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.

Zoonotic transmission of Chlamydia felis from domestic cats; A case series of chronic follicular conjunctivitis in humans

“…In case 2, treatment with azithromycin appeared to be clinically successful however, azithromycin was given in combination with tetracycline eye ointment after the patient had been treated with chloramphenicol eye drops for two weeks. Treatment failure up to 17 % with this antibiotic regimen has been reported for several infections caused by C. trachomatis , especially in rectal infections [ [19] , [20] , [21] , [22] , [23] ] and the treatment of trachoma in young children. Azithromycin is no longer the first-choice antibiotic for these infections, instead 100 mg doxycycline orally twice a day for between 7 and 21 days is recommended and has been shown to be more effective [ 24 ].…”

2021 CDC Update: Treatment and Complications of Sexually Transmitted Infections (STIs)

“…Alternative regimens include azithromycin 1 g PO × 1 or levofloxacin 500 mg PO daily × 7. Although rates of adherence to doxycycline's longer course, compared to azithromycin's single dose, have perennially been called into question [35,36], doxycycline appears to have a higher efficacy rate, even with suboptimal compliance to treatment [37,38]. Indeed, doxycycline is effective against urogenital, rectal, and oropharyngeal infections.…”

Liposomal Encapsulation Increases the Efficacy of Azithromycin against Chlamydia trachomatis

“…While both antibiotic regimens are effective, treatment failures have also been reported. Systemic reviews and meta-analyses of clinical trials assessed the AZT effectivity of 96-97%, but the relative risk of treatment failure was 2.45 compared to that for doxycycline [4]. Multiple factors could lead to C. trachomatis treatment failures including a higher bacterial load [5], homotypic resistance due to chromosomal mutations, such as the mutations of the 23S rRNA [6], and heterotypic resistance, where a certain sub-population of a Chlamydia pool displays higher antimicrobial resistance, but this phenotypic feature is not encoded genetically [7].…”