Background:
NGU is common, yet up to 50% of cases have no identified etiology and idiopathic urethritis remains poorly characterized.

Objective:
Identify characteristics associated with NGU by etiology.

Method:
From January-September 2007, 105 male STD clinic patients entered a clinical trial of therapies for NGU, defined as visible urethral discharge and/or ≥5PMNs/HPF from urethral exudate. Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT), Trichomonas vaginalis (TV), and Mycoplasma genitalium (MG) were detected in urine using APTIMA Combo 2® (NG/CT), and research-use only APTIMA® TV analyte-specific reagents and MG TMA assays (Gen-Probe Incorporated, San Diego, CA). Research-use only TMA (Gen-Probe) and in-house PCR assays detected differentiated Ureaplasma urealyticum (UU) and Ureaplasma parvum (UP). Signs, symptoms, sociodemographics, and history data were collected by clinicians and computer-assisted self-interview. CT-MG-TV-UU-negative cases were considered idiopathic.

Result:
CT was detected in 27 (25.7%) men, MG in 12 (11.4%), UU in 16 (15.2%), UP in 8 (7.6%), and TV in 3 (2.9%); 53 (50.5%) men had idiopathic urethritis. Among all men, 57.1% complained of discharge, 87.5% had visible discharge and 62.9% had ≥10PMNs/HPF, with no differences in clinical presentation by etiology (p>0.30 for all comparisons). However, among men with urethral symptoms, MG-positive cases reported longer duration of discharge prior to diagnosis than MG-negative cases (p=0.03), while idiopathic cases reported shorter duration of discharge (p=0.008) and dysuria (p=0.02) than pathogen-positive cases. In multivariate analyses of non-Chlamydial-NGU, idiopathic cases were more likely to be non-Black (aOR=8.0[95%CI:1.9-32.9]p=0.004), earn >$10,000/year (aOR=7.3[2.0-27.0]p=0.003), and/or report prior NGU (aOR=4.9[1.1-23.1]p=0.04) compared to those with MG, UU, or TV.

Conclusion:
Half of all NGU cases had no identified pathogens and idiopathic urethritis was associated with unique characteristics. Nevertheless, there were few differences in the clinical presentation of NGU by etiology.

Implications:
Future research should define clinical implications and management strategies for the heterogeneous urethral infections classified as NGU.