24 June 2021

Wiping out rectal chlamydia

Clinical Pharmaceuticals Sex

The best method for treating chlamydia has long been up for debate, but new evidence indicates we’re on the right track.

About one in ten men who have sex with men test positive for rectal chlamydia during STI screening, and researchers are increasingly concerned that rectal infection in women may also cause urogenital chlamydia through autoinoculation.

Now University of Melbourne researchers have found that a seven-day course of doxycycline is significantly more effective in treating rectal chlamydia than the single-dose course of azithromycin, in a large study looking at men who have sex with men.

As well as supporting the current Australian guidelines, which recommend doxycycline as first-line treatment for rectal chlamydia, this may have implications for how women with urogenital chlamydia should be treated.

Until now, azithromycin has remained attractive due to it being a single-dose therapy, and is listed in Australian guidelines as the alternative treatment.

The authors of the paper, published in NEJM, acknowledged that evidence in support of the guidelines was previously thin and was not based on any direct comparison between the antibiotics.

“In the absence of a randomised, controlled trial that directly compares azithromycin with doxycycline for rectal chlamydia, any decision about changing the current guidelines could be considered premature,” the researchers wrote.

To better understand the efficacy of these antibiotics, they conducted a double-blind RCT of nearly 600 men who have sex with men, from five sexual health clinics across Victoria, New South Wales and South Australia all of whom tested positive for rectal chlamydia at baseline.

The men were randomly assigned to receive one dose of azithromycin, or a seven-day course of doxycycline. All participants were required to return to the clinic after four weeks for test-of-cure assessment.

Almost all (97%) of the men who were given doxycycline were clear from infection at check-up; only 76% of men who received azithromycin had cleared their infection over the same period.

The study authors said they were unsure exactly why doxycycline was superior.

“It is unclear why azithromycin is less efficacious than doxycycline for rectal chlamydia, since the results from other randomised controlled trials have shown the drug to be only slightly less effective than doxycycline for urogenital infection (94% vs 97%),” they wrote in the NEJM.

One theory was that the immune response to chlamydia was dampened in the rectum – a phenomenon observed in previous studies – and this could potentially inhibit azithromycin delivery.

In addition, 45% of people in the azithromycin group reported an adverse side effect, while just 33% of people in the doxycycline group did.

Although the trial was limited to men, the authors said the results were generalisable to heterosexual women as well, given the similar rectal chlamydial load between the sexes.

“Although azithromycin is likely to cure urogenital infection in women, it may not cure rectal chlamydia,” the authors added.

“This factor may be an issue if rectal chlamydia causes urogenital infection through autoinoculation.

“Treating urogenital chlamydia in women with doxycycline will clear rectal chlamydia, which reduces the risk of autoinoculation.”

NEJM 2021, 24 June

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