Push to use antibiotics to prevent sexually transmitted infections raises concerns

The gonorrhea bacteria (pictured) is developing resistance to certain antibiotics. Credit: SPL

A United States health department has become one of the first to recommend that people at high risk of contracting a sexually transmitted infection (STI) take a preventative dose of antibiotics after unprotected sex. Clinical trials have shown the strategy can reduce infections such as chlamydia, syphilis and gonorrhea. But some researchers worry it could contribute to antibiotic resistance.

Last month, the San Francisco Department of Public Health recommended that people at high risk of infection take a dose of the antibiotic doxycycline after unprotected sex to prevent bacterial STIs.

Rates of bacterial STIs have steadily increased over the past decade, particularly among men who have sex with men (MSM). “We have no tools to reduce the rate of [bacterial] STIs, except asking people to use condoms ”, including for oral sex, explains Jean-Michel Molina, infectious disease specialist at the University of Paris.

Molina led the first trial1 doxycycline post-exposure prophylaxis—a preventative treatment strategy known as doxyPEP—which reported results in 2018. In this trial, 22% of people using doxyPEP, and 44% who were not not, have been infected with an STI for nine months. Antibiotic use resulted in a 70% reduction in chlamydia infections and a 73% reduction in syphilis infections among participants. Gonorrhea infections were not significantly reduced.

DoxyPEP is similar to the extremely effective strategy of taking antivirals before unprotected sex to prevent HIV infection, known as HIV-PrEP. PrEP-HIV reduces the risk of contracting HIV through sex by about 99%.

Trial success

San Francisco adopted the policy after interim results from another trial — called DoxyPEP — were presented at the International AIDS Conference in Montreal in late July. This trial, involving MSM and transgender women living with HIV or taking PrEP for HIV, was terminated prematurely because taking doxycycline after unprotected sex was so effective in reducing STIs. Everyone enrolled in the trial, led by infectious disease physician Annie Luetkemeyer of the University of California, San Francisco, was then offered doxyPEP. Chlamydia and syphilis infections were more than 70% lower, and gonorrhea infections were 55% lower during each three-month period in those taking doxyPEP. Among people who did not take doxyPrep, about 30% became infected with one or more STIs each trimester.

Syphilis in men can cause serious health problems, such as blindness and nerve damage if left untreated. Chlamydia and gonorrhea infections in men are rarely serious, but in women they can lead to infertility. And syphilis can be passed to unborn children and cause miscarriage, stillbirth, or brain and organ damage in babies born with the disease.

But researchers are divided on whether the evidence of efficacy in MSM alone is enough to make the decision to officially roll out doxyPEP. Manik Kohli, a sexual health physician and researcher at University College London, says more data from multiple trials is needed to show whether doxyPEP leads to antibiotic resistance.

Other jurisdictions are taking a more cautious approach than the San Francisco Department of Public Health, which did not respond to of nature request for comment. The UK Health Safety Agency and the UK Association for Sexual Health and HIV say they do not endorse the doxyPEP strategy for the prevention of syphilis or chlamydia, in part due to a lack of resistance data to antimicrobials.

Facing resistance

When exposed to antibiotics, resistant and surviving bacteria can spread. Chris Kenyon, a microbiologist at the Institute of Tropical Medicine in Antwerp, Belgium, says using doxycycline to prevent infections dramatically increases a person’s exposure to the antibiotic, which could lead to resistance. . In the DoxyPEP trial, some participants took more than 20 doses of doxycycline each month, an amount Kenyon describes as “astronomical”.

Doxycycline is a “critically important” antibiotic for the treatment of other conditions, including skin infections caused by Staphylococcus aureus and bacterial pneumonia, Kenyon says. DoxyPEP could lead to the emergence of antibiotic resistance in the bacteria that cause these infections and limit treatment options, he says.

He says healthcare workers should take a precautionary approach when prescribing antibiotics as a preventative treatment, especially among MSM. They are a key population for the emergence of antibiotic resistance if antibiotic use is high, as people tend to have multiple sexual partners and networks that increase the chances of spreading resistant bacteria. Sex workers are another group in which antimicrobial resistance has emerged in the past.

Resistance to antibiotics of the tetracycline class, which includes doxycycline, is already common for gonorrhea. In the United States, approximately 25% of gonorrhea cases are caused by tetracycline-resistant bacteria. Elsewhere, resistance rates are higher, with studies reporting rates closer to 60% or 70% in Europe1,3.

Molina expects that the effectiveness of doxyPEP against gonorrhea depends on resistance rates in the local community and likely decreases over time as resistance levels increase.

But Luetkemeyer says early results from a second French trial, called DOXYVAC, show doxycycline reduces gonorrhea infections – despite high levels of resistance. The results suggest that the drug still prevents an infection from taking hold, even if it is ineffective in treating an established infection. “It often takes far less medication to prevent a disease than to cure a disease,” she says.

Other infections

Doxycycline resistance has not emerged in chlamydia or syphilis. Determining whether doxyPEP leads to resistance to these infections could take years, Molina says.

Luetkemeyer and his colleagues collected swab and stool samples to see if people using doxycycline as a preventive tool change the community of microorganisms that live in the gut or increase antibiotic resistance. These results will be presented at a conference in February 2023. Luetkemeyer also notes that there are other sources of doxycycline in the community that could contribute to resistance.

One of the hopes is that the use of doxyPEP among MSM could reduce rates of bacterial STIs in the wider community – including among women, who experience the greatest effects of chlamydia and gonorrhea infections. – just as HIV PrEP did for HIV in high-income countries.

But Kenyon is skeptical that doxyPEP will reduce STI rates, which can remain stubbornly high even after large-scale interventions. In the late 1990s, a mass treatment campaign with the antibiotic azithromycin to eliminate a syphilis epidemic in Vancouver initially drove rates down, but they quickly rebounded2.

Off-label use

Ever since Molina and his colleagues published the results of the first doxyPEP study in 2018, people have been using off-label doxycycline as a preventative tool, he says. Kenyon fears that doxyPEP could expose people to the antibiotic for years or even decades.

For people already using doxyPEP, public health recommendations are unlikely to convince them to quit, Kohli says. Following Luetkemeyer’s presentation at the International AIDS Conference in July, the US Centers for Disease Control and Prevention released information to guide the use of doxyPEP. The agency will issue further guidance when the final data is released and reviewed, a spokesperson said. Nature.

Usage guidelines are important for informing people about the safety of a strategy they might already be using, and for making preventative treatment available to people who might not be able to defend themselves. doxyPEP, says sexual health physician Jenell Stewart at Hennepin Healthcare in Minneapolis, Minnesota. Stewart is leading a doxycycline prophylaxis trial in Kenya for women taking HIV-PrEP4.

Despite the unknowns, Stewart says the benefits outweigh the risks. “People should have access to this tool, if it makes sense for them and their way of life,” she says.

Leave a Reply

Your email address will not be published. Required fields are marked *