In 07/2021, the CDC released the first updates to their guidelines in 5 years on the treatment of sexually transmitted infections (STIs). These are consensus guidelines meant to provide an approach for those providers treating suspected and documented sexually transmitted infections, especially in the setting of increasing antibiotic resistance and globalization resulting in increasing prevalence of STIs previously seen mostly abroad. Although some of these guidelines have been previously stated by the CDC, this is the first comprehensive set of guidelines in the last 5 years. This core post will provide a summary of the most relevant aspects of the CDC recommendations.

Primary and Secondary Prevention:

Although as Emergency Medicine providers we are often used to treating patients for active infections, we must also be prepared to encourage primary and secondary prevention among our patients, given many patients do not see providers outside of the ED. When relevant, it is important to encourage and, when possible, offer vaccination for HPV, HAV, and HBV. This is especially relevant to populations at higher risk of contracting these diseases, such as the HAV vaccine for men who have sex with men (MSM). In addition, current recommendations are to offer pre-exposure prophylaxis (PrEP) for HIV to any sexually active adult and adolescent with an STI infection or an HIV-negative person at risk for contracting HIV. In particular, one in 15 MSM will contract HIV within one year of infection with rectal gonorrhea or chlamydia, demonstrating the importance of encouraging prevention among this population. For patients with newly diagnosed HIV, it is important to reinforce that those with HIV with an undetectable viral load cannot transmit HIV to potential partners, so treating themselves provides protection to potential partners.

Partner Co-Treatment:

All patients experiencing symptoms of STIs or with confirmed STI testing should be encouraged to notify their sex partners and urge them to seek evaluation and treatment when relevant. In many states, expedited partner therapy (EPT) is legal and is encouraged where available. Almost every state has some form of EPT for various STIs so it is important to be aware of treatment options. Three US clinical trials involving heterosexual men and women with chlamydia and gonorrhea have shown that offering EPT results in a statistically significant decrease in rates of reinfection. Co-testing for other infections, especially HIV, should also be encouraged.

Gonorrhea and Chlamydia:

Gonorrhea and chlamydia remain the two most commonly reported bacterial communicable diseases in the US. Although they are often asymptomatic, they can cause urethritis, cervicitis, and widespread symptoms in extreme cases (conjunctivitis, arthritis, skin lesions, meningitis, endocarditis). For a simple chlamydial infection, the recommended treatment is 100 mg of doxycycline PO BID for 7 days. For patients with concern for treatment compliance, you can consider a single dose of azithromycin. For a simple gonorrheal infection, the recommended treatment is 500 mg of IM ceftriaxone (note: this is double the previously recommended dose). Co-treatment with azithromycin or doxycycline for gonorrheal infections where chlamydia co-infection has been excluded is no longer recommended. Given rising resistance among strains of both gonorrhea and chlamydia, if patients do not have symptom resolution within 3-5 days, it is recommended that they get re-tested and possibly re-treated with alternative regimens. It is also important to test all relevant exposed mucous membranes in our patients, including rectal and pharyngeal testing in those patients who practice receptive anal or oral sex.

Pelvic Inflammatory Disease:

Pelvic inflammatory disease (PID) constitutes a series of infections of various pelvic organs involving any combination of endometritis, salpingitis, tubo-ovarian abscess, and pelvic peritonitis. The clinical criteria include cervical motion tenderness, uterine tenderness, or adnexal tenderness.  Although initially thought to be caused predominantly by gonorrhea or chlamydia, recent studies have shown that the number of cases attributable to those organisms are falling, with some studies showing that only about 50% of women with PID had positive tests for gonorrhea or chlamydia with organisms compromising the vaginal flora such as Gardnerella vaginalis and H. influenzae acting as other causative organisms.  As a result, treatment for PID is with ceftriaxone or cefoxitin PLUS doxycycline PLUS metronidazole. Importantly, due to an increasing number of women presenting with more advanced PID after initially presenting with vague, non-specific symptoms, the CDC recommends presumptive PID treatment for women at risk for STIs if they are experiencing pelvic or lower abdominal pain and no other cause for this pain can be identified.


Epididymo-orchitis is defined by pain, swelling, and inflammation of the epididymis or testicle. It is typically unilateral although may be bilateral. Importantly, this is a clinical diagnosis and, although often seen on ultrasound, a negative ultrasound does not rule out epididymitis. It is caused by either STIs or enteric organisms and treatment should be based on a given patient’s risk factors. For patients at higher risk for STIs, treatment should with ceftriaxone and doxycycline targeted at gonorrhea and chlamydia. For men who practice insertive anal sex, treatment should target both enteric and STIs so recommended treatment is with ceftriaxone and levofloxacin. For men who are at low risk for an STI, treatment for enteric organisms with levofloxacin alone is appropriate.

Mycoplasma genitalium:

Mycoplasma genitalium can cause urethritis in men and has associations with infertility, spontaneous abortion, cervicitis, PID, and preterm delivery in women. It is often asymptomatic, although can be symptomatic in men. Current evidence indicates that M. genitalium is responsible for 15-20% of non-gonococcal urethritis, 20%-25% of non-chlamydial non-gonococcal urethritis, and 40% of persistent or recurrent urethritis. Rectal and pharyngeal infections have also been identified and are typically asymptomatic. There is NAAT testing available for urine and urethral, penile, vaginal, and endocervical samples. Testing is recommended for men with recurrent non-gonococcal urethritis and women with recurrent cervicitis, as well as considered for women with PID. Resistance testing should be ordered if available as both macrolide and quinolone resistance is increasing. Resistance-guided therapy should be used whenever possible and should begin with empiric doxycycline as initial therapy, followed by treat with either high-dose azithromycin or moxifloxacin pending resistance testing. Screening for asymptomatic infections is not recommended.

Lymphogranuloma Venereum:

Lymphogranuloma venereum (LGV) is a common STI globally with the causative organism chlamydia trachomatis serovars L1, L2, or L3. The most common presentation is proctocolitis which can mimic inflammatory bowel disease with mucoid or hemorrhagic discharge, anal pain, constipation, fever, and tenesmus. In heterosexual patients, they may solely have unilateral tender inguinal or femoral lymphadenopathy (buboes). Occasionally patients may have a self-limited ulcer or papule. It is recommended that all patients with proctocolitis be tested for LGV (if available) and suspicion should be high among MSM, especially those with a recent positive rectal chlamydia test as our common assays for chlamydia do not distinguish LGV from typical chlamydial infections. For persons with acute proctitis, if a rectal chlamydia NAAT test is positive and severe symptoms such as rectal ulcers, bleeding, or anal discharge are present, then they should be treated empirically for LGV. Treatment is with doxycycline for three weeks.


Chancroid is characterized by one or more deep and painful genital ulcers along with tender suppurative inguinal lymphadenopathy, although this is seen in less than 50% of cases. It is caused by Haemophilus ducreyi. Per CDC recommendations, it is reasonable to treat any patient with one or more painful ulcers (factoring in their appearance) if syphilis testing is negative and HSV is either unlikely or testing is negative. Treatment is with either azithromycin or ceftriaxone.

HSV-1 and HSV-2:

HSV-1 and HSV-2 are very common causes of both oral and genital lesions. The lesions are self-limited, recurrent, painful, and vesicular or ulcerative lesions. It is estimated that 11.9% of people between ages 14-49 are infected and most of these individuals have not had their condition diagnosed due to mild or unrecognized infection. Despite this, those patients intermittently shed the virus. Treatment is recommended based on a suspected first episode of genital herpes as both of length of infection and rates of recurrence can depend on prompt initiation of initial treatment. Infection can be confirmed with testing by NAAT or culture of the lesions if they are present, but treatment should not wait pending test results. Type-specific serologic tests can be helpful in diagnosing HSV infection if no lesions are present and can be valuable for prognostic reasons. Presence of HSV-2 type-specific antibodies implies anogenital infection since HSV-2 is almost entirely sexually acquired, while HSV-1 type specific antibodies may indicate previous oral or anogenital infection. Possible treatment options include acyclovir, valacyclovir, and famciclovir depending on the patient’s insurance status.


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  5. Workowski KA, Bachmann LH, Chan PA, et al. Sexually transmitted infections treatment guidelines, 2021. Centers for Disease Control and Prevention. July 26, 2021. Accessed December 20, 2021.