What is the recommended treatment for uncomplicated urogenital gonorrhea in an adult male, including management of possible Chlamydia co‑infection, penicillin or beta‑lactam allergy, partner therapy, and follow‑up testing?

Treatment for Gonorrhea in Men

The recommended treatment for uncomplicated urogenital gonorrhea in adult men is ceftriaxone 500 mg intramuscularly as a single dose PLUS doxycycline 100 mg orally twice daily for 7 days (if chlamydial co-infection has not been excluded). 1, 2

Primary Treatment Regimen

• Ceftriaxone 500 mg IM (single dose) is the only acceptable first-line agent for gonorrhea, achieving a 99.1% cure rate for uncomplicated urogenital and anorectal infections. 1, 3
• Add doxycycline 100 mg orally twice daily for 7 days to address the 20–50% likelihood of concurrent chlamydial co-infection, unless chlamydia has been definitively excluded by testing. 1, 2
• Azithromycin 1 g orally as a single dose may be substituted for doxycycline when compliance with a 7-day regimen is uncertain, though doxycycline is now preferred due to rising azithromycin resistance. 1, 2

The 500 mg dose represents an increase from the historical 250 mg recommendation and reflects antimicrobial stewardship concerns about emerging resistance patterns. 2

Alternative Regimens When Ceftriaxone Is Unavailable

• Cefixime 400 mg orally (single dose) PLUS azithromycin 1 g orally (single dose) is acceptable only when ceftriaxone cannot be obtained. 1, 4
• This oral regimen achieves only 97.4% cure for urogenital infections compared to ceftriaxone's 99.1%, and mandatory test-of-cure at 1 week is required. 5, 1
• Cefixime provides lower and less sustained bactericidal levels than ceftriaxone, contributing to reduced efficacy. 5, 6

Management of Penicillin or Beta-Lactam Allergy

• For severe cephalosporin allergy, use azithromycin 2 g orally as a single dose, with mandatory test-of-cure at 1 week. 1, 7
• This regimen has lower efficacy (approximately 93%) and causes significant gastrointestinal side effects. 5, 1
• Gentamicin 240 mg IM (single dose) PLUS azithromycin 2 g orally (single dose) is an alternative that achieved 100% cure in clinical trials, though it has poor efficacy (only 20%) for pharyngeal infections. 1
• Spectinomycin 2 g IM is another option for urogenital infection but cures only 52% of pharyngeal infections and should be avoided if pharyngeal exposure is suspected. 5, 1

Cross-reactivity between penicillins and cephalosporins is lower than historically believed; cephalosporins with dissimilar side chains can often be used safely in penicillin-allergic patients. 1

Absolutely Contraindicated Medications

• Fluoroquinolones (ciprofloxacin, ofloxacin, levofloxacin) are completely contraindicated for gonorrhea treatment due to widespread resistance, despite historical cure rates exceeding 99%. 5, 1, 8
• Azithromycin 1 g alone should never be used for gonorrhea treatment, as it achieves only 93% efficacy and risks rapid resistance emergence. 5, 1

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 doxycycline or azithromycin), regardless of symptoms or test results. 5, 1
• If the patient's last sexual contact occurred more than 60 days before symptom onset or diagnosis, treat the most recent partner. 5, 1
• Expedited partner therapy (providing medication directly to partners) may be considered with oral combination therapy (cefixime 400 mg plus azithromycin 1 g) when partners cannot access timely clinical evaluation. 1
• Do not use expedited partner therapy for men who have sex with men (MSM) due to high risk of undiagnosed co-existing STDs or HIV. 1
• Patients must abstain from sexual intercourse until therapy is completed and both patient and all partners are asymptomatic. 5, 1

Follow-Up Testing

• Patients treated with the recommended ceftriaxone-based regimen do NOT need routine test-of-cure unless symptoms persist after treatment. 5, 1, 2
• If symptoms persist, obtain culture with antimicrobial susceptibility testing from all potentially infected sites; persistent infections usually represent reinfection rather than treatment failure. 5, 1
• Retest all patients at 3 months due to high reinfection rates (20–30%), using the same testing method as initial diagnosis. 1, 8
• If nucleic acid amplification testing (NAAT) is positive at follow-up, confirm with culture and perform phenotypic antimicrobial susceptibility testing. 1

Site-Specific Considerations

Pharyngeal Gonorrhea

• Pharyngeal infections are significantly more difficult to eradicate than urogenital or anorectal infections. 1, 7
• Ceftriaxone 500 mg IM is the only reliably effective treatment for pharyngeal gonorrhea; oral cephalosporins cure only 78.9% of pharyngeal infections. 5, 1
• Spectinomycin achieves only 52% cure for pharyngeal sites and should be avoided. 5, 1
• Gentamicin has only 20% efficacy for pharyngeal infections. 1

Gonococcal Conjunctivitis

• Treat with ceftriaxone 1 g IM as a single dose plus a single saline lavage of the affected eye. 1

Disseminated Gonococcal Infection (DGI)

• Hospitalization is recommended for initial management. 1
• Initial regimen: ceftriaxone 1 g IM or IV every 24 hours for 24–48 hours until clinical improvement, then switch to oral cefixime 400 mg twice daily to complete 1 week total therapy. 1
• Assess for endocarditis and meningitis as part of the evaluation. 1
• Provide presumptive treatment for concurrent chlamydial infection. 1

Special Populations

Men Who Have Sex with Men (MSM)

• Ceftriaxone is the only recommended treatment for MSM due to higher prevalence of resistant strains. 1, 7
• Never use quinolones in this population. 1

Patients with Recent Foreign Travel

• Use ceftriaxone 500 mg IM as the preferred agent due to increased risk of resistant strains acquired abroad. 1

HIV-Positive Patients

• Treat with the same regimen as HIV-negative patients. 1

Ancillary Testing and Screening

• Screen for syphilis with serology at the time of gonorrhea diagnosis, given high rates of co-infection and overlapping risk factors. 1, 7
• Offer HIV testing, as gonorrhea facilitates HIV transmission. 1, 8
• Test for other sexually transmitted infections as clinically indicated. 8

Treatment Failure Management

• If treatment failure is suspected, obtain specimens for culture and antimicrobial susceptibility testing immediately from all potentially infected sites. 1
• Report the case to local public health officials within 24 hours. 1
• Consult an infectious disease specialist. 1
• Recommended salvage regimens include:
  • Gentamicin 240 mg IM PLUS azithromycin 2 g orally (single dose), OR
  • Ertapenem 1 g IM for 3 days 1

Common Pitfalls to Avoid

• Never assume oral cephalosporins are equivalent to ceftriaxone—they have inferior efficacy, particularly for pharyngeal infections. 5, 1
• Do not omit chlamydia treatment even when chlamydia testing is negative, given the 20–50% co-infection rate and the possibility of false-negative results. 1, 4
• Do not use cefixime without mandatory test-of-cure at 1 week, as documented treatment failures have occurred in Europe. 1
• Most post-treatment positive tests represent reinfection, not treatment failure—focus on partner treatment and behavioral counseling. 1
• Never use patient-delivered partner therapy for MSM due to undiagnosed co-infections. 1