A recent study presented at the 2023 CROI (Conference on Retroviruses and Opportunistic Infections) indicates that doxy-PEP, a strategy involving the use of doxycycline after unprotected sex, is highly effective in preventing sexually transmitted infections (STIs). The research, led by UC San Francisco, the San Francisco Department of Public Health, and the University of Washington, suggests that this approach is associated with only a limited increase in antibiotic-resistant bacteria.
Doxy-PEP involves taking a 200mg pill of doxycycline, a tetracycline antibiotic, within three days after condomless sex. The study focused on men who have sex with men (MSM) and transgender women, a population with elevated STI rates. The results showed a significant reduction in bacterial STIs, including gonorrhea, chlamydia, and syphilis, by approximately two-thirds each quarter during the one-year study period.
Impact on Antibiotic Resistance
Researchers are encouraged by the seemingly small effects on antibiotic resistance observed thus far. However, they emphasize the need for continued monitoring to fully understand the long-term impact of intermittent doxycycline use on antimicrobial resistance. According to Annie Luetkemeyer, MD, professor of infectious diseases at Zuckerberg San Francisco General Hospital and UCSF, "Doxy-PEP may mitigate the amount of antibiotics used, including broader spectrum antibiotics like ceftriaxone, the use of which was reduced by 50% in those taking doxy-PEP."
The study's examination of antimicrobial resistance during doxy-PEP use considered gonorrhea and two other bacterial types: Staphylococcus aureus (found on the skin) and non-disease-causing Neisseria species (found in the throat).
Gonorrhea Resistance
Among participants diagnosed with gonorrhea during the study, a higher prevalence of tetracycline-resistant gonorrhea was observed in those using doxy-PEP compared to those who were not (30% vs. 11%). This suggests that doxy-PEP may be less effective against gonorrhea strains already exhibiting tetracycline resistance. Further population-based studies are necessary to determine if doxy-PEP use contributes to increased tetracycline resistance in gonorrhea.
Staphylococcus aureus Colonization
Doxy-PEP influenced the colonization rates of Staphylococcus aureus. While it reduced overall colonization from 44% to 31%, the proportion of doxycycline-resistant cultures increased from 5% to 13%, a statistically significant but small rise. Importantly, there was no overall increase in methicillin-resistant Staphylococcus aureus (MRSA) or doxycycline-resistant MRSA. This is particularly relevant as doxycycline is sometimes used in MRSA treatment.
Neisseria Species
Neisseria species, commonly found in the throat, serve as a potential reservoir for resistance genes. Doxy-PEP use did not appear to significantly affect these bacteria, as doxycycline resistance was already present in approximately two-thirds of the Neisseria species, and this level remained relatively stable after 12 months of doxy-PEP.
Future Research
The ZSFG HIV clinic and the SF City Clinic are continuing to assess the effect of doxy-PEP on the gut microbiome and other STIs, such as mycoplasma genitalium and chlamydia.
Clinical Implications
Connie Celum, MD, professor of global health, medicine, and epidemiology at the University of Washington, stated, "Doxy-PEP is a promising strategy to reduce sexually transmitted infections in populations that are disproportionately affected by high rates of sexually transmitted infections, specifically, men who have sex with men and transgender women who have had recent STIs. It will be important to monitor the impact of doxy-PEP on antibiotic resistance over time and weigh this against the demonstrated benefit of reduced STIs."
