Fannyhessea vaginae and clearance of Lactobacillus iners are associated with incident non-chlamydial non-Mycoplasma genitalium urethritis in men who have sex with women.

Background: The etiology of nongonococcal urethritis (NGU) is incompletely understood. We sought to determine if genitourinary bacterial diversity or specific taxa were associated with incident NGU.

Methods: From August 2014-July 2018, men who have sex with women attending a sexual health clinic were clinically evaluated, including Mycoplasma genitalium (MG) and Chlamydia trachomatis (CT) testing, at enrollment and six monthly visits. New cases of NGU (≥5 PMNs/HPF in urethral exudates plus either symptoms or visible discharge) and their visit preceding NGU diagnosis were matched 1:1 to two sequential visits without NGU (controls). We determined associations with incident NGU and applied broad-range 16S rRNA gene polymerase chain reaction and sequencing to urine samples from each visit. We used conditional logistic regression to evaluate the association of Shannon Diversity Index (SDI), species richness, Haemophilus influenzae, Fannyhessea vaginae, Lactobacillus iners, and Streptococcus mitis group with incident non-CT-non-MG-NGU (NCNM-NGU).

Results: Of 62 matched case-control pairs, median age was 32. Higher SDI the previous month was associated with higher odds of incident NCNM-NGU (adjusted odds ratio [aOR] = 2.8 per unit increase; 95% CI = 1.03-7.47), as was F. vaginae at NGU diagnosis (aOR = 5.1; 95% CI = 1.28-20.15), F. vaginae acquisition (aOR = 13.8; 95% CI = 1.96-97.33) and consistent carriage of F. vaginae (aOR = 16.1; 95% CI = 1.66-156.29). Odds of NCNM-NGU were higher when L. iners cleared between visits (aOR = 18.0; 95% CI = 1.08-299.24). Neither H. influenzae nor S. mitis group were associated with incident NCNM-NGU.

Conclusions: F. vaginae acquisition/detection and L. iners clearance were associated with urethritis. This merits investigation in larger longitudinal studies using species-specific detection methods.