Molecular Characterization of Carbapenem Resistant Klebsiella pneumoniae in Malaysia Hospital.

Min Yi Lau,Chun Wie Chong,Fui Enn Teng,Cindy Shuan Ju Teh,Kartini Abdul Jabar,Kek Heng Chua,Sasheela Ponnampalavanar

doi:10.3390/pathogens10030279

Abstract

The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) is a great concern, as carbapenems are the last-line therapy for multidrug-resistant Gram-negative bacteria infections. This study aims to report the epidemiology of CRKP in a teaching hospital in Malaysia based on the molecular genotypic and clinical characteristics of the isolates. Sixty-three CRKP strains were isolated from a tertiary teaching hospital from January 2016 until August 2017. Carbapenemase genes were detected in 55 isolates, with blaOXA-48 (63.5%) as the predominant carbapenemase gene, followed by blaNDM (36.5%). At least one porin loss was detected in nine isolates. Overall, 63 isolates were divided into 30 clusters at similarity of 80% with PFGE analysis. Statistical analysis showed that in-hospital mortality was significantly associated with the usage of central venous catheter, infection or colonization by CRKP, particularly NDM-producers. In comparison, survival analysis using Cox proportional hazards regression identified a higher hazard ratio for patients with a stoma and patients treated with imipenem but a lower hazard ratio for patients with NDM-producing CRKP. OXA-48 carbapenemase gene was the predominant carbapenemase gene in this study. As CRKP infection could lead to a high rate of in-hospital mortality, early detection of the isolates was important to reduce their dissemination.

Highlights

Carbapenems are often used as the last line defence to treat nosocomial infection caused by extended spectrum β-lactamases (ESBL) producing Gram-negative bacteria.selective pressure from the overuse or misuse of carbapenems has resulted in the emergence of carbapenem-resistant Enterobacteriaceae (CRE)
carbapenem-resistant Klebsiella pneumoniae (CRKP) has disseminated in many countries across the world over the past decade, Malaysia notdisseminated being an exception
Detection in our hospital setting has in many countries across the world over the past decad continuously increased from 17 reported CRKP cases in 2013 to 46 reported CRKP cases

Summary

Introduction

Selective pressure from the overuse or misuse of carbapenems has resulted in the emergence of carbapenem-resistant Enterobacteriaceae (CRE). Within the increasing number of reported CRE cases worldwide, carbapenem-resistant Klebsiella pneumoniae (CRKP) takes precedence as the predominant isolate [1,2]. Carbapenem resistance in CRKP is mainly by means of the production of specific carbapenem-hydrolysing β-lactamases known as carbapenemases, and the production of either cephalosporinases (AmpC β-lactamases) or ESBLs with a very low level of carbapenem-hydrolysing activity combined with decreased permeability due to porin loss or alteration [5]. Carbapenem resistance in K. pneumoniae is mainly the result of the acquisition of carbapenemase genes through the horizontal transfer of resistance plasmids, conjugation being the most common means of transfer [6].

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