Re-evaluating the treatment of nongonococcal urethritis: emphasizing emerging pathogens--a randomized clinical trial

Clin Infect Dis. 2011 Jan 15;52(2):163-70. doi: 10.1093/cid/ciq074.


Background: Nongonococcal urethritis (NGU) is a common chlamydia-associated syndrome in men; however, Trichomonas vaginalis and Mycoplasma genitalium are associated with its etiology and should be considered in approaches to therapy. We sought to determine whether the addition of tinidazole, an anti-trichomonal agent, to the treatment regimen would result in higher cure rates than those achieved with treatment with doxycycline or azithromycin alone. A secondary aim was to compare the efficacy of doxycycline therapy and with that of azithromycin therapy.

Methods: Randomized, controlled, double-blinded phase IIB trial of men with NGU. Participants were randomized to receive doxycycline plus or minus tinidazole or azithromycin plus or minus tinidazole and were observed for up to 45 days.

Results: The prevalences of Chlamydia trachomatis, M. genitalium, and T. vaginalis were 43%, 31%, and 13%, respectively. No pathogens were identified in 29% of participants. Clinical cure rates at the first follow-up visit were 74.5% (111 of 149 patients) for doxycycline-containing regimens and 68.6% (107 of 156 patients) for azithromycin-containing regimens. By the final visit, cure rates were 49% (73 of 149 patients) for doxycycline-containing regimens and 43.6% (68 of 156 patients) for azithromycin-containing regimens. There were no significant differences in clinical response rates among the treatment arms. However, the chlamydia clearance rate was 94.8% (55 of 58 patients) for the doxycycline arm and 77.4% (41 of 53 patients) for the azithromycin arm (P = .011), and the M. genitalium clearance rate was 30.8% (12 of 39 patients) for the doxycycline arm and 66.7% (30 of 45 patients) for the azithromycin arm (P = .002).

Conclusions: Addition of tinidazole to the treatment regimen did not result in higher cure rates but effectively eradicated trichomonas. Clinical cure rates were not significantly different between patients treated with doxycycline and those treated with azithromycin; however, doxycycline had significantly better efficacy against Chlamydia, whereas azithromycin was superior to doxycycline for the treatment of M. genitalium.

Publication types

  • Clinical Trial, Phase II
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Anti-Bacterial Agents / administration & dosage*
  • Antiprotozoal Agents / administration & dosage*
  • Azithromycin / administration & dosage*
  • Chlamydia Infections / drug therapy
  • Chlamydia trachomatis / isolation & purification
  • Double-Blind Method
  • Doxycycline / administration & dosage*
  • Drug Therapy, Combination / methods
  • Humans
  • Male
  • Middle Aged
  • Mycoplasma Infections / drug therapy
  • Mycoplasma genitalium / isolation & purification
  • Tinidazole / administration & dosage*
  • Treatment Outcome
  • Trichomonas Infections / drug therapy
  • Trichomonas vaginalis / isolation & purification
  • Urethritis / drug therapy*
  • Urethritis / microbiology
  • Urethritis / parasitology
  • Young Adult


  • Anti-Bacterial Agents
  • Antiprotozoal Agents
  • Tinidazole
  • Azithromycin
  • Doxycycline