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Gonorrhea May Become Untreatable Due to Resistance, Experts Warn


Neisseria gonorrhoeae,the bacteria that cause gonorrhea, are becoming increasingly resistant to existing drugs and more difficult to treat in the U.S., public health experts warn in the February 9, 2012, New England Journal of Medicine.

Gonorrhea, which spreads through sexual contact, is the second most commonly reported communicable disease in the U.S., with an estimated incidence of more than 600,000 cases per year, the authors note. Initially gonorrhea causes genital ulcers that facilitate transmission of HIV. If left untreated, it can lead to pelvic inflammatory disease, infertility, and disseminated infection affecting the joints and heart.

"Neisseria gonorrhoeaehas always readily developed resistance to antimicrobial agents," they continued, starting with sulfanilamide in the 1940s, followed by penicillin and tetracycline in the 1980s, and finally fluoroquinolones by 2007.

When the prevalence of drug resistant gonorrhea exceeds 5%, the CDC typically changes its national treatment recommendations. But the bacteria are rapidly becoming more resistant to the current recommended therapy -- third-generation cephalosporins -- and there is no good substitute in the pipeline. Only 1 clinical trial (sponsored by the National Institute of Allergy and Infectious Diseases) is underway to examine novel combinations of existing drugs for gonorrhea, and a vaccine is not expected in the near future.

Bolan and colleagues noted that cephalosporin resistance has increased rapidly, from 0.1% of N. gonorrhoeaeisolates in 2006 to 1.7% in 2011. This increase was most pronounced in the western U.S. (rising to 3.6%) and among men who have sex with men (reaching 4.7%). These geographic and demographic patterns are similar to those previously observed for fluoroquinolone resistance.

If history is any guide, they wrote, "we should anticipate the emergence of fit cephalosporin-resistant strains that can spread widely." While it is not yet clear whether higher drug doses will overcome resistance, they emphasize that, "investing in rebuilding our defenses against gonococcal infections now, with involvement of the health care, public health, and research communities, is paramount if we are to control the spread and reduce the consequences of cephalosporin-resistant strains."

For now, they continued, the first priority is to treat all cases of gonorrhea with the most effective regimen, consisting of a 250 mg intramuscular injection of ceftriaxone plus 1 gram of oral azithromycin to cover coexisting pathogens and provide additional antimicrobial activity against N. gonorrhoeaeaimed at a different molecular target. For people who are allergic to cephalosporins, the only option is a 2 gram oral dose of azithromycin. This recommendation is the same for HIV positive and HIV negative people.

Sex partners during the previous 2 months should also be treated. "All patients treated for gonorrhea should routinely be offered condoms, referred for risk-reduction counseling, and retested for gonorrhea 3 months later," the authors recommend. "All patients with gonorrhea should be tested for HIV, and those who test negative should be retested 3 to 6 months later."

Providers should be vigilant for cases of cephalosporin treatment failure and people with persistent or recurrent symptoms shortly after treatment should undergo more intensive testing.

"Clinicians caring for men who have sex with men, especially on the West Coast or in Hawaii, should consider performing a test of cure with a culture or a nucleic acid amplification test 1 week after treatment," the authors recommended. "Any case of suspected treatment failure or a positive result after gonorrhea treatment should be reported promptly to local or state health departments."

Investigator affiliations: Division of STD Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA; Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC; Departments of Global Health, Medicine, and Epidemiology, University of Washington, Seattle. WA.



G.A. Bolan, P.F. Sparling, and J.N. Wasserheit. The Emerging Threat of Untreatable Gonococcal Infection. New England Journal of Medicine 366(6):485-487. February 9, 2012.