bThe Klebsiella pneumoniae carbapenemase (KPC), first described in the United States in 1996, is now a widespread global problem in several Gram-negative species. A worldwide surveillance study collected Gram-negative pathogens from 202 global sites in 40 countries during 2012 to 2014 and determined susceptibility to -lactams and other class agents by broth microdilution testing. Molecular mechanisms of -lactam resistance among carbapenem-nonsusceptible Enterobacteriaceae and Pseudomonas aeruginosa were determined using PCR and sequencing. Genes encoding KPC enzymes were found in 586 isolates from 22 countries (76 medical centers), including countries in the Asia-Pacific region (32 isolates), Europe (264 isolates), Latin America (210 isolates), and the Middle East (19 isolates, Israel only) and the United States (61 isolates). The majority of isolates were K. pneumoniae (83.4%); however, KPC was detected in 13 additional species. KPC-2 (69.6%) was more common than KPC-3 (29.5%), with regional variation observed. A novel KPC variant, KPC-18 (KPC-3[V8I]), was identified during the study. Few antimicrobial agents tested remained effective in vitro against KPC-producing isolates, with ceftazidime-avibactam (MIC 90 , 4 g/ml), aztreonam-avibactam (MIC 90 , 0.5 g/ml), and tigecycline (MIC 90 , 2 g/ml) retaining the greatest activity against Enterobacteriaceae cocarrying KPC and other -lactamases, whereas colistin (MIC 90 , 2 g/ml) demonstrated the greatest in vitro activity against KPC-positive P. aeruginosa. This analysis of surveillance data demonstrated that KPC is widely disseminated. KPC was found in multiple species of Enterobacteriaceae and P. aeruginosa and has now become a global problem.
Infections caused by carbapenem-resistant Enterobacteriaceae (CRE) contribute to attributable mortality higher than that for patients infected with carbapenem-susceptible isolates (1). The effect of CRE on morbidity and mortality can vary significantly between countries and may depend upon the -lactam resistance mechanisms that are most problematic in certain regions (2-5). Population movements, poor infection control, and the lack of antimicrobial stewardship initiatives have perpetuated the dissemination of genes that encode carbapenemases among clinically significant bacterial species on a global scale (2, 4, 6, 7). Detection of CRE and their associated resistance mechanisms is essential in order to determine the appropriate therapeutic options required for a positive patient infection outcome (8-10).The Klebsiella pneumoniae carbapenemase (KPC) is a class A serine carbapenemase first recognized in the northeastern United States in 1996 (11). Bacterial pathogens expressing KPC are clinically significant in that they are often multi-or pan-drug resistant, including resistance to currently available latest-in-line therapeutic options (7, 12, 13). The impact of KPC became more fully recognized as this family of enzymes became a global threat to public health, in that the gene encoding KPC (bla KPC ) has now been observed ...