Treatment of Gonorrhea in Patients with Penicillin Allergy
For patients with penicillin allergy and gonorrhea, ceftriaxone 500 mg intramuscularly as a single dose remains the first-line treatment, as true cross-reactivity between penicillins and third-generation cephalosporins is rare (approximately 1-3%), and this regimen should be combined with azithromycin 1 g orally or doxycycline 100 mg orally twice daily for 7 days to cover presumptive chlamydial coinfection. 1, 2
Primary Treatment Approach for Most Penicillin-Allergic Patients
Ceftriaxone is NOT a penicillin—it is a third-generation cephalosporin with minimal cross-reactivity risk, making it safe for the vast majority of patients reporting penicillin allergy. 1
The recommended regimen is ceftriaxone 500 mg intramuscularly as a single dose plus either azithromycin 1 g orally as a single dose OR doxycycline 100 mg orally twice daily for 7 days. 1, 2
Approximately 90% of patients who report penicillin allergy are no longer truly allergic, and the cross-reactivity rate between penicillins and third-generation cephalosporins is only 1-3%. 3, 1
Ceftriaxone has demonstrated superior efficacy compared to other injectable agents, with significantly better outcomes than cefuroxime, cephaloridine, kanamycin, penicillin, and spectinomycin, making it the most effective injectable drug (p score of 0.924). 4
Treatment for Patients with Documented Severe Cephalosporin Allergy
If the patient has documented anaphylaxis to beta-lactams or severe IgE-mediated reactions, cephalosporins are absolutely contraindicated, and alternative regimens must be used. 3, 1
First Alternative: Spectinomycin (When Available)
Spectinomycin 2 g intramuscularly as a single dose achieves 98.2% cure rates for uncomplicated urogenital and anorectal gonorrhea. 3, 1
Critical limitation: Spectinomycin has only 52% efficacy against pharyngeal gonorrhea, making it inadequate for pharyngeal infections. 3, 1
Spectinomycin availability is extremely limited in the United States, and updated information on availability should be obtained from the CDC. 5
Second Alternative: Azithromycin Monotherapy (With Mandatory Test-of-Cure)
Azithromycin 2 g orally as a single dose can be used when cephalosporins are contraindicated. 1, 6
Test-of-cure is mandatory 1 week after treatment using culture (preferred) or nucleic acid amplification testing (NAAT), as culture allows antimicrobial susceptibility testing. 1
Azithromycin 2 g achieves 98.9% cure rates for uncomplicated gonorrhea and simultaneously treats chlamydial coinfection. 6
Major caveat: Gastrointestinal adverse events occur in 35.3% of patients, with moderate symptoms in 10.1% and severe symptoms in 2.9%. 6
Third Alternative: Gentamicin Plus Azithromycin
Gentamicin 240 mg intramuscularly plus azithromycin 2 g orally achieved 100% microbiological cure (95% CI lower bound 98.5%) in a randomized trial. 7
This regimen cured 10 of 10 pharyngeal infections and 1 of 1 rectal infection, demonstrating efficacy at all anatomic sites. 7
Gastrointestinal adverse events are common with this combination due to the azithromycin 2 g dose. 7
Fourth Alternative: Gemifloxacin Plus Azithromycin
Gemifloxacin 320 mg orally plus azithromycin 2 g orally achieved 99.5% microbiological cure (95% CI lower bound 97.6%). 7
This regimen cured 15 of 15 pharyngeal infections and 5 of 5 rectal infections. 7
Fluoroquinolones should NOT be used in men who have sex with men (MSM), patients with recent foreign travel, or infections acquired in areas with known quinolone-resistant N. gonorrhoeae (QRNG). 3
Last Resort: Fluoroquinolones (Only With Susceptibility Testing)
Ciprofloxacin 500 mg orally or levofloxacin 250 mg orally can be considered ONLY if antimicrobial susceptibility testing confirms susceptibility. 3, 1
Quinolones should never be used without susceptibility testing due to widespread resistance. 1, 8
Site-Specific Treatment Considerations
Pharyngeal gonorrhea is more difficult to eradicate than urogenital infections, and ceftriaxone remains the most effective option. 1
Spectinomycin is inadequate for pharyngeal infections (only 52% efficacy), and if cephalosporins are contraindicated, fluoroquinolones are the only viable option if susceptibility permits. 3, 1
Pharyngeal culture is required 3-5 days post-treatment if spectinomycin is used for suspected pharyngeal infection. 1
Essential Management Steps
Always treat presumptively for chlamydia unless ruled out, using azithromycin 1 g orally as a single dose or doxycycline 100 mg orally twice daily for 7 days. 1, 2
All sexual partners from the preceding 60 days must be evaluated and treated with the same dual therapy regimen for both gonorrhea and chlamydia. 3, 1
Patients must abstain from sexual intercourse for 7 days after single-dose therapy or until completion of 7-day regimen, and until both partners are asymptomatic. 3, 1
Test-of-cure is NOT routinely required for patients treated with recommended ceftriaxone-based regimens unless symptoms persist. 3
Special Populations
Pregnant women with penicillin allergy should receive ceftriaxone, as the cross-reactivity risk is acceptable. 1
Spectinomycin 2 g intramuscularly is an alternative if cephalosporin is absolutely contraindicated in pregnancy. 1
Never use doxycycline, quinolones, or tetracyclines in pregnancy. 5, 1
Critical Pitfalls to Avoid
Do not assume penicillin allergy precludes cephalosporin use—most patients can safely receive ceftriaxone. 1
Never use azithromycin 1 g as monotherapy for gonorrhea—it has insufficient efficacy. 1
Never use azithromycin 2 g alone routinely—the CDC does not recommend widespread use due to concerns over emerging macrolide resistance. 5
Never use macrolides (erythromycin) for gonorrhea—N. gonorrhoeae in the United States is not adequately susceptible. 3
Never assume spectinomycin will work for pharyngeal infections—efficacy is only 52% at this site. 3
Do not use quinolones without susceptibility testing—resistance is widespread. 1, 8