Antibiotic Use in STI Prevention and the Global Threat of Antimicrobial Resistance

Antimicrobial resistance is rapidly becoming one of the largest public health threats to date, with a growing number of common bacterial pathogens becoming resistant to antimicrobials. At this moment, antimicrobial resistance has been estimated to cause 1.2 million deaths annually worldwide (1). Antibiotics have long been used as preexposure prophylaxis (PrEP) as well as postexposure prophylaxis (PEP) in both inpatient and outpatient settings for various indications. Recently, there has been a rise in a trend called doxyPEP, in which individuals who engaged in sexual activity prophylactically medicate with doxycycline afterward for the purpose of preventing bacterial sexually transmitted infections (STIs). One study found that 1 in 10 PrEP users self-prescribed with STI prophylaxis (2). With increased use of antibiotics in PEP, are we unnecessarily worsening the inescapable rise of antimicrobial resistance?

PrEP and PEP are not novel concepts themselves. However, modern public health campaigns targeting audiences who engage in high-risk sexual activity, like men who have sex with men (MSM); bisexual, gay, and lesbian individuals; and transgender people, have become much more commonplace. PrEP has been effective in the prevention of HIV infection in those who engage in high-risk activity (3). HIV PrEP use has been shown to have a relative risk reduction of 86% in those who use PrEP continuously and intermittently (3). Riding on the successes of PrEP adoption comes the use of PEP with antimicrobials to prevent infection with a few highly transmissible bacterial pathogens.

Currently, there are no vaccines and only a few chemical prophylactic options for preventing bacterial STIs, such as gonorrhea, syphilis, and chlamydia (4). Given that these infections have a greater occurrence in gay, bisexual, and other MSM and transgender women (TGW), these communities are now increasingly adopting the use of antibiotics to ward off bacterial STIs after a sexual encounter (4). DoxyPEP, postexposure prophylaxis with doxycycline, is a novel patient-administered and -managed strategy for STI prevention in certain at-risk populations (4). Currently, the Centers for Disease Control and Prevention (CDC) recommends offering doxyPEP for MSM and TGW who have had a confirmed syphilis, chlamydia, or gonorrhea infection in the past 12 months, to be used up to 72 hours after oral, vaginal, or anal sex (4). The current guidelines from the CDC call for use of 200 mg of doxycycline, with the dose not to exceed 200 mg in a 24-hour period (4). Even with utility in certain communities, does the risk mitigated by PEP with antibiotics warrant the risk for creating superbugs?

There is increasing alarm over the rising prevalence of multidrug-resistant (MDR) bacterial STIs. Three such MDR STIs of concern also happen to be primary targets in the use of PEP: syphilis, gonorrhea, and chlamydia (5). To put some statistics to the worry, in 2012, 33.4% of isolated Neisseria gonorrhoeae samples (n = 334,826 total reported cases) were resistant to penicillin, tetracycline, ciprofloxacin, or combinations of these drugs (5). Even though there has been a rise in antibiotic resistance over recent years, unfortunately pharmaceutical development of new antimicrobials has been slow to match the ballooning resistance. Currently, it takes about 10 to 15 years with a research and development cost of about $1 billion to bring a new antibiotic to market (only about 1.5% of new drugs come to market) (1).

While antibiotics can be valuable for preventing bacterial STIs in high-risk populations, their use must be cautious and well regulated. Allowing patients to self-administer antibiotics like doxycycline for up to 12 months, per CDC recommendations, risks contributing to the rise of drug-resistant organisms. Broad-spectrum antibiotics like doxycycline, in particular, can exacerbate this issue. Before such practices become widespread, it is crucial for physicians and health care providers to advocate more research into their risks and benefits and engage in discussions about the ethical implications. Responsible prescribing, patient education, and ongoing research are essential to mitigate the development of antibiotic-resistant superbugs and ensure effective STI prevention.

References

1. Howard-Anderson J, Boucher HW. New antibiotics for resistant infections: what happens after approval? Ann Intern Med. 2024;177:674-675. [PMID: 38639541] doi:10.7326/M24-0192
2. O'Halloran C, Croxford S, Mohammed H, et al. Factors associated with reporting antibiotic use as STI prophylaxis among HIV PrEP users: findings from a cross-sectional online community survey, May-July 2019, UK. Sex Transm Infect. 2021;97:429-433. [PMID: 33082235] doi:10.1136/sextrans-2020-054592
3. Spinner CD, Boesecke C, Zink A, et al. HIV pre-exposure prophylaxis (PrEP): a review of current knowledge of oral systemic HIV PrEP in humans. Infection. 2016;44:151-8. [PMID: 26471511] doi:10.1007/s15010-015-0850-2
4. Bachmann LH, Barbee LA, Chan P, et al. CDC clinical guidelines on the use of doxycycline postexposure prophylaxis for bacterial sexually transmitted infection prevention, United States, 2024. MMWR Recomm Rep. 2024;73:1-8. [PMID: 38833414] doi:10.15585/mmwr.rr7302a1
5. Krupp K, Madhivanan P. Antibiotic resistance in prevalent bacterial and protozoan sexually transmitted infections. Indian J Sex Transm Dis AIDS. 2015;36:3-8. [PMID: 26392647] doi:10.4103/0253-7184.156680

Patrick O'Dowd, MS

Patrick O'Dowd, MS, is a third-year medical student at Ross University School of Medicine. He graduated with a BS in forensic science from Madonna University in Livonia, MI, going on to earn an MS in toxicology from the Rackham Graduate School at the University of Michigan–Ann Arbor. Patrick is interested in hospitalist medicine, gastroenterology, and medical education. He plans on pursuing a residency in internal medicine.