From the Guidelines
Carbapenemase enzymes are primarily classified into three main molecular classes: Class A, Class B, and Class D, according to the Ambler classification system, which is crucial for guiding antibiotic therapy. The main classes of carbapenemases include:
- Class A: KPC (Klebsiella pneumoniae carbapenemase) 1
- Class B: metallo-β-lactamases (MBLs), such as NDM, VIM, and IMP 1
- Class D: OXA-48-like β-lactamases 1 Understanding the molecular mechanism responsible for the carbapenem-resistant phenotype is essential because each class of enzymes confers variable susceptibility profiles that require different treatment strategies 1. Rapid testing strategies to identify specific carbapenemases are strongly recommended to guide antibiotic therapy and improve patient outcomes 1. The ability to hydrolyse all classes of β-lactams, except monobactams (aztreonam), and the inability of classic serine β-lactamase inhibitors to inhibit MBLs, make them particularly worrisome 1. Key considerations in the treatment of infections caused by carbapenemase-producing Enterobacteriaceae include the use of newer beta-lactam/beta-lactamase inhibitor combinations, such as ceftazidime-avibactam, which are active against Class A and some Class D carbapenemases, but not against Class B metallo-beta-lactamases 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 classes: A, B, C, and D.
- Class A carbapenemases are serine-based enzymes that hydrolyze penicillins, cephalosporins, monobactams, and carbapenems, and are inhibited by clavulanate and tazobactam 2, 3.
- Class B carbapenemases are metallo-beta-lactamases that contain zinc in the active site and hydrolyze all beta-lactams except aztreonam 2, 4.
- Class D carbapenemases are serine-based enzymes that hydrolyze penicillins, cephalosporins, and carbapenems, and are often detected in Acinetobacter baumannii 2, 4.
Bush/Jacoby Classification
The Bush/Jacoby classification system is a functional classification scheme that groups beta-lactamases based on their substrate and inhibitor profiles 5.
- Group 1 includes class C cephalosporinases.
- Group 2 includes classes A and D broad-spectrum, inhibitor-resistant, and extended-spectrum beta-lactamases and serine carbapenemases, which are divided into four phenotypically different groups: 2br, 2be, 2e, and 2f 3.
- Group 3 includes metallo-beta-lactamases, which belong to class B.
Carbapenemase Enzymes
Carbapenemase enzymes are beta-lactamases that hydrolyze carbapenems, which are often used as last-resort antibiotics to treat serious infections 2, 6, 4.