In update, CDC recommends ceftriaxone alone for uncomplicated gonorrhea
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In updated guidance published Friday in MMWR, the CDC recommended a 500 mg intramuscular dose of ceftriaxone by itself to treat uncomplicated gonorrhea.
Since 2010, the CDC had recommended a single 250 mg dose of intramuscular ceftriaxone and 1 g of oral azithromycin “as a strategy for preventing ceftriaxone resistance and treating possible coinfection with Chlamydia trachomatis,” Sancta St. Cyr, MD, and colleagues from the CDC’s Division of STD Prevention, wrote.
“Increasing concern for antimicrobial stewardship and the potential impact of dual therapy on commensal organisms and concurrent pathogens, in conjunction with the continued low incidence of ceftriaxone resistance and the increased incidence of azithromycin resistance, has led to reevaluation of this recommendation,” they wrote.
The updated guidance now recommends adding 100 mg of oral doxycycline — not azithromycin — twice a day for 7 days if chlamydial coinfection has not been ruled out.
“Continuing to monitor for emergence of ceftriaxone resistance through surveillance and health care providers’ reporting of treatment failures is essential to ensuring continued efficacy of recommended regimens,” St. Cyr and colleagues wrote.
Supporting the updated recommendation, the researchers cited — among other data — evidence from the MORDOR trial that demonstrated increased antibiotic resistance among children who received twice-yearly doses of azithromycin during a mass-dosing campaign in Africa.
“Although dual drug therapy with different mechanisms of action (ceftriaxone and azithromycin) might have mitigated emergence of reduced susceptibility to ceftriaxone in N. gonorrhoeae, concerns regarding potential harm to the microbiome and the effect on other pathogens diminishes the benefits of maintaining dual therapy as the recommended treatment regimen,” they wrote.
Additionally, St. Cyr and colleagues cited pharmacokinetic and pharmacodynamic considerations for the update — including that tests demonstrated the previous dose of 250 mg of ceftriaxone was inadequate to eradicate susceptible strains of N. gonorrhoeae — and data showing changes in azithromycin susceptibility.
The new recommendation of a single 500 mg injection is for patients weighing less than 300 pounds. For patients who weight more than 300 pounds, the CDC recommends a single 1 g intramuscular dose of ceftriaxone. In patients with a cephalosporin allergy, a single 240 mg intramuscular dose of gentamicin plus a single 2 g oral dose of azithromycin is an option, St. Cyr and colleagues said.
“Continued support of gonorrhea prevention and control efforts remains fundamental, and preventing antibiotic resistance is crucial,” they wrote. “The high frequency of pharyngeal gonorrhea with substantial underscreening and the increased understanding of wide individual pharmacokinetic and pharmacodynamic variability has contributed to the recommendation for the increased ceftriaxone dose. These recommendations also include a test-of-cure for persons with pharyngeal gonorrhea to ensure eradication or detection of a possible treatment failure.”
Perspective
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The updated gonorrhea treatment guidelines were developed after reviewing the evidence. The percent of N. gonorrheae isolates with reduced susceptibility to azithromycin is now a concern and has increased more than seven-fold in the past 5 years. This problem has been particularly concerning for men who have sex with men, in whom close to 10% of isolates now have a reduced susceptibility to azithromycin. As a result, the CDC’s treatment guidelines have been modified and the recommendation is now to give a single intramuscular dose of 500 mg of ceftriaxone for uncomplicated gonorrhea. This is double the prior recommended dose of ceftriaxone. Coadministration of azithromycin 100 mg PO daily for 7 days is still recommended for treatment of C. trachomatis coinfection.
Ceftriaxone is now the only drug available to treat gonorrhea and the possibility of the emergence of strains with decreased susceptibility to this drug remain. We could be seeing in the future untreatable gonorrhea. For this reason, clinical trials testing new drugs for gonorrhea are critically important.
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