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Microbial Population Diversity in the Urethras of Healthy Males and Males Suffering from Nonchlamydial, Nongonococcal Urethritis

W. A. Riemersma,^1, C. J. C. van der Schee,² W. I. van der Meijden,¹ H. A. Verbrugh,² and A. van Belkum^2*

Department of Dermatology and Venereology,¹ Department Medical Microbiology and Infectious Diseases, Erasmus MC, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands²

Received 28 October 2002/ Returned for modification 17 January 2003/ Accepted 11 February 2003

Nonchlamydial, nongonococcal urethritis (NCNGU) is suggested to be a sexually transmitted disease in men. NCNGU patients were compared to control subjects with regard to the presence of potentially infectious bacteria in the first void urine. Patients' pre- and post-antibiotic-treatment urine samples and two samples obtained 2 weeks apart from healthy volunteers, who did not receive antibiotic therapy, were analyzed with broad-spectrum PCR tests aiming at eubacterial small subunit rRNA genes. Restriction fragment length polymorphism analysis of the amplicons cloned from the mixtures of PCR products revealed that many different species of microorganisms were found to be colonizing the male urethra. We document here clear differences in the composition of the resident urethral flora between samples obtained from various individuals and between samples obtained at various points in time for a single individual. No major changes in population complexity were found upon antimicrobial treatment. In two of five patients a previously suggested pathogen (Mycoplasma genitalium or Haemophilus parainfluenzae) was accurately identified on the basis of DNA sequencing. No ubiquitous, azithromycin-sensitive organism was identified as a common pathogen in all patients, but up to 40% of all clones represented as-yet-unclassified bacterial species. Relatively often Pseudomonas spp. or Pseudomonas-like organisms were identified in the bacterial flora of patients. Interestingly, an as-yet-uncharacterized microbial species was identified as a negative predictor of NCNGU. This species was identified in all control subjects and was absent from all of the patient' samples (5 of 5 versus 0 of 5, P = 0.0079). This suggests that NCNGU might also be diagnosed by assessing the absence rather than the presence of certain bacterial species.

Present address: University Hospital Groningen, Department of Dermatology, 9713 GZ Groningen, The Netherlands.

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