A Review of Carbapenem Resistance in Enterobacterales and Its Detection Techniques

Abstract

Infectious disease outbreaks have caused thousands of deaths and hospitalizations, along with severe negative global economic impacts. Among these, infections caused by antimicrobial-resistant microorganisms are a major growing concern. The misuse and overuse of antimicrobials have resulted in the emergence of antimicrobial resistance (AMR) worldwide. Carbapenem-resistant Enterobacterales (CRE) are among the bacteria that need urgent attention globally. The emergence and spread of carbapenem-resistant bacteria are mainly due to the rapid dissemination of genes that encode carbapenemases through horizontal gene transfer (HGT). The rapid dissemination enables the development of host colonization and infection cases in humans who do not use the antibiotic (carbapenem) or those who are not hospitalized but interacting with environments and hosts colonized with carbapenemase-producing (CP) bacteria. There are continuing efforts to characterize and differentiate carbapenem-resistant bacteria from susceptible bacteria to allow for the appropriate diagnosis, treatment, prevention, and control of infections. This review presents an overview of the factors that cause the emergence of AMR, particularly CRE, where they have been reported, and then, it outlines carbapenemases and how they are disseminated through humans, the environment, and food systems. Then, current and emerging techniques for the detection and surveillance of AMR, primarily CRE, and gaps in detection technologies are presented. This review can assist in developing prevention and control measures to minimize the spread of carbapenem resistance in the human ecosystem, including hospitals, food supply chains, and water treatment facilities. Furthermore, the development of rapid and affordable detection techniques is helpful in controlling the negative impact of infections caused by AMR/CRE. Since delays in diagnostics and appropriate antibiotic treatment for such infections lead to increased mortality rates and hospital costs, it is, therefore, imperative that rapid tests be a priority.

Genomic Insights into the First Emergence of blaNDM-5-Carrying Carbapenem-Resistant Salmonella enterica Serovar London Strain in China

“…NDM-5 carbapenemase was primarily detected in E. coli and remains relatively rare in other members of the Enterobacteriaceae family, such as NTS and Klebsiella pneumoniae. 34,35 However, our study reveals the emergence of a Salmonella strain, designated as A132, harboring the NDM-5 carbapenemase gene. A132 belongs to the serovar London, which recognized as one of the top five prevalent serovars responsible for human salmonellosis in China.…”

In vitro activity of ceftazidime–avibactam and comparators against OXA-48-like Enterobacterales collected between 2016 and 2020

“…Carbapenems are a class of broad-spectrum β-lactam antibiotics, initially approved in 1985 ( 1 ). These have been used to treat multidrug-resistant bacteria, including Enterobacterales producing extended-spectrum β-lactamases (ESBLs) and ampicillinase-C ( 1 – 3 ).…”

“…Carbapenems are a class of broad-spectrum β-lactam antibiotics, initially approved in 1985 ( 1 ). These have been used to treat multidrug-resistant bacteria, including Enterobacterales producing extended-spectrum β-lactamases (ESBLs) and ampicillinase-C ( 1 – 3 ). However, overuse of carbapenems led to the emergence of carbapenem-resistant Enterobacterales (CREs), which was first identified in 1996 ( 1 , 3 ).…”

“…These have been used to treat multidrug-resistant bacteria, including Enterobacterales producing extended-spectrum β-lactamases (ESBLs) and ampicillinase-C ( 1 – 3 ). However, overuse of carbapenems led to the emergence of carbapenem-resistant Enterobacterales (CREs), which was first identified in 1996 ( 1 , 3 ). Notably, prior to 2001, about 99.9% of Enterobacterales were susceptible to carbapenems ( 4 ).…”

Potentiation of Antibiotic Activity of Aztreonam against Metallo-β-Lactamase-Producing Multidrug-Resistant Pseudomonas aeruginosa by 3-O-Substituted Difluoroquercetin Derivatives

“…Like other β-lactam antibiotics, carbapenems have a four-membered lactam ring that is vulnerable to hydrolysis by bacterial enzymes called carbapenemases, a class of β-lactamases [ 5 ]. Most β-lactamases are divided into four groups (Ambler classes A, B, C, and D), among which KPC (class A), OXA-48 types (class D), and class B metallo-β-lactamases (MBLs: NDM, VIM, and IMP) are the most effective in terms of the enzymatic activity and geographical spread [ 6 , 7 ]. Therefore, numerous efforts have been put forth to discover inhibitors against these resistance-related bacterial targets.…”