The development of antibiotic resistance in Neisseria gonorrhoeae is an urgent public health threat, in particular because the United States gonorrhea control strategy relies on effective antibiotic therapy. Since antibiotics were first used for treatment of gonorrhea, N. gonorrhoeae has progressively developed resistance to the antibiotic drugs prescribed to treat it: sulfonilamides, penicillin, tetracycline, and fluoroquinolones, such as ciprofloxacin. Currently, CDC STD treatment guidelines recommend dual therapy with the injectable cephalosporin ceftriaxone and either azithromycin or doxycycline to treat all uncomplicated gonococcal infections among adults and adolescents in the United States. Dual therapy is recommended to address the potential emergence of gonococcal cephalosporin resistance. Given the ability of N. gonorrhoeae to readily develop antibiotic resistance, it is critical to continuously monitor gonococcal antibiotic resistance and encourage research and development of new treatment regimens for gonorrhea.
Surveillance for antimicrobial resistance in N. gonorrhoeae in the United States is conducted through the Gonococcal Isolate Surveillance Project (GISP), which was established in 1986. Each year, 25-30 sites and 4-5 regional laboratories across the United States participate in GISP. Data from this project have been reported and have directly contributed to CDC's STD Treatment Guidelines in 1989, 1993, 1998, 2002, 2006, and 2010.
Clinicians are asked to report any N. gonorrhoeae specimen with decreased cephalosporin susceptibility and any gonorrhea cephalosporin treatment failure to CDC through their state/local public health authorities.
In the United States, reports of apparent failures of infections to respond to treatment with CDC recommended therapies should be reported to Robert D. Kirkcaldy, MD, MPH (firstname.lastname@example.org; 404-639-8659). Surveillance & Data Management Branch,, Division of STD Prevention, Centers for Disease Control and Prevention, 1600 Clifton Rd. NE, Mailstop E02, Atlanta, GA 30333.
In the United States, it is also recommended that isolates from certain infections be submitted to the Neisseria Reference Laboratory at CDC for confirmation; these infections comprise those that fail to respond to CDC-recommended therapy and isolates determined to exhibit intermediate resistance or resistance (see pg. 6, Recommended Testing and Confirmatory Testing, for a complete list): John Papp, Ph.D. JPapp@cdc.gov; 404-639-3785), Neisseria Reference Laboratory, Centers for Disease Control and Prevention, 1600 Clifton Rd. NE, Mailstop A12, Atlanta, GA 30333.
In 1993, ciprofloxacin (a fluoroquinolone) and cephalosporins (ceftriaxone and cefixime) were the recommended treatments for gonorrhea. However, in the late 1990s and early 2000s, ciprofloxacin resistance was detected in Hawaii and the West Coast, and by 2004, ciprofloxacin resistance was detected among men who have sex with men (MSM) with gonorrhea. By 2006, 13.8% of isolates exhibited resistance to ciprofloxacin, and ciprofloxacin resistance was present in all regions of the country and the heterosexual population. On April 13, 2007, CDC stopped recommending fluoroquinolones as empiric treatment for gonococcal infections for all persons in the United States. The cephalosporins, either cefixime or ceftriaxone, were the only remaining recommended treatments.
Similar to trends observed elsewhere in the world, CDC has observed recent worrisome trends of decreasing cephalosporin susceptibility, especially to the oral cephalosporin cefixime. In 2010, CDC changed its treatment recommendations to recommend dual therapy for the treatment of gonorrhea and increased the recommended dose of ceftriaxone to 250 mg. Following continued declines in cefixime susceptibility, CDC again updated its recommendations in 2012 to recommend ceftriaxone plus either azithromycin or doxycycline as the only first-line treatment. Starting in 2012, the percentage of GISP isolates with elevated cefixime minimum inhibitory concentrations (MICs) decreased. CDC has not received any reports of verified clinical treatment failures to any cephalosporin in the United States.
See ARG Statistics.
A major challenge to monitoring emerging antimicrobial resistance of N. gonorrhoeae is the substantial decline in the capability of many clinicians and laboratories to perform essential gonorrhea culture techniques required for antibiotic susceptibility testing. This decline results from an increased use of newer non-culture-based laboratory technology, such as a diagnostic test called the Nucleic Acid Amplification Test (NAAT). Currently, there is no well-studied reliable technology that allows for antibiotic susceptibility testing from non-culture specimens. Increased laboratory culture capacity is needed.
CDC recommends that all state and local health department labs maintain or develop the capacity to perform gonorrhea culture, or form partnerships with experienced laboratories that can perform this type of testing.