What is the recommended treatment for a female patient with a vaginal swab result showing gram-negative cocci in pairs, suggestive of Neisseria gonorrhoeae?

Treatment for Gram-Negative Cocci in Pairs on Vaginal Swab

For a vaginal swab showing gram-negative cocci in pairs suggestive of Neisseria gonorrhoeae, treat immediately with ceftriaxone 500 mg intramuscularly once PLUS azithromycin 1 g orally once (or doxycycline 100 mg orally twice daily for 7 days if chlamydial coinfection has not been excluded). 1, 2

Primary Treatment Regimen

• Ceftriaxone 500 mg IM as a single dose is the cornerstone of therapy, providing 99.1% cure rates for uncomplicated urogenital and anorectal gonorrhea 1, 3
• Add azithromycin 1 g orally once to address the extremely common coinfection with Chlamydia trachomatis (present in 40-50% of gonorrhea cases) 1, 3
• Alternatively, use doxycycline 100 mg orally twice daily for 7 days if chlamydial coinfection has not been excluded by testing 2
• The dual therapy approach improves treatment efficacy and helps delay emergence of cephalosporin resistance 1

Critical Diagnostic Considerations

• Gram stain of endocervical specimens is not sufficient to detect infection and specific testing for N. gonorrhoeae is required 4
• Culture, nucleic acid hybridization tests, or nucleic acid amplification tests (NAATs) should be used for definitive diagnosis 4
• All patients must be tested for other STDs including chlamydia, syphilis, and HIV at the time of gonorrhea diagnosis 4, 1

Why This Specific Regimen

• The 500 mg ceftriaxone dose (increased from previous 250 mg recommendations) addresses rising minimum inhibitory concentrations and provides adequate coverage for all anatomic sites including pharyngeal infections 1, 2
• Azithromycin 1 g alone is insufficient for gonorrhea treatment (only 93% efficacy) and should never be used as monotherapy 1
• Quinolones (ciprofloxacin, ofloxacin) are no longer recommended due to widespread resistance, despite historical cure rates of 99.8% 1, 3

Special Population Considerations

Pregnancy

• Use the same dual therapy: ceftriaxone 500 mg IM plus azithromycin 1 g orally 1, 5
• Never use quinolones or tetracyclines in pregnancy 4, 1
• If injection is refused, cefixime 400 mg orally plus azithromycin 1 g orally can be considered, but requires test-of-cure at 1 week 1

Severe Cephalosporin Allergy

• Azithromycin 2 g orally as a single dose is the alternative, but has lower efficacy (93%) and high gastrointestinal side effects 1
• Mandatory test-of-cure at 1 week is required with this regimen 1
• Gentamicin 240 mg IM plus azithromycin 2 g orally is another alternative with 100% cure rate in trials 1

Partner Management

• Evaluate and treat all sexual partners from the preceding 60 days with the same dual therapy regimen 1, 3
• Partners should receive treatment for both gonorrhea and chlamydia regardless of their test results 1
• Patients must avoid sexual intercourse until both they and their partners complete therapy and are asymptomatic 4, 3
• Expedited partner therapy with oral combination therapy (cefixime 400 mg plus azithromycin 1 g) may be considered if partners cannot be linked to timely evaluation, except in men who have sex with men due to high risk of undiagnosed coexisting STDs or HIV 1

Follow-Up Requirements

• No routine test-of-cure is needed for patients treated with the recommended ceftriaxone plus azithromycin regimen 1, 5
• If symptoms persist after treatment, obtain culture with antimicrobial susceptibility testing immediately 4, 1
• Retest all patients 3 months after treatment due to high risk of reinfection (most post-treatment infections are reinfections, not treatment failures) 4, 5, 2
• Pregnant women with antenatal gonococcal infection should be retested in the third trimester unless recently treated 5

Critical Pitfalls to Avoid

• Never use azithromycin 1 g alone for gonorrhea treatment 1
• Never use fluoroquinolones (ciprofloxacin, ofloxacin) due to widespread resistance 1, 3
• Do not use cefixime as first-line therapy; it has declining effectiveness and requires mandatory test-of-cure 1
• Pharyngeal gonorrhea is significantly more difficult to eradicate than urogenital infections—ceftriaxone 500 mg IM is the only reliably effective treatment for pharyngeal sites 1
• Spectinomycin has only 52% efficacy for pharyngeal infections and should be avoided for this site 1

Treatment Failure Management

• If treatment failure is suspected, obtain specimens for culture and antimicrobial susceptibility testing immediately 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

Antimicrobial Resistance Context

• Ceftriaxone MICs have remained stable in the United States with <0.1% exhibiting elevated MICs, but international ceftriaxone-resistant strains are spreading 2
• The first global treatment failure with recommended dual therapy was reported in 2016, and isolates with combined ceftriaxone resistance and high-level azithromycin resistance emerged in 2018 6
• The dual therapy approach has likely contributed to decreasing cephalosporin resistance levels internationally 6