Cephalosporins Losing Effectiveness Against Gonorrhea

CDC Sounds Alarm on Lack of Options

Sandra Yin

July 08, 2011

July 8, 2011 — The last line of defense for treating gonorrhea is crumbling, according to an article published in the July 8 issue of the Centers for Disease Control and Prevention's (CDC's) Morbidity and Mortality Weekly Report.

Cephalosporins, the last class of antibiotics that treat gonorrhea, seem to be losing their effectiveness as the pathogen quickly evolves to bypass the antibiotic.

CDC researchers monitoring the share of gonorrhea isolates that need higher doses of antibiotics to stop their growth in the lab noted an increase in the percentage of isolates with elevated minimum inhibitory concentrations, the lowest concentration of antibiotics needed to stop the bacteria's growth. The analysis was based on 10 years' worth of gonorrhea samples collected through the CDC's Gonococcal Isolate Surveillance Project from male patients in 30 US cities. Close to 6000 isolates were collected each year.

"We're concerned that we're now seeing the potential for emerging resistance," Gail Bolan, MD, director of CDC's Division of Sexually Transmitted Disease Prevention, told Medscape Medical News.

Although no treatment failures have been reported yet in the United States, there have been reports from Asia and other parts of the world suggesting gonorrhea's declining susceptibility to cephalosporin, said Hillard Weinstock, MD, MPH, from the same division.

At an Impasse

Historically, since the advent of antibiotics in the United States in the 1930s and 1940s, antibiotics have successfully treated gonorrhea. However, during the past 40 years, the bacteria Neisseria gonorrhoeae has developed resistance to several drugs, including sulfonamides, penicillin, and tetracycline. As recently as 2007, the CDC stopped recommending any fluoroquinolone regimens to treat gonorrhea, leaving cephalosporins the last antibiotics standing.

"We are at an impasse, with no new drugs in development," said Dr. Bolan. "We want to sound the alarm."

The CDC is down to recommending a cephalosporin (cefixime or ceftriaxone), along with a macrolide antibiotic, preferably azithromycin. Ceftriaxone is the most effective cephalosporin for treating gonorrhea, and azithromycin is better than doxycycline for dual therapy with ceftriaxone, the CDC notes. (Dosing recommendations are available in the article.)

Gonorrhea is one of the most common sexually transmitted diseases. Among serious health consequences, it can lead to infertility in women and increase a person's risk of acquiring HIV.

Given the possibility of rising resistance, clinicians should be on the lookout for treatment failures, Dr. Bolan said, which will show up as persistent symptoms or a positive follow-up test despite treatment with CDC-recommended antibiotics. Clinicians should also obtain specimens for gonococcal culture from patients whose treatments may have failed. "You need to find labs that are still doing the [gonococcal] culture," she said.

CDC Recommendations

The CDC recommends that individual providers:

  • promptly treat all patients diagnosed with gonorrhea according to CDC Treatment Guidelines,

  • obtain cultures to test for decreased susceptibility from any patients with suspected or documented gonorrhea treatment failures, and

  • report any suspected treatment failure to local or state public health officials within 24 hours, helping to ensure that any future resistance is recognized early.

Clinicians who care for patients with gonorrhea, especially men who have sex with men in the western United States, should consider having patients return 1 week after treatment for test-of-cure with culture, preferably, or with nucleic acid amplification tests. The CDC report notes that the pattern of cephalosporin susceptibility in the West and among men who have sex with men during 2009 to 2010 resembles the drop in effectiveness observed earlier when a fluoroquinolone-resistant N gonorrhoeae emerged in the United States.

Although Dr. Bolan said she was not aware of any new drug development in the pipeline, the CDC and the National Institutes of Health are running a treatment trial on existing drugs: gentamicin, azithromycin, and gemifloxacin. The trial is expected to yield results by late 2012, said Bob Kirkcaldy, MD, MPH, from the CDC's Office of Workforce Development and Division of STD Prevention.

"We really do want to have more treatment trials so that we have more treatment options down the pike," Dr. Bolan said.

However, the development of new antibiotics is unlikely, according to Brad Spellberg, MD, author of Rising Plague: The Global Threat from Deadly Bacteria and Our Dwindling Arsenal to Fight Them. A fellow of the Infectious Diseases Society of America who sits on its antimicrobial availability taskforce, Dr. Spellberg characterized the next several decades as "a very barren period of time" in terms of antibiotics development.

Dr. Spellberg offered 3 reasons to explain his outlook: First, there is a significant scientific challenge. After 60 years of antibiotic discovery, all the low-hanging fruit has been plucked, and developing new antibiotics would be difficult. Second, pharmaceutical companies have found that they make much more money off drugs that target chronic illnesses, not ones consumers will take for only 14 days. Third, "nobody even knows how to do drug trials for antibiotics anymore," Dr. Spellberg said, and the US Food and Drug Administration's requirements, he explained, are unclear, infeasible, and/or unreasonable.

"There's never going to be an endgame to this," he said. Industry, he predicted, will exit antibiotic development. "It doesn't make enough money for them, and the regulatory morass exacerbates the problem."

Morb Mortal Wkly Rep. 2011:60;873-877. Full text

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