Tweet
https://www.cidrap.umn.edu/antimicro...inst-gonorrhea
Study shows doxyPEP’s diminished effectiveness against gonorrhea
Chris Dall, MA
59 minutes ago.
Antimicrobial Stewardship
Chlamydia
Gonorrhea
Sexually Transmitted Infections A strategy for preventing sexually transmitted infections (STIs) appears to be rapidly losing effectiveness against gonorrhea, according to a new study.
The strategy, known as doxycycline post-exposure prophylaxis (doxyPEP), involves taking a dose of the antibiotic doxycycline within 72 hours of unprotected sex. After a clinical trial conducted in Seattle and San Francisco found that the strategy was highly effective at preventing chlamydia, syphilis, and gonorrhea infections in men who have sex with men (MSM) and transgender women who are at high risk of STIs, California became an early adopter of the intervention.
In June 2024, the Centers for Disease Control and Prevention (CDC) recommended that clinicians discuss the use of doxyPEP with high-risk patients and consider prescribing it. The agency has suggested that doxyPEP may have played a part in recent small declines in syphilis, chlamydia, and gonorrhea, the three most common STIs reported in the United States.
But in an observational study published last week in The Lancet Infectious Disease, researchers in California found that, although doxyPEP remains very effective in preventing chlamydia and syphilis two years after statewide implementation, its effectiveness against gonorrhea has faded over time. And the loss of effectiveness appears to be linked to a rise in strains carrying genes that make gonorrhea resistant to tetracyclines, the class of antibiotics that includes doxycycline.
“Early on, the protection with doxyPEP against gonorrhea was moderate, but it just diminished rapidly and was no longer evident within a year after implementation,” co-lead study author Sara Tartof, PhD, an infectious disease epidemiologist with Kaiser Permanente Southern California (KPSC), told CIDRAP News.
Longstanding questions about effectiveness against gonorrhea
The findings aren’t necessarily a surprise. Even in the Doxy-PEP trial, in which incidence of chlamydia and syphilis fell by 88% and 87%, respectively, gonorrhea infections were reduced by a more modest 55%. And in a subsequent 2025 observational study in San Francisco after citywide implementation in October 2022, chlamydia and syphilis cases were cut in half, but researchers found no decline in gonorrhea incidence.
A trial conducted in France in 2021 and 2022 found doxyPEP was even less effective at reducing gonorrhea incidence, and further analysis of data from the trial suggested the result was associated with high-level tetracycline resistance in gonorrhea samples from doxyPEP users.
US research also suggests that increases in tetracycline-resistant gonorrhea strains may be linked to rising use of doxyPEP. A 2025 study by researchers at the University of Washington found that, among gonorrhea isolates collected at a sexual health clinic in Seattle, where the strategy was implemented in June 2023, the prevalence of tetracycline-resistance genes rose from 27% in 2017 to 70% by the middle of 2024.
In a July 2025 letter to the New England Journal of Medicine, researchers reported that the presence of the tetM gene, which confers high-level tetracycline resistance, in US gonorrhea samples rose from less than 10% in 2020 to 30% in the first quarter of 2024. The highest prevalence of gonorrhea isolates carrying tetM genes was found in the Pacific Northwest.
Early on, the protection with doxyPEP against gonorrhea was moderate, but it just diminished rapidly and was no longer evident within a year after implementation.
In last week’s study, a team led by researchers from KPSC and the University of California, Berkeley, assessed STI incidence in KPSC members of any gender identity who were assigned male sex at birth and were living with HIV or received doxyPEP or HIV pre-exposure prophylaxis (PrEP). The primary outcomes were lab-confirmed chlamydia, syphilis, and gonorrhea among patients within 90 days of filling a doxyPEP prescription.
Among the 26,582 patients who had at least one STI test from January 2023 to June 30, 2025, overall preventive effectiveness was 66.5% against chlamydia, 60.7% against syphilis, and –1.8% against gonorrhea. Over the study period, effectiveness against gonorrhea fell from 42.3% from January to April 2023, when statewide implementation of doxyPEP guidelines in California were announced, to –15% by the end of the study.
The decline in effectiveness against gonorrhea was associated with a rapid increase in the prevalence of tetM resistance genes in gonorrhea samples collected from sexual health clinics in three counties (Los Angeles, Orange, and San Diego), the researchers found.
“We saw that when tetM prevalence was about 20% to 30%, doxyPEP provided still provided some protection, but as prevalence increased to around 50% or higher, we did not see effectiveness,” Tartof said
And while the study doesn’t prove that doxyPEP implementation has caused the increase in tetracycline-resistant gonorrhea, the researchers note that the rates of tetM prevalence in gonorrhea strains rapidly accelerated shortly after statewide doxyPEP implementation, despite modest uptake, Tartof said.
“To see such a decline in this period of time in the context of relatively low uptake, I think was a little surprising and really worth thinking about,” she said.
Intervention ‘still have value’
Paul Adamson, MD, MPH, an infectious disease physician and assistant professor at the David Geffen School of Medicine at the University of California, Los Angeles, who specializes in STI prevention, says he’s not totally surprised by the findings.
“The lifespan for preventing gonorrhea was always going to be short, and this shows that it was probably a little bit shorter than expected,” said Adamson, who was not involved in the study. But he suspects, based on his experience as a clinician, that the increase in tetracycline-resistant gonorrhea strains in southern California may have begun before the statewide doxyPEP guidelines were implemented.
“A lot of my patients were coming to me asking about doxyPEP even prior to the [Doxy-PEP] trial results being released,” he said. “I was sort of shocked at how quickly the community was taking it up.”
Another explanation, he added, is increased use of doxycycline as a first-line treatment for chlamydia and an alternative treatment for syphilis.
But Adamson said it’s important to keep sight of the fact that doxyPEP’s effectiveness against chlamydia and syphilis remains high, given the continued rise in US syphilis cases, including maternal and congenital syphilis.
“It’s a big benefit to be able to prevent syphilis, so I still think it has value,” he said.
Study shows doxyPEP’s diminished effectiveness against gonorrhea
Chris Dall, MA
59 minutes ago.
Antimicrobial Stewardship
Chlamydia
Gonorrhea
Sexually Transmitted Infections A strategy for preventing sexually transmitted infections (STIs) appears to be rapidly losing effectiveness against gonorrhea, according to a new study.
The strategy, known as doxycycline post-exposure prophylaxis (doxyPEP), involves taking a dose of the antibiotic doxycycline within 72 hours of unprotected sex. After a clinical trial conducted in Seattle and San Francisco found that the strategy was highly effective at preventing chlamydia, syphilis, and gonorrhea infections in men who have sex with men (MSM) and transgender women who are at high risk of STIs, California became an early adopter of the intervention.
In June 2024, the Centers for Disease Control and Prevention (CDC) recommended that clinicians discuss the use of doxyPEP with high-risk patients and consider prescribing it. The agency has suggested that doxyPEP may have played a part in recent small declines in syphilis, chlamydia, and gonorrhea, the three most common STIs reported in the United States.
But in an observational study published last week in The Lancet Infectious Disease, researchers in California found that, although doxyPEP remains very effective in preventing chlamydia and syphilis two years after statewide implementation, its effectiveness against gonorrhea has faded over time. And the loss of effectiveness appears to be linked to a rise in strains carrying genes that make gonorrhea resistant to tetracyclines, the class of antibiotics that includes doxycycline.
“Early on, the protection with doxyPEP against gonorrhea was moderate, but it just diminished rapidly and was no longer evident within a year after implementation,” co-lead study author Sara Tartof, PhD, an infectious disease epidemiologist with Kaiser Permanente Southern California (KPSC), told CIDRAP News.
Longstanding questions about effectiveness against gonorrhea
The findings aren’t necessarily a surprise. Even in the Doxy-PEP trial, in which incidence of chlamydia and syphilis fell by 88% and 87%, respectively, gonorrhea infections were reduced by a more modest 55%. And in a subsequent 2025 observational study in San Francisco after citywide implementation in October 2022, chlamydia and syphilis cases were cut in half, but researchers found no decline in gonorrhea incidence.
A trial conducted in France in 2021 and 2022 found doxyPEP was even less effective at reducing gonorrhea incidence, and further analysis of data from the trial suggested the result was associated with high-level tetracycline resistance in gonorrhea samples from doxyPEP users.
US research also suggests that increases in tetracycline-resistant gonorrhea strains may be linked to rising use of doxyPEP. A 2025 study by researchers at the University of Washington found that, among gonorrhea isolates collected at a sexual health clinic in Seattle, where the strategy was implemented in June 2023, the prevalence of tetracycline-resistance genes rose from 27% in 2017 to 70% by the middle of 2024.
In a July 2025 letter to the New England Journal of Medicine, researchers reported that the presence of the tetM gene, which confers high-level tetracycline resistance, in US gonorrhea samples rose from less than 10% in 2020 to 30% in the first quarter of 2024. The highest prevalence of gonorrhea isolates carrying tetM genes was found in the Pacific Northwest.
Early on, the protection with doxyPEP against gonorrhea was moderate, but it just diminished rapidly and was no longer evident within a year after implementation.
In last week’s study, a team led by researchers from KPSC and the University of California, Berkeley, assessed STI incidence in KPSC members of any gender identity who were assigned male sex at birth and were living with HIV or received doxyPEP or HIV pre-exposure prophylaxis (PrEP). The primary outcomes were lab-confirmed chlamydia, syphilis, and gonorrhea among patients within 90 days of filling a doxyPEP prescription.
Among the 26,582 patients who had at least one STI test from January 2023 to June 30, 2025, overall preventive effectiveness was 66.5% against chlamydia, 60.7% against syphilis, and –1.8% against gonorrhea. Over the study period, effectiveness against gonorrhea fell from 42.3% from January to April 2023, when statewide implementation of doxyPEP guidelines in California were announced, to –15% by the end of the study.
The decline in effectiveness against gonorrhea was associated with a rapid increase in the prevalence of tetM resistance genes in gonorrhea samples collected from sexual health clinics in three counties (Los Angeles, Orange, and San Diego), the researchers found.
“We saw that when tetM prevalence was about 20% to 30%, doxyPEP provided still provided some protection, but as prevalence increased to around 50% or higher, we did not see effectiveness,” Tartof said
And while the study doesn’t prove that doxyPEP implementation has caused the increase in tetracycline-resistant gonorrhea, the researchers note that the rates of tetM prevalence in gonorrhea strains rapidly accelerated shortly after statewide doxyPEP implementation, despite modest uptake, Tartof said.
“To see such a decline in this period of time in the context of relatively low uptake, I think was a little surprising and really worth thinking about,” she said.
Intervention ‘still have value’
Paul Adamson, MD, MPH, an infectious disease physician and assistant professor at the David Geffen School of Medicine at the University of California, Los Angeles, who specializes in STI prevention, says he’s not totally surprised by the findings.
“The lifespan for preventing gonorrhea was always going to be short, and this shows that it was probably a little bit shorter than expected,” said Adamson, who was not involved in the study. But he suspects, based on his experience as a clinician, that the increase in tetracycline-resistant gonorrhea strains in southern California may have begun before the statewide doxyPEP guidelines were implemented.
“A lot of my patients were coming to me asking about doxyPEP even prior to the [Doxy-PEP] trial results being released,” he said. “I was sort of shocked at how quickly the community was taking it up.”
Another explanation, he added, is increased use of doxycycline as a first-line treatment for chlamydia and an alternative treatment for syphilis.
But Adamson said it’s important to keep sight of the fact that doxyPEP’s effectiveness against chlamydia and syphilis remains high, given the continued rise in US syphilis cases, including maternal and congenital syphilis.
“It’s a big benefit to be able to prevent syphilis, so I still think it has value,” he said.