SExUally Transmitted Diseases ContRol Branch

California Sexually Transmitted Infections (STI) Treatment Guidelines for Adults and Adolescents

These guidelines reflect the 2021 CDC STI Treatment Guidelines for adults and adolescents who are HIV negative as well as those with HIV. Call the local health department for assistance with confidential notification of sexual partners of patients with STIs or HIV. For complex STI clinical management consultation (such as in cases of multiple allergies or treatment failure), contact the California Department of Public Health STD Control Branch at stdcb@cdph.ca.gov or 510-620-3400 or submit your question online to the STD Clinical Consultation Network webpage

Included below are recommended treatment regimens for the following STIs and conditions:

Note: Alternative regimens included below are only to be used if there is a medical contraindication to the recommended regimen.

A PDF version of these treatment guidelines is available: California STI Treatment Guidelines for Adults and Adolescents (PDF).

Chlamydia (CT)

Scenario	Recommended Regimens	Alternative Regimens
Urogenital/Rectal/Pharyngeal Infections	Doxycycline¹ 100 mg po bid x 7 d	Azithromycin 1 g po x 1 dose OR Levofloxacin 500 mg po once daily x 7 d
Pregnant Patients²	Azithromycin 1 g po x 1 dose	Amoxicillin 500 mg po tid x 7 d

Scenario

Recommended Regimens

Alternative Regimens

Urogenital/Rectal/Pharyngeal Infections

Doxycycline¹ 100 mg po bid x 7 d

Azithromycin 1 g po x 1 dose OR
Levofloxacin 500 mg po once daily x 7 d

Pregnant Patients²

Azithromycin 1 g po x 1 dose

Amoxicillin 500 mg po tid x 7 d

Gonorrhea (GC)

Monotherapy with IM ceftriaxone is recommended for all patients with gonorrhea, including pregnant patients. If co-infection with chlamydia has not been excluded, add doxycycline 100 mg po bid x 7 d for non-pregnant persons or azithromycin 1 g po x 1 dose for pregnant persons.

Scenario	Recomended Regimens	Alternative Regimens
Urogenital/Rectal Infections³	Ceftriaxone 500 mg IM x 1 dose for persons weighing <150kg⁴OR Ceftriaxone 1 g IM x 1 dose for persons weighing > 150kg	If cephalosporin allergy: dual therapy with Gentamicin¹ 240 mg IM x 1 dose PLUS Azithromycin 2 g po x 1 dose If ceftriaxone not available or feasible, but no allergy concerns: Cefixime 800mg x 1 dose⁵
Pharyngeal Infections^3,6	Ceftriaxone 500 mg IM x 1 dose for persons weighing <150kg⁴ OR Ceftriaxone 1 g IM x 1 dose for persons weighing>150kg	No reliable treatment alternatives. Consult an infectious disease specialist or submit a question online at www.stdccn.org.

Scenario

Recomended Regimens

Alternative Regimens

Urogenital/Rectal Infections³

Ceftriaxone 500 mg IM x 1 dose for persons weighing <150kg⁴OR
Ceftriaxone 1 g IM x 1 dose for persons weighing > 150kg

If cephalosporin allergy: dual therapy with

Gentamicin¹ 240 mg IM x 1 dose PLUS Azithromycin 2 g po x 1 dose

If ceftriaxone not available or feasible, but no allergy concerns:

Cefixime 800mg x 1 dose⁵

Pharyngeal Infections^3,6

Ceftriaxone 500 mg IM x 1 dose for persons weighing <150kg⁴ OR
Ceftriaxone 1 g IM x 1 dose for persons weighing>150kg

No reliable treatment alternatives. Consult an infectious disease specialist or submit a question online at www.stdccn.org.

Pelvic Inflammatory Disease (PID)⁷

(Etiologies: CT, GC, anaerobes, possibly M. genitalium, others)

Recommened Regimens	Alternative Regimens
Parenteral Ceftriaxone 1 g IV q 24 hrs PLUS Doxycycline¹ 100 mg IV or po q 12 hrs PLUS Metronidazole 500 mg IV or po q 12 hrs OR Cefotetan 2 g IV q 12 h PLUS Doxycycline¹ 100 mg po or IV q 12 hrs OR Cefoxitin 2 g IV q 6 h PLUS Doxycycline¹ 100 mg po or IV q 12 hrs IM/Oral Ceftriaxone 500 mg IM x 1 dose⁴ (or another 3rd generation cephalosporin⁸) PLUS Doxycycline¹ 100 mg po bid x 14 d WITH Metronidazole 500 mg po bid x 14 d OR Cefoxitin 2 g IM x 1 dose administered with Probenecid 1 g po x 1 dose PLUS Doxycylcline¹ 100 mg po bid x 14 d WITH Metronidazole 500 mg po bid x 14 d	Parenteral Ampicillin/Sulbactam 3 g IV q 6 hrs PLUS Doxycycline¹ 100 mg po or IV q 12 hrs OR Clindamycin 900 mg IV q 8 hrs PLUS Gentamicin¹ 2 mg/kg IV or IM x 1 as loading dose FOLLOWED BY Gentamicin¹ 1.5 mg/kg IV or IM q 8 h as maintenance dose (or can substitute with Gentamicin¹ 3–3 mg/kg IM or IV 1x daily) IM/Oral⁹ Levofloxacin 500 mg po daily WITH Metronidazole 500 mg po bid x 14 d OR Moxifloxacin 400 mg po daily WITH Metronidazole 500 mg po bid x 14 d OR Azithromycin 500 mg IV daily x 1–2 doses followed by 250 mg po daily WITH Metronidazole 500 mg po bid x 12–14 d

Recommened Regimens

Alternative Regimens

Parenteral

Ceftriaxone 1 g IV q 24 hrs PLUS Doxycycline¹ 100 mg IV or po q 12 hrs PLUS Metronidazole 500 mg IV or po q 12 hrs OR
Cefotetan 2 g IV q 12 h PLUS Doxycycline¹ 100 mg po or IV q 12 hrs OR
Cefoxitin 2 g IV q 6 h PLUS Doxycycline¹ 100 mg po or IV q 12 hrs

IM/Oral

Ceftriaxone 500 mg IM x 1 dose⁴ (or another 3rd generation cephalosporin⁸) PLUS Doxycycline¹ 100 mg po bid x 14 d WITH Metronidazole 500 mg po bid x 14 d OR
Cefoxitin 2 g IM x 1 dose administered with Probenecid 1 g po x 1 dose PLUS Doxycylcline¹ 100 mg po bid x 14 d WITH Metronidazole 500 mg po bid x 14 d

Parenteral

Ampicillin/Sulbactam 3 g IV q 6 hrs PLUS Doxycycline¹ 100 mg po or IV q 12 hrs OR
Clindamycin 900 mg IV q 8 hrs PLUS Gentamicin¹ 2 mg/kg IV or IM x 1 as loading dose
FOLLOWED BY
Gentamicin¹ 1.5 mg/kg IV or IM q 8 h as maintenance dose (or can substitute with Gentamicin¹ 3–3 mg/kg IM or IV 1x daily)

IM/Oral⁹

Levofloxacin 500 mg po daily WITH Metronidazole 500 mg po bid x 14 d OR
Moxifloxacin 400 mg po daily WITH Metronidazole 500 mg po bid x 14 d OR
Azithromycin 500 mg IV daily x 1–2 doses followed by 250 mg po daily WITH Metronidazole 500 mg po bid x 12–14 d

Cervicitis¹⁰

(Etiologies: CT, GC, T. vaginalis, HSV, possibly M. genitalium)

Recommended Regimens	Alternative Regimens
Doxycycline¹ 100 mg po bid x 7 d	Azithromycin 1 g po x 1 dose

Nongonococcal Urethritis (NGU)¹⁰

Recommended Regimens	Alternative Regimens
Doxycycline¹ 100 mg po bid x 7 d	Azithromycin 1 g po x 1 dose OR Azithromycin 500 mg po x 1 dose, then 250 mg po daily x 4 d

Recurrent/Persistent NGU

(Etiolgies: M. genitalium (MG), T.vaginalis, other bacteria)

Recommended Regimens	Alternative Regimens
1) Test for M. gentalium (MG) If MG test positive but resistance testing unavailable, use: Doxycyline¹ 100 mg po bid x 7 d FOLLOWED BY Moxifloxacin 400 mg po daily x 7 d If MG test positive and resistance testing is available, use: Macrolide sensitive: Doxycycline¹100 mg po bid x 7 d FOLLOWED BY Azithromycin 1 g po once, then 500 mg daily on next 3 d Macrolide resistant: Doxycycline¹100 mg po bid x 7 d FOLLOWED BY Moxifloxacin 400 mg po daily x 7 d 2)Test and treat presumptively for T. vaginalis in men who have sex with women (MSW) in areas where infection is prevalent Metronidazole or Tinidazole 2 g po x 1 dose (applies to both medications)	For settings without MG resistance testing and when moxifloxacin cannot be used: Doxycycline¹ 100 mg po bid x 7 d PLUS Azithromycin 1 g po x 1 dose on first day FOLLOWED BY Azithromycin 500 mg po once daily for 3 d AND Perform a test of cure 21 d after treatment

Recommended Regimens

Alternative Regimens

1) Test for M. gentalium (MG)
If MG test positive but resistance testing unavailable, use:

Doxycyline¹ 100 mg po bid x 7 d
FOLLOWED BY
Moxifloxacin 400 mg po daily x 7 d

If MG test positive and resistance testing is available, use:
Macrolide sensitive:

Doxycycline¹100 mg po bid x 7 d
FOLLOWED BY
Azithromycin 1 g po once, then 500 mg daily on next 3 d

Macrolide resistant:

Doxycycline¹100 mg po bid x 7 d
FOLLOWED BY
Moxifloxacin 400 mg po daily x 7 d

2)Test and treat presumptively for T. vaginalis in men who have sex with women (MSW) in areas where infection is prevalent

Metronidazole or Tinidazole 2 g po x 1 dose (applies to both medications)

For settings without MG resistance testing and when moxifloxacin cannot be used:

Doxycycline¹ 100 mg po bid x 7 d PLUS Azithromycin 1 g po x 1 dose on first day FOLLOWED BY
Azithromycin 500 mg po once daily for 3 d
AND
Perform a test of cure 21 d after treatment

Proctitis

(Etiologies: GC, CT including LGV, HSV, T. pallidum, possibly M. genitalium)

Recommended Regimens
Ceftriaxone 500 mg IM x 1 dose for persons weighing <150 kg⁴ OR Ceftriaxone 1 g IM x 1 dose for persons weighing >150 kg PLUS Doxycycline1 100 mg po bid x 7 d¹¹

Note: There are no alternative regimens recommended for proctitis.

Lymphogranuloma Venereum (LGV)

Recommended Regimens	Alternative Regimens
Doxycycline¹ 100 mg po bid x 21 d	Azithromycin 1 g po once weekly x 3 weeks¹²OR Erthromycin 500 mg po qid x 21 days

Trichomoniasis¹³

Note: Treatment recommendations fo not vary by HIV status.

Scenario	Recommended Regimens	Alternative Regimens
Cervicovaginal infection	Metronidazole 500 mg po bid x 7 d	Tinidazole¹⁴ 2 g po x 1 dose OR Secnidazole¹⁵ 2 g po x 1 dose
Penile infection	Metronidazole 2 g po x 1 dose	Tinidazole¹⁴ 2 g po x 1 dose OR Secnidazole¹⁵ 2 g po x 1 dose

Bacterial Vaginosis

Recommended Regimens	Alternative Regimens
Metronidazole 500 mg po bid x 7 day OR Metronidazole gel 0.75% one full applicator (5 g) intravaginally once daily x 5 d OR Clindamycin cream 2% one full applicator (5 g) intravaginally qhs x 7 d	Tinidazole¹⁴ 2 g po daily x 2 d OR Tinidazole¹⁴ 1 g po daily x 5 d OR Secnidazole¹⁵ 2 g po x 1 dose OR Clindamycin 300 mg po bid x 7 d OR Clindamycin ovules¹⁶ 100 mg intravaginally qhs x 3 d

Epididymitis

Recommended Regimens
If likely due to GC or CT Ceftriaxone 500 mg IM x 1 dose⁴ PLUS Doxycycline 100 mg po bid x 10 d If likely due to GC, CT or enteric organisms (history of insertive anal sex) Ceftriaxone 500 mg IM x 1 dose⁴ PLUS Levofloxacin 500 mg po daily x 10 d If most likely due to enteric organisms alone (GC and CT tests negative) Levofloxacin¹⁷ 500 mg po daily x 10 d

Recommended Regimens

If likely due to GC or CT

Ceftriaxone 500 mg IM x 1 dose⁴ PLUS Doxycycline 100 mg po bid x 10 d

If likely due to GC, CT or enteric organisms (history of insertive anal sex)

Ceftriaxone 500 mg IM x 1 dose⁴ PLUS Levofloxacin 500 mg po daily x 10 d

If most likely due to enteric organisms alone (GC and CT tests negative)

Levofloxacin¹⁷ 500 mg po daily x 10 d

Note: There are no alternative regimens recommended for epididymitis.

Anogenital Warts

Scenario	Recommended Regimens	Alternative Regimens*
External Genital/Perianal Warts	Patient-Applied Imiquimod^18,19 5% cream topically qhs 3x/wk up 10 16 wks OR Imiquimod^18,19 3.75% cream topically qhs for up to 8 wks OR Podofilox 0.5% solution or gel topically bid x 3 d then 4 d off, repeat up to 4 cycles OR Sinecatechins¹⁸ 15% ointment topically tid for up to 16 wks Provider-Administered Cryotherapy with liquid nitrogen, apply once q 1–2 weeks OR Trichloroacetic acid (TCA) 80–90%, apply once q 1–2 wks OR Bichloroacetic acid (BCA) 80–90%, apply once q 1–2 wks OR Surgical removal	Provider-Administered Podophyllin resin²⁰ 10–25% in tincture of benzoin, applied weekly PRN OR Intralesional interferon OR Photodynamic therapy OR Topical cidofovir
Mucosal Genital Warts	Urethral meatus, Vaginal, Cervical, Intra-Anal Cryotherapy²¹ with liquid nitrogen OR Surgical removal OR Vaginal, Cervical, Intra-Anal TCA or BCA 80–90%	None

Scenario

Recommended Regimens

Alternative Regimens*

External Genital/Perianal Warts

Patient-Applied

Imiquimod^18,19 5% cream topically qhs 3x/wk up 10 16 wks OR
Imiquimod^18,19 3.75% cream topically qhs for up to 8 wks OR
Podofilox 0.5% solution or gel topically bid x 3 d then 4 d off, repeat up to 4 cycles OR
Sinecatechins¹⁸ 15% ointment topically tid for up to 16 wks

Provider-Administered

Cryotherapy with liquid nitrogen, apply once q 1–2 weeks OR
Trichloroacetic acid (TCA) 80–90%, apply once q 1–2 wks OR
Bichloroacetic acid (BCA) 80–90%, apply once q 1–2 wks OR
Surgical removal

Provider-Administered

Podophyllin resin²⁰ 10–25% in tincture of benzoin, applied weekly PRN OR
Intralesional interferon OR
Photodynamic therapy OR
Topical cidofovir

Mucosal Genital Warts

Urethral meatus, Vaginal, Cervical, Intra-Anal

Cryotherapy²¹ with liquid nitrogen OR
Surgical removal OR

Vaginal, Cervical, Intra-Anal

TCA or BCA 80–90%

None

*Fewer data available.

Anogenital Herpes

Scenario	Recommended Regimens
First Clinical Episode of Herpes²²	Acyclovir 400 mg po tid x 7–10 d OR Valacyclovir 1 g po bid x 7–10 d OR Famciclovir 250 mg po td x 7–10 d
Daily Suppressive Therapy for Recurrences (if no HIV co-infection)	Acyclovir 400 mg po bid OR Valacyclovir 500 mg po daily²³OR Valacyclovir 1 g po daily OR Famciclovir²⁴ 250 mg po bid
Daily Supressive Therapy for Persons with HIV²⁵	Acyclovir 400–800 mg po 2–3 times daily OR Valacyclovir 500 mg po bid OR Famciclovir²⁴ 500 mg po bid
Daily Suppressive Therapy in Pregnant Patients (start at 36 weeks gestation)	Acyclovir 400 mg po tid OR Valacyclovir 500 mg po bid
Episodic Therapy for Recurrences (If no HIV co-infection)	Acyclovir 800 mg po bid x 5 d OR Acyclovir 800 mg po tid x 2 d OR Valacyclovir 500 mg po bid x 3 d OR Valacyclovir 1 g po daily x 5 d OR Famciclovir 1 gm po bid x 1 d OR Famciclovir 500 mg po once, then 250 mg po bid x 2 d OR Famciclovir 125 mg po bid x 5 d
Episodic Therapy for Recurrences for Persons with HIV²⁵	Acyclovir 400 mg po tid x 5–10 d OR Valacyclovir 1 g po bid x 5–10 d OR Famciclovir 500 mg po bid x 5–10 d

Note: There are no alternative regimens recommended for anogenital herpes.

Syphilis in Non-Pregnant Patients²⁶

Treatment recommendations do not vary by HIV status.

Scenario	Recommended Regimens	Alternative Regimens
Primary, Secondary, and Early Latent	Benzathine penicillin G 2.4 million units IM x 1 dose	Doxycycline²⁷ 100 mg po bid x 14 d OR Tetracycline²⁷ 500 mg po qid x 14 d OR Ceftriaxone²⁷ 1 g IM or IV daily x 10–14 d
Late Latent or Syphilis of Unknown Duration OR Tertiary Syphilis with normal CSF	Benzathine penicillin G 7.2 milllion units total, administered as 3 doses of 2.4 million units IM each at 1 week intervals²⁸	Doxycycline²⁷ 100 mg po bid x 28 d OR Tetracycline²⁷ 500 mg po qid x 28 d
Neurosyphilis and Ocular Syphilis²⁹	Aqueous crystalline penicillin G 18–24 million units daily, administered as 3–4 million units IV q 4 hrs or as continuous infusion x 10–14 d	Procaine penicillin G 2.4 million units IM daily x 10–14 d PLUS Probenecid 500 mg po qid x 10–14 d OR, in the setting of severe penicillin allergy Ceftriaxone²⁷ 1–2 gm IM or IV daily x 10–14 d

Scenario

Recommended Regimens

Alternative Regimens

Primary, Secondary, and Early Latent

Benzathine penicillin G 2.4 million units IM x 1 dose

Doxycycline²⁷ 100 mg po bid x 14 d OR
Tetracycline²⁷ 500 mg po qid x 14 d OR
Ceftriaxone²⁷ 1 g IM or IV daily x 10–14 d

Late Latent or Syphilis of Unknown Duration OR Tertiary Syphilis with normal CSF

Benzathine penicillin G 7.2 milllion units total, administered as 3 doses of 2.4 million units IM each at 1 week intervals²⁸

Doxycycline²⁷ 100 mg po bid x 28 d OR
Tetracycline²⁷ 500 mg po qid x 28 d

Neurosyphilis and Ocular Syphilis²⁹

Aqueous crystalline penicillin G 18–24 million units daily, administered as 3–4 million units IV q 4 hrs or as continuous infusion x 10–14 d

Procaine penicillin G 2.4 million units IM daily x 10–14 d PLUS Probenecid 500 mg po qid x 10–14 d

OR, in the setting of severe penicillin allergy

Ceftriaxone²⁷ 1–2 gm IM or IV daily x 10–14 d

Syphilis in Pregnant Patients³⁰

Pregnant patients who miss any dose of therapy must repeat the full couse of treatment.

Scenario	Recommended Regimens	Alternative Regimens
Primary, Secondary, and Early Latent	Benzathine penicillin G 2.4 million units IM x 1 dose³¹	None
Late Latent or Syphilis of Unknown Duration OR Tertiary Syphilis with normal CSF	Benzathine penicilling G 7.2 million units total, administered as 3 doses of 2.4 million units IM each, at 1-week intervals³²	None
Neurosyphilis and Ocular Syphilis²⁹	Aqueous crystalline penicillin G 18–24 million units daily, administered as 3–4 million units IV q 4 hrs or as continuous infusion x 10–14 d	Procaine penicillin G 2.4 million units IM daily x 10–14 d PLUS Probenecid 500 mg po qid x 10–14 d

¹Contraindicated for pregnant patients.

²Every effort should be made to use a recommended regimen. Test-of-cure follow-up with a nucleic acid amplification test (NAAT) 4 weeks after completion of therapy is recommended in pregnancy.

³See Gonorrhea Treatment Guidelines and Management of Suspected Treatment Failure (PDF) if suspected GC treatment failure.

⁴For persons weighing >150 kg, use 1 gm IM ceftriaxone x 1 dose instead.

⁵Oral cephalosporins give lower and less-sustained bactericidal levels than ceftriaxone. Cefixime should only be used when ceftriaxone is not available.

⁶Test of cure by culture or NAAT is recommended 14 days after treatment of pharyngeal GC.

⁷If parenteral therapy is selected initially, discontinue 24–48 hours after patient improves clinically and continue with either IM or oral therapy for a total of 14 days.

⁸Other parenteral third-generation cephalosporin (e.g. cefotaxime or ceftizoxime) could be substituted for ceftriaxone.

⁹If allergy to cephalosporins, can consider fluoroquinolones/azithromycin for PID treatment if community prevalence and individual risk of GC is low, and follow-up is assured. Obtain NAAT testing and GC culture before using fluoroquinolone/azithromycin treatment.

¹⁰If patient lives in community with high GC prevalence, or has risk factors (e.g. age <25 years, new partner, partner with concurrent sex partners, or sex partner with a STI), consider empiric treatment for GC.

¹¹Extend doxycycline course to 21 days to cover LGV if perianal or mucosal ulcers, bloody rectal discharge, or tenesmus and rectal CT positive. If perianal or mucosal ulcers present, consider treating for HSV as well.

¹²Because this regimen has not been rigorously validated, consider a test of cure with CT NAAT four weeks after treatment.

¹³For suspected drug-resistant trichomoniasis consult the 2021 CDC STI treatment guidelines, contact the CA STD Control Branch, or consult the STD Clinical Consultation Network webpage.

¹⁴Safety in pregnancy has not been established, avoid during pregnancy. When using tinidazole, breastfeeding should be deferred for 72 hours after 2 g dose.

¹⁵Sprinkle oral granules on applesauce/yogurt/pudding before ingestion. Glass of water after dose can aid in swallowing. FDA-approved for treatment of trichomonas after the release of the CDC’s 2021 STI Treatment Guidelines.

¹⁶Clindamycin ovules may weaken latex or rubber products (such as condoms and diaphragms). Use of such products within 72 hours following use of clindamycin ovules is not recommended.

¹⁷Gonorrhea should be ruled out prior to starting a fluroquinolone-based regimen.

¹⁸May weaken condoms and vaginal diaphragms. Advise patients to follow package insert directions carefully. Imiquimod users wash area 6–10 hours after application. Sinecatechin ointment should not be washed off.

¹⁹Limited human data on imiquimod use in pregnancy; animal data suggest low risk.

²⁰Podophyllin resin is an alternative rather than recommended regimen due to reports of severe toxicity. The safety of podophyllin in pregnancy has not been established.

²¹The use of a cryoprobe in the vagina is not advised due to risk of vaginal perforation and fistula formation.

²²Treatment can be extended if healing is incomplete after 10 days of antiviral therapy.

²³Consider high dose valacyclovir (1 gm daily) or acyclovir in people who have frequent recurrences (i.e., 10 or more episodes annually).

²⁴Famciclovir is somewhat less effective for suppression of viral shedding.

²⁵If concern for resistance based on persistent HSV lesions, obtain a viral isolate for sensitivity testing. Consultation with an infectious disease expert is recommended.

²⁶Benzathine penicillin G is available in only one long-acting formulation, Bicillin® L-A (the trade name), which contains only benzathine penicillin G. Other combination products, such as Bicillin® C-R, contain both long- and short-acting penicillins and are not effective for treating syphilis.

²⁷Alternative regimens should be used only for penicillin-allergic patients. If compliance or follow-up cannot be ensured, the patient should be desensitized and treated with benzathine penicillin.

²⁸In non-pregnant patients, pharmacologic considerations reveal an interval of 7–9 days is ideal.

²⁹Some specialists recommend 2.4 million units of benzathine penicillin G once weekly for 1 to 3 weeks immediately after completion of neurosyphilis treatment.

³⁰Pregnant patients allergic to penicillin should be desensitized and treated with penicillin. There are no alternatives.

³¹For early syphilis, many experts give a 2nd dose of benzathine penicillin G 2.4 million units IM one week after the initial dose.

³²The optimal treatment interval in pregnancy is 7 days. If treatment occurs outside of 6–8-day intervals, the full treatment course should be restarted.

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