Carbapenem Resistance: Mechanisms and Drivers of Global Menace

Abstract

The emergence of carbapenem-resistant bacterial pathogens is a significant and mounting health concern across the globe. At present, carbapenem resistance (CR) is considered as one of the most concerning resistance mechanisms and mainly found in gram-negative bacteria of the Enterobacteriaceae family. Although carbapenem resistance has been recognized in Enterobacteriaceae from last 20 years or so, recently it emerged as a global health issue as CR clonal dissemination of various Enterobacteriaceae members especially E. coli, and Klebsiella pneumoniae are reported from across the globe at an alarming rate. Phenotypically, carbapenems resistance is in due to the two key mechanisms, like structural mutation coupled with β-lactamase production and the ability of the pathogen to produce carbapenemases which ultimately hydrolyze the carbapenem. Additionally, penicillin-binding protein modification and efflux pumps are also responsible for the development of carbapenem resistance. Carbapenemases are classified into different classes which include Ambler classes A, B, and D. Several mobile genetic elements (MGEs) have their potential role in carbapenem resistance like Tn4401, Class I integrons, IncFIIK2, IncF1A, and IncI2. Taking together, resistance against carbapenems is continuously evolving and posing a significant health threat to the community. Variable mechanisms that are associated with carbapenem resistance, different MGEs, and supplementary mechanisms of antibiotic resistance in association with virulence factors are expanding day by day. Timely demonstration of this global health concern by using molecular tools, epidemiological investigations, and screening may permit the suitable measures to control this public health menace.

The Emergence of Carbapenem-Resistant Gram-Negative Bacteria in Mizoram, Northeast India

“…Class B is found in Acinetobacter species, P. aeruginosa, and Enterobacteriaceae and includes VIM, SPM, GIM, and IMP-type enzymes. Class D includes the OXA-type, which is again more common among Acinetobacter [5].…”

Nanobiosystems for Antimicrobial Drug-Resistant Infections

“…They are very potent against resistant bacteria, including various ESBL (extended spectrum β-lactamases)-producing microbes. Carbapenems are usually the last resort antimicrobials considered as “treatment of choice” against serious infections due to their “concentration-independent killing effect” [ 132 ].…”

Detection of blaKPC and blaNDM carbapenemase genes among Klebsiella pneumoniae isolates in Addis Ababa, Ethiopia: Dominance of blaNDM

“…Resistance to carbapenems is mainly through carbapenemase enzyme production. Productions of other enzymes that have weak carbapenemase activity such as ESBLs and AmpC β-lactamases together with porin alteration, drug efflux pumps, as well as alterations in penicillin-binding proteins are also mentioned as additional resistance mechanisms [ 1 , 5 – 7 ]. Based on their molecular structures (Ambler classification system) carbapenemases belong to class A, B, and D of β-lactamases [ 5 – 8 ].…”