Background U. urealyticum (UU) but not U. parvum (UP) is associated with non-gonococcal urethritis (NGU), while UP may be associated with adverse pregnancy outcomes. Treatment failure may differ byspecies; therefore, we examined the efficacy of CDC-recommended therapies for NGU against UU and UP separately.

Methods From May 2007 to July 2011, men aged ≥ 16 years attending an STD clinic in Seattle, Washington with NGU (urethral discharge or urethral symptoms plus ≥ 5 PMNs/HPF) were enrolled in a randomised treatment trial. Participants received active azithromycin (1g) and placebo doxycycline or active doxycycline (100 mg bid × 7d) and placebo azithromycin. Ureaplasma species were detected in broth urine culture followed by species-specific PCR. Microbiologic failure (detected by PCR) was determined at 3, 6, and 9 weeks. At 3 weeks, men who failed initial treatment received the alternate therapy (active doxycycline if they first received active azithromycin and vice versa). Persistent failures received moxifloxacin at 6 weeks.

Results Of 479 enrolled men, 107 (22.3%) and 59 (12.3%) were infected with UU and UP, respectively, and returned at 3 weeks. Among men who received azithromycin, microbiologic failure at 3 weeks occurred in 46.7% (14/30) of UP-infected men and 25.0% (13/52) of UU-infected men (P = 0.04). Among doxycycline-treated men, failure occurred in 24.1% (7/29) and 30.9% (17/55), respectively (P = 0.64). At 6 weeks, 80% (4/5) of UP and 58% (7/12) of UU-infected men originally treated with doxycycline and re-treated with azithromycin were failures; failure among men originally treated with azithromycin and re-treated with doxycycline was 57% (8/14) and 55% (6/11), respectively. At 9 weeks, failure after treatment with moxifloxacin occurred in 27.3% (3/11) of UP and 36.4% (4/11) of UU-infected men.

Conclusion Azithromycin was less effective against UP than UU. Failure after re-treatment with alternate therapy and moxifloxacin was common for both UU and UP.