Doxy PEP Effectiveness Declines Against Gonorrhea But Remains High for Chlamydia and Syphilis

Doxycycline post-exposure prophylaxis (doxy PEP) is becoming less effective at preventing gonorrhea infections due to rising antibiotic resistance, according to a study of more than 26,000 transgender women and men who have sex with men in Southern California. While the strategy remains highly effective against chlamydia and syphilis, researchers found that its ability to prevent gonorrhea declined rapidly as the treatment became more widely available between 2023 and 2025.

The data indicates that doxy PEP maintained a 67% effectiveness rate against chlamydia and a 61% effectiveness rate against syphilis throughout the study period.

Gonorrhea prevention showed a different trend. According to the researchers, doxy PEP was approximately 42% effective against gonorrhea early in the study, but that percentage dropped quickly as the prevention strategy saw increased adoption in California.

Antibiotic resistance and gonorrhea trends

Researchers linked the decline in effectiveness to a rapid increase in tetracycline-resistant bacteria. Doxycycline belongs to the tetracycline class of antibiotics, and the bacteria that cause gonorrhea developed resistance to this class as early as the 1980s.

The Southern California study found that doxy PEP was less effective when antibiotic-resistant gonorrhea was circulating and more effective when other strains were more common. Because drug-resistant versions of gonorrhea can be passed from person to person, infections caused by these strains are harder to treat because certain antibiotics no longer work.

Some experts expressed concern that the increased use of doxy PEP could exacerbate the problem by further driving antibiotic resistance.

CDC guidelines and doxy PEP application

The Centers for Disease Control and Prevention (CDC) began recommending doxy PEP in 2024. This recommendation followed earlier studies in California which suggested the strategy could reduce the likelihood of contracting syphilis and chlamydia by roughly 80% and gonorrhea by about 50%.

Doxy PEP involves taking a dose of the antibiotic doxycycline after condomless oral or anal sex. The strategy is intended for adult men who have sex with men and transgender women who have sex with men, specifically those more likely to be exposed to bacterial STIs, such as those who had an infection within the previous year.

The CDC guidelines do not extend to cisgender women who have penis-in-vagina sex, as the strategy has not been shown to be effective for that group.

Future of STI prevention strategies

The researchers stated that these findings emphasize the necessity of continuous monitoring of antibiotic resistance. They suggested that because the effectiveness against gonorrhea is declining, public health recommendations for using doxy PEP to prevent that specific infection may need to change.

Because doxy PEP is a relatively new prevention tool, the relationship between its widespread use and the evolution of resistant bacteria remains a primary focus for public health officials determining future usage protocols.