What is the recommended treatment and management for gonorrhea in sexually active women, including those with potential co-infections and allergies?

Gonorrhea Treatment in Women

The recommended first-line treatment for gonorrhea in women is ceftriaxone 500 mg intramuscularly as a single dose, combined with doxycycline 100 mg orally twice daily for 7 days to cover concurrent chlamydial infection. 1, 2

Primary Treatment Regimen

• Ceftriaxone 500 mg IM (single dose) PLUS doxycycline 100 mg orally twice daily for 7 days is the current CDC-recommended regimen for uncomplicated urogenital, anorectal, and pharyngeal gonorrhea 1, 2
• The dose increase from 250 mg to 500 mg reflects evolving resistance patterns and provides superior efficacy, particularly for pharyngeal infections where cephalosporins have marked variability in tissue penetration 1, 3
• Azithromycin 1 g orally as a single dose may be substituted for doxycycline for chlamydial coverage, offering better compliance with single-dose therapy 1

Critical Clinical Context

Gonorrhea causes serious reproductive complications in women, including pelvic inflammatory disease, ectopic pregnancy, and infertility 4, 5. Many infections are asymptomatic, making screening essential rather than relying on symptoms alone 5. The infection also facilitates HIV transmission, necessitating concurrent HIV testing 1, 2.

Alternative Regimens

When Ceftriaxone is Unavailable

• Cefixime 400 mg orally (single dose) PLUS azithromycin 1 g orally (single dose) can be used, but requires mandatory test-of-cure at 1 week due to documented treatment failures in Europe 1, 6
• Oral cephalosporins are no longer first-line agents because of declining susceptibility 4, 1

For Severe Cephalosporin Allergy

• Azithromycin 2 g orally (single dose) with mandatory test-of-cure at 1 week 1
• This regimen has lower efficacy (93%) and high gastrointestinal side effects 1
• Gentamicin 240 mg IM (single dose) PLUS azithromycin 2 g orally (single dose) achieved 100% cure rates in clinical trials but has poor pharyngeal efficacy (only 20%) 1

For Pregnant Women

• Ceftriaxone 500 mg IM (single dose) PLUS azithromycin 1 g orally (single dose) 1, 3
• Never use quinolones, tetracyclines, or doxycycline in pregnancy 1, 3

Medications to Avoid

Fluoroquinolones (ciprofloxacin, ofloxacin) are absolutely contraindicated due to widespread resistance, despite historical cure rates of 99.8% 4, 1, 7, 3. This represents a critical shift from 1990s practice when quinolones were first-line therapy 7.

Azithromycin 1 g alone is insufficient for gonorrhea treatment with only 93% efficacy 1. Never use azithromycin monotherapy at this dose 1.

Site-Specific Considerations

• Pharyngeal gonorrhea is significantly more difficult to eradicate than urogenital or anorectal infections 1, 3
• Ceftriaxone has superior efficacy for pharyngeal infections compared to all alternatives 1
• Spectinomycin has only 52% efficacy for pharyngeal infections and should be avoided for this site 1, 3
• Gentamicin similarly has poor pharyngeal efficacy 1

Co-Infection Management

Routine dual therapy for both gonorrhea and chlamydia is essential because 10-40% of patients with gonorrhea have concurrent chlamydial infection 1, 7, 3. The cost of empiric chlamydia treatment is less than the cost of testing, making routine dual therapy cost-effective 7, 3.

Testing and Screening Recommendations

• Nucleic acid amplification tests (NAATs) are the diagnostic standard with sensitivity and specificity comparable to culture 8, 5
• Urine NAATs are acceptable, though vaginal swabs (provider or self-collected) are increasingly supported 5
• Screen all sexually active women at risk annually, including all women under 25 years and older women with risk factors (new/multiple partners, inconsistent condom use, previous STI, drug use, commercial sex work, HIV infection) 5
• Test for syphilis with serology and HIV at the time of gonorrhea diagnosis 1
• Screen for bacterial STIs every 6 months in high-risk populations 4

Follow-Up Requirements

Standard Follow-Up

• Patients treated with recommended ceftriaxone regimens do not require routine test-of-cure unless symptoms persist 1, 7
• Mandatory test-of-cure at 1 week is required for patients receiving cefixime or azithromycin monotherapy 1
• Retest all patients 3 months after treatment due to high reinfection rates, especially in women and adolescents 1, 3, 8

For Persistent Symptoms

• Obtain culture with antimicrobial susceptibility testing immediately 1
• Report suspected treatment failures to local public health officials within 24 hours 1
• Consult an infectious disease specialist 1

Treatment Failure Management

If treatment failure occurs (most commonly involving pharyngeal sites):

• Gentamicin 240 mg IM PLUS azithromycin 2 g orally (single dose) 1
• Spectinomycin 2 g IM PLUS azithromycin 2 g orally 1
• Ertapenem 1 g IM for 3 days 1

Partner Management

• Evaluate and treat all sexual partners from the preceding 60 days with the same dual therapy regimen for both gonorrhea and chlamydia 1, 3
• Expedited partner therapy with oral combination therapy (cefixime 400 mg plus azithromycin 1 g) may be considered when partners cannot be linked to timely evaluation 1
• Patients should avoid sexual intercourse for 7 days after single-dose therapy or until completion of 7-day regimen and both partners are asymptomatic 1, 3

Common Pitfalls to Avoid

• Never rely on oral cephalosporins as first-line therapy due to documented treatment failures 4, 1
• Never use fluoroquinolones regardless of patient preference for oral therapy 1, 3
• Never use azithromycin 1 g alone for gonorrhea treatment 1
• Do not assume treatment failure when symptoms persist—most cases represent reinfection rather than true treatment failure, emphasizing the importance of partner treatment 7, 3
• Do not neglect pharyngeal screening in high-risk populations, as direct culture or NAAT is necessary to identify these often asymptomatic infections 5
• Dispense medications on-site when possible with the first dose directly observed to maximize compliance 3