Challenges in Treating Chlamydia trachomatis, Including Rectal Infections: Is It Time to Go Back to Doxycycline?

Abstract

Objective: To evaluate recent publications on efficacy of single-dose azithromycin and 7-day doxycycline when treating Chlamydia trachomatis. Data Sources: A literature search of MEDLINE, EMBASE, PubMed, and Cochrane library was conducted (1990 to June 13, 2021) using the terms: Chlamydia trachomatis, genital chlamydia, rectal chlamydia, extragenital chlamydia, azithromycin, doxycycline, and treatment guidelines. ClinicalTrials.gov was searched to identify ongoing trials. Study Selection and Data Extraction: English language studies, including controlled studies, retrospective analyses, systematic reviews, meta-analyses, and case reports, reporting microbiological or clinical outcomes in adolescents and adults were considered. Data Synthesis: Systemic reviews and meta-analyses of randomized trials reported azithromycin efficacy of 96% to 97% in genital chlamydia. However, reports of treatment failure have emerged, especially among symptomatic males, with an increased risk of microbiological failure after azithromycin than doxycycline (relative risk = 2.45; 95% CI = 1.36-4.41). Retrospective analyses and prospective observational cohort studies reported lower efficacy range following azithromycin than doxycycline (74%-87% vs 92%-100%, respectively) in rectal chlamydia. First randomized controlled trial comparing azithromycin and doxycycline reported significantly higher microbiological cure following doxycycline, with absolute difference of 26% (95% CI = 16%-36%; P < 0.001). The proposed 2021 Centers for Disease Control and Prevention treatment guidelines designate doxycycline as the preferred agent for treatment at any site. Relevance to Patient Care and Clinical Practice: A growing body of evidence for treatment failure following azithromycin, especially in rectal chlamydia supports updating current practice. Conclusions: Doxycycline continues to achieve high efficacy in genital and rectal chlamydia. Clinicians should consider efficacy with convenience of dosing regimen, medication compliance, and sexual behavior risks when treating chlamydia infections.