Background Traditional cultivation approaches have not identified additional pathogens responsible for the 45% of non-gonococcal urethritis (NGU) cases with no identified aetiology. Cultivation-independent methods have identified novel bacteria associated with female reproductive tract disease, particularly bacterial vaginosis (BV). We evaluated the association of NGU and 5 newly described BV-associated bacteria (BVAB).

Methods English-speaking, heterosexual men aged 16 years attending the STD clinic in Seattle, WA between May 2007 and July 2011 were eligible if PCR tests for Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, Mycoplasma genitalium, and Ureaplasma urealyticum-biovar2 were negative. Cases were men with visible urethral discharge or 5 PMNs/HPF in urethral exudates. Controls were men with no visible urethral discharge and < 5 PMNs/HPF. Urine was tested for Atopobium, BVAB-2, BVAB-3, Megasphaera spp., and Leptotrichia/Sneathia spp. using quantitative taxon-directed PCR.

Results Cases (n = 157) and controls (n = 191) were similar with respect to age, education, and income. Mean age was 34.7 (SD ±9.9) and most were white. Leptotrichia/Sneathia was significantly associated with NGU (25/157 (15.3%) vs. 6/102 (5.9%), p = 0.03) and BVAB-2 was detected more often in cases than controls (7/157 (4.5%) vs. 1/102 (1.0%), p = 0.15). BVAB-3 (n = 2) and Megasphaera (n = 1) were uncommon, but only detected in men with NGU. In contrast, Atopobium was not associated with NGU (8.3% vs. 7.8%, p = 1.0). Quantity of bacteria did not differ between cases and controls for any of the 5 candidate pathogens. Among treated cases, doxycycline was somewhat more effective than azithromycin for clinical cure of men with Leptotrichia/Sneathia(9/10 (90%) vs. 7/12 (58%), p = 0.16), and BVAB-2 (3/3 (100%) vs. 0/3 (0%), p = 0.10).

Conclusion Leptotrichia/Sneathia was significantly associated with NGU. BVAB-2, BVAB-3, and Megasphaera were less commonly detected, but most often identified in men with NGU and rarely or never in men without NGU. Doxycycline may be more effective against these newly identified bacteria than azithromycin.