STI Treatment in the Emergency Department
Primary Recommendation
For patients presenting to the ED with suspected STI, initiate empiric dual therapy immediately before test results are available: ceftriaxone 250 mg IM PLUS either azithromycin 1 g orally (single dose) OR doxycycline 100 mg orally twice daily for 7 days. 1, 2
This approach addresses the most common STIs (gonorrhea and chlamydia) which frequently coexist and can lead to serious complications including pelvic inflammatory disease, infertility, and facilitation of HIV transmission if left untreated. 1, 3
Clinical Approach Algorithm
Step 1: Identify High-Risk Presentations Requiring Immediate Treatment
Treat empirically when patients present with:
- Urethritis symptoms (dysuria, urethral discharge) 4
- Cervicitis (vaginal discharge, cervical motion tenderness) 4, 5
- Pelvic inflammatory disease (uterine/adnexal/cervical motion tenderness, fever >38.3°C) 4
- Epididymitis (unilateral testicular pain, palpable epididymal swelling) 4
- Known STI exposure within preceding 60 days 1, 2
Critical pitfall: Most gonorrhea and chlamydia infections (53-100% of extragenital cases, 70% of trichomoniasis) are asymptomatic, so absence of symptoms does not rule out infection. 3 Younger age (<25 years) and presence of Trichomonas on wet prep are the only reliable predictors of gonorrhea/chlamydia infection. 5
Step 2: Obtain Diagnostic Testing (But Don't Delay Treatment)
Before initiating antibiotics, collect:
- Nucleic acid amplification tests (NAATs) for gonorrhea and chlamydia (sensitivity 86.1-100%, specificity 97.1-100%) 3
- Gram stain of urethral discharge (≥5 PMNs per oil immersion field indicates urethritis) 4
- Syphilis serology (sequential treponemal and nontreponemal testing) 4, 3
- HIV testing and counseling (gonorrhea facilitates HIV transmission) 4, 6
Do not wait for test results to initiate treatment. 4, 7
Specific Treatment Regimens by Clinical Syndrome
Uncomplicated Urethritis/Cervicitis (Gonorrhea/Chlamydia)
Recommended regimen:
- Ceftriaxone 250 mg IM single dose 1, 2
- PLUS azithromycin 1 g orally single dose (preferred over doxycycline due to single-dose compliance and tetracycline resistance) 1, 2
Alternative if ceftriaxone unavailable:
- Cefixime 400 mg orally single dose PLUS azithromycin 1 g orally 2
- Mandatory test-of-cure at 1 week (cefixime has declining susceptibility) 2
Severe cephalosporin allergy:
- Azithromycin 2 g orally single dose 2
- Mandatory test-of-cure at 1 week and infectious disease consultation 2
Critical warning: Never use fluoroquinolones (ciprofloxacin, ofloxacin, levofloxacin) due to widespread resistance. 2
Epididymitis
For men <35 years (likely gonorrhea/chlamydia):
For men ≥35 years or enteric organisms suspected:
- Ofloxacin 300 mg orally twice daily for 10 days 4
- OR levofloxacin 500 mg orally once daily for 10 days 4
Adjunctive therapy: Bed rest, scrotal elevation, and analgesics until fever and inflammation subside. 4
Emergency consideration: Rule out testicular torsion immediately if sudden severe pain, especially in adolescents without signs of infection—this is a surgical emergency requiring immediate consultation. 4
Pelvic Inflammatory Disease (PID)
Outpatient regimen (mild-moderate disease):
- Ceftriaxone 250 mg IM single dose 4
- PLUS doxycycline 100 mg orally twice daily for 14 days 4
- Consider adding metronidazole for anaerobic coverage 4
Indications for hospitalization and parenteral therapy:
- Pregnancy 4, 7
- Failure to respond to oral therapy within 72 hours 4
- Severe illness, tubo-ovarian abscess, or inability to tolerate oral medications 4
Critical management: Reevaluate within 72 hours—patients not improving require hospitalization, additional testing, and possible surgical intervention. 4
Disseminated Gonococcal Infection (Gonococcal Arthritis)
Initial parenteral therapy:
Transition to oral therapy after 24-48 hours of clinical improvement:
Total duration: 7 days for uncomplicated arthritis; 10-14 days if meningitis documented. 6
Partner Management (Critical for Preventing Reinfection)
All sexual partners from preceding 60 days must be treated empirically with the same dual therapy regimen, regardless of symptoms or test results. 1, 2, 6 If last contact was >60 days before diagnosis, treat the most recent partner. 1
Expedited partner therapy (patient-delivered medication):
- Acceptable for heterosexual contacts: provide cefixime 400 mg plus azithromycin 1 g 2
- Do NOT use for men who have sex with men due to high rates of undiagnosed coexisting STIs and HIV 1, 2
Abstinence requirement: Both patient and partners must avoid sexual intercourse until 7 days after therapy initiation and complete symptom resolution. 1, 6
Special Populations
Pregnant Women
- Ceftriaxone 250 mg IM PLUS azithromycin 1 g orally 2, 6
- Avoid doxycycline and fluoroquinolones 4, 2
- Hospitalize if PID suspected due to high risk of maternal morbidity, fetal wastage, and preterm delivery 4, 7
HIV-Infected Patients
- Use identical treatment regimens as HIV-negative patients 4, 2
- Consider fungi and mycobacteria as causes of epididymitis in immunosuppressed patients 4
Patients with Cephalosporin Allergy
- Azithromycin 2 g orally single dose (lower efficacy, high GI side effects) 2
- Consider gentamicin 240 mg IM plus azithromycin 2 g orally (poor pharyngeal efficacy) 6
- Mandatory test-of-cure at 1 week 2
Follow-Up and Test-of-Cure
Test-of-cure NOT routinely needed for patients treated with recommended ceftriaxone-based dual therapy. 2
Test-of-cure IS mandatory at 1 week for:
- Alternative regimens (cefixime-based or azithromycin 2 g monotherapy) 2
- Use culture when possible to allow antimicrobial susceptibility testing 2
Retest ALL patients at 3 months due to high reinfection rates (majority of post-treatment infections are reinfections, not treatment failures). 2, 3
Failure to improve within 3 days requires reevaluation of diagnosis and therapy. 4
Key Clinical Pitfalls to Avoid
Do not rely on symptoms alone: 53-100% of extragenital gonorrhea/chlamydia infections are asymptomatic. 3 ED providers empirically over-treat ~20 uninfected patients for every one laboratory-confirmed infection when relying on clinical findings. 5
Never use fluoroquinolones for gonorrhea due to widespread resistance. 2
Do not use cefixime as first-line therapy—declining susceptibility requires test-of-cure. 2
Do not skip partner treatment—reinfection is the primary cause of treatment failure. 1, 2
Do not use expedited partner therapy for MSM—high rates of undiagnosed coexisting STIs and HIV require in-person evaluation. 1, 2
Always test for syphilis and HIV at time of STI diagnosis. 4, 6
Dual antimicrobial therapy is essential to slow emergence of cephalosporin resistance. 2