By Rebecca H. Allen, MD, MPH

Associate Professor, Department of Obstetrics and Gynecology, Warren Alpert Medical School of Brown University, Women & Infants Hospital, Providence, RI

SYNOPSIS: The CDC updated their sexually transmitted infections treatment guidelines with new recommendations for Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, pelvic inflammatory disease, and Mycoplasma genitalium.

SOURCE: Workowski KA, Bachmann LH, Chan PA, et al. Sexually transmitted infections treatment guidelines, 2021. MMWR Recomm Rep 2021;70:1-187.

Highlights from the CDC Sexually Transmitted Infections (STI) Treatment Guidelines, 2021 are as follows:

For women, Chlamydia trachomatis and Neisseria gonorrhoeae urogenital infection can be diagnosed by vaginal or cervical swabs or first-void urine with nucleic acid amplification tests (NAATs). NAATs that are FDA-approved for use with vaginal swab specimens can be collected by a provider or patient in the clinic. Patient-collected vaginal swab specimens are equivalent in sensitivity and specificity to those collected by a provider. Vaginal swabs are more sensitive than first-void urine testing and, therefore, are the optimal route of sample collection. Annual screening of all sexually active women younger than age 25 years is recommended, as is screening of older women at increased risk for infection (e.g., women age 25 years or older) who have a new sex partner, more than one sex partner, a sex partner with concurrent partners, or a sex partner who has an STI).

The recommended regimen for the treatment of C. trachomatis in women has changed to a dose of doxycycline 100 mg orally twice a day for seven days. Alternative regimens are azithromycin 1 g orally once or levofloxacin 500 mg once daily for seven days. However, pregnant women still can be treated with azithromycin preferentially.

The recommended regimen for the treatment of N. gonorrhoeae urogenital infection in women is ceftriaxone 500 mg intramuscularly (IM) in a single dose for patients weighing less than 150 kg and, for those weighing more, 1 g of ceftriaxone should be administered. Alternative regimens are gentamicin 240 mg IM in a single dose with azithromycin 2 g orally in a single dose or cefixime 800 mg orally in a single dose. For pregnant women who are allergic to cephalosporins, because gentamicin cannot be given, consultation with an infectious disease expert is recommended.

Mycoplasma genitalium is increasingly recognized as a pathogen. There is one NAAT approved for use by the FDA for testing. However, screening of asymptomatic M. genitalium infection among women is not recommended. Nevertheless, women with recurrent cervicitis should be tested for M. genitalium, and testing should be considered among women with pelvic inflammatory disease (PID). Testing should be accompanied with resistance testing, if available. In clinical practice, if testing is unavailable, M. genitalium should be suspected in cases of persistent or recurrent cervicitis and considered for PID.

The recommended treatment for trichomoniasis among women has changed to metronidazole 500 mg orally twice a day for seven days. Two grams of metronidazole is no longer recommended. Tinidazole 2 g orally in a single dose is an alternative option but is more expensive. Topical metronidazole vaginal gel is not recommended because it does not reach therapeutic levels in the urethra and perivaginal glands. Importantly, we no longer need to counsel patients to avoid alcohol consumption while taking metronidazole, since a review found there was no convincing evidence of a disulfiram-like reaction.

Whereas before, the addition of metronidazole to the treatment regimens for PID was recommended in the case of tubo-ovarian abscess, the guidelines now recommend routine use of metronidazole with both intravenous and oral therapy for all cases of PID. The recommended outpatient IM/oral treatment regimens for PID now are ceftriaxone 500 mg IM in a single dose with doxycycline 100 mg orally twice a day and metronidazole 500 mg orally twice a day for 14 days. Alternative regimens include cefoxitin 2 g IM in a single dose and probenecid 1 g orally administered concurrently in a single dose with doxycycline 100 mg orally twice a day and metronidazole 500 mg orally twice a day for 14 days or other parenteral third-generation cephalosporin (e.g., ceftizoxime or cefotaxime) with doxycycline 100 mg orally twice a day and metronidazole 500 mg orally twice a day for 14 days. The CDC also endorsed the recommendation from the United States Selected Practice Recommendations for Contraceptive Use that intrauterine devices (IUDs) do not automatically need to be removed during treatment of PID, stating “if no clinical improvement occurs within 48 to 72 hours of initiating treatment, providers should consider removing the IUD.” 


The last update of the CDC sexually transmitted disease treatment guidelines occurred in 2015. One important change this time is the title. The CDC changed “disease” to “infection” to reduce the stigma associated with sexually transmitted infections and recognize that “disease” refers to the condition that results from an infection in some, but not all, cases.

The rationale for the change in chlamydia treatment from a single dose of azithromycin to a seven-day course of doxycycline stems from the fact studies show doxycycline is more effective for rectal chlamydia in both men and women.1 However, the CDC acknowledges adherence to this regimen is more difficult than with a single dose. Nevertheless, they state concomitant rectal chlamydia infection can occur in women and place them at risk for repeat urogenital infection through autoinoculation from the rectal site. Interestingly, in one study, C. trachomatis was detected at the anorectal site among 33% to 83% of women who had urogenital C. trachomatis infection. Its detection was not associated with a report of receptive anorectal sexual activity.2 The CDC states “when nonadherence to doxycycline regimen is a substantial concern, azithromycin 1 g regimen is an alternative treatment option but might require posttreatment evaluation and testing because it has demonstrated lower treatment efficacy among persons with rectal infection.”

For gonorrhea treatment, the dose of ceftriaxone rose from 250 mg to 500 mg (the CDC had released this already) to maximize efficacy against any isolates with elevated minimal inhibitory concentrations. For trichomoniasis treatment, the single 2-g dose of metronidazole was eliminated after trials found it was inferior to the seven-day regimen.3

Currently, the CDC believes M. genitalium can cause cervicitis and may contribute to PID, but routine screening of asymptomatic women is not warranted. Rather, the organism should be suspected in cases of recurrent cervicitis and should be considered in PID. The treatment of M. genitalium is difficult, and while the CDC recommends resistance testing, this may not be routinely available. Treatment without resistance testing involves doxycycline 100 mg orally twice a day for seven days, followed by moxifloxacin 400 mg orally once daily for seven days. The doxycycline reduces the load of the organism and the moxifloxacin eradicates it. Although current PID treatment regimens do not cover M. genitalium, the CDC does not recommend routinely adding moxifloxacin; rather, it recommends only treating the organism if it happens to be detected. They state, “No data have been published that assess the benefits of testing women with PID for M. genitalium, and the importance of directing treatment against this organism is unknown.”

Finally, the CDC now recommends the routine addition of metronidazole to PID treatment regimens because this regimen eradicates anaerobic organisms more effectively from the upper genital tract.4 

There are other important changes to the guidelines regarding novel treatments for bacterial vaginosis, human papillomavirus vaccine recommendations and counseling messages, expanded risk factors for syphilis testing among pregnant women, and two-step testing for serologic diagnosis of genital herpes simplex virus. All these should be incorporated into clinical practice as needed. The app for the 2021 guidelines for iOS or Android is not yet available from the CDC; however, there are posters and pocket guides that can be downloaded from the website.


  1. Páez-Canro C, Alzate JP, González LM, et al. Antibiotics for treating urogenital Chlamydia trachomatis infection in men and non-pregnant women. Cochrane Database Syst Rev 2019;1:CD010871.
  2. Rank RG, Yeruva L. An alternative scenario to explain rectal positivity in Chlamydia-infected individuals. Clin Infect Dis 2015;60:1585-1586.
  3. Howe K, Kissinger PJ. Single-dose compared with multidose metronidazole for the treatment of trichomoniasis in women: A meta-analysis. Sex Transm Dis 2017;44:29-34.
  4. Wiesenfeld HC, Meyn LA, Darville T, et al. A randomized controlled trial of ceftriaxone and doxycycline, with or without metronidazole, for the treatment of acute pelvic inflammatory disease. Clin Infect Dis 2021;72:1181-1189.