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Journal Club: Predictors and persistence after therapy in men with nongonococcal urethritis

Article reviewed

Seña, AC, Lensing S, Rompalo A et al. Chlamydia trachomatis, Mycoplasma genitalium, and Trichomonas vaginalis infections in men with nongonococcal urethritis: Predictors and persistence after therapy. J Inf Dis. 2012; 206: 357-65.

Purpose of study

The three main sexually transmitted infections (STIs) associated with nongonococcal urethritis (NGU) in men are Chlamydia trachomatis (CT), Mycoplasma genitalium (MG), and Trichomonas vaginalis (TV). Current empiric therapy is directed toward treating chlamydial infection, however, the clinical manifestations of these pathogens are a challenge to distinguish and may require different treatments regimens. Persistent NGU arises in a significant proportion of men, and whether this is due to persistence of a pathogen causing symptoms is unknown.

This study sought to identify the pathogens responsible for persistent NGU in a population of symptomatic heterosexual males, as well as determine predictors associated with persistence after therapy.


This study is based on a multicenter, randomized clinical trial involving 293 symptomatic heterosexual males, aged 16-45 years old, from four STI clinics in the United States (1). Of note, 98% of the participants were African-American, and were quite comparable in terms of their demographics across treatment arms. Eligible participants were randomized to one of four treatment arms, either doxycycline or azithromycin, with or without tinidazole (1). Urine nucleic acid amplification tests for the detection of CT, MG, and TV, as well as urethral gram stains to quantify the number of polymorphonuclear cells per high power field were specimens obtained at baseline (initial visit), at follow up 1 week (visit 2) and 3-4 weeks post-treatment (visit 3). Analysis of the data collected by Schwebke et al. (1) was done to identify characteristics associated with CT, MG, and TV infection at baseline and after therapy in heterosexual symptomatic men with NGU.


At baseline, 44% of males had CT infection, 31% had MG, and 13% had TV. Persistent CT infection was seen in 12% and persistent MG infection was seen in 44% of participants after 4 weeks post-treatment.

Persistent CT was found in 23% of participants treated with azithromycin vs 5% treated with doxycycline (p=0.011). Persistent MG was seen in 68% of participants after doxycycline treatment vs 33% following azithromycin treatment (p=0.001). Regarding TV infection, all expect 1 participant cleared the infection on tinidazole.

In terms of characteristics and predictors associated with persistent CT, MG, and TV infection in men with NGU, the following associations were seen. Using multivariate analysis, CT infection was significantly associated with young age and contact with an STI-infected individual. Young age was a significant predictor of MG infection.

Relevance to clinical practice

This study highlighted that clinical failure among heterosexual males treated with currently recommended therapies for NGU is a common occurrence, and the majority of infections are due to the MG pathogen. Unfortunately, commercially available tests are not readily available at this time to detect MG, and this precludes the diagnosis of MG in clinical practice. The current study suggests that a heterosexual male patient with persistent NGU who has failed empiric doxycycline treatment may benefit from azithromycin with the intention of treating presumed MG infection.

Further Information and References

    1.  Schwebke JR et al. Re-Evaluating the treatment of nongonococcal urethritis: emphasizing emerging pathogens – a randomized clinical trial. Clin Inf Dis. 2011;52(2):163-170.
    2.  Bachman LH et al. Trichomonas Vaginalis Genital Infections: Progress and Challenges. Clin Inf Dis. 2011;53(S3):S160-72.


Dr. Richard Lester, Medical Head, STI/HIV Control, Clinical Prevention Services, BCCDC