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Three Part Question

In [sexually active males having been diagnosed with non-gonococcal urethritis], is [single dose azithromycin better then doxycycline] for [successfully eradicating the infection]?

Clinical Scenario

A 45-year-old man has been diagnosed with non-gonococcal urethritis. He needs antibiotics, and you wonder whether he should be given azithromycin or doxycycline.

Search Strategy

Medline - 1966 to June week 2 2006
Embase - 1980 to 2006 Week 24
CINAHL - 1982 to June Week 2 2006
The Cochrane Library 2006 issue 2
Medline/Embase/CINAHL: [exp Chlamydia Infections/ OR exp Urethritis/ OR exp Chlamydia trachomatis/ OR chlamydia.mp. OR non-gonococcal.mp.] AND [exp Azithromycin/ OR zithromax.mp.] AND [exp Doxycycline/ OR vibramycin.mp.] limit to humans, males and English language.
Cochrane: (Chlamydia [MESH] OR chlamydia trachomatis OR non gonococcal OR NGU) AND (azithromycin) AND (doxycycline).

Search Outcome

Altogether, 33 papers were identified using Medline, 118 using Embase, 2 using CINAHL and 34 using Cochrane. In Medline 10 papers were relevant, one of which was a meta-analysis which encompassed 8 of the other papers. No additional papers were found elsewhere.
The extra paper found in Medline was unavailable. However, it was done 11 years previously to the meta-analysis, and also was not a randomized trial, so did not fit the inclusion criteria for the meta-analysis. It was not thought to be important that this paper could not be included in the BET.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Lau C, Qureshi AK. Sept 2002 United States	726 males and 817 females receiving either oral doxycyline (100 mg 2x a day for 7 days) or oral azithromycin (1g once) for genital chlamydial infection in 12 studies ranging from 1990 to 1999.	Meta-analysis	Microbial cure	96.5% (853/884) azithromycin v. 97.9% (645/659) doxycycline. Pooled efficacy difference (ED) = 0.008% (95% CI, -0.007-0.022) z=1.05;p=0.296.	There was inadequate assessment of the methodologic quality of the primary studies.
			Test for homogeneity	Individual trials are consistent with overall pooled ED. chi-square = 10.48;df = 11;p = 0.488
			Adverse events	25.0% (319/1274) azithromycin v. 22.9% (205/897) doxycycline. Pooled Risk Difference (RD) = 0.009 (95% CI, -.019-0.037). Z = 0.62;P=0.533
			Test for homogeneity	Individual trials are consistent with overall pooled RD. chi-square = 6.63;df = 8;p=0.577
			Publication bias between studies	No evidence of publication bias. Egger's test bias coefficient = 0.53 (95% CI, -0.70-1.66) t=1.03;p=0.327. Beggs funnel plot - no trials outside of pseudo-95% CI (z=0.55;p=0.583)

Comment(s)

Doxycyline and azithromycin are equally efficacious in the treatment of genital Chlamydia trachomatis infection, and are not associated with statistically different rates of adverse events. However, the fact that azithromycin is a single-dose treatment whereas doxycycline involves a twice-daily 7-day regimen, makes azithromycin the best overall treatment.

Clinical Bottom Line

In men with non-gonococcal urethritis, azithromycin 1g single dose orally should be the treatment of choice.

References

1. Lau C. Qureshi AK Azithromycin versus doxycycline for genital chlamydial infections: a meta-analysis of randomized clinical trials. Sexually Transmitted Diseases 2002;29(9): 497-502.