Are antibiotics risky before STI exposure?

December 9, 2022 – Using antibiotics to prevent – ​​not just treat – sexually transmitted infections was an idea just a decade ago. It is now backed by several studies and has received the green light from a California Department of Public Health.

Posted by Jeffrey Klausner, MD, an infectious disease physician and professor of public health at the University of Southern California the first randomized controlled trial On whether doxycycline, an antibiotic commonly used to treat infections including syphilis, chlamydia and others, can prevent STIs in 2015. At first, he said, the National Institutes of Health did not want to fund the work, citing concerns about the potential for antimicrobial resistance.

In the worst-case scenario, the microbes change over time and no longer respond to the drug, and treatments stop.

But with the growing STI crisis, health professionals are looking for new ways to help.

“It was more than 170,000 cases of syphilis [in the U.S.] last year, and the annual cases have doubled in the last five years,” says Klausner.

Repeated studies with slightly different designs also found lower rates of sexually transmitted diseases in people who took doxycycline daily or after sex. The method known as pre-exposure doxycycline prophylaxis now has its own name: doxyPEP.

And in October, the San Francisco Department of Public Health recommended doxyPEP for cisgender men and transgender women who have had a bacterial STI in the past year and have had unprotected oral or anal sex with one or more cis men or trans women in the past year.

For those who meet the second criterion but have not been diagnosed with an STI in the past year, the department recommends a “shared decision-making approach” where doctors discuss the benefits and risks of doxyPEP and prescribe it to patients who feel they will benefit then, explains Stephanie Cohen, MD, director of disease prevention and control in the department’s division of public health.

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The department also recommends doxyPEP to anyone diagnosed with syphilis, regardless of gender or sexual partner.

According to Cohen, the United States has one of the highest rates of sexually transmitted infections in the world, and that “San Francisco, in particular, has the highest rate of sexually transmitted infections in the country.”

Latest results

Most recent study doxiPEP followed 501 men and trans women in Seattle and San Francisco. About two-thirds were taking HIV pre-exposure prophylaxis (HIV PrEP) and the rest were HIV-infected. The results of this study were shared by the International AIDS Society (IAS) Conference Earlier this year, they found that sexually transmitted infections were lower in the group who had to take a single dose of doxycycline within 72 hours of unprotected sex. The STI reduction rate was 66% in the HIV PrEP group and 62% in the HIV-positive group.

“It might be a bit of a paradigm shift to talk about using antibiotics before someone gets an infection,” says Annie Luetkemeyer, MD, an infectious disease physician and STI researcher at the University of California, San Francisco, who co-led the study. .

He recalls that when HIV PreP came out, it was pushed back that it would lead to riskier sex or increased HIV drug resistance. Indeed, “we have learned that for certain segments of the population, access to HIV PrEP is essential to reduce HIV risk.”

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A drawback of doxyPEP is that it may lead to greater antimicrobial resistance. However, Luetkemeyer points out that the highest-risk populations targeted by the intervention are already at high rates of antibiotic use, mainly to treat STIs.

The rate of STIs in the control group of the study was 32% over a 3-month period, compared to 11% in the doxyPEP group. However, the use of doxiPEP was not perfect, and study participants reported taking it after an average of 87% of unprotected sexual encounters.

“It’s not a matter of taking doxycycline or not taking antibiotics,” says Luetkemeyer. In fact, the control group had a 50% higher exposure to ceftriaxone, a broad-spectrum antibiotic with greater potential than doxycycline to induce drug-resistant gonorrhea.

Still, Luetkemeyer and Klausner say monitoring for drug-resistant STIs and other infections, such as doxycycline-resistant ones, is important. Staphylococcus aureusso that doxyPEP does not increase them.

Is it worse?

Luetkemeyer and colleagues are now investigating whether doxyPEP increases the number of drug-resistant bacteria in those who take it. No red flags yet, but research is ongoing.

While the San Francisco Department of Public Health gave the first official approval for doxyPEP, doctors working with high-risk populations have been prescribing the drug for years. Klausner says that when he treated patients with or at risk of HIV infection, he prescribed prophylactic doxycycline daily or after condomless sex, depending on the frequency of the patient’s sexual activity. Start with 15 doses, 200 milligram doses, with refills as needed.

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He also notes that there isn’t a permanent group of people who need doxiPEP, pointing out that people may benefit from periods between monogamous or relatively monogamous relationships, for example.

“People’s risk profiles are dynamic. doxyPEP is not a strategy that we encourage people to adopt forever,” he says.

And while doxyPEP may increase the risk of drug-resistant infections, it could also theoretically reduce it by reducing the burden of STDs in the population and reducing the need for antibiotic treatments, Klausner says.

“It’s been known since the 1970s that sexually transmitted infections — like chlamydia, gonorrhea, syphilis — are perpetuated by a core group,” he says, typically men who have sex with many male partners for more than a month. “If you can control the spread of the infection in the core group, the rest of the population is better protected.”

Cohen, of the San Francisco Department of Public Health, said that while it’s “certainly a priority to do surveillance to see if there are signs of antimicrobial resistance,” for now, “the community’s desire for new tools. protection against STIs outweighs the potential and unknown risks of antimicrobial resistance.”

What is certain is that decades of experience show that the only other prevention tool, the condom, will not be used by everyone, due to partner or personal preferences.

“For some populations with very high rates of sexually transmitted infections, what we’re offering right now isn’t working, so we really need new tools,” says Luetkemeyer.