Doxycycline Bests Azithromycin for Anogenital Chlamydia in Women

Doxycycline was superior to azithromycin for women with both anorectal and vaginal Chlamydia trachomatis infections, French researchers found in an open-label randomized trial.

In a modified intention-to-treat analysis, microbiological anorectal cure occurred at 6 weeks in 94% of women who received a 1-week course of doxycycline versus 85% of those who received azithromycin (adjusted OR with imputation of missing values 0.43, 95% CI 0.21-0.91, P=0.0274), reported Bertille de Barbeyrac, PharmD, of Université de Bordeaux in France, and colleagues, on behalf of the CHLAZIDOXY Study Group.

The most common adverse events among both groups were gastrointestinal disorders, the authors noted in Lancet Infectious Diseases.

Three-quarters of women with C. trachomatis infection are asymptomatic, and 45% to 100% of those who test positive for urogenital C. trachomatis can acquire anorectal infections, which are also asymptomatic.

The CDC recommends doxycycline as first-line treatment for chlamydia infection, citing higher microbiological cure rates among men who have sex with men compared with azithromycin.

However, de Barbeyrac’s group noted that in studies of rectal C. trachomatis treatment, “women are largely underrepresented, and no [randomized] controlled trials of rectal infections are available in women.”

In an accompanying editorial, Christopher Fairley, PhD, of Monash University in Melbourne, Australia, and colleagues characterized the results of this study as “no surprise,” noting that antibiotic resistance is the reason that doxycycline should be the first-line treatment for C. trachomatis, except in special circumstances like pregnancy and allergic reactions.

“The widespread adoption of azithromycin has almost certainly caused the rapid increase in macrolide resistance in Mycoplasma genitalium infections,” they wrote, adding that its widespread use is also “temporarily associated with the development and rapid spread of syphilis that is now commonly resistant to azithromycin across the globe.”

“We strongly support the widespread adoption of doxycycline as the first-line treatment for anogenital chlamydia, regardless of sex, with azithromycin being reserved as a second-line option,” they concluded. “If this universal recommendation is adopted for all chlamydial infections, then adherence to the treatment guideline will be increased.”

CHLAZIDOXY was a randomized, open-label trial conducted at four sexually transmitted infection (STI) screening centers and three pregnancy termination centers in France from Oct. 19, 2018 to April 17, 2020. Sexually active adult women who tested positive for C. trachomatis via vaginal swab were included and provided self-collected anorectal swabs to test for anorectal C. trachomatis. The groups were randomized to receive either a single dose of azithromycin or doxycycline twice daily for 7 days.

The modified intention-to-treat population included 357 of 456 (78%) participants who tested positive for anorectal C. trachomatis at baseline — 184 in the doxycycline group and 173 in the azithromycin group. Among this group, mean age was 21, 68% were single, and only 20% had a history of STIs. While 48% had no genital symptoms, nearly all (92%) had no anal symptoms. A little over a third of the women reported a history of anal sex, and 86% reported “oral intercourse in their lifetime.”

The researchers noted that the primary analysis had “multiple imputation of missing values” due to missing data for women in both groups.

At 6 weeks, 16 women were still C. trachomatis-positive on anorectal swab, though they had cleared their vaginal infection. All four women in the doxycycline group cleared their anorectal infection at 4 months. Of the nine in the azithromycin group, two cleared their anorectal infection, five had persistent infection with the same strain as at baseline, and one woman had a different strain than at baseline. Three women total were lost to follow-up.

As for safety, 11% of the doxycycline group and 13% of the azithromycin group reported potential treatment-related adverse events (AEs), most frequently gastrointestinal disorders, such as nausea, diarrhea. and vomiting. Nine participants — one in the doxycycline group and eight in the azithromycin group — experienced serious AEs unrelated to the treatment.

Limitations to the study included that the trial was unblinded, de Barbeyrac and colleagues noted, though the biologists testing for chlamydia were blinded to the participants’ drug regimen. In addition, the results may not be generalizable to a low-risk population, and patient-collected anal swabs may have been contaminated during the collection process, they said.