09. Sexually Transmitted Infections (STIs)

Faculty Editor: Luis Rubio, MD

BOTTOM LINE

✔ STIs are common and often asymptomatic

✔ Yearly screening for chlamydia and gonorrhea indicated in sexually active women <25 years old and those older with risk factors

✔ When treating, consider HIV status, pregnancy, and partners

Background

  • Commonly reportable diseases in urban settings are chlamydia and gonorrhea, and to a lesser extent, syphilis and HIV.
  • HPV, HSV, and trichomonas are other common, non-reportable sexually transmitted infections (STIs) with a high nationwide prevalence.
  • ~50% of all sexually active adults will get an STI by age 25
  • In San Francisco, rates of chlamydia, gonorrhea and early syphilis continue to rise, particularly in the MSM population. >75% of syphilis cases are diagnosed in MSM. The rate of HIV in SF has declined since 2006.
  • Sexually active MSM still account for >50% of all new HIV cases and highest rates of syphilis infection
  • Specific groups at higher risk:
    • Young age (15 to 24 years old): Adolescents are at high risk for STIs as they frequently have unprotected intercourse, are engaged in sexual partnerships frequently of limited duration, and face multiple obstacles to accessing health care.
    • New sex partner in past 60 days
    • No or inconsistent condom use when not in mutually monogamous partnerships
    • Multiple sexual partners
    • History of a prior STI
    • Illicit drug use
    • Admission to correctional facility or juvenile detention center
    • Meeting partners on the Internet
    • Contact with sex workers or engaging in sex work (for money or drugs)
  • Antimicrobial resistance in Neisseria gonorrhea and Mycoplasma genitalium increasing worldwide

Signs and symptoms

History

  • Any new sexual partner(s) and frequency of condom use
  • Multiple sexual partners
  • History of STIs, and genital ulceration (which can increase the risk of HIV acquisition)
  • Types of sexual exposures (which will guide decisions about which mucosal sites to test diagnostically): oral, vaginal, anal (receptive versus insertive)

Symptoms

  • Dysuria
  • Discharge
  • Abdominal pain
  • Dyspareunia (pain during sexual intercourse)
  • Painful defecation
  • Acute retroviral syndrome: fever, lymphadenopathy, sore throat, rash, myalgia/arthralgia, diarrhea, headache

Signs

• Differ depending on STI; see “Diagnosis and Treatment of STI” table below

Evaluation

  • Characteristic lesions seen on physical exam:
    • HPV/warts tend to have cauliflower like lesions
    • HSV are painful, vesicular, and ulcerated lesions
    • Syphilitic chancres are painless ulcerations
    • Chancroid can be painful or painless and is often associated with painful lymphadenitis     
  • See “Diagnosis and Treatment of STI” table below for diagnostic signs and labs for common STIs
  • Universal screening for HIV at least once in lifetime is recommended for all adolescents and adults by USPSTF and CDC
  • Screening for STIs in all patients is not practical. Recommended to screen those who are at high risk and specific groups with high prevalence for STIs. SFDPH STD and HIV Screening Guidelines in persons without symptoms or in need of diagnostic testing are below:
    • Women
      • < age 25
        • Chlamydia and gonorrhea yearly
        • Syphilis at least one lifetime test
        • HIV at least one lifetime test
      • ≥ age 25
        • Chlamydia and gonorrhea not routinely recommended unless risk factors present
        • Syphilis at least one lifetime test
        • HIV at least one lifetime test
      • Women who are HIV+ should be screened annually for trichomoniasis
    • Pregnant persons all ages
      • Chlamydia and gonorrhea in 1st trimester, repeat in 3rd if at increased risk
      • Syphilis in 1st and 3rd trimester, and at delivery
      • HIV first prenatal visit, repeat in 3rd trimester if at increased risk
    • Men who have sex with Women
      • Chlamydia, gonorrhea, and syphilis not routinely recommended unless risk factors present
      • HIV at least one lifetime test
    • Men who have sex with men:
      • Chlamydia, gonorrhea, syphilis and HIV every 3 months
      • Depending on sexual practices, rectal chlamydia and oropharyngeal gonorrhea testing may be indicated
    • Transgender men and transgender women who have sex with men:
      • Chlamydia, gonorrhea, syphilis and HIV every 3 months
      • Depending on sexual practices, rectal chlamydia and oropharyngeal gonorrhea testing may be indicated
    • Individuals seeking STI evaluation: gonorrhea/chlamydia (at genital, rectal and pharyngeal depending on exposure), syphilis, HIV, trichomonas, HSV-2 (if lesions present)

Treatment

Symptomatic and asymptomatic patients

  • See “Diagnosis and Treatment of STIs” below for infection-specific treatment regimens.
  • Consider screening for pregnancy prior to prescribing antibiotics.
  • If treating for chlamydia, gonorrhea, or trichomonas, advise abstaining from sex for 7 days to prevent spreading infection to partners.
  • Re-testing should be done 3 months after chlamydia, gonorrhea, or trichomonas infections are treated, regardless if partner was treated, because re-infection rates are high. 
  • California state law requires providers to report all cases of syphilis, chlamydia, gonorrhea, chancroid, pelvic inflammatory disease, HIV, HBV and HCV to their local health department; syphilis must be reported within 1 working day, while other STIs must be reported with 7 calendar days. To report a newly diagnosed STI in San Francisco, including HIV, call STD Clinic at 415-487-5555.
  • CDC no longer recommends avoiding alcohol consumption while taking systemic metronidazole as review found no evidence of disulfiram like interaction between alcohol and metronidazole

Partner therapy

  • Patient-delivered partner therapy (PDPT) is legal in California, but may not be covered by the patient’s insurance
  • PDPT has been shown to be a safe and cost effective treatment strategy in heterosexual couples for gonorrhea and chlamydia. Limited data in trichomoniasis and no data in syphilis.
  • PDPT data limited in MSM, but all persons with bacterial STI diagnoses and their sex partners should be tested for HIV
  • If PDPT is prescribed, the partner should be encouraged to seek clinical evaluation in addition to PDPT. Advise about symptoms of PID for persons at risk and to seek medical care immediately should these occur (i.e. pelvic or abdominal pain). 
  • Counsel about risks of drug reaction (and risks with pregnancy), but this should not limit prescribing. Advice to partners should be in writing and a copy kept in the chart.

Primary Prevention

  • HPV: HPV vaccination is recommended for all girls and boys at age 11-12. Catch-up vaccination is recommended through age 45.
  • PrEP (pre-exposure prophylaxis):
  • Daily Truvada (TDF/FTC) is an option for HIV prevention among all adults at risk of HIV acquisition through sex or injection drug use
  • Daily Descovy (TAF/FTC) is another option for HIV prevention for cis gender men and transger women who have sex with men
  • Bimonthly (every 8 weeks) injectable cabotegravir is another option for HIV prevention amongst all adults at risk of acquiring HIV through sex

References

Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2021. MMWR 2021; 70(RR-4):1-187.

Centers for Disease Control and Prevention. Update to CDC’s Sexually Transmitted Diseases Treatment Guidelines, 2010: Oral Cephalosporins no longer a recommended treatment for gonococcal infections, MMWR 2012; 61(31):590-594

Centers for Disease Control and Prevention. US Public Health Service: Preexposure prophylaxis for the prevention of HIV infection in the United States- 2021 Update: a clinical practice guideline. https://www.cdc.gov/hiv/pdf/risk/prep/cdc-hiv-prep-guidelines-2021.pdf Published 2021

Centers for Disease Control and Prevention Fact Sheet. What Gay, Bisexual and Other Men Who Have Sex with Men Need to Know About Sexually Transmitted Diseases, MMWR. 2013.

Unemo M, Jensen JS. Antimicrobial-resistant sexually transmitted infections: gonorrhoeae and Mycoplasma genitalium. Nat Rev Urol. 2017;14(3):139-152.

San Francisco City Clinic Clinical Protocols. Sexually Transmitted Infections. Sexually Transmitted Diseases Prevention and Control Services. San Francisco Department of Public Health, San Francisco, California. https://www.sfcityclinic.org/sites/default/files/2021-09/SFCC%20STI%20Protocols%202021.pdf

Table: Diagnosis and Treatment of STIs

 

Indication

 

Diagnosis

 

 

CDC recommended treatments

Bacterial vaginosis

Patient must have 3 out of 4:

  1. Vaginal pH > 4.5
  2. Homogeneous, grayish white discharge smoothly coating vaginal walls
  3. Positive whiff-amine test (when KOH added to vaginal discharge)
  4. Wet mount: clue cells

Recommended Regimens

Metronidazole 500mg PO BID x 7d

Metrogel (0.75%) 5g intravaginally Daily x 5d

Clindamycin 2% cream 5g intravaginally at bedtime x 7d

 

Alternative Regimens

Clindamycin 300mg PO BID x 7d

Clindamycin ovules 100mg intravaginally at bedtime x 3d

Tindizaole 2g PO daily x2d

Tinidazole 1g PO daily x5d

 

Pregnant patients can be treated with either oral or vaginal regimens recommended for nonpregnant patients

Chancroid

(Not common in US)

H.ducreyi, culture on special media or PCR (done through DPH).  

If negative for syphilis and HSV, consider treating empirically in specific cases.

The combination of a painful genital ulcer and tender suppurative inguinal adenopathy suggests the diagnosis.

Azithromycin 1g PO x 1 dose

Ceftriaxone 250mg IM x 1 dose

Ciprofloxacin 500mg PO BID x 3d (contraindicated in pregnancy)

Erythromycin base 500 mg orally TID x7d

Cervicitis

(Chlamydia, GC and Trichomonas)

Either or both signs may be present on pelvic exam:

1) Purulent or mucopurulent endocervical exudate visible in the endocervical canal or on an endocervical swab specimen;

2) Sustained endocervical bleeding easily induced by gentle passage of a cotton swab through the cervical os.

Recommended Regimen

Doxycycline 100mg PO BID x7d

 

Alternative Regimen

Azithromycin 1g PO x 1 dose  

 

Must empirically treat chlamydia, and if patient is high-risk, strongly consider concurrent gonococcal treatment. Based on diagnostic testing, may require treatment of trichomonas, symptomatic BV, HSV.

Confirm with PCR (NAAT) or culture

 

Chlamydia

Nucleic acid amplification techniques on urine (first void), cervical, urethral or anal specimens

Recommended Regimen

Doxycycline 100mg PO BID x 7d

 

Alternative Regimens

Azithromycin 1g PO x1 dose

Levofloxacin 500 mg PO daily x7d

 

Pregnant patients

Azithromycin 1g PO x1 dose

Amoxicillin 500mg PO TID x 7d

 

Retest in 3 months, as re-occurrence is common.

Epididymitis

Urethral swab, TTP on tip of testicle

If Gonococcal or Chlamydia suspected

Ceftriaxone 500 mg IM x1 dose

and

Doxycycline 100mg PO BID x 10d

 

If Gonococcal, Chlamydia, or enteric organism suspects

Ceftriaxone 500 mg IM x1 dose

and

Levofloxacin 500 mg PO Daily x10d

 

If enteric organisms suspected only (men > 35y who practice insertive anal intercourse)

Levofloxacin 500mg PO Daily x 10d

Gonococcal infection

Urethral, cervical, anal swabs: gram stain, culture on Thayer-Martin media, DNA probes, and DNA amplification techniques

Recommended regimen:

Ceftriaxone 500mg IM x1 dose (for patients weight >150 kg: Ceftriaxone 1g IM x1)

 

Alternative regimen if ceftriaxone unavailable:

Cefixime 800 mg PO once

 

Alternative regimen for patients with allergy

Gentamicin 240 mg IM x1 (use with caution in pregnancy)

and

Azithromycin 2g PO x1

 

For disseminated GC – expert consultation recommended

Ceftriaxone 1g IM/IV Q24h x1-2 days

After clinical improvement begins, oral antibiotic to complete remainder of 7-14d course

 

Notes: If chlamydia has not been excluded, treat for chlamydia with doxycycline 100 mg PO BID x7d

FQs are no longer recommended as treatment for GC given the high incidence of Quinolone Resistant GC (QRGC).

Retest in 3 months, as re-occurrence is common.

 

 

Genital or anal HSV-2 infection

Viral culture, DFA staining, Tzanck prep (less common), or PCR. Serologies are helpful for diagnosis if there is no active disease, but there are high false negatives in early infection. Note that routine serologic testing is not recommended for screening.

First episode

Acyclovir 400mg PO TID x 7-10d

Famciclovir 250mg PO TID x 7-10d

Valacyclovir 1g PO BID x 10d

(treatment may be extended if healing has not yet occurred)

 

Suppressive therapy

Acyclovir 400mg PO BID

Famciclovir 250mg PO BID

Valacyclovir 500mg PO Daily (maybe less effective; use for patients with <9 recurrences/year) 

Valacyclovir 1g PO Daily (use for patients with >10 recurrences/year)

 

Suppressive therapy among persons with HIV Infection

Acyclovir 400-800mg PO BID-TID

Famciclovir 500mg PO BID

Valacyclovir 500mg PO BID

 

Episodic therapy for recurrent HSV-2

Acyclovir 800mg PO BID x 5d

Acyclovir 800mg PO TID x 2d

Famciclovir 1g PO BID x 1d

Famciclovir 500 mg PO x1 then 250 mg BID x2d

Famciclovir 125mg PO BID x 5d

Valacyclovir 500mg PO BID x 3d

Valacyclovir 1g PO Daily x5d

 

Episodic therapy for recurrent HSV-2 among persons with HIV Infection

Acyclovir 400mg PO TID x 5-10d

Famciclovir 500mg PO BID 5-10d

Valacyclovir 1g PO BID x 5-10d

Severe disease (i.e. disseminated infection, pneumonitis, hepatitis, meningitis, encephalitis) requires IV acyclovir (10-12mg/kg/dose q8h).

 

 

Genital warts (HPV)

The presence of genital warts +/- biopsy.

(No data support the routine use of PCR to detect HPV in visible warts).

For external warts

Patient applied

Podofilox 0.5% solution or gel apply BID to visible warts x 3d, followed by 4d of no therapy. Repeat cycle as necessary up to four cycles.

Imiquimod 5% cream: once Daily at bedtime, 3x/week for up to 16 weeks. Treatment area should be washed with soap and water 6-10 hours after the application.

Sinecatechins 15% ointment: Apply TID until clearance for maximum 16 weeks. Do not wash off. Not recommend in people with HIV or immunocompromising conditions.

 

Provider-administered

Cryotherapy with liquid nitrogen or cryoprobe (repeat applications every 1-2 weeks) or

Podophyllin resin 10%-25% in a compound tincture of benzoin: air dry and then repeat weekly if necessary

or

Trichloroacetic acid or Bichloroacetic acid 80-90%; if excess acid applied, treated area should be powdered with talc, sodium bicarbonate or liquid soap. Maybe repeated weekly. 

Other options include surgical removal (shave excision, curettage or electrosurgery), intralesional interferon, and laser surgery

 

For vaginal warts

Cryotherapy

or

TCA or BCA 80-90% applied to warts

 

For cervical warts –biopsy to exclude HSIL should be done prior to treatment

Cryotherapy

or

Surgical removal

or

TCA or BCA 80-90%

 

For urethral meatus

Cryotherapy

or

Surgical removal

 

For Intra-anal warts

Cryotherapy

or

TCA or BCA 80-90%

or

Surgical removal

 

Lymphogranuloma venereum

No commercially available test and diagnosis should be considered based on clinical presentation (proctotitis/proctocolitis, tender inguinal LAD).

 

Serology not helpful for diagnosis.

 

NAATs for chlamydia do not distinguish between LGV and non-LGV serovars.

 

SFDPH PHL has validated LGV PCR from swabs from rectum, urethra, and genital ulcers. Will only be run if chlamydia NAAT positive.

Doxycycline 100mg PO BID x 21 days (1st line)

Azithromycin 1g PO weekly x 3 weeks (as per CDC, may be effective)

Erythromycin base 500mg PO QID x 21d

 

Mycoplasma genitalium

NAAT through urine sample or urethral, meatal, vaginal, endocervical swabs, and vaginal swab. Should be considered in cases of persistent or recurrent urethritis, epididymitis, vaginitis, cervicitis, PID, dysuria, pyuria, and intermenstrual or post coital bleeding

If macrolide sensitive (if M. genitalium resistance testing available)

Doxycycline 100 mg PO BID x7d, followed by azithromycin 1g PO initial dose then 500 mg PO x3d

 

If macrolide resistant or M. genitalium resistance testing not available

Doxycycline 100 mg PO BID x7d, followed by moxifloxacin 400 mg PO x7d

 

 

 

Pelvic Inflammatory disease (PID)

Minimum criteria:

Lower abdominal or pelvic pain and

CMT or uterine tenderness or adnexal tenderness and absence of other causes of pelvic pain

 

Additional useful criteria: Temp > 38.3, abnormal cervical or vaginal discharge, cervical friability, presence of WBC on saline microscopy of vaginal secretions, evidence of infection with N. gonorrhoeae, C. Trachomatis, or M. genitalium

Parenteral

Ceftriaxone 1g Q24H + Doxycycline 100 mg PO BID + Metronidazole 500 mg PO/IV BID

 

Cefotetan 2g IV q12 + Doxycycline 100mg PO BID

 

Cefoxitin 2g IV Q6h + Doxycycline 100mg PO BID

 

Alternative Parenteral regimens

Ampicillin/sulbactam 3g IV Q6 + Doxycycline 100mg PO BID

 

Clindamycin 900mg IV Q8 + Gentamicin loading (2mg/kg IV or IM then maintenance dose 1.5mg/kg q8h)

 

IM or Oral Regimens

Ceftriaxone 500mg IM x1 (1g if > 150 kg) + Doxycycline 100mg PO BID x14d + Metronidazole 500 mg PO BID

 

Cefoxitin 2g IM + Probenecid 1g PO x 1 dose + Doxycycline 100mg PO BID x 14d + Metronidazole 500 mg PO BID

 

3rd generation cephalosporin + Doxycycline 100mg PO BID x 14d + Metronidazole

500mg PO BID x 14d

 

If M. genitalium identified by NAAT

Moxifloxacin 400 mg Daily x 14 days

 

Prophylaxis after sexual assault

 

Recommend sending to trained provider for forensic evaluation

Ceftriaxone 500mg IM x 1 dose (1g if >150 kg)

Doxycycline 100mg PO BID x 7d

Metronidazole 500mg BID x7d (in persons with a vagina)

 

Consider post-exposure HIV prophylaxis if victim will not return for follow up.

Trichomoniasis

Wet mount: can see motile trichomonads, culture/PCR is much more sensitive. T. vaginalis susceptibility testing available from CDC (404-718-4141)

Recommended initial regimens:

Vaginal infections: metronidazole 500 mg PO BID x7d

 

Penile Urethritis: metronidazole 2g PO x1

Alternative initial regimen (all genders): Tinidazole 2g PO x1

 

Persistent infection/treatment failure:

If re-infection likely, re-treat with regimens above

Persistent vaginitis: Metronidazole 2g PO daily x7d or tinidazole 2g PO Daily x7d

Persistent penile urethritis: metronidazole 500 mg PO BID x7d

 

Pregnancy

Metronidazole 500 mg PO BID x7d

Tinidazole should not be used

 

Nitroimidazole allergy

Patients with allergies to metronidazole or tinidazole should undergo oral desensitization

 

Retest in 3 months, as re-occurrence is common.

Nongonoccocal urethritis

Gram stain of urethral swab, purulent or mucopurulent discharge; urine with positive leukocyte esterase or >10 WBC per HPF

Recommended regimen

Doxycycline 100mg PO BID x 7d

 

Alternative regimens

Azithromycin 1g PO x1 followed by 500 mg daily x3d

Azithromycin 500 mg PO x1 followed by 250 mg daily x4d

Azithromycin 1g PO x1

 

Recurrent or persistent urethritis

Retreatment with above if patient noncompliant or partner was not adequately treated.

Test for M. genitalium

 

Otherwise:

Metronidazole 2g PO x 1 dose or Tinidazole 2g PO x 1 dose (in areas where T. vaginalis prevalent)

 

Syphilis

Primary, secondary and early latent syphilis: dark field microscopy (available only at DPH clinic in SF), DFA-TP; RPR and VDRL are first line serologic markers. If positive, confirm with treponemal tests FTA-Ab, MHA-TP or TPPA.

Note that some labs may run treponemal tests as initial screening.

Early Syphilis (<1 years duration): Primary, secondary and early latent

Benzathine Penicillin G 2.4 million units IM x1

Alternative (PCN allergic): Doxycycline 100 mg PO BID x 14d

 

Late Syphilis (>1 year duration or of unknown duration)

Benzathine Penicillin G 2.4 million units IM weekly x 3 doses

Alternative (PCN allergic): Doxycycline 100 mg PO BID x 4 weeks

 

Restart three dose series if >14 days elapse between doses

Restart three dose series if >9 days elapse in pregnant patients

 

Neurosyphilis

Recommended

Aqueous crystalline penicillin G 3-4 million units IV Q4 hours

or

18-24 million units continuous IV infusion x 10-14d

 

Alternative

Procaine Penicillin 2.4 million units IM QDay + Probenecid 500 mg PO QID x 10-14d

 

Contacts/Clusters

Benzathine Penicillin G 2.4 million units IM x1

Alternative (PCN allergic): Doxycycline 100 mg PO BID x 14d

 

*Desensitization is necessary for pregnant patients allergic to PCN