The carbapenem class of antibiotics is typically considered the last resort for the treatment of multi-drug resistant organisms (MDROs). Some CRE produces carbapenemase (beta-lactamases) as a mechanism of resistance that hydrolyzes or breaks down carbapenems and related antimicrobials making them ineffective. These organisms, referred to as carbapenemase-producing Enterobacterales (CPE), are of key concern because they are often associated with extensive, sometimes complete, antibiotic resistance.
The carbapenemases are included in molecular classes A, B, and D:
- Class A enzymes: Serine carbapenemases, including Klebsiella pneumoniae carbapenemase (KPC)
- Class B enzymes: Metallo-beta-lactamase (MBL) carbapenemases that require zinc for activity which includes VIM, New Delhi Metallo-beta-lactamase (NDM), and IMP
- Class D enzymes: Oxacillinase (OXA) carbapenemases, including OXA-48
The production of KPC is currently the most common carbapenemase among CRE in the United States, most commonly encountered on plasmids in K. pneumoniae isolates. KPC can also occur with K. oxytoca, Enterobacter species, E. coli, Citrobacter freundii, Salmonella species, Serratia species, and other gram-negative bacilli.
Of the different types of beta-lactamases with carbapenemase activity, the MBLs are of the greatest concern globally. This is because MBLs were previously only found in Pseudomonas aeruginosa. Recently, reports of Klebsiella pneumoniae that produce MBLs now have scientists concerned with new transmissible carbapenem resistance mechanisms that are occurring in Enterobacterales. NDM is the most common MBL worldwide; frequently encountered in India and Pakistan.
