Evaluation of Resistance Mechanisms in Carbapenem-Resistant Enterobacteriaceae

Naser Alizadeh,1,2 Mohammad Ahangarzadeh Rezaee,1,3 Hossein Samadi Kafil,3 Alka Hasani,3 Mohammad Hossein Soroush Barhaghi,3 Morteza Milani,4 Fatemeh Yeganeh Sefidan,3 Mohammad Yousef Memar,3,5 Aidin Lalehzadeh,3 Reza Ghotaslou1,3 1Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; 2Students’ Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran; 3Department of Bacteriology and Virology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, IR, Iran; 4Department of Medical Nanotechnology, Faculty of Advanced Medical Science, Medical, University of Tabriz, Tabriz, Iran; 5Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, IranCorrespondence: Reza GhotaslouImmunology Research Center, Tabriz University of Medical Sciences, Tabriz, IranTel/Fax + 984133364661Email rzgottaslo@yahoo.comBackground: Carbapenem-resistant Enterobacteriaceae (CRE) is a major concern leading to morbidity and mortality in the world. CRE often is becoming a cause of therapeutic failure in both hospital and community-acquired infections.Aim: This study aimed to investigate the resistance mechanisms of CRE by phenotypic and molecular methods.Materials and Methods: Sixty CRE (50 Klebsiella pneumoniae, 6 Escherichia coli, and 4 Enterobacter spp.) were isolated from October 2018 to June 2019. Antimicrobial susceptibility testing was carried out using phenotypic methods. The carbapenem resistance mechanisms including efflux pump hyperexpression, AmpC overproduction, carbapenemase genes, and deficiency in OmpK35 and OmpK36 were determined by phenotypic and molecular methods, respectively.Results: Sixty CRE (50 Klebsiella pneumoniae, 6 Escherichia coli, and 4 Enterobacter spp.) were isolated from October 2018 to June 2019. Amikacin was found to be the most effective drug against CRE isolates. All isolates were resistant to imipenem and meropenem by the micro-broth dilution. AmpC overproduction was observed in all Enterobacter spp. and three K. pneumoniae isolates. No efflux pump activity was found. Carba NP test and Modified Hodge Test could find carbapenemase in 59 (98%) isolates and 57 (95%) isolates, respectively. The most common carbapenemase gene was blaOXA-48-like (72.8%) followed by blaNDM (50.8%), blaIMP (18.6%), blaVIM (11.8%), and blaKPC (6.7%). The ompK35 and ompK36 genes were not detected in 10 and 7 K. pneumoniae isolates, respectively.Conclusion: The amikacin is considered as a very efficient antibiotic for the treatment of CRE isolates in our region. Carbapenemase production and overproduction of AmpC are the main carbapenem resistance mechanisms in CRE isolates. Finally, Carba NP test is a rapid and reliable test for early detection of carbapenemase-producing isolates.Keywords: amikacin, carbapenemase genes, carbapenem-resistant Enterobacteriaceae, Carba NP test