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Am Fam Physician. 2022;105(5):514-520

Related practice guideline: Sexually Transmitted Infections: Updated Guideline From the CDC

This clinical content conforms to AAFP criteria for CME.

Author disclosure: No relevant financial relationships.

Sexually transmitted infection (STI) rates are increasing for most nationally notifiable disease categories in the United States. The 2021 Centers for Disease Control and Prevention STI guidelines provide several updated, evidence-based testing and treatment recommendations. The recommended treatment for gonorrhea is ceftriaxone monotherapy given intramuscularly, with dosing based on the patient's body weight. For chlamydia, doxycycline is the preferred treatment. A test-of-cure is recommended for all cases of pharyngeal gonorrhea and for rectal chlamydia if treated with azithromycin. Vaginal trichomoniasis should be treated with a seven-day regimen of metronidazole. Treatment of pelvic inflammatory disease routinely includes metronidazole with doxycycline and an increased dosage of ceftriaxone. Syphilis of less than one year's duration should be treated with a single dose of intramuscular penicillin G benzathine, 2.4 million units. Syphilis of more than one year's or unknown duration should be treated with three consecutive weekly doses of intramuscular penicillin G benzathine, 2.4 million units each. A thorough evaluation for otic, ophthalmic, and neurologic symptoms is essential for anyone with syphilis because these complications can occur at any stage and require 10 to 14 days of treatment with intravenous aqueous crystalline penicillin G. Family physicians can reduce STI rates by taking a thorough sexual history, especially in teens and young adults, ordering screening tests and treatment based on the updated Centers for Disease Control and Prevention STI guidelines, and collaborating with public health departments for disease reporting and partner services.

From 2014 to 2019, U.S. rates of sexually transmitted infections (STIs) increased for chlamydia (19%), gonorrhea (56%), primary and secondary syphilis (74%), and congenital syphilis (279%).1 The combined epidemics of STIs and opioid use, compounded by reduced screening and treatment opportunities during the COVID-19 pandemic, will likely further exacerbate this trend. Family physicians can reduce infection rates by discussing sexual history, especially with teens and young adults, ordering screening tests and treatment based on the 2021 Centers for Disease Control and Prevention (CDC) STI treatment guidelines (Table 12), and collaborating with public health departments for disease reporting and partner services.

Clinical recommendationEvidence ratingComments
Review vaccination status and update preexposure vaccines against human papillomavirus infection, hepatitis A, and hepatitis B when appropriate.2 CExpert opinion
Screen for Mycoplasma genitalium with nucleic acid amplification testing in patients with recurrent or persistent urethritis.2,10 BObservational studies showing high rates of M. genitalium in recurrent urethritis
Treat gonorrhea with a single intramuscular dose of ceftriaxone, 500 mg (in patients weighing less than 300 lb [136 kg]) or 1,000 mg (in patients weighing more than 300 lb)2 ; co-treatment with azithromycin (Zithromax) or doxycycline is no longer required.CPersistently low ceftriaxone minimal inhibitory concentrations, antimicrobial stewardship concerns, and potential harm to the microbiome
Treat chlamydia preferentially with doxycycline, 100 mg twice per day for seven days1214 ; azithromycin, 1 g, remains an acceptable alternative, is preferred in pregnancy, and may be more appropriate for patients with confidentiality concerns or those unable to adhere to seven-day regimens.2 AConsistent evidence from randomized controlled trials
Screen pregnant people for syphilis in high-incidence areas and those who have risk factors at the time of pregnancy diagnosis, at 28 weeks' gestation, and at delivery.1,2 BMultiple case series
Routinely treat pelvic inflammatory disease with 14 days of metronidazole (Flagyl), 500 mg twice per day; 14 days of doxycycline, 100 mg twice per day; and intra-muscular ceftriaxone at increased weight-based dosing to cover gonorrhea.2 CExpert opinion
FactorRecommendation updates
Asymptomatic extragenital (rectum, pharynx) infectionPerform rectal Chlamydia trachomatis NAAT testing in MSM, consider in women at risk
If rectal C. trachomatis infection is treated with azithromycin (Zithromax), perform test-of-cure
Perform routine test-of-cure 14 days after treatment of pharyngeal gonorrhea
Perform rectal and oropharyngeal gonorrhea NAAT in MSM, consider in women at risk
EpididymitisCover for enteric pathogens if patient reports having insertive rectal intercourse
Consider Mycoplasma genitalium in cases of persistent epididymitis
Expedited partner therapyFor partners of patients with gonorrhea, increase cefixime (Suprax) dose to 800 mg orally
HepatitisOffer preexposure vaccination for hepatitis A and hepatitis B (Table 2)
Perform serologic testing for hepatitis B after vaccination in people starting PrEP
Screen for hepatitis C in all pregnant patients (unless prevalence is known to be < 0.1%) and yearly for those on PrEP
HPVOffer patients routine vaccination through 26 years of age and shared decision-making for those 27 to 45 years of age
Perform digital anorectal examination in people with HIV infection and possibly in MSM without HIV who have a history of receptive anal intercourse
Pelvic inflammatory diseaseRoutinely treat with 14 days of metronidazole (Flagyl), 500 mg twice per day; 14 days of doxycycline, 100 mg twice per day; and intramuscular ceftriaxone at increased weight-based dosing to cover gonorrhea
ProctitisTreat empirically with ceftriaxone, 500 mg, plus doxycycline, 100 mg twice per day for seven days
For proctocolitis, consider treating lymphogranuloma venereum with doxycycline, 100 mg twice per day for 21 days
For fever and diarrhea, perform enteropathogen testing
Ulcerative disease
 HSVType-specific polymerase chain reaction testing of a lesion is preferred over culture for herpes diagnosis
Perform two-step serologic testing when used to diagnose genital herpes
 SyphilisScreen pregnant patients in high-incidence areas and those with risk factors at the time of pregnancy diagnosis, at 28 weeks' gestation, and at delivery
Urethritis/cervicitis
 Chlamydia (C. trachomatis)Treat with doxycycline, 100 mg twice per day for seven days (preferred regimen)
 GonorrheaProvide monotherapy with a single intramuscular dose of ceftriaxone, 500 mg in patients weighing less than 300 lb (136 kg) or 1,000 mg in patients weighing more than 300 lb
M. genitaliumTesting should be performed only for symptomatic patients with persistent urethritis or cervicitis; testing can be considered in pelvic inflammatory disease and in persistent epididymitis, but it should not be performed for vaginal discharge alone
If M. genitalium is macrolide-resistant or sensitivity testing is not available, treat with doxycycline, 100 mg twice per day for seven days, followed by moxifloxacin (Avelox), 400 mg daily for seven days
If M. genitalium is macrolide-sensitive, treat with doxycycline, 100 mg twice per day for seven days, followed by azithromycin, 1 g on day 1 and 500 mg on days 2 through 4
 Nongonococcal urethritisProvide doxycycline, 100 mg twice per day for seven days (first-line treatment)
Consider screening patients with persistent or recurrent non-gonococcal urethritis for Trichomonas vaginalis and M. genitalium
Vaginitis
 Bacterial vaginosisBe aware that bacterial vaginosis increases the risk of STI acquisition, including HIV
Do not screen asymptomatic pregnant patients
 CandidaFor recurrent vulvovaginal candidiasis with more than three episodes per year, consider weekly fluconazole (Diflucan) for six months
T. vaginalisConsider testing asymptomatic patients at high risk or in high-prevalence settings
Treat vaginal trichomoniasis with metronidazole, 500 mg twice per day for seven days

Prevention

Taking a thorough sexual history using gender-inclusive and sexual orientation–inclusive language can improve rapport, ensure appropriate screening of all sites of exposure, and allow for a focused and patient-specific discussion of risk reduction. Include the Five P's—partners, practices, protection from STIs, past STIs, and pregnancy intention— in the discussion.3 The U.S. Preventive Services Task Force recommends behavioral counseling with a focus on condom use and decreasing sexual risk behaviors.4 Physicians should encourage vaccination against hepatitis A, hepatitis B, and human papillomavirus, as recommended for age and additional risk factors such as sexual acts that risk fecal–oral and blood-borne exposure (Table 2).2

Vaccine-preventable illnessRecommended population
Hepatitis AMen who have sex with men
People who inject drugs
People with chronic liver disease
People with HIV or hepatitis C (without a history of hepatitis A or hepatitis B)
People who are homeless
Hepatitis BSame as hepatitis A recommended population
All unvaccinated, uninfected people who are sexually active with more than one partner or who are being evaluated or treated for a sexually transmitted infection
Human papillomavirusPatients 11 to 12 years of age, with two doses six to 12 months apart
Catch-up through 26 years of age for those not previously vaccinated with three-dose regimen if started at 15 years or older
Shared clinical decision-making for certain adults 27 to 45 years of age (public health benefit of vaccination in this age range is minimal; some people who are not adequately vaccinated might benefit)

HIV preexposure prophylaxis (PrEP) with emtricitabine and tenofovir alafenamide (Descovy; for those with a creatinine clearance of 30 mL per minute per 1.73 m2 [0.50 mL per second per m2] or more, not at risk of vaginal HIV exposure) or emtricitabine and tenofovir disoproxil fumarate (Truvada; creatinine clearance of 60 mL per minute per 1.73 m2 [1.00 mL per second per m2] or more) is safe and effective. The U.S. Preventive Services Task Force recommends offering PrEP to individuals at risk, including those who have had gonorrhea or syphilis during the previous six months, those who share drug injection equipment, those who are HIV-negative but whose sex partner has HIV infection, and those with inconsistent use of condoms during receptive or insertive anal sex.5

Expedited partner therapy, the provision of medication to sex partners of people with STIs without examination or testing of the partner, has been shown to reduce the spread of infection at the community level and prevent reinfection of the index case.6,7 The American Academy of Family Physicians advocates for the use of expedited partner therapy whenever possible to help address increasing rates of STIs. 8 Cefixime (Suprax), with a dosing increase to 800 mg, is the recommended expedited partner therapy regimen for gonorrhea (Table 12), with the addition of doxycycline, 100 mg twice daily for seven days, if concurrent chlamydia has not been excluded. There are no changes to the recommended expedited partner therapy regimen for chlamydial infection (i.e., 1 g of azithromycin [Zithromax] in a single oral dose or 100 mg of doxycycline given twice daily for seven days).

ANTIBIOTIC STEWARDSHIP

The new guidelines highlight antibiotic stewardship in addressing patient-reported penicillin allergy.2 Although as many as 10% of patients report a penicillin allergy, 90% of those patients tolerate penicillins when allergy tested.9 Physicians should carefully define allergies, separating those with reactions mediated by immunoglobulin E (IgE) from those experiencing common adverse effects. The PEN-FAST rule is a validated clinical tool to guide risk assessment and treatment decisions (Table 3).9 Physicians should use ceftriaxone and penicillins when risk of true allergy is low and consider penicillin allergy testing for those with possible allergy to preserve treatment options.

Assess risk factorsCalculate scoreEstimated risk of a positive result on allergy testing
Allergy event occurring five or fewer years ago (2 points)0 = very low0.6% risk (1 out of 164)
Anaphylaxis/angioedema or severe cutaneous adverse reaction (2 points)1 = low5% risk (16 out of 296)
2 to 3 = moderate19% risk (25 out of 132)
Treatment required for the episode (1 point)4 to 5 = high53% risk (16 out of 30)

Urethritis and Cervicitis

Urethritis is characterized by dysuria, urethral pruritus or burning, and/or visible discharge. Neisseria gonorrhoeae and Chlamydia trachomatis are the most common causes, but Mycoplasma genitalium is increasingly recognized as an important cause of urethritis, particularly in patients presumptively treated for chlamydial infection with persistent symptoms.10 Patients with suspected urethritis should be evaluated for gonorrhea and chlamydia using nucleic acid amplification testing, and patients with persistent symptoms should be tested for M. genitalium infection.2,11 Other causative organisms, including Neisseria meningitidis and Trichomonas vaginalis, have also been implicated in urethritis.

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