1-day azithromycin was as effective as 7-day doxycycline for nongonococcal urethritis syndrome in men
ACP J Club. 1996 May-June;124:70. doi:10.7326/ACPJC-1996-124-3-070
Stamm WE, Hicks CB, Martin DH, et al. Azithromycin for empirical treatment of the nongonococcal urethritis syndrome in men. A randomized double-blind study. JAMA. 1995 Aug 16;274:545-9. [PubMed ID: 7629982]
To determine whether a single dose of azithromycin is as effective as 7 days of treatment with doxycycline for men with nongonococcal urethritis syndrome.
Randomized, double-blind, placebo-controlled trial with follow-up at 2 and 5 weeks.
11 sexually transmitted disease clinics in the United States.
452 men ≥ 18 years of age (mean age 26 y, 77% black) with typical symptoms of urethritis that had been present for ≤ 14 days. Inclusion criteria were the presence of a visible urethral discharge and > 4 polymorphonuclear leukocytes per high-power field on Gram stain, without evidence of gonococcal infection. Exclusion criteria were other serious illness, urologic abnormalities, known HIV infection, allergy to or use of study drugs, need for other antibiotics, use of an antimicrobial in the previous 2 weeks, or conditions preventing absorption of drugs. Follow-up was > 80%.
301 men were allocated to azithromycin (four 250-mg capsules in 1 dose in the clinic and 7 days of doxycycline placebo twice daily). 151 men were allocated to placebo azithromycin in the clinic and doxycycline, 100 mg, twice daily for 7 days.
Main Outcome Measures
Men were tested for Neisseria gonorrhoeae, Chlamydia trachomatis, Ureaplasma urealyticum, and syphilis before and after treatment. Clinical failure was defined as persistent symptoms and ≥ 5 polymorphonuclear leukocytes per oil immersion field or persistent urethral discharge at 2 weeks and a persistent discharge or a positive Gram stain at 5 weeks. All who did not meet these criteria were considered to have clinical cures.
Analysis was by intention to treat; power calculations showed that the sample size was adequate to show differences in efficacy of 10%. Men in the azithromycin-treated group compared with men in the doxycycline-treated group did not differ for clinical cures at 2 weeks (90% vs 89%), clinical cures at 5 weeks (89% vs 85%), cumulative cure rates (81% vs 77%), clinical cure rates stratified for infections positive for C. trachomatis (75% vs 69%) or U. urealyticum (80% vs 74%), microbiologic cure rates, and adverse effects (23% vs 29%). The overall microbiologic cure rate was higher in men with C. trachomatis (83% cure in the azithromycin group vs 90% cure in the doxycycline group) than in men with U. urealyticum (45% cure in the azithromycin group vs 47% cure in the doxycycline group).
In men with the nongonococcal urethritis syndrome, a single dose of azithromycin was as effective as doxycycline that was taken for 7 days.
Source of funding: Pfizer Central Research.
For article reprint: Dr. W.E. Stamm, University of Washington Medical Center, 1959 Northeast Pacific (Box 356523), Seattle, WA 98195, USA.
The article by Stamm and colleagues reports the results of a comparison of doxycycline and azithromycin as treatment for the clinical syndrome of nongonococcal urethritis. This study was well done. The authors studied a large number of well-described patients who presented to multiple clinics in different geographic areas; had reasonable definitions of both the illness and the appropriate outcome; used random assignment to help ensure balanced, unbiased groups; and held their loss to follow-up to acceptable levels. I think there is every reason to believe the results are valid: Doxycycline and azithromycin provided comparable clinical results.
Why, then, should we advocate the substitution of the more-expensive azithromycin for doxycycline when this study showed that they produced clinically comparable results? The effectiveness of either medication is directly related to patient compliance. Azithromycin is given as a single dose, which can be directly observed to ensure compliance. Doxycycline must be taken twice a day for 7 days, and compliance becomes much more uncertain. Recent evidence from our institution indicates that more than half of all the doxycycline prescriptions written for men with urethritis are never filled (in contrast to this study in which patients were given the medication and closely followed). No further formal cost-effectiveness analysis is required to decide what to do: We are switching to azithromycin just as soon as we can. Others who care for similarly noncompliant patients probably should do the same.
Paul G. Shekelle, MD
West Los Angeles Veterans Affairs Medical CenterLos Angeles, California, USA