Background
Incidence of sexually transmitted infections (STIs) caused by Neisseria gonorrhoeae, Chlamydia trachomatis, and Treponema pallidum continues to increase in the United States (1). Novel approaches are needed to address the STI epidemic, especially for populations disproportionately affected (2). Postexposure prophylaxis (PEP) involves taking a medication to prevent an infection after a possible exposure and is a common strategy for prevention of HIV and other infections. PEP is a form of chemoprophylaxis and is distinct from pre-exposure prophylaxis (PrEP), which involves taking a medication before exposure occurs. Doxycycline is used as PrEP or PEP to prevent infections such as malaria and Lyme disease (3) but, until recently, has not been used to prevent STIs. These CDC recommendations for an ongoing, patient-managed STI prevention strategy include a novel approach to PEP that provides the patient a prescription allowing them to have doxycycline for self-administration as soon as possible after sex to prevent syphilis, chlamydia, and gonorrhea.
Doxycycline, a broad-spectrum tetracycline antimicrobial, is well absorbed and tolerated, with a half-life of approximately 12 hours (4). Adverse effects most associated with doxycycline include photosensitivity and gastrointestinal symptoms including esophageal erosion and ulceration (5). Most adverse effects resolve with discontinuation of the medication. Doxycycline is the recommended treatment regimen for chlamydia and an alternative treatment for syphilis in nonpregnant patients with severe penicillin allergy or when penicillin is not available (6). Although currently not a recommended treatment for gonorrhea because of elevated antimicrobial resistance, doxycycline remains effective against many strains of N. gonorrhoeae in the United States (7).
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In 2015, the treatment arm of a randomized clinical controlled trial studied the use of oral doxycycline hyclate 100 mg daily as STI PrEP among 30 men who have sex with men (MSM) with HIV receiving antiretrovirals (8). At 48 weeks, persons who were assigned daily STI PrEP had a 73% reduction in bacterial STI incidence compared with persons in the comparison arm demonstrated by decreases in chlamydia and syphilis but not gonorrhea. The 2021 CDC STI treatment guidelines included a systematic review of the available literature on STI PrEP and PEP and concluded that further studies were necessary to determine whether STI chemoprophylaxis would be an effective strategy for bacterial STI prevention (6). Since the study in 2015, there have been no new studies of STI PrEP, but three large randomized controlled trials among MSM and transgender women (TGW) studied STI PEP in the form of 200 mg of doxycycline taken after sex. These trials all demonstrated significant reductions in bacterial STI acquisition (syphilis, chlamydia, and gonorrhea). Between 2023 and 2024, certain countries have issued varying position statements on the practice of doxy PEP ranging from recommending against widespread use because of concerns about antimicrobial resistance (9) to conditional use for MSM and TGW at risk for syphilis (10) or on a case-by-case basis (11). This report presents CDC’s updated clinical guidelines for health care providers to inform MSM and TGW who have had a bacterial STI (specifically syphilis, chlamydia, and gonorrhea) diagnosed in the past 12 months about the use of doxy PEP for preventing these bacterial STI infections.
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