collected from symptomatic and asymptomatic subjects enrolled in a prospective multi-center US clinical study.

Methods: Aliquots from residual specimens obtained from symptomatic (cervicitis, vaginitis, urethritis) and asymptomatic women ages 14-47, enrolled from 7 geographically diverse US clinical sites, were tested using a research-use only TMA assay for Mgen 16s rRNA (Hologic, Inc). Specimens positive for Mgen by TMA were evaluated by reverse transcription-PCR and Sanger sequencing of 23s rRNA and mRNAs from gyrA and parC genes to identify the presence of antibiotic resistance mutations (23s rRNA: A2058G/A2059G; gryA: L61F, D99Y, D116H, A131T; parC: P62S, A69T, S83I, S104F).

Results: Of 88 Mgen TMA-positive subjects, 10 (11.4%, 95% CI: 6.3-19.7) had amino acid-altering mutations in parC mRNA, while 2 of 77 (2.6%, 95% CI: 0.7-9.0) had such mutations in gyrA. parC mutations were of slightly higher prevalence in subjects of older age (>30 vs ≤ 30; OR 1.75, P=0.5122), with symptomatic status (OR 1.73, P=0.614 vs asymptomatic), or of white race (OR 3.73, P=0.0706 vs black race), but none of the differences were significant at the P=0.05 level. Of 58 patients with 23S, gyrA, and parC results, 2 (3.4%, 95% CI: 1.0-11.7) had mutations in both parC and 23S. Over half of these 58 patients had mutations in 23S associated with macrolide resistance (31/58, 53.4%, 95% CI: 40.8-65.7).  

Conclusions: Mgen infections containing potential fluoroquinolone resistance markers were of low to moderate prevalence in urogenital specimens, while 23S rRNA mutations were of high prevalence, in this cohort of female US subjects. Identification of patients infected with Mgen strains resistant to both antibiotic classes raises concern for the advent of multi-drug resistant M. genitalium.