Azithromycin Efficacy in Asymptomatic Rectal Chlamydial Infection in Men Who Have Sex With Men: A More Definitive Answer Soon?

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Asymptomatic rectal Chlamydia trachomatis (CT) infections are common among men who have sex with men (MSM),1 and frequently exist apart from urethral infections: up to 88% of those with rectal CT are negative at the urethra.2 The Centers for Disease Control (CDC) recommends rectal screening for CT among MSM at least yearly, and for those positive, rescreening in approximately 3 months due to a substantial rate of repeat infections.3 Currently, CDC treatment recommendations for asymptomatic rectal infections include either azithromycin 1 g orally as a single dose, or doxycycline 100 mg orally bid for 7 days.3 Treatment recommendations for symptomatic proctitis and severe proctocolitis differ because pathogens other than CT, including Neisseria gonorrhoeae and herpes simplex virus, can cause these syndromes. Severe disease also suggests lymphogranuloma venereum, caused by LGV strains of CT, for which 21 days of doxycycline is recommended.
Notwithstanding the CDC guidelines, the best treatment for asymptomatic rectal infections in MSM is not clear. A number of observational studies, both retrospective and prospective, have been reported since 2009. A systematic review and meta-analysis of 8 of these studies estimated a pooled efficacy for azithromycin of 82.9%; 5 of the studies also included doxycycline, with an estimated pooled efficacy of 99.6%.4 The largest experience among these was a retrospective study in Seattle where among MSM with repeat CT testing within 90 days of treatment, the adjusted relative risk for persistence/recurrence among azithromycin treated men was 5.2 (95% confidence interval, 1.3–21).5 A follow-up report of one of the studies in the meta-analysis comprised 532 doxycycline-treated men and women with rectal CT, and reported an estimated failure rate of 0.9%.6 Finally, a recent retrospective experience among asymptomatic rectal CT in MSM reported an azithromycin efficacy of 83.6% among 171 azithromycin treated individuals. Of note, biomarkers including ompA sequencing and multilocus sequence typing and behavioral data were used to help discern treatment failure from reinfection.7 This study also suggests that organism load estimated at the index infection before treatment is associated with treatment failure.
Another contribution to this literature is the report in this issue by Smith et al.8 In a prospective observational cohort within the REACT randomized trial in Australia, repeat CT infections were sought among men who have sex with women (MSW) (n = 89), women who have sex with men (WSM) (n = 100) and MSM (n = 101) who were CT-infected at baseline and treated with single-dose azithromycin. In MSW and WSM, urogenital sites were sampled, and among MSM, urogenital and rectal sites. The authors used an algorithm which included detailed behaviors, ompA genotyping and multilocus sequence typing to distinguish treatment failures from likely reinfections. They found that treatment failures differed between the pooled MSW/WSM groups (2.6%) as compared with MSM (8.9%); among MSM, most treatment failures were at the rectal site. Although the number of repeated infections evaluated was relatively small (n = 43), the analyses are detailed and carefully done. Initial organism load in MSM again was associated with treatment failure. As previously reported, CT genotype distributions differed between the pooled MSW/WSM groups and the MSM group—another research question is whether this is a product of a largely nonintersecting epidemiology, or of bacterial factors that provide a competitive advantage at the rectal site. Finally, the study result supports the contention that azithromycin is less effective at the rectal site as opposed to genital sites.
The available literature, although observational in nature, points to the possibility of superior microbiological effectiveness of doxycycline over azithromycin in rectal CT infections in MSM.

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