Carbapenem-Nonsusceptible Enterobacteriaceae in Taiwan

March Carbapenem-Nonsusceptible Enterobacteriaceae in Taiwan Jann-Tay Wang 0 1 Un-In Wu 0 1 Tsai-Ling Yang Lauderdale 0 1 Mei-Chen Chen 0 1 Shu-Ying Li 0 1 Le-Yin Hsu 0 1 Shan-Chwen Chang 0 1 0 1 Department of Internal Medicine, National Taiwan University Hospital , Taipei, Taiwan , 2 Department of Medical Research, National Taiwan University Hospital , Taipei, Taiwan , 3 National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Taiwan, 4 Centers for Disease Control , Taipei, Taiwan , 5 Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University , Taipei, Taiwan , 6 Graduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University , Taipei , Taiwan 1 Academic Editor: Hiroshi Nishiura, The University of Tokyo , JAPAN A total of 1135 carbapenem-resistant (nonsusceptible) Enterobacteriaceae (CRE) isolates were recovered between November 2010 and July 2012 (517 from 2010-2011 and 618 from 2012) from 4 hospitals in Taiwan. Carbapenemase-producing Enterobacteriaceae (CPE) comprised 5.0% (57 isolates), including 17 KPC-2 (16 Klebsiella pneumoniae and 1 Escherichia coli), 1 NDM-1 (K. oxytoca), 37 IMP-8 (26 Enterobacter cloacae, 4 Citrobacter freundii, 4 Raoultella planticola, 1 K. pneumoniae, 1 E. coli and 1 K. oxytoca), and 2 VIM-1 (1 E. cloacae, 1 E. coli). The KPC-2-positive K. pneumoniae were highly clonal even in isolates from different hospitals, and all were ST11. IMP-8 positive E. cloacae from the same hospitals showed higher similarity in PFGE pattern than those from different hospitals. A total of 518 CRE isolates (45.6%) were positive for blaESBL, while 704 (62.0%) isolates were blaAmpC-positive, 382 (33.6% overall) of which carried both blaESBL and blaAmpC. CTX-M (414, 80.0%) was the most common blaESBL, while DHA (497, 70.6%) and CMY (157, 22.3%) were the most common blaAmpC. Co-carriage of blaESBL and blaAmpC was detected in 31 (54.4%) and 15 (26.3%) of the 57 CPE, respectively. KPC-2 was the most common carbapenemase detected in K. pneumoniae (2.8%), while IMP-8 was the most common in E. cloacae (9.7%). All KPC-2-positive CRE were resistant to all three tested carbapenems. However, fourteen of the 37 IMP-8-positive CRE were susceptible to both imipenem and meropenem in vitro. Intra- and inter-hospital spread of KPC-2-producing K. pneumoniae and IMP-8-producing E. cloacae likely occurred. Although the prevalence of CPE is still low, careful monitoring is urgently needed. Non-susceptibility to ertapenem might need to be considered as one criterion of definition for CRE in areas where IMP type carbapenemase is prevalent. - Competing Interests: The authors have declared that no competing interests exist. Bacteria belonging to Enterobacteriaceae, such as Escherichia coli, Klebsiella pneumoniae, Enterobacter spp., Citrobacter spp, Serratia spp, Proteus spp, and Morganella, are all important human pathogens [1]. They cause a wide array of diseases including urinary tract, respiratory tract, bloodstream, intra-abdominal, and skin and soft tissue infections [1]. Treatment of infections caused by these bacteria has become challenging particularly those with increasing resistance to extended spectrum -lactams due to expression of extended-spectrum -lactamase (ESBL) and/or AmpC -lactamase [2,3]. In addition to being resistant to commonly used extended spectrum -lactams [4], these isolates are usually resistant to other classes of antibiotics including fluoroquinolones and aminoglycosides at the same time [5]. Therefore, carbapenems have been the major last agent of choice for treating infections caused by these multidrug-resistant isolates [2,5,6]. However, carbapenem resistance among Enterobacteriaceae has increased gradually over the years in different regions [3,714]. The emergence of carbapenem-resistant Enterobacteriaceae (CRE) is worrisome because treatment options are very limited [3,9,15]. The mechanisms of carbapenem resistance among Enterobacteriaceae include production of ESBL and/or AmpC enzymes in combination with loss of outer membrane protein or up-regulation of efflux pump, and secretion of carbapenemases. Among the carbapenemases found in Enterobacteriaceae, K. pneumoniae carbapenemase (KPC) and New-Delhi metallo--lactamase1 (NDM-1) have been most noteworthy because they can confer high-level carbapenem resistance and because genes encoding these enzymes are mostly plasmid-borne and have spread between different species of Enterobacteriaceae worldwide [3,9,15]. The prevalence of CRE in Taiwan, although remained low, has increased in recent years [1620]. These CRE isolates may be resistant to one or all of the three carbapenem agents, ertapenem, imipenem, and/or meropenem depending on the agents tested by the clinical microbiology laboratories in Taiwan. Prior studies from Taiwan limited their scope in single bacterial species or single infection syndrome, which might not demonstrate the whole picture of CRE in Taiwan. The present study aimed to increase our understanding on the epidemiology of CRE in Taiwan by studying different species of CRE isolated from various clinical specimens over a 2-year period from 4 hospitals. The objectives of the study were to investigate the drug susceptibilities of CRE to commonly used broad-spectrum antibiotics and to determine the distribution of carbapenemases as well as ESBLs and AmpC -lactamases in these CREs. Since carbapenemase-producing Enterobacteriaceae (CPE) is the most worrisome threat, we performed further molecular characterizations on the CPE isolates to study their clonal relatedness and genetic background. The possible effects of ESBLs and/or AmpC -lactamase co-carriage on the carbapenem minimum inhibitory concentrations (MICs) of CPE were also determined. Between November 2010 and July 2012, non-duplicate Enterobacteriaceae (CRE) isolates nonsusceptible to ertapenem, imipenem, and/or meropenem recovered from adult patients at 2 major medical centers [National Taiwan University Hospital (NTUH) and Far Eastern Memorial Hospital (FEMH)] and 2 regional hospitals (NTUH Hsin-Chu Branch and NTUH YunLin Branch) were collected. The 2 medical centers are located in northern Taiwan; while the 2 regional hospitals are located in central and southern Taiwan, respectively. Isolates determined to be nonsusceptible to ertapenem, imipenem, and/or meropenem by the participating hospitals were collected and then subjected to antimicrobial susceptibility test described below. Only those confirmed to be carbapenem-nonsusceptible (either of ertapenem, imipenem, or meropenem) based on the 2012 Clinical and Laboratory Standard Institutes (CLSI) criteria [ertapenem (S, 0.5; I,1; R, 2 g/mL), imipenem (S 1; I, 2; R, 4 g/mL), and/or meropenem (S, 1; I, 2; R, 4 g/mL) were considered CRE [21]. Isolates were stored at -70C in 20% glycerol containing Trypticase soy broth. The study was approved by the NTUH Inst (...truncated)