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New Antibiotic Regimens Shown Effective Against Drug-resistant Gonorrhea

A pair of antibiotic regimens using the existing drugs gentamicin or gemifloxacin plus azithromycin work against resistant gonorrhea, but come with side effects, CDC and NIH researchers reported at the 20th Meeting of the International Society for Sexually Transmitted Diseases Research this week in Vienna.

In recent years Neisseria gonorrhoeae bacteria have become highly drug-resistant, with cephalosporin-resistant strains first reported in North America earlier this year. With a dearth of new antibiotics in development, the Centers for Disease Control and Prevention (CDC) and the NIH's National Institute of Allergy and Infectious Diseases and sponsored a Phase 4 trial to test novel regimens comprised of existing drugs:

• Gentamicin given as a 240 mg intramuscular injection plus 2 g oral azithromycin;
• Gemifloxacin given as a 320 mg pill plus 2 g oral azithromycin.

In these regimens, gentamicin and gemifloxacin are used in place of the cephalosporins cefixime or ceftriaxone, the latter of which is included in thecurrent preferred regimen according to CDC guidelines.

Principle investigator Robert Kirkcaldy of the CDC's Division of STD Prevention presented findings from trial, which began in 2010. It included 401 evaluable participants age 16-50 years (mean 30 years). Just over half were heterosexual men, about one-third were men who have sex with men, and 10% were women.

Participants were randomly assigned (1:1) to receive one of the new regimens, with the primary outcome being microbiological cure of urogenital infection, indicated by a negative follow-up culture, at 10-17 days post-treatment.

Results

• All participants treated with gentamicin/azithromycin achieved a microbiological cure of urogenital infection, as did 99.5% of those treated with gemifloxacin/azithromycin.
• Both regimens also cured all cases of pharyngeal (throat) infections (25 total cases) and rectal infections (6 total cases).
• For both regimens, the most common adverse events were gastrointestinal symptoms, including nausea (28% for gentamicin/azithromycin, 37% for gemifloxacin/azithromycin), diarrhea (19% and 23%, respectively), and abdominal pain (7% and 11%).

"Both study regimens were highly effective," the researchers concluded. "These results provide alternative gonorrhea treatment options for patients who cannot be treated with cephalosporins."

"These trial results are an exciting step in the right direction in the fight against drug-resistant gonorrhea," CDC Division of STD Prevention director Gail Bolan stated in a press release. "But patients need more oral options with fewer side effects. It is imperative that researchers and pharmaceutical companies prioritize research to continue to identify new, effective, better-tolerated drugs and drug combinations."

The CDC's recommended first-line regimen remains injectable ceftriaxone plus either oral azithromycin or doxycycline. "This regimen remains highly effective in treating gonorrhea and causes limited side effects," according to the release. "However, providers may consider using the regimens studied in this trial as alternative options when ceftriaxone cannot be used, such as in the case of a severe allergy." The agency said it will take the new findings into consideration for inclusion in future guidelines.

"[W]hile the results of the trials are promising, we must remember these are existing antibiotics and gonorrhea has shown a remarkable ability to develop resistance quickly to all of our existing families of antibiotics," warned National Coalition of STD Directors executive director William Smith. "So while these treatments may buy us some additional time, we need investments in the creation of new antibiotics immediately."

7/19/13

Reference

R Kirkcaldy. Treatment of gonorrhea in an era of emerging cephalosporin resistance and results of a randomized trial of new potential treatment options. 20th Meeting of the International Society for Sexually Transmitted Diseases Research. Vienna, July 14-17, 2013. Abstract S08.1.

Other Sources

CDC and NIAID. Two New Promising Treatment Regimens for Gonorrhea.Press release. July 15, 2013.

National Coalition of STD Directors. Results from Exciting New Clinical Trial Show Promise for Gonorrhea. Press release. July 16, 2013.