Does Doxycycline Postexposure Prophylaxis Reduce Bacterial Sexually Transmitted Infections?
Date First Published:
November 29, 2025
Last Updated:
November 29, 2025
Report by:
David Porter MD, Jennifer Bach MD, Senior EM resident, EM faculty (Corewell Health/Michigan State University Emergency Medicine Residency Program)
Search checked by:
Jeffrey Jones MD, Research Director
Three-Part Question:
In [high-risk adults following sexual intercourse] s the [receipt of doxycycline postexposure prophylaxis] [compared to placebo or no prophylaxis] associated with [a decline in incidence of bacterial sexually transmitted infections]?
Clinical Scenario:
A 23-year-old male with no significant past medical history presents to the emergency department due to concerns that he may have contracted a sexually transmitted infection (STI). The patient reports that he has been sexually active with multiple new partners which he met using a dating app. He denies any systemic or genitourinary symptoms, but states that he just felt like he should “get checked out”. He states that he uses condoms infrequently and has never been treated for an STI in the past. He is a student at the local university and does not have a primary care physician. As his physician, you wonder if this patient would benefit from prophylactic antibiotics given his high-risk sexual behavior.
Search Strategy:
Medline 1966-10/25 using PubMed, Cochrane Library (2025), and Embase
Search Details:
[(Sexually transmitted diseases/prevention and control) AND (doxycycline) AND (post-exposure prophylaxis)]. Limit to English
Outcome:
27 articles were found; two systematic reviews using meta-analysis and one RCT were recently published and addressed the clinical question.
Relevant Paper(s):
| Study Title | Patient Group | Study type (level of evidence) | Outcomes | Key results | Study Weaknesses |
|---|---|---|---|---|---|
| Efficacy of Doxycycline as Preexposure and/or Postexposure Prophylaxis to Prevent Sexually Transmitted Diseases: A Systematic Review and Meta-Analysis. Boschiero MN, Sansone NMS, Matos LR, et al. February 2025 Brazil | 1182 patients at high-risk for sexually transmitted infections | A systematic review and meta-analysis of 3 randomized clinical trials of a high-risk group of individuals was conducted to evaluate whether doxycycline is effective as postexposure prophylaxis in preventing bacterial STIs. | Incidence of bacterial STIs and individual STI infections. | The incidence of the first STI was lower in the doxy-PEP group | Only a few studies were included, which might have led to under- or overestimation in the analysis. The authors did not have access to individual patient data. Most of the studies were conducted in different places, with different bacterial resistance profiles, which were not considered. Most studies had different inclusion criteria for the control group. High heterogeneity was observed in all the outcomes, and a study bias was also observed. |
| (HR, 0.538; P < 0.05). The incidence of individual infection of C. trachomatis was also lower compared with controls (RR, 0.291; P < 0.05). | |||||
| Efficacy of postexposure prophylaxis with doxycycline (Doxy-PEP) in reducing sexually transmitted infections: a systematic review and meta-analysis Sokoll PR, Migliavaca CB, Döring S, et al. January 2025 Germany/Brazil/UK | 1727 participants at high-risk risk of having bacterial sexually transmitted infections (STIs), | Randomized clinical trials evaluating the efficacy of Doxy-PEP (a single dose of 200 mg of doxycycline within 72 hours after condomless sex) in comparison with no doxycycline use. | Risk of having any STI, risk of chlamydia, risk of gonorrhoea and risk of syphilis infection. | Doxy-PEP reduced the risk of having any bacterial STI in different populations by 46% (hazard ratio), the risk of chlamydia by 65% (relative risk) and syphilis by 77% (RR) without significant effect for risk of gonorrhoea infection (RR 0.90). | A small number of studies included and the short duration of follow-up. The characteristics of the participants were very similar. |
| Doxycycline to prevent bacterial sexually transmitted infections in the USA: final results from the DoxyPEP multicentre, open-label, randomised controlled trial and open-label extension Luetkemeyer AF, Donnell D, Cohen SE, et al. August 2025 USA | 637 participants, aged 18 years or older, were assigned male at birth, were living with HIV or taking or planning to start HIV PrEP, had condomless sexual contact with another person assigned male at birth in the past 12 months, and had a history of at least one bacterial STI (ie, N gonorrhoeae, C trachomatis, or early syphilis) in the past 12 months. | RCT assigned participants to doxy-PEP (200 mg doxycycline delayed-release tablets 24–72 h after condomless sex) or standard care. | Presence of one or more bacterial STIs. Secondary outcomes were incidence of each individual | STIs were present in 129 (12.0%) of 1077 quarters in the doxy-PEP group versus 139 (30.5%) of 455 quarters in the standard-care group during the as-randomised period, showing an absolute difference of 19 percentage points and a relative risk of 0.39 (p<0·0001). Throughout all quarters for participants on doxy-PEP, there was one grade 2 laboratory abnormality and five grade 3 adverse events that were possibly or probably related to doxy-PEP. Of the participants with positive gonorrhoea cultures during the study, eight (27%) of | Limited follow-up; and intercurrent events, such as waves of COVID-19 and mpox emergence, could have affected sexual behavior during the study. |
| STI (ie, gonorrhoea, chlamydia, and syphilis); safety; and association of doxycycline use with resistance in N gonorrhoeae and C trachomatis. | 29 taking doxy-PEP versus five (24%) of 21 not taking doxy-PEP had tetracycline resistance (minimum inhibitory concentration ≥2 µg/mL). |
Author Commentary:
With the prevalence of sexually transmitted infections within the community, new treatment strategies, including post-exposure prophylaxis with doxycycline, are being considered. These treatments appear to be especially beneficial in high-risk populations or in those who engage in high-risk sexual behaviors.
Bottom Line:
Doxycycline post-exposure prophylaxis appears to be helpful in preventing chlamydia and syphilis in high-risk individuals, however additional research is needed to determine if adverse consequences (e.g. increased antimicrobial resistance) exist.
Level of Evidence:
Level 1: Recent well-done systematic review was considered or a study of high quality is available
References:
- Boschiero MN, Sansone NMS, Matos LR, et al.. Efficacy of Doxycycline as Preexposure and/or Postexposure Prophylaxis to Prevent Sexually Transmitted Diseases: A Systematic Review and Meta-Analysis.
- Sokoll PR, Migliavaca CB, Döring S, et al.. Efficacy of postexposure prophylaxis with doxycycline (Doxy-PEP) in reducing sexually transmitted infections: a systematic review and meta-analysis
- Luetkemeyer AF, Donnell D, Cohen SE, et al.. Doxycycline to prevent bacterial sexually transmitted infections in the USA: final results from the DoxyPEP multicentre, open-label, randomised controlled trial and open-label extension