Molecular epidemiology of carbapenemase-producing Enterobacteriaceae in a primary care hospital in Japan, 2010-2013

Recently, carbapenemase-producing Enterobacteriaceae (CPE) have been spreading worldwide and have become a threat in healthcare systems. We investigated the isolation frequency and molecular epidemiological characteristics of CPE isolated from clinical samples collected at a primary care hospital over the four years of 2010-2013 in Japan. CPE were detected in 17 (0.34%) of 4875 isolates by the broth microdilution method, sodium mercaptoacetate inhibition test, and modified Hodge test using meropenem disks. The frequency of CPE isolates was 0.09% in 2010, 0.17% in 2011, 0.16% in 2012 and 0.82% in 2013. Isolates positive for carbapenemase included Klebsiella pneumoniae (0.92%), Escherichia coli (0.12%), Enterobacter cloacae (0.80%), Klebsiella oxytoca (0.55%), Enterobacter aerogenes (0.81%) and Proteus mirabilis (0.08%). Antimicrobial susceptibility testing showed low MICs for piperacillin-tazobactam, amikacin, ciprofloxacin and levofloxacin, and only one multidrug-resistant strain. The carbapenemase genotype of all strains was IMP-6, and 94% of the strains were simultaneous CTX-M-2 producers. Two K. pneumoniae and 3 E. coli isolates showed the same pulsed-field gel electrophoresis group. Multilocus sequence typing detected no international high-risk clone types. Plasmid replicon typing detected IncN from all CPE strains, and IncF and IncFIB were simultaneously detected in 24% and 18%, respectively. All patients with detected CPE were inpatients, and many were elderly long-term hospitalized patients or had a history of prior vancomycin or levofloxacin antibiotic administration. The rapid spread of CPE is a concern in Japan. Preventive measures must be implemented against the spread of CPE after considering the epidemiological trend of CPE detection, antibiograms, and risk factors.