Background Antibiotic resistance profiles of recent Mycoplasma genitalium (MG) isolates have not been extensively evaluated nor correlated with treatment outcomes for NGU. Urine specimens from men with NGU enrolled in a treatment trial in Seattle, WA were used to culture MG strains and assess the association of their susceptibility to azithromycin and doxycycline with treatment outcomes.

Methods Urines from all MG-positive (by PCR) men were co-cultured with VERO cells. MG growth was detected by an increase in genomes using an MG-specific quantitative PCR (qPCR); minimum inhibitory concentrations (MICs) were defined by the antibiotic concentration that resulted in 99% growth inhibition. MICs were measured at baseline (V1), 3-week (V2) and 6-week follow-up (V3). Clinical cure (V2, V3) was defined < 5 PMNs/HPF, no urethral discharge or symptoms; microbiologic cure was defined by a negative MG-specific PCR result.

Results Viable MG strains were recovered from 141 (92%) of 153 MG PCR-positive specimens; MICs were determined on 103 isolates. Azithromycin MICs were clearly bimodal; 46% (48/103) were ≤ 0.001–0.5 μg/ml, considered susceptible, and 54% (55/103) were ≥ 8 μg/ml considered resistant. Except for two strains with MICs of ≥ 8 μg/ml doxycycline, MICs were < 0.125–2 μg/ml. Doxycycline MICs did not correlate with treatment outcomes. At baseline, 33/57 (57.9%) of isolates had azithromycin MICs that were resistant. Of men in the azithromycin arm with MIC data and treatment outcomes at V2, 11/13 clinical failures (84.6%) and 16/20 microbiologic failures (80.0%) had azithromycin resistant isolates at baseline. After receiving azithromycin, 9/10 V2 clinical failures (90%) and 12/13 microbiologic failures (92.3%) had V2 azithromycin resistant MICs. All V3 clinical (7/7) and microbiologic (10/10) failures had V3 azithromycin resistant MICs.

Conclusion Approximately 60% of MG strains were resistant to azithromycin at baseline; azithromycin treatment failures occurred in 90–100% of men who received azithromycin. Development of new antimicrobial therapies for MG is essential.