[Investigation of carbapenemases in carbapenem-resistant Escherichia coli and Klebsiella pneumoniae strains isolated in 2014 in Turkey].

Carbapenems are the choice of treatment in infections caused by multidrug resistant Enterobacteriaceae. In recent years carbapenem-resistant Enterobacteriaceae isolates due to carbapenemases have been increasingly reported worldwide. Multicenter studies on carbapenemases are scarce in Turkey. The aim of this study was to determine the distribution of carbapenemases from different parts of Turkey as a part of the European Survey of Carbapenemase Producing Enterobacteriaceae (EuSCAPE) project. Beginning in November 2013, carbapenem-resistant isolates resistant to at least one of the agents, namely imipenem, meropenem, and ertapenem were sent to the coordinating center. Minimum inhibitory concentrations for these carbapenems were determined by microdilution tests following EUCAST guidelines. Production of carbapenemase was confirmed by combination disk synergy tests. Types of carbapenemases were investigated using specific primers for VIM, IMP; NDM, KPC and OXA-48 genes by multiplex polymerase chain reaction. In a six month period, 155 suspected carbapenemase-positive isolates were sent to the coordinating center of which 21 (13.5%) were E.coli and 134 (86.5%) were K.pneumoniae. Nineteen (90.5%) strains among E.coli and 124 (92.5%) strains among K.pneumoniae were shown to harbour at least one carbapenemase gene by molecular tests, with a total of 92.3% (143/155). Carbapenemases were determined as a single enzyme in 136 strains (OXA-48: 84.6%; NDM: 6.3%; VIM: 2.8%; IMP: 1.4%) and as a combination in seven isolates (OXA-48 + NDM: 2.1%; OXA-48 + VIM: 2.1%; VIM + NDM: 0.7%). KPC was not detected in any of the isolates. According to the microdilution test results, resistance to imipenem, meropenem and ertapenem in OXA-48 isolates were 59.5%, 52.9% and 100%, respectively. The combination disk synergy test was 100% compatible with the molecular test results. As most of the OXA-48 producing isolates were susceptible to meropenem but all were resistant to ertapenem, ertapenem seems to be the most sensitive agent in screening carbapenemases in areas where OXA-48 is prevalent and phenotypic combination tests can be useful in centers where molecular tests are not available.

[1]  J. Hrabák,et al.  Detection of OXA-48-type carbapenemase-producing Enterobacteriaceae in diagnostic laboratories can be enhanced by addition of bicarbonates to cultivation media or reaction buffers , 2014, Folia Microbiologica.

[2]  Bilgul Mete,et al.  Blood stream infections due to OXA-48-like carbapenemase-producing Enterobacteriaceae: treatment and survival. , 2014, International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases.

[3]  G. Palù,et al.  Comparison of phenotypic methods for the detection of carbapenem non-susceptible Enterobacteriaceae , 2014, Gut Pathogens.

[4]  A. Fluit,et al.  A disc diffusion assay for detection of class A, B and OXA-48 carbapenemases in Enterobacteriaceae using phenyl boronic acid, dipicolinic acid and temocillin. , 2014, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[5]  G. Peirano,et al.  Molecular epidemiology of Enterobacteriaceae that produce VIMs and IMPs from the SMART surveillance program. , 2014, Diagnostic microbiology and infectious disease.

[6]  P. Nordmann,et al.  KPC-producing Klebsiella pneumoniae, finally targeting Turkey , 2014, New microbes and new infections.

[7]  P. Nordmann,et al.  Spread of NDM-1-Producing Enterobacteriaceae in a Neonatal Intensive Care Unit in Istanbul, Turkey , 2014, Antimicrobial Agents and Chemotherapy.

[8]  N. Woodford,et al.  In vitro activity of temocillin against multidrug-resistant clinical isolates of Escherichia coli, Klebsiella spp. and Enterobacter spp., and evaluation of high-level temocillin resistance as a diagnostic marker for OXA-48 carbapenemase. , 2014, The Journal of antimicrobial chemotherapy.

[9]  P. Nordmann Carbapenemase-producing Enterobacteriaceae: overview of a major public health challenge. , 2014, Medecine et maladies infectieuses.

[10]  P. Nordmann,et al.  Temocillin and piperacillin/tazobactam resistance by disc diffusion as antimicrobial surrogate markers for the detection of carbapenemase-producing Enterobacteriaceae in geographical areas with a high prevalence of OXA-48 producers. , 2014, The Journal of antimicrobial chemotherapy.

[11]  F. Yılmaz,et al.  Detection and spread of oxa-48-producing Klebsiella oxytoca isolates in Istanbul, Turkey. , 2014, The Southeast Asian journal of tropical medicine and public health.

[12]  V. Miriagou,et al.  Combined disc methods for the detection of KPC- and/or VIM-positive Klebsiella pneumoniae: improving reliability for the double carbapenemase producers. , 2013, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[13]  P. Nordmann,et al.  Intercontinental spread of OXA-48 beta-lactamase-producing Enterobacteriaceae over a 11-year period, 2001 to 2011. , 2013, Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin.

[14]  Samir N. Patel,et al.  OXA-48-like carbapenemase-producing Enterobacteriaceae in Ottawa, Canada. , 2013, Diagnostic microbiology and infectious disease.

[15]  E. Alp,et al.  Molecular characterization of carbapenem-resistant Klebsiella pneumoniae in a tertiary university hospital in Turkey. , 2013, The Journal of hospital infection.

[16]  M. Landini,et al.  Evaluation of phenotypic and genotypic approaches for the detection of class A and class B carbapenemases in Enterobacteriaceae. , 2013, Microbial Drug Resistance.

[17]  A P MacGowan,et al.  EUCAST expert rules in antimicrobial susceptibility testing. , 2013, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[18]  J. Verhaegen,et al.  Towards a phenotypic screening strategy for emerging β-lactamases in Gram-negative bacilli. , 2013, International journal of antimicrobial agents.

[19]  J. Mingorance,et al.  Bacteraemia due to OXA-48-carbapenemase-producing Enterobacteriaceae: a major clinical challenge. , 2013, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[20]  G. Peirano,et al.  Laboratory Detection of Enterobacteriaceae That Produce Carbapenemases , 2012, Journal of Clinical Microbiology.

[21]  A. Sundsfjord,et al.  Evaluation of Rosco Neo‐Sensitabs for phenotypic detection and subgrouping of ESBL‐, AmpC‐ and carbapenemase‐producing Enterobacteriaceae , 2012, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[22]  P. Nordmann,et al.  OXA-48-like carbapenemases: the phantom menace. , 2012, The Journal of antimicrobial chemotherapy.

[23]  V. Miriagou,et al.  Rapid evolution and spread of carbapenemases among Enterobacteriaceae in Europe. , 2012, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[24]  P. Nordmann,et al.  Carbapenem resistance in Enterobacteriaceae: here is the storm! , 2012, Trends in molecular medicine.

[25]  P. Nordmann,et al.  NDM-1-Producing Klebsiella pneumoniae Now in Turkey , 2012, Antimicrobial Agents and Chemotherapy.

[26]  Y. Glupczynski,et al.  Rapid emergence and spread of OXA-48-producing carbapenem-resistant Enterobacteriaceae isolates in Belgian hospitals. , 2012, International journal of antimicrobial agents.

[27]  N. Woodford,et al.  A sensitive and specific phenotypic assay for detection of metallo-β-lactamases and KPC in Klebsiella pneumoniae with the use of meropenem disks supplemented with aminophenylboronic acid, dipicolinic acid and cloxacillin. , 2011, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[28]  G. Rossolini,et al.  First Detection of VIM-1 Type Metallo-β-Lactamase in a Multidrug-Resistant Klebsiella pneumoniae Clinical Isolate from Turkey also Producing the CTX-M-15 Extended-Spectrum β-Lactamase , 2007, Journal of chemotherapy.

[29]  N. Woodford,et al.  Multiplex PCR for rapid detection of genes encoding acquired metallo-beta-lactamases. , 2006, The Journal of antimicrobial chemotherapy.

[30]  P. Nordmann,et al.  First IMP-1-producing Klebsiella pneumoniae isolate in Turkey. , 2006, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[31]  P. Nordmann,et al.  Emergence of Oxacillinase-Mediated Resistance to Imipenem in Klebsiella pneumoniae , 2004, Antimicrobial Agents and Chemotherapy.