Title: CDC Gonococcal Treatment Guideline Updates (Authored by Lauren Groft, PharmD; Infectious Disease Pharmacist)<br/>Author: Wesley Oliver<br/><a href='mailto:1911'>[Click to email author]</a><hr/><div>
<u><strong>Take-Home Point:</strong></u></div>
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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.</div>
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<u><strong>Background:</strong></u></div>
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• Neisseria gonorrhoeae is the second most commonly reported notifiable sexually transmitted</div>
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infection (STI) in the United States</div>
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• Treatment of gonococcal infections prevents complications and transmission, but resistance has</div>
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developed against several treatment options (i.e., penicillin, fluoroquinolones, cefixime, and</div>
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most recently, azithromycin) leading to changes in treatment recommendations over the years</div>
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<table border="1" cellpadding="0" cellspacing="0">
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<strong>Uncomplicated Gonococcal</strong></p>
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<strong>Infections</strong></p>
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<strong>2015 Recommendations [1]</strong></p>
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<strong>2020 Recommendations [2]</strong></p>
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Cervical, urethral, rectal, and</p>
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pharyngeal infection</p>
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Ceftriaxone 250 mg IM x 1 dose, plus azithromycin 1 g PO x 1 dose</p>
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Ceftriaxone 500 mg IM x 1 dose</p>
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<td style="width:208px;">
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>=150 kg</p>
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No recommendation</p>
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Ceftriaxone 1 g IM x 1 dose</p>
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If coinfection with chlamydia</p>
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cannot be excluded</p>
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Coverage provided by gonococcal treatment regimen</p>
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Add doxycycline 100 mg PO BID x 7 days</p>
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<u><strong>Clinical Data:</strong></u></div>
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• Efficacy of ceftriaxone is best predicted by the fraction of time the unbound drug concentration</div>
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exceeds the minimum inhibitory concentration (fT>MIC)</div>
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• Monte Carlo simulations estimated fT>MIC of 20-24 hours is required for effective urogenital</div>
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gonococcal treatment – a 250 mg-dose did not achieve reliable levels for an extended duration,</div>
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while a 500 mg-dose did [3]</div>
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• In a gonorrhea mouse model, 5 mg/kg (which correlates to 500 mg for an 80-100 kg human) was</div>
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the lowest dose 100% effective at eradicating ceftriaxone-susceptible N. gonorrhoeae 48 hours</div>
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after treatment, with fT>MIC of 23.6 hours [4]</div>
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<u><strong>Conclusion:</strong></u></div>
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• Higher intramuscular doses of ceftriaxone are required in order to optimize urogenital</div>
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gonococcal eradication</div>
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• Practical considerations pose challenges in implementing a protocol for delayed treatment of</div>
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chlamydial coinfection pending laboratory confirmation</div>
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• If treating for chlamydial coinfection:</div>
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o Heavily consider patient adherence to a 7-day course of doxycycline</div>
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o If adherence is a concern, treat with 1 gm oral azithromycin</div>
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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]</div>
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<strong>Lauren Groft, PharmD; Infectious Disease Pharmacist</strong></div>
<fieldset><legend>References</legend>
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1. MMWR Morb Mortal Wkly Rep. 2015;64(3).</p>
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2. MMWR Morb Mortal Wkly Rep. 2020;69(50):1911-16.</p>
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3. Chisholm SA, et al. J Antimicrob Chemother. 2010;65:2141-48.</p>
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4. Connolly KL, et al. Antimicrob Agents Chemother. 2019;63:e01644-18.</p>
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5. Duke-Muijrers N, et al. Clin Infect Dis. 2019;69(11):1946-54.</p>
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6. Mizushima D, et al. J Antimicrob Chemother. 2021;76:495-98.</p>
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