Cephalosporin-Resistant Gonorrhea in North America
Authors: Robert D. Kirkcaldy, Gail A. Bolan, Judith N. Wasserheit
Journal: JAMA (2013)

GONORRHEA HAS AFFECTED HUMANS FOR CENTUries and remains common. Worldwide, an estimated 106.1 million cases occur annually. In 2011, gonorrhea again was the second most commonly reported notifiable infection in the United States with 321 849 cases reported. Because gonorrhea often can be asymptomatic, the true disease burden may be closer to 700 000. Gonorrhea disproportionately affects racial, ethnic, and sexual minorities. Untreated gonococcal infection can lead to pelvic inflammatory disease, ectopic pregnancy, and infertility in women and can facilitate transmission of human immunodeficiency virus. Childhood blindness still affects infants born to mothers infected with gonorrhea, particularly in resource-limited countries. For years, gonorrhea has been easily treated with a single oral dose of antibiotics. However, Neisseria gonorrhoeae has progressively acquired resistance to each new agent: sulfonamides in the 1940s, penicillins and tetracyclines in the 1970s and 1980s, and fluoroquinolones by 2007 in the United States. Since then, cephalosporins have been the only antibiotics recommended for gonorrhea treatment. However, gonococcal susceptibility to oral cephalosporins is declining, and the effectiveness of these drugs is threatened. Increasing cephalosporin minimum inhibitory concentrations (MICs), an early warning of impending resistance, and treatment failures with cephalosporins have been reported from east Asia since the early 2000s and recently have been reported from Europe. In the United States, the Gonococcal Isolate Surveillance Project (GISP), a national surveillance system that monitors trends in antibiotic susceptibility, has documented increasing cefixime MICs since 2009. The steepest cefixime MIC increases have been reported in the western United States and among individuals who have had male-to-male sexual contact, the region and population in which fluoroquinolone resistance initially emerged. However, data are lacking on the cefixime MICs at which clinical effectiveness wanes. In this issue of JAMA, Allen and colleagues report a retrospective cohort study conducted to determine the risk of gonorrhea treatment failure associated with N gonorrhoeae strains exhibiting reduced cefixime susceptibility (defined by the authors as MIC 0.12 g/mL). The authors used data from an Ontario clinic that routinely obtained cultures from patients with gonorrhea; treated them with cefixime, 400 mg, orally; and requested test of cure 2 to 4 weeks after treatment. Patients were considered to have experienced treatment failure if, at follow-up, they were culture-positive with a gonococcal isolate that was identical to the pretreatment isolate by molecular characterization and they denied sexual reexposure. Of 291 patients with positive cultures for N gonorrhoeae, 133 (46%) returned for tests of cure, 9 (6.8%) of whom met the case definition for treatment failure. Among the 28 patients whose pretreatment isolates demonstrated cefixime MICs 0.12 g/mL or greater, 25% failed treatment. To account for possible bias, the authors also calculated treatment failure rate assuming that those who did not return were successfully treated; in this analysis, the treatment failure rate among patients whose pretreatment isolates demonstrated reduced cefixime susceptibility was 11.9% (7/59). Several caveats should be noted in interpreting these results. At least some of the patients who met the treatment failure case definition may have been reinfected. The treatment failure case definition relied on medical record documentation that a patient was not reexposed and molecular techniques to determine that pretreatment and posttreatment isolates were identical. Social desirability bias, stigma, or shame could contribute to inaccurate reporting of interim sexual activity. Furthermore, although pretreatment and posttreatment isolates were identical by molecular techniques, patients reinfected from an untreated partner would be expected to be reinfected with the same strain.