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Considerations for Strengthening Surveillance of Neisseria gonorrhoeae Antimicrobial Resistance and Interpreting Surveillance Data.

Since the introduction of antimicrobials in the first half of the 20th century, Neisseria gonorrhoeae has repeatedly acquired resistance to the drugs used for treatment. The victims of the bacterium's relentless acquisition of resistance have included sulfonamides, penicillin, tetracycline, and fluoroquinolones. During the past several years, gonococcal resistance has received substantial attention in the United States. Circulating strains of N. gonorrhoeae have been found to have reduced susceptibility to recommended treatment options, the antibiotic pipeline remains at a trickle, and STD public health programs are stretched increasingly thin as syphilis, chlamydia, and gonorrhea case rates are increasing. Taking its place among the ranks of Clostridium difficile and carbapenem-resistant Enterobacteriaceae, N. gonorrhoeae was labeled an “urgent” antibiotic resistance threat by the Centers for Disease Control and Prevention in (CDC) in 2013. N. gonorrhoeae antimicrobial resistance is a reminder of our global interconnectedness. Penicillinase-producing N. gonorrhoeae, fluoroquinolone-resistant N. gonorrhoeae, and strains with reduced cephalosporin susceptibility seem to have initially emerged or at least been initially detected in East Asia before being detected in other countries around the world in subsequent years, including the United States. In someways, gonococcal resistance trends and developments in East Asia have served as a canary in a coal mine, allowing us to anticipate possible future developments elsewhere. Thus antimicrobial susceptibility surveillance data from Japan, such as presented in this issue by Yasuda et al, are welcome contributions to our understanding of gonococcal resistance worldwide. Yasuda et al report antimicrobial susceptibilities of 2471 gonococcal isolates collected during 2000 to 2015 by medical facilities in 9 regions of Japan. Across the study period, the annual percentages of isolates with resistance to penicillin, tetracycline, or levofloxacin were strikingly high, ranging from 38.6% to 94.3%. Isolates with reduced cephalosporin susceptibility were common in Japan by the early 2000s, nearly a decade before the percentage of isolates with elevated cefixime or ceftriaxone minimum inhibitory concentrations (MICs) in the United States increased, albeit at much lower percentages. In this Japanese sample, the percentage of isolates with cefixime MICs of 0.5 μg/mL or greater was 19.3% in 2000 and was as high as 42.9% (in 2007); the percentage with ceftriaxone MICs 0.25 μg/mL or greater was 6.7% in 2001, and as high as 22.3% (in 2011). Because of methodological limitations (discussed below), assessing trends in the Japanese sample is problematic. It is nevertheless intriguing that the percentage of isolates with reduced cephalosporin susceptibility appears to have declined between 2011 and 2012, echoing similar declines in the United States and United Kingdom during approximately the same period, and also perhaps casting doubt on the speculation that changes in treatment guidelines contributed to the declines in those countries. In the Japanese sample, the percentage of isolates with azithromycin MICs of 1 μg/mL or greater increased sharply between 2003 and 2004 (from 1.1% to 23.8%) and remained high in subsequent years. A further disquieting finding is the identification of isolates exhibiting reduced susceptibility to both ceftriaxone and azithromycin. Although the percentage of such isolates remains low, and the true resistance breakpoint (ie, indicating likely treatment failure) for both azithromycin and ceftriaxone is not clearly established, spread of isolates with resistance to both drugs could severely threaten gonorrhea treatment worldwide. This warrants careful monitoring.