In the News / Politics:

The “Morning-After” Antibiotic

By: Anureet Kaur, PharmD Candidate c/o 2024 

According to surveillance data from the United States Centers for Disease Control and Prevention (CDC), the sexually transmitted infection (STI) epidemic is escalating at an alarming rate. The health agency reports that in 2019, there were 1.8 million cases of chlamydia, more than 600,000 cases of gonorrhea, and nearly 130,000 cases of syphilis in the United States (U.S.) – reaching an all-time high for the sixth consecutive year.1 Although reports from 2020 to 2023 are limited due to COVID-19-related STI testing and treatment disruptions, preliminary data does not look promising.1

In a bid against the STI epidemic, the CDC suggests an old antibiotic as a new way to prevent chlamydia, gonorrhea, and syphilis “the morning after” – doxycycline.2

Doxycycline belongs to the tetracycline drug class and is used to treat sexually transmitted diseases. It is a broad-spectrum antibacterial with excellent gram-negative activity and some protozoal activity. Growing research suggests its role as post-exposure prophylaxis (PEP) in men who have sex with men (MSM) and transgender women if taken as a 200 mg dose within 72 hours after condomless sex.3

In a randomized, open-label clinical trial conducted in San Francisco and Seattle, researchers evaluated the effectiveness of doxycycline PEP (doxy-PEP) versus standard care without doxy-PEP. Approximately 500 adult MSM and transgender women who were taking preexposure prophylaxis (PrEP) against human immunodeficiency virus (HIV) infection (PrEP cohort) or living with HIV infection (persons living with HIV infection [PLWH] cohort) and had a history of chlamydia, gonorrhea, and syphilis within the last year were enrolled from August 19, 2020, through May 13, 2022.4

The primary effectiveness endpoint of the study was incidence of at least one bacterial STI – chlamydia, gonorrhea, or syphilis. Assessments were performed quarterly or every three months by a blinded independent committee.4

In the PrEP cohort, at least one STI was diagnosed in 61 of 570 quarterly visits (10.7%) in the doxy-PEP group and 82 of 257 quarterly visits (31.9%) in the standard care group.3 Relative risk was 0.34 (95% confidence interval [CI], 0.24 to 0.46; P < 0.001). In the PLWH cohort, at least one STI was diagnosed in 36 of 305 quarterly visits (11.8%) in the doxy-PEP group and 39 of 128 quarterly visits (30.5%) in the standard care group. Relative risk was 0.38 (95% CI, 0.24 to 0.60; P < 0.001).3 Overall, the number needed to treat to prevent a quarter with an incident STI was 5 in the PrEP cohort and 6 in the PLWH cohort.4

The safety outcome of the study was incidence of adverse events. Results showed a low incidence of adverse events, with nausea and vomiting as most common. Bacterial resistance was a secondary outcome but limited in its findings due to lack of follow-up on cultures. These results suggesting doxy-PEP superiority over standard care without doxy-PEP in MSM and transgender women are supported by the results of preceding studies, including the IPERGAY trial and the DOXYVAC trial.3

PEP is not a new concept. The practice of prescribing antiretrovirals and antibiotics following possible exposure to a pathogen has been instituted for a long time. However, its use for STI prevention is new and necessary, as suggested by STI incidence trends in the last decade. The CDC plans to finalize draft guidelines regarding the use of the “morning-after” antibiotic, doxycycline, for PEP after a 45-day public comment period from its release on October 2, 2023.2


  1. Reported STDs reach all-time high for 6th consecutive year. Centers for Disease Control and Prevention. Updated April 13, 2023.
  2. Guidelines for the use of doxycycline post-exposure prophylaxis for bacterial STI prevention. Centers for Disease Control and Prevention. Updated September 29, 2023.
  3. DiMarco DE, Urban MA, Fine SM, et al. Doxycycline Post-Exposure Prophylaxis to Prevent Bacterial Sexually Transmitted Infections. Baltimore (MD): Johns Hopkins University; September 2023.   
  4. Luetkemeyer AF, Donnell D, Dombrowski JC, et al. Postexposure Doxycycline to Prevent Bacterial Sexually Transmitted Infections. N Engl J Med. 2023;388(14):1296-1306. doi:10.1056/NEJMoa2211934
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