The push to use antibiotics to prevent sexually transmitted infections raises concerns

Color scanning electron micrograph (SEM) of gonorrhea bacteria.

The gonorrhea bacterium (pictured) has developed resistance to certain antibiotics. Credit: SPL

A health department in the United States has become one of the first to recommend that people at high risk of contracting a sexually transmitted infection (STD) receive a preventive dose of antibiotics after unprotected sex. Clinical trials have shown that the strategy can reduce infections such as chlamydia, syphilis and gonorrhea. However, some researchers worry that it will 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 STDs.

Rates of bacterial STDs have been steadily increasing over the past decade, particularly among men who have sex with men (MSM). “We have no tool to reduce the rate [bacterial] Sexually transmitted diseases, in addition to asking people to use condoms, including oral sex, says infectious disease doctor Jean-Michel Molina at the University of Paris.

Molina presided over the first trial1 of post-exposure prophylaxis with doxycycline—a preventive treatment strategy known as doxyPEP—which reported results in 2018. In that trial, 22 percent of those who used doxyPEP and 44 percent who did not became infected with an STD over nine months. Antibiotic use led to a 70% reduction in chlamydia infections and a 73% reduction in syphilis infections among participants. Gonorrhea infections did not decrease significantly.

DoxyPEP is similar to the highly successful strategy of taking antiviral drugs before unprotected sex to prevent HIV infection – known as HIV-PrEP. Taking HIV-PrEP reduces the risk of sexually transmitted infection by about 99%.

Trial success

San Francisco adopted the policy after presenting interim results of another trial — called DoxyPEP — at the International AIDS Conference in Montreal in late July. This trial, which involved MSM and trans women either living with HIV or taking HIV-PrEP, was stopped early because taking doxycycline after unprotected sex was so effective at reducing STIs. Everyone enrolled in the trial, led by pathologist Annie Luetkemeyer at the University of California, San Francisco, then received doxyPEP. Chlamydia and syphilis infections were more than 70% lower and gonorrhea infections were 55% lower in each trimester in those receiving doxyPEP. In people who did not take doxyPrep, about 30% contracted 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.

However, researchers are divided on whether the evidence of efficacy in MSM alone is sufficient to make the decision to formally launch doxyPEP. Manik Kohli, a sexual health doctor and researcher at University College London, says more data from multiple trials is needed to see if doxyPEP causes antibiotic resistance.

Other jurisdictions are taking a more cautious approach than the San Francisco Department of Public Health, which did not respond of nature request for comment. The UK Health Safety Agency and the British Association for Sexual Health and HIV say they do not support the doxyPEP strategy for syphilis or chlamydia prevention, partly because of a lack of evidence on antimicrobial resistance.

Facing resistance

When exposed to antibiotics, bacteria that have resistance and survive can spread. Chris Kenyon, a microbiologist at the Institute of Tropical Medicine in Antwerp, Belgium, says that using doxycycline to prevent infections drastically increases a person’s exposure to the antibiotic, which could cause 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 treating other conditions, including skin infections caused by Staphylococcus disease 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 health care workers should take a proactive approach when prescribing antibiotics as a preventative treatment, particularly for MSDs. They are a key population for the emergence of antibiotic resistance if antibiotic use is high, because people tend to have multiple sexual partners and networks that increase the likelihood of the spread of resistant bacteria. Sex workers are another group in which antimicrobial resistance has emerged in the past.

Resistance to the tetracycline class of antibiotics, which includes doxycycline, is already common for gonorrhea. In the United States, about 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 doxyPEP’s effectiveness against gonorrhea will depend on rates of resistance in the local community and will likely decline over time as resistance levels rise.

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

Other infections

Resistance to doxycycline has not occurred in chlamydia or syphilis. Testing whether doxyPEP leads to resistance to these infections could take years, Molina says.

Luetkemeyer and her colleagues have collected swab and stool samples to see if people using doxycycline as a preventative change the community of microbes living 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 hope is that the use of doxyPEP in MSM could reduce rates of bacterial STIs in the wider community – including women, who bear the brunt of chlamydia and gonorrhea infections – as HIV-PrEP has done for HIV in high-prevalence countries. income.

But Kenyon is skeptical that doxyPEP will reduce STD rates, which can remain stubbornly high even after large-scale interventions. In the late 1990s, a mass treatment campaign with the antibiotic azithromycin to eradicate an outbreak of syphilis in Vancouver initially reduced rates, but they soon recovered2.

Off-label use

Since Molina and his colleagues published the results of the first doxyPEP study in 2018, people have been using doxycycline off-label 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 persuade them to stop, Kohli says. After 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 follow-up guidance when final data are released and reviewed, a spokesman said Nature.

Guidelines for use are important for informing people about the safety of a strategy they may already be using and for making preventive treatment available to people who may not be able to support doxyPEP on their own, says Dr. of sexual health Jenell Stewart at Hennepin Healthcare in Minneapolis, Minnesota. Stewart leads 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 lifestyle,” he says.

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