What is the recommended treatment for an adult with uncomplicated gonorrhea‑chlamydia co‑infection who has a penicillin allergy?

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Treatment for Uncomplicated Gonorrhea-Chlamydia Co-Infection with Penicillin Allergy

For adults with penicillin allergy and uncomplicated gonorrhea-chlamydia co-infection, administer ceftriaxone 500 mg intramuscularly as a single dose PLUS azithromycin 1 g orally as a single dose. 1

Why Ceftriaxone Despite Penicillin Allergy

  • Penicillin allergy does NOT contraindicate cephalosporin use in most patients. Cross-reactivity between penicillins and third-generation cephalosporins like ceftriaxone is extremely low (approximately 1-3%), and ceftriaxone remains the recommended first-line treatment even in patients reporting penicillin allergy. 1, 2

  • Ceftriaxone 500 mg IM plus azithromycin 1 g orally achieves 98.9% cure rates for urogenital and anorectal gonorrhea, and is the only reliably effective regimen for pharyngeal infections. 3, 1

  • The dual therapy addresses both gonorrhea and presumptive chlamydial co-infection, which occurs in 40-50% of gonorrhea cases. 1, 4

Only for TRUE Severe Cephalosporin Allergy

If the patient has documented severe, IgE-mediated cephalosporin allergy (anaphylaxis, angioedema, bronchospasm), use gentamicin 240 mg intramuscularly PLUS azithromycin 2 g orally as a single dose. 1, 5

Critical Limitations of This Alternative

  • Gentamicin has significantly inferior efficacy for pharyngeal gonorrhea (only 80% cure rate vs. 96% for ceftriaxone) and rectal gonorrhea (90% vs. 98%). 6, 7

  • Mandatory test-of-cure at 1 week is required when using gentamicin, using culture (preferred) or nucleic acid amplification testing. 1, 2

  • Genital-only infections respond adequately to gentamicin (94% cure rate), making this a reasonable alternative for isolated urogenital disease in patients with true cephalosporin allergy. 6, 7

  • A recent randomized trial demonstrated 100% cure rates for rectal and pharyngeal gonorrhea when gentamicin 240 mg was combined with azithromycin 2 g (rather than 1 g), supporting the higher azithromycin dose in this regimen. 5

Regimens to NEVER Use

  • Never use fluoroquinolones (ciprofloxacin, ofloxacin) due to widespread resistance, despite historical cure rates of 99.8%. 3, 1

  • Never use azithromycin 1 g alone for gonorrhea due to insufficient efficacy (only 93% cure rate) and rapid resistance emergence. 3, 1

  • Never use spectinomycin for pharyngeal infections due to only 52% efficacy at this site. 3, 1

Follow-Up Requirements

  • Patients treated with the recommended ceftriaxone-based regimen do NOT require routine test-of-cure unless symptoms persist. 1, 2

  • All patients should be retested approximately 3 months after treatment due to high reinfection rates (not treatment failure). 1, 2

  • If symptoms persist after treatment, obtain culture with antimicrobial susceptibility testing immediately and report to local public health officials within 24 hours. 1, 2

Partner Management

  • All sexual partners from the preceding 60 days must be evaluated and treated with the same dual therapy regimen (ceftriaxone 500 mg IM plus azithromycin 1 g orally), regardless of symptoms or test results. 1, 4, 2

  • Patients should abstain from sexual intercourse until therapy is completed and both patient and partners are asymptomatic. 3, 1

  • Consider expedited partner therapy with oral cefixime 400 mg plus azithromycin 1 g if partners cannot access timely clinical evaluation. 1, 2

Special Populations

  • In pregnancy, use ceftriaxone 500 mg IM plus azithromycin 1 g orally; never use doxycycline, quinolones, or tetracyclines. 1, 4, 2

  • For men who have sex with men (MSM), ceftriaxone is the only recommended treatment due to higher prevalence of resistant strains; do not use patient-delivered partner therapy in this population due to high risk of undiagnosed HIV or other STIs. 1, 2

Additional Screening

  • Screen for syphilis with serology and HIV at the time of gonorrhea diagnosis, as gonorrhea facilitates HIV transmission and co-infection rates are high. 1, 2

References

Guideline

Gonorrhea Treatment Guidelines

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Guideline

Gonorrhea and Chlamydia Treatment Guidelines

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Single-Dose Empiric Therapy for Gonorrhea and Chlamydia

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Research

Gentamicin 240 mg plus azithromycin 2 g vs. ceftriaxone 500 mg plus azithromycin 2 g for treatment of rectal and pharyngeal gonorrhoea: a randomized controlled trial.

Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases, 2020

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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