Sexually Transmitted Infection Update and Prevention with Doxy-PEP

Educational Objectives

The goal of this program is to improve the prevention of sexually transmitted infections (STI) using doxycycline postexposure prophylaxis (DOXY-PEP). After hearing and assimilating this program, the clinician will be better able to:

1. Employ a guideline-based approach for STI screening in various age groups.
2. Prescribe pre- and postexposure prophylaxis regimens to populations at high risk for STIs.
3. Screen for chlamydia, gonorrhea, and syphilis in high-risk groups.

Summary

Epidemiology: in 2021, the Centers for Disease Control and Prevention (CDC) reported rising sexually transmitted infection (STI) cases in the United States (US), with chlamydia increasing by 4% to 1.6 million, gonorrhea by ≈30% to 700,000, and a 75% surge in syphilis, including a 200% rise in congenital syphilis rates since 2017; chlamydia rates consistently increased yearly from 1984 to 2020, with a temporary decline from 2020 to 2022 because of reduced office visits during the COVID-19 pandemic; as clinics resume operations, chlamydia cases are on the rise again; chlamydia and gonorrhea predominantly affect younger age groups, with women 20 to 24 yr of age having the highest rates; syphilis is more prevalent in older age groups, with the highest diagnosis rates in women in their late 20s

Gonorrhea and Chlamydia

Indications: annual screening for gonorrhea and chlamydia, using nucleic acid amplification tests (NAAT), is recommended by the US Preventive Services Task Force (USPSTF) for sexually active, nonpregnant women ≤24 yr of age; women ≥25 yr of age should be screened based on individual risk factors; there are no specific screening guidelines for men; in California, the STI prevention branch suggests screening based on practice-specific prevalence, ie, if chlamydia is >3% or gonorrhea is >1%, all individuals in a particular age group should be screened; practice-specific data can be obtained by requesting a breakdown of test positivity by age from the laboratory for the past 2 yr

Risk factors: screening for STIs in individuals ≥25 yr of age, as per USPSTF, considers risk factors, eg, a history of previous STIs, concurrent infections, and multiple partners; in California, screening is recommended for those with recent gonorrhea, chlamydia, or pelvic inflammatory disease (PID), multiple recent partners, a new partner within the last 90 days, or involvement in exchange of sex for drugs or money; screening is also advised in areas with high gonorrhea and chlamydia prevalence (“hot spots”)

Site of testing: California Family PACT allows testing of samples for gonorrhea and chlamydia from the throat and vaginal and anal sites due to the prevalence of oral and anal sex; this guideline initially was for men having sex with men (MSM; testing at 3 sites [“the triple dip”]); recently, CDC extended this recommendation to ciswomen; if a patient discloses engaging in receptive anal intercourse, rectal gonorrhea and chlamydia NAATs are advised; if a patient reports receptive oral intercourse, pharyngeal gonorrhea and chlamydia samples are recommended; the CDC emphasizes discussion of shared decision-making with the patient

Sampling the sites: rectal swab technique involves gentle insertion of the swab 3 to 4 cm into the rectum, rotating the wrist for a 360-degree sweep along the rectal walls; self-swabbing can be done with proper instruction

Changes in Treatment per the 2021 CDC Guidelines

Chlamydia: due to rising azithromycin (AZM) resistance, the CDC now recommends doxycycline (DOXY) as the preferred treatment for chlamydia; DOXY 100 mg twice daily for 1 wk (standard dose) is more effective than AZM; an alternative is extended-release DOXY (once daily [less accessible]); AZM remains the first-line option in pregnancy; DOXY outperforms AZM for rectal chlamydia, with cure rates >90% vs 80% with AZM

Treatment algorithm: for a positive chlamydia test or a pending NAAT test with a high suspicion of chlamydia, especially with possible rectal involvement based on sexual history, initiating DOXY is advisable; however, when treating pregnant patients diagnosed with chlamydia (eg, new obstetric patients or those with a positive pregnancy test), AZM is preferred; for all other cases, a shared decision-making process with the patient is essential; in these instances, factors to consider include the effectiveness of DOXY, which requires a week of treatment but is more potent, versus the convenience of AZM, which is a single-dose option but is less effective for rectal chlamydia

Gonorrhea: remains a significant concern due to rising drug resistance; the CDC's vigilance stems from the high number of cases (>500,000 annually) and associated costs; studies assessing resistance between 2009 and 2019 reveal concerning trends; resistance to cephalosporins remains low, while AZM-resistant strains of gonorrhea are increasing; consequently, CDC guidelines recommend single-dose ceftriaxone (500 mg intramuscular [IM; doubled for individuals >150 kg]) as the preferred treatment for gonorrhea in the cervix, urethra, or rectum because of its effectiveness and lower resistance rates

Treatment algorithm: in cases where chlamydia has not been ruled out, an empirical treatment is initiated in the form of combination of ceftriaxone (500 mg) and DOXY (100 mg twice daily for 7 days), representing a shift from the previous ceftriaxone-plus-AZM regimen; an alternative oral option for gonorrhea treatment is cefixime (Suprax; 800 mg once daily) and, if chlamydia coinfection is uncertain, DOXY (standard dose) is added; for individuals allergic to cephalosporins, an alternative regimen is gentamicin plus AZM

Gonococcal pharyngeal infections: difficult to treat; protocol includes ceftriaxone 500 mg IM, with a double dose for heavier individuals, followed by 1 wk of DOXY; due to limited responsiveness of gonococcal pharyngitis to AZM, use of DOXY is emphasized; a follow-up test is recommended 1 to 2 wk after antibiotic therapy to ensure complete clearance

Prevention: patient-delivered partner therapy has been instrumental in treating partners; vaccination is available for human papillomavirus, monkeypox, and hepatitis A and B; drug regimens like preexposure prophylaxis (PrEP) for HIV and antivirals (eg, valacyclovir) offer preventive options for herpes simplex virus and other infections

PEP regimens: different regimens exist based on the type of exposure, eg, occupational (eg, needle stick) or nonoccupational (eg, exposure to a partner with HIV); a novel approach involves using DOXY for postexposure prophylaxis (PEP) against bacterial STIs, often referred to as the “morning after” pill for bacterial STI

Evidence: Luetkemeyer et al (2023) — studied the efficacy of single-dose DOXY (200 mg) within 72 hr of condomless oral, anal, or vaginal sex in MSM and transgender women; results showed ≈50% reduction in gonorrhea and a substantial reduction (75%-88%) in chlamydia and syphilis; while gonorrhea protection was moderate due to resistance, the approach offered good, though not perfect, protection against chlamydia and syphilis; Stewart et al (2023) — assessed the efficacy of DOXY-PEP in preventing STIs in high-risk women in Kenya; observed a nonsignificant 12% reduction in the incident rate of STIs in the DOXY-PEP group compared with the standard group; credibility concerns arose because of noncompliance, emphasizing the need for additional research in heterosexual women

CDC guideline: recommends DOXY 200 mg orally within 72 hr of sex for gay and bisexual men, MSM, and transgender women with a history of bacterial STIs; emphasizes regular gonorrhea and chlamydia screening every 3 mo, includes counseling on side effects of DOXY, and advises against antacids or calcium supplements

California Department of Public Health guideline: recommends offering DOXY-PEP to MSM or transgender women with a history of ≥1 bacterial STI in the last 12 mo; advocates for shared decision-making on DOXY-PEP use for nonpregnant individuals at increased risk for bacterial STIs, considering it as a gender equity measure; the approach emphasizes holistic sexual health counseling that covers various topics beyond DOXY-PEP

Rules about using DOXY-PEP: ideally within 24 hr of a high-risk contact but no later than 72 hr

Mucopurulent cervicitis (MC): cloudy white discharge during pelvic examination raises concerns for gonorrhea, chlamydia, and Mycoplasma genitalium; termed a “snotty cervix”, this discharge may also be attributed to other factors, ie, strict herpes or natural variations, eg, cervical mucus cloudiness due to ovulation or contraceptive use (eg, birth control pills, patches, rings, intrauterine device [eg, Mirena, Paragard, Skyla]); the updated 2021 recommendation for treating MC is a week-long course of DOXY; an alternative option is a single dose of AZM

Mycoplasma genitalium: increasingly recognized in women, not just men with recurrent urethritis; baseline prevalence is ≈2% but can reach 15% to 20% in high-risk populations; in addition to cervicitis and PID, M genitalium raises concerns about obstetrical complications, eg, preterm birth, spontaneous miscarriage, and infertility; CDC recommends testing for M genitalium in individuals with recurrent urethritis, cervicitis, or diagnosed PID, but routine screening for asymptomatic individuals is not yet established

Treatment: challenging; involves 7 days of DOXY followed by 7 days of moxifloxacin at a daily dose of 400 mg; obtaining moxifloxacin may be challenging; in such cases, an alternative regimen involves starting with DOXY for 7 days followed by AZM for 4 days; this alternative regimen includes a loading dose of 1 g, followed by 500 mg for 3 days; the CDC expresses concerns about potential resistance issues

Syphilis: screening is influenced by social determinants, with USPSTF guidelines considering factors such as incarceration history and involvement in commercial sex work; regional variations, notably in hot spots like East Los Angeles and Fresno, impact syphilis rates; in California, state guidelines emphasize the need for syphilis screening at least twice during pregnancy (at the first prenatal visit and in the third trimester or at delivery); the traditional method (nontreponemal tests followed by treponemal tests, if positive) or a reverse sequence algorithm (starting with a Treponema-specific test) can be utilized for screening; providers in hot spots should be aware of positivity rates, keep clinicians updated, and offer screening in relevant situations; shortages in penicillin G benzathine (Bicillin LA) can affect treatment; educators can access free STI curriculum from the University of Washington, and consultations for tough cases are available through the STD Clinical Consultation Network

Readings

Centers for Disease Control and Prevention. Chlamydial infections - STI treatment guidelines. Centers for Disease Control and Prevention. Published 2021. Available from: https://www.cdc.gov/std/treatment-guidelines/chlamydia.htm; Cyr SS. Update to CDC’s Treatment Guidelines for Gonococcal Infection, 2020. MMWR Morbidity and Mortality Weekly Report. 2020;69(50). doi:https://doi.org/10.15585/mmwr.mm6950a6; Dalby J, Stoner BP. Sexually transmitted infections: updates from the 2021 CDC guidelines. Am Fam Physician. 2022;105(5):514-520; Doxycycline postexposure prophylaxis for prevention of STIs among cisgender women - CROI Conference. Published March 4, 2023. https://www.croiconference.org/abstract/doxycycline-postexposure-prophylaxis-for-prevention-of-stis-among-cisgender-women/; Htet KZ, Lindrose AR, O'Connell S, et al. The burden of chlamydia, gonorrhea, and syphilis in older adults in the United States: A systematic review. Int J STD AIDS. 2023;34(5):288-298. doi:10.1177/09564624221149770; 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; Stewart J, Bukusi E, Sesay FA, et al. Doxycycline post-exposure prophylaxis for prevention of sexually transmitted infections among Kenyan women using HIV pre-exposure prophylaxis: study protocol for an open-label randomized trial. Trials. 2022;23(1):495. Published 2022 Jun 16. doi:10.1186/s13063-022-06458-8; USPSTF. Recommendation | United States Preventive Services Taskforce. www.uspreventiveservicestaskforce.org. Published 2021. https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/chlamydia-and-gonorrhea-screening.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Policar was recorded at Obstetrics and Gynecology Update: What Does the Evidence Tell Us, held October 11-13, 2023, in San Francisco, CA, and presented by University of California, San Francisco School of Medicine. For information on upcoming CME activities from this presenter, please visit meded.ucsf.edu/continuing-education. Audio Digest thanks the speakers and presenters for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 1.50 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 1.50 CE contact hours.

Lecture ID:

OB710401

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.