Background Recent treatment trials have demonstrated low efficacy of doxycycline against Mycoplasma genitalium (MG) and increasing resistance to azithromycin. Treatment with azithromycin is recommended for persistent NGU if not used for the initial episode. We evaluated microbiologic cure rates for men with NGU and persistent detection of MG.

Methods English-speaking men aged 16 years attending the STD clinic in Seattle, WA with NGU (urethral discharge or urethral symptoms plus ≥ 5 PMNs/HPF) were enrolled in a randomised trial of NGU therapy between January 2007 and July 2011. Urine was tested for MG by PCR. Men received 1g azithromycin plus placebo doxycycline or doxycycline (100mg bid x 7d) plus placebo azithromycin. Treatment failures after 3 weeks received ‘reverse therapy’ (active doxycycline if they first received active azithromycin and vice versa). Persistent failures after 6 weeks received moxifloxacin (400mg x 7d). After September 2010, microbiologic failures at 3 weeks received moxifloxacin.

Results Of 606 enrolled men, 65 were positive for MG at enrollment and returned after 3 weeks. Microbiologic failure (positive MG test) occurred in 23/38 (60.5%) who received azithromycin and 19/27 (70.4%) who received doxycycline (p = 0.41). Of the 37 men with microbiologic treatment failure who received ‘reverse therapy’ and returned after 6 weeks, 19 (51.4%) had persistent detection of MG, including 14/20 (70.0%) retreated with doxycycline and 5/17 (29.4%) retreated with azithromycin (p = 0.02). All 19 men were prescribed moxifloxacin; 16 returned at 9 weeks and 2 (12.5%) had microbiologic failure, despite clinical cure. Four men received moxifloxacin after initial failure; 1 had microbiologic failure at 6 weeks, was retreated with moxifloxacin and microbiologically cured at 9 weeks.

Conclusion One half of MG-positive men retreated with a second standard NGU treatment regimen experienced microbiologic treatment failure. Moxifloxacin treatment failure, while not common, did occur, suggesting antimicrobial susceptibility in MG merits careful monitoring.