2021 Sexually Transmitted Infections Treatment Guidelines

The guidelines for the treatment of people who have, or are at risk for, sexually transmitted infections (STIs) have been updated by the Centers for Disease Control and Prevention (CDC). The previous guideline was published in 2015. The CDC recently reported that the number of STIs in the United States reached an all-time high for the sixth consecutive year. The agency’s STI surveillance report found 26 million new STIs occurring each year—a nearly 30% increase in reportable STIs between 2015 and 2019. The sharpest increase was seen in cases of congenital syphilis, which nearly quadrupled between 2015 and 2019.

The CDC warns that despite STIs being at an all-time high, they have not been part of the national conversation. STIs are preventable and treatable health threats with substantial personal and economic impact, and there is an urgent need to reverse the trend of increasing STIs. STIs can have serious health consequences and do not always have symptoms, but if left untreated, some STIs can increase the risk of HIV infection or can cause pelvic inflammatory disease, infertility, and/or severe complications in pregnancy and for newborns.

The burden of STIs has increased overall and across many groups, but it continues to have the biggest impact on racial and ethnic minorities, gay and bisexual men, and youth between 15 and 24 years of age. STIs are common and costly to the nation’s health and economy, with nearly $16 billion in direct lifetime healthcare costs resulting from STIs acquired in 2018.

The latest STI Treatment Guidelines, 2021,1 provide current, evidence-based diagnostic, management, and treatment recommendations for STIs, and serve as a source of clinical guidance for managing STIs for primary care healthcare providers. Although the guidelines emphasize treatment, prevention strategies and diagnostic recommendations are also discussed and are applicable to any patient care setting that serves persons at risk for STIs, including family planning clinics, HIV care clinics, correctional healthcare settings, private healthcare providers’ offices, Federally Qualified Health Centers, clinics, and other primary care facilities.

The guidance describes on-site treatment and partner services and indicates when STI-related conditions should be managed through consultation with or referral to a specialist. The recommended regimens described are intended to be of primary use; alternative regimens can be considered in instances of notable drug allergy or other contraindications to the recommended regimens. However, alternative regimens are considered inferior to the recommended regimens based on available evidence about principal outcomes and disadvantages of the regimens.

The 2021 STI guidelines include the following changes from the 2015 guidelines:

  • Updated treatment recommendations for chlamydia, trichomoniasis, and pelvic inflammatory disease, including the addition of metronidazole to the recommended treatment regimen for pelvic inflammatory disease (see Table 1 and Table 2).
  • Information on diagnostic tests for Mycoplasma genitalium and rectal and pharyngeal chlamydia and gonorrhea (eg, FDA-approved nucleic acid amplification tests for M. genitalium is cleared for use with urine and urethral, penile meatal, endocervical, and vaginal swab samples).
  • Secnidazole oral granules, multiple oral tinidazole regimens, or clindamycin (oral or intravaginal) are considered alternative treatment options for bac terial vaginosis (see Table 1).
  • CDC recommends two-step serologic testing for diagnosing genital herpes simplex virus because of the poor specificity of commercially available type-specific enzyme-linked immuno sorbent assays. A confirmatory test (Biokit or Western blot) with a second method should be performed before test interpretation. Use of confirmatory testing with Biokit or Western blot assays have been reported to improve the accuracy of HSV-2 serologic testing.
  • Updated recommendations for human papillomavirus (HPV) vaccination with recommendations and counseling messages. The HPV vaccination series is recommended through age 26 years for those not vaccinated previously at the routine age of 11 or 12 years. HPV vaccination is recommended for all men, including men who have sex with men; transgender persons; young adult women who have sex with women; and women who have sex with women and men; as well as immunocompromised males.
  • Recommended universal hepatitis C testing is in alignment with CDC’s 2020 hepatitis C testing recommendations. CDC recommends hepatitis C screening at least once in a lifetime for all adults aged 18 years of age and older, and for all women during each pregnancy, except in settings where the prevalence of HCV infection is less than 0.1%. One-time hepatitis C testing is also recommended regardless of age, setting, or recognized conditions or exposures (eg, HIV infection, history of injecting drug use, or children born to women with HCV infection). Routine periodic HCV testing is recommended for persons with ongoing risk factors (eg, injecting drug use or hemodialysis).

Table 1. Summary of Selected CDC STI Treatment Recommendations, 2021

Disease Recommended regimen Alternative regimen
Bacterial vaginosis Metronidazole 500 mg PO BID for 7 days
Or
Metronidazole gel 0.75%, one 5-g applicator intravaginally, QD for 5 days
Or
Clindamycin cream 2%, one 5-g applicator intravaginally, at bedtime for 7 days
Clindamycin 300 mg PO BID for 7 days
Or
Clindamycin ovules 100 mg intravaginally at bedtime for 3 days
Or
Secnidazole 2 g PO for 1 dose
Or
Tinidazole 2 g PO QD for 2 days
Or
Tinidazole 1 g PO QD for 5 days
Chlamydial infections
(Adults and adolescents)
Doxycycline 100 mg PO BID for 7 days Azithromycin 1 g PO for 1 dose
Or
Levofloxacin 500 mg PO QD for 7 days
Trichomoniasis (Women) Metronidazole 500 mg PO BID for 7 days Tinidazole 2 g PO in a single dose
Trichomoniasis (Men) Metronidazole 2 g PO in a single dose Tinidazole 2 g PO in a single dose
Acute epididymitis
Most likely caused by sexually transmitted chlamydia and gonorrhea
Ceftriaxone 500 mg IM in a single dose PLUS doxycycline 100 mg PO BID for 10 days No alternative mentioned
Acute epididymitis
Most likely caused by chlamydia, gonorrhea, or enteric organisms (insertive partner in anal sex)
Ceftriaxone 500 mg IM in a single dose PLUS levofloxacin 500 mg PO QD for 10 days No alternative mentioned
Acute epididymitis
Most likely caused by enteric organisms only
Levofloxacin 500 mg PO QD for 10 days No alternative mentioned
Source: CDC. Sexually Transmitted Infections Treatment Guidelines, 2021, available at https://www.cdc.gov/std/treatment-guidelines/default.htm

Table 2. Recommended Treatment Regimens for Pelvic Inflammatory Disease

Risk category Recommended regimen Alternatives
Parenteral treatment Ceftriaxone 1 g IV QD PLUS doxycycline 100 mg PO or IV BID PLUS metronidazole 500 mg PO or IV BID
Or
cefotetan 2 g IV BID PLUS doxycycline 100 mg PO or IV BID
Or
cefoxitin 2 g IV every 6 hours PLUS doxycycline 100 mg PO or IV BID
Ampicillin-sulbactam 3 g IV every 6 hours PLUS doxycycline 100 mg PO or IV BID
Or
clindamycin 900 mg IV every 8 hours PLUS gentamicin 2 mg/kg body weight IV or IM FOLLOWED BY 1.5 mg/kg body weight every 8 hours. Can substitute with 3-5 mg/kg body weight QD.
Intramuscular/
oral treatment
Ceftriaxone 500 mg IM single dose PLUS doxycycline 100 mg PO BID for 14 days WITH metronidazole 500 mg PO BID for 14 days
Or
cefoxitin 2 g IM in a single dose AND probenecid 1 g PO, administered concurrently in a single dose PLUS doxy cycline 100 mg PO BID for 14 days WITH metronidazole 500 mg PO BID for 14 days
Or
other parenteral third-generation cephalosporin (eg, ceftizoxime or cefotaxime) PLUS doxycycline 100 mg PO BID for 14 days WITH metronidazole 500 mg PO BID for 14 days
No alternative mentioned
Source: CDC. Sexually Transmitted Infections Treatment Guidelines, 2021, available at https://www.cdc.gov/std/treatment-guidelines/default.htm
Abbreviations: BID, twice daily; IM, intramuscularly; IV, intravenously; PO, orally; QD, once daily.

Visit the CDC website for a pocket guide reflecting the recommended regimens in the CDC’s Sexually Transmitted Infections Treatment Guidelines, 2021.

Reference
1. Workowski KA, Bachmann LH, Chan PA, et al. Sexually transmitted infections treatment guidelines, 2021. Centers for Disease Control and Prevention. July 26, 2021. Accessed August 25, 2021. https://www.cdc.gov/std/treatment-guidelines/toc.htm