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CDC Recommendation: Dual Treatment to Curb Tide of Drug-Resistant Gonorrhea

Increasing fears about the emergence of antibiotic resistant gonorrhea in the U.S. have prompted new treatment and surveillance recommendations from the Centers for Disease Control and Prevention (CDC). Gail Bolan, director of the agency's Division of STD Prevention, called the move "a critical pre-emptive strike to preserve the last effective treatment option."

Gonorrhea, caused by the bacterium Neisseria gonorrhoeae, is the CDC's second most frequently reported notifiable disease. In 2010 there were 309,341 documented new cases. Under-reporting is thought to be common, however, due to lack of public education on sexually transmitted diseases (STDs), insufficient availability of STD testing, and prevalence of asymptomatic cases. Experts estimate that the real incidence is closer to 700,000 annual cases.  

Symptoms of gonorrhea can include discharge, pain, and bleeding. Long-term untreated infection may result in pelvic inflammatory disease (PID) -- a major cause of ectopic pregnancy, infertility, and chronic abdominal pain.

Gonorrhea also carries an increased risk of HIV transmission, as inflammation facilitates viral replication. One study, for example, found that men with urethritis (a symptom of gonorrhea) showed an 8-fold increase in HIV viral load. For HIV negative people, immune activation in response to gonorrhea brings CD4 T-cells and other susceptible immune cells to the site of infection, increasing the likelihood of HIV acquisition.

Gonorrhea has progressively developed resistance to treatment through accumulation of mutations that allow the bacteria to evade different classes of antibiotics, which have been used to treat the disease since the 1940s. Previous therapies have included penicillin, tetracycline, and ciprofloxacin.

In 2010, of the samples tested by the Gonococcal Isolate Surveillance Project (GISP), 27% were shown to be resistant to some combination of antimicrobial agents, and 7% of isolates were resistant to 3 types of drugs.

Multidrug-resistant gonorrhea is a growing concern worldwide. Recently countries including France, Sweden, the U.K., Australia, and Japan have reported cases that are resistant to cephalosporin antibiotics, the last remaining treatment option. This past June the World Health Organization issued an alert calling for greater vigilance on the correct use of antibiotics and more research into alternative treatment regimens.

The CDC, in an effort to address the concern of growing resistance, last week changed its gonorrhea treatment guidelines. As described in the August 10, 2012, Morbidity and Mortality Weekly Report, the agency now recommends a dual regimen of injectable ceftriaxone (a cephalosporin) in combination with either 1 gram oral azithromycin or 100 mg oral doxycycline twice-daily for 7 days.

Alternative regimens may be used in special circumstances, for example if ceftriaxone is not available or a patient is allergic to cephalosporins.

The oral cephalosporin cefixime should no longer be considered first-line treatment option, according to the CDC.As bacteria that develop resistance to 1 cephalosporin may develop cross-resistance to the entire drug class, the hope is that limiting the use of cefixime now may help preserve ceftriaxone as a treatment option for a while longer.

"Changing how we treat infections now may buy the time needed to develop new treatment options," said Kevin Fenton, director of the CDC’s National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention.

This recommendation was released along with a report entitled Cephalosporin-Resistant Neisseria Gonorrhoeae Public Health Response Plan that calls for increased action on the public health, scientific research, and individual clinician fronts.

In addition to attempts to stop the spread of resistant bacteria through combination treatment, the CDC also called for enhanced surveillance.  Recommendations suggest investigating reports of individuals with multiple gonorrhea infections within 30-60 days to determine if such cases are due to treatment failures. Clinicians should inform patients about resistant gonorrhea and ask them to return for testing if symptoms do not resolve within 3 to 5 days.  Health departments with a high prevalence of gonorrhea are advised to institute a "test of cure" practice, retesting patients 7 to 10 days post-treatment.

It is currently unknown how this recommendation will impact
"Patient-Delivered Partner Therapy" programs -- the practice of providing prescription treatment for a diagnosed individual to give to their sexual partners, without a healthcare provider first examining the exposed individuals.   

While the major challenge to combating the emerging threat of multidrug-resistant gonorrhea is the lack of well-studied and effective alternatives to cephalosporins, the problem is compounded by declining STD public health resources and infrastructure.

In a press release from the National Coalition of STD Directors applauding the CDC's updated guidelines, NCSD executive director William Smith states, "The response plan includes a number of recommendations that are imperative to protect the public’s health, but NCSD’s member health departments throughout the country have seen drastic budget cuts, layoffs of staff, and constricted program activities over the past several years to the point where most are as bare bones as one can imagine."

The call for preventive care and increased research and resources cautions that immediate action is necessary to avoid long-term financial and human costs. In 2011 federal support for STD prevention came in under $155 million, whereas the CDC estimates that the impact of drug resistant gonorrhea could cost three-quarters of a billion dollars in lifetime medical costs over the next 7 years, as well as nearly 800 additional HIV infections and a quarter million cases of PID.

The CDC plan is pre-emptive, as most cases of gonorrhea found in the U.S. currently are not resistant to cephalosporins. However, lack of widespread testing and research means that strategies will need to be reviewed and revised in response to this developing dilemma.

"It is imperative that researchers and pharmaceutical companies prioritize research to identify or develop new, effective drugs or drug combinations," Bolan said.

8/17/12

Reference

C del Rio, G Hall, K Holmes, et al.Update to CDC's Sexually Transmitted Diseases Treatment Guidelines, 2010: Oral Cephalosporins No Longer a Recommended Treatment for Gonococcal Infections. Morbidity and Mortality Weekly Report 61(31):590-594. August 10, 2012.

Other Sources

CDC National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention. CDC No Longer Recommends Oral Drug for Gonorrhea Treatment. Press release. August 9, 2012.

National Coalition of STD Directors.With Resistance to Treatment Rising, CDC Updates Gonorrhea Treatment Guidelines. Press release. August 9, 2012.