Azithromycin in the treatment of rectogenital Chlamydia trachomatis infections: end of an era?

ABSTRACT

Introduction

Azithromycin was recommended as the first-line therapeutic regimen for treatment of genital infections in men and women by the Centers for Disease Control in 1998. A series of studies of azithromycin for treatment of rectal chlamydial infection in men who have sex with men (MSM) found that azithromycin was significantly less effective than doxycycline.

Areas covered

Literature on treatment of rectal C. trachomatis from 2000 through May 2020 was searched using PubMed. Retrospective and observational studies were identified documenting the frequency and treatment of rectal chlamydial infection in MSM, heterosexual men and women that reported lower efficacy of single-dose azithromycin compared to doxycycline. Literature on possible reasons for the lower efficacy were also reviewed including studies of antibiotic resistance, impact of organism load, and persistent infection in rectal specimens and pharmacokinetics and pharmacodynamics of azithromycin in rectal tissue.

Expert opinion

The available data suggests that single-dose azithromycin is not as effective as azithromycin for the treatment of rectal infection in MSM and women. Most of these data have been retrospective or from observational studies. Final recommendations will depend on the outcome of prospective, randomized, treatment studies. We may also need to examine other dosage regimens for azithromycin.

KEYWORDS:

• Azithromycin
• doxycycline
• rectal infection
• chlamydia
• chlamydia trachomatis

Article highlights

• Available data suggests that single-dose azithromycin is not as effective as 7 days of doxycycline for the treatment of rectal C. trachomatis infection in MSM and women.

• The use of NAATs in rectal specimens has facilitated the screening of both men and women at that site. A surprising finding has been the presence of rectal infection in women who do not give a history of anal intercourse. However, the clinical impact of rectal infection in women is not clear.

• Reasons for the lower efficacy of azithromycin for treatment of rectal infections are not clear. It does not appear to be due to development of antibiotic resistance to azithromycin, pharmacokinetics of azithromycin in rectal tissue, or chlamydial persistence.

• There may be an association of lower efficacy of azithromycin with higher organism loads and local pH in rectal tissue.

• Even pending the results of the randomized controlled studies, azithromycin can no longer be recommended as first-line therapy for treatment of rectal C. trachomatis in MSM. Azithromycin is still the drug of choice for treating C. trachomatis infection in women. A reassessment of azithromycin dosing for rectal infections may be necessary.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.