CDC Updates Sexually Transmitted Infection Treatment Guidelines

Laura Bachmann, MD, MPH; Laura Quilter, MD, MPH; Kim Workowski, MD


October 12, 2022

Editorial Collaboration

Medscape &

Sexually Transmitted Infections: Common, Costly, Preventable

The Centers for Disease Control and Prevention (CDC) released the Sexually Transmitted Infections (STI) Treatment Guidelines, 2021, which provide current evidence-based diagnostic, management, and treatment recommendations.

The updated STI Tx Guide app is now available for free on Apple and Android mobile devices. Use it, as well as CDC's other provider resources, to navigate the guidelines quickly.

STIs are common and costly to the nation's health and economy.[1,2] Each year, 26 million new STIs occur,[1] totaling nearly $16 billion in medical costs.[2] Following evidence-based recommendations is one important way to prevent infections and protect people.

Here are five changes to know about the 2021 STI Treatment Guidelines:

1. Treatment recommendations changed for chlamydia, trichomoniasis, and pelvic inflammatory disease (PID)

Chlamydia and trichomoniasis account for 11 million new infections each year (about 4 million and 7 million, respectively).[1] PID, an infection of the upper genital tract, may be less common, but 2 million reproductive-aged women self-reported this syndrome over 10 years.[3]

All three infections disproportionately affect women.[1] Chlamydia can lead to PID, which can result in chronic pelvic pain, tubal factor infertility, and potentially fatal ectopic pregnancy. Pregnant women with trichomoniasis are at an increased risk for preterm delivery and low birthweight. Chlamydia and trichomoniasis are both associated with increased risk for HIV acquisition and transmission.

Prompt and appropriate treatment with the following regimens is critical to avoid severe health complications:

  • Chlamydia: Doxycycline is now the first-line recommended treatment; 100 mg orally twice a day for 7 days.

  • Trichomoniasis: Metronidazole is recommended for treating all women; 500 mg orally twice a day for 7 days.

  • PID: The recommended outpatient regimen is ceftriaxone 500 mg intramuscularly in a single dose + doxycycline 100 mg orally twice a day for 14 days + metronidazole 500 mg orally twice a day for 14 days.

Because of high reinfection rates, CDC recommends retesting patients 3 months after receiving chlamydia and/or trichomoniasis treatment.

2. Updated and expanded gonorrhea treatment recommendations to minimize the threat of drug resistance

CDC estimates that more than a million new gonorrhea infections occur each year, and about half of all infections are resistant to at least one antibiotic.[4] In late 2020, CDC updated gonorrhea treatment guidelines for adolescents and adults to ensure effective treatment and minimize the threat of drug resistance.[5] The full STI Treatment guidelines expand on recommendations for neonates, children, and other specific clinical situations (ie, disseminated gonococcal infection, proctitis, epididymitis, PID, and sexual assault).

Providers should treat uncomplicated gonorrhea among adolescents and adults with a single 500 mg injection of ceftriaxone and, if chlamydia has not been ruled out, treat with 100 mg doxycycline orally twice a day for 7 days. A test of cure is recommended in people with pharyngeal gonorrhea. Either a culture or a nucleic acid amplification test (NAAT) is recommended, 7-14 days after the initial treatment, regardless of the regimen. Providers should retest patients 3 months after treatment to detect possible reinfection.

3. Prompt testing and treatment are key to managing nongonococcal urethritis (NGU)

NGU is a nonspecific diagnosis with several causes, including, but not limited to, Chlamydia trachomatis, Mycoplasma genitalium, and Trichomonas vaginalis. Prompt diagnosis and appropriate treatment can reduce further health complications, reinfection, and sexual transmission to partners. First, test all men who have suspected or confirmed NGU for chlamydia and gonorrhea using NAATs. The guidelines now recommend to presumptively treat NGU at diagnosis with doxycycline 100 mg orally twice a day for 7 days.

For recurrent or persistent NGU, the guidelines also now recommend additional tests for men after initial empiric treatment to guide further management decisions. Specifically:

  • Test for M genitalium. It is the most common cause of persistent or recurrent NGU. CDC recommends a two-stage therapy approach, ideally using resistance-guided therapy if available.

  • Test for trichomoniasis (1) in areas where it is prevalent and (2) if the patient has sex with women. Presumptively treat with an oral single dose of either 2 g metronidazole or 2 g tinidazole. Partners should be evaluated and treated, if needed.

4. Know what places pregnant patients at risk for syphilis; test and treat accordingly

Syphilis testing among pregnant patients is crucial to identifying infection, especially during the ongoing and dramatic rise in congenital syphilis.[6] While CDC recommends universal screening at the first prenatal visit, two additional screenings — one at 28 weeks and the other at delivery — are recommended for patients who live in communities with high syphilis rates and/or patients at increased risk for syphilis acquisition. Providers should also assess for ongoing risk behaviors of sex partners.

The updated guidelines expand on the specific risk factors that may place a patient at risk for infection during pregnancy, including:

  • sex with multiple partners

  • sex in conjunction with drug use or transactional sex

  • late entry to prenatal care or no prenatal care

  • methamphetamine or heroin use

  • incarceration of the patient or their partner

  • unstable housing or homelessness

5. Use two-step serologic testing to diagnose genital herpes

Genital herpes is a chronic, lifelong viral infection that affects millions of people in the United States each year.[1] NAATs are recommended for patients with symptoms, while serologic testing can be used to help diagnose herpes in the absence of genital lesions. The most commonly used type-specific serology test — the HerpeSelect HSV-2 enzyme immunoassay (EIA) — has poor specificity, especially with low index values. For this reason, the updated guidelines recommend a confirmatory test using a different test methodology before interpreting the results (ie, Biokit or Western blot). Use of a two-step approach has demonstrated improvement in the accuracy of HSV-2 type-specific serologic testing.


CDC: 2021 STI Treatment Guidelines Website

CDC: 2021 STI Treatment Guidelines Pocket Guide

CDC: 2021 STI Treatment Guidelines Wall Chart

CDC: A Guide to Taking a Sexual History

The University of Washington STD Prevention Training Center: National STD Curriculum

National Network of STD Clinical Prevention Training Centers: STD Clinical Consultation Network

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