Characterisation of Non-Carbapenemase-Producing Carbapenem-Resistant Klebsiella pneumoniae Based on Their Clinical and Molecular Profile in Malaysia

Abstract

Non-carbapenemase-producing carbapenem-resistant Klebsiella pneumoniae (NC-CRKP) confers carbapenem resistance through a combination of chromosomal mutations and acquired non-carbapenemase resistance mechanisms. In this study, we aimed to evaluate the clinical and molecular profiles of NC-CRKP isolated from patients in a tertiary teaching hospital in Malaysia from January 2013 to October 2019. During the study period, 54 NC-CRKP-infected/colonised patients’ isolates were obtained. Clinical parameters were assessed in 52 patients. The all-cause in-hospital mortality rate among NC-CRKP patients was 46.2% (24/52). Twenty-three (44.2%) patients were infected, while others were colonised. Based on the Charlson Comorbidity Index (CCI) score, 92.3% (48/52) of the infected/colonised patients had a score of ≥ 1. Resistance genes found among the 54 NC-CRKP isolates were blaTEM, blaSHV, blaCTX-M, blaOXA, and blaDHA. Porin loss was detected in 25/54 (46.3%) strains. None of the isolated strains conferred carbapenem resistance through the efflux pumps system. In conclusion, only 25/54 (46.3%) NC-CRKP conferred carbapenem resistance through a combination of porin loss and the acquisition of non-carbapenemase resistance mechanisms. The carbapenem resistance mechanisms for the remaining strains (53.7%) should be further investigated as rapid identification and distinction of the NC-CRKP mechanisms enable optimal treatment and infection control efforts.

Genomic and functional characterization of carbapenem-resistant Klebsiella pneumoniae from hospital wastewater

“…This is an interesting phenomenon. NC-CRKP confers carbapenem resistance association with chromosomal mutations (such as porin gene mutation, and overproduction of efflux pump) and acquired non-carbapenemase resistance mechanisms (acquisition or upregulation of a β-lactamase such as ESBL or AmpC β-lactamase) [ 26 , 27 ]. Meanwhile, loss or deficiency of outer membrane porins were associated with carbapenem resistance [ 28 ].…”

Antimicrobial and Diagnostic Stewardship of the Novel β-Lactam/β-Lactamase Inhibitors for Infections Due to Carbapenem-Resistant Enterobacterales Species and Pseudomonas aeruginosa

“…A review of the advantages and limitations of the most common phenotypic detection tests is provided in Table 2 . Genotypic testing methods are more sensitive and can detect the presence of efflux pumps or porin deletions that can contribute to carbapenem resistance [ 68 ]. However, they are associated with increased costs and require specialized equipment.…”

Diverse Role of blaCTX-M and Porins in Mediating Ertapenem Resistance among Carbapenem-Resistant Enterobacterales

“…However, the implications of carbapenem resistance occurring in strains that lack a carbapenemase (NCP) have been less studied. NCP-related infections have exhibited similar infection-related mortality and healthcare utilization as CPE-related infections [5]. While carbapenemase-producing Enterobacterales (CPE) is the predominant global driver of CRE, NCPE predominance has been emerging in some regions, including South Texas, with rates as high as 61% [6,7].…”

“…Moreover, NCPE is attributable to its diverse underlying mechanisms, which most frequently are combinatorial and concerted and cannot be detected by the presence/absence of a specific gene. It is suspected that higher production of cephalosporinases including extended-spectrum β-lactamase (ESBL) enzymes, like bla CTX-M , Ambler class C (e.g., bla AmpC ), and certain variants of bla SHV contribute to carbapenem resistance among NCP-CRE (4,5). However, additional concerted anti-carbapenem resistance mechanisms with cephalosporinase production, such as loss or altered outer membrane protein (Omp) impacting intracellular carbapenem concentration and rate of hydrolysis (level of activity of cephalosporinases) have been implicated and requires further investigation [5].…”