UMEM Educational Pearls

Take-Home Point:
Based on antibiotic resistance and PK/PD data, CDC recommends a single dose of intramuscular ceftriaxone 500 mg for uncomplicated gonococcal infections. Treatment for coinfection with Chlamydia trachomatis is now only recommended if coinfection cannot be excluded. Doxycycline 100 mg BID x 7 days is recommended as treatment for chlamydial coinfection, but adherence should be heavily considered and may preclude the use of doxycycline instead of previously recommended single dose of oral azithromycin 1 g.
• Neisseria gonorrhoeae is the second most commonly reported notifiable sexually transmitted
infection (STI) in the United States
• Treatment of gonococcal infections prevents complications and transmission, but resistance has
developed against several treatment options (i.e., penicillin, fluoroquinolones, cefixime, and
most recently, azithromycin) leading to changes in treatment recommendations over the years

Uncomplicated Gonococcal


2015 Recommendations [1]

2020 Recommendations [2]

Cervical, urethral, rectal, and

pharyngeal infection

Ceftriaxone 250 mg IM x 1 dose, plus azithromycin 1 g PO x 1 dose

Ceftriaxone 500 mg IM x 1 dose

>=150 kg

No recommendation

Ceftriaxone 1 g IM x 1 dose

If coinfection with chlamydia

cannot be excluded

Coverage provided by gonococcal treatment regimen

Add doxycycline 100 mg PO BID x 7 days

Clinical Data:
• Efficacy of ceftriaxone is best predicted by the fraction of time the unbound drug concentration
exceeds the minimum inhibitory concentration (fT>MIC)
• Monte Carlo simulations estimated fT>MIC of 20-24 hours is required for effective urogenital
gonococcal treatment – a 250 mg-dose did not achieve reliable levels for an extended duration,
while a 500 mg-dose did [3]
• In a gonorrhea mouse model, 5 mg/kg (which correlates to 500 mg for an 80-100 kg human) was
the lowest dose 100% effective at eradicating ceftriaxone-susceptible N. gonorrhoeae 48 hours
after treatment, with fT>MIC of 23.6 hours [4]
• Higher intramuscular doses of ceftriaxone are required in order to optimize urogenital
gonococcal eradication
• Practical considerations pose challenges in implementing a protocol for delayed treatment of
chlamydial coinfection pending laboratory confirmation
• If treating for chlamydial coinfection:
o Heavily consider patient adherence to a 7-day course of doxycycline
o If adherence is a concern, treat with 1 gm oral azithromycin
o There are instances (i.e., rectal chlamydia) where doxycycline has demonstrated higher rates of treatment success compared to azithromycin and may be considered as first-line therapy [5,6]
Lauren Groft, PharmD; Infectious Disease Pharmacist


1. MMWR Morb Mortal Wkly Rep. 2015;64(3).

2. MMWR Morb Mortal Wkly Rep. 2020;69(50):1911-16.

3. Chisholm SA, et al. J Antimicrob Chemother. 2010;65:2141-48.

4. Connolly KL, et al. Antimicrob Agents Chemother. 2019;63:e01644-18.

5. Duke-Muijrers N, et al. Clin Infect Dis. 2019;69(11):1946-54.

6. Mizushima D, et al. J Antimicrob Chemother. 2021;76:495-98.