From the Guidelines
The Bush-Jacoby classification system is not the primary system used for organizing carbapenemase enzymes, instead, the Ambler classification system is utilized, which categorizes these enzymes into Class A, Class B, and Class D. The Ambler classification system is crucial for understanding the molecular mechanisms of carbapenem resistance in Enterobacteriaceae, as it guides treatment decisions based on the variable susceptibility profiles conferred by each class of enzymes 1.
Key Classes of Carbapenemases
- Class A carbapenemases include KPC (Klebsiella pneumoniae carbapenemase), which remains the most common carbapenemase, although there is an increasing detection of non-KPC-producing CRE worldwide 1.
- Class B carbapenemases, also known as metallo-β-lactamases (MBLs), include NDM, VIM, and IMP enzymes, which are particularly worrisome due to their ability to hydrolyze all classes of β-lactams, except monobactams (aztreonam) 1.
- Class D carbapenemases primarily consist of OXA-type enzymes, such as OXA-48-like β-lactamases, which show variable inhibition by traditional inhibitors 1.
Clinical Importance
Understanding the molecular class of a carbapenemase is crucial because it influences the choice of antibiotic therapy, with different classes requiring different treatment strategies 1. Rapid testing strategies to identify specific carbapenemases are strongly recommended to guide antibiotic therapy and improve outcomes in critically ill patients. This is particularly important because the time from blood culture collection to the start of active antibiotic therapy significantly influences the outcome of patients with bloodstream infections caused by KPC-producing K. pneumoniae 1.
From the Research
Molecular Classification of Carbapenemase Enzymes
The molecular classification of carbapenemase enzymes is based on their amino acid sequence and divides them into four main classes: A, B, C, and D.
- Class A carbapenemases are serine-based enzymes that hydrolyze penicillins, cephalosporins, monobactams, and carbapenems 2.
- Class B enzymes are metallo-beta-lactamases that contain zinc in the active site and hydrolyze all beta-lactams except aztreonam 3, 4.
- Class D carbapenemases are also serine-based enzymes and are often found in Acinetobacter baumannii, where they compromise the efficacy of imipenem and meropenem 3, 4.
Bush-Jacoby-Medeiros Classification System
The Bush-Jacoby-Medeiros classification system is a functional classification scheme that groups beta-lactamases based on their substrate and inhibitor profiles 5.
- Class A carbapenemases are divided into four phenotypically different groups (2br, 2be, 2e, and 2f) according to this system 2.
- The system also includes group 1 (class C) cephalosporinases, group 2 (classes A and D) broad-spectrum, inhibitor-resistant, and extended-spectrum beta-lactamases and serine carbapenemases, and group 3 metallo-beta-lactamases 5.
Carbapenemase Enzymes and Their Characteristics
Carbapenemase enzymes have the ability to hydrolyze a wide range of beta-lactam antibiotics, including penicillins, cephalosporins, monobactams, and carbapenems 3, 4.