From the Guidelines
Carbapenemase enzymes are primarily classified using the Ambler classification, which divides them into four molecular classes: Class A, Class B, Class C, and Class D, and the Bush-Jacoby classification, which organizes them into three main groups: Group 1, Group 2, and Group 3. The Ambler classification is structure-based and includes Class A (serine carbapenemases like KPC and SME), Class B (metallo-β-lactamases that require zinc ions, including NDM, VIM, and IMP), Class C (primarily cephalosporinases with limited carbapenemase activity like CMY), and Class D (OXA-type carbapenemases) 1. The Bush-Jacoby classification is function-based and considers substrate profiles and inhibitor susceptibility, organizing carbapenemases into Group 1 (cephalosporinases), Group 2 (serine β-lactamases with multiple subgroups, with carbapenemases mainly in 2f), and Group 3 (metallo-β-lactamases) 1. Key points to consider in the classification and management of carbapenemase-producing organisms include:
- The global spread of carbapenemase-producing organisms, particularly KPC, NDM, and OXA-48, represents a significant clinical challenge requiring proper identification for effective management.
- Understanding the classification systems is essential for identifying appropriate treatment strategies, as different carbapenemase types respond differently to β-lactamase inhibitors.
- Rapid testing should be used to identify specific carbapenemase families (e.g., KPC, NDM, VIM, OXA-48-like) to guide antibiotic therapy, with a strong recommendation for its use in patients with infections caused by carbapenem-resistant Enterobacterales (CRE) 1. The most recent and highest quality study, published in the International Journal of Antimicrobial Agents in 2022 1, emphasizes the importance of knowing the molecular mechanism responsible for the carbapenem-resistant phenotype, as each class of enzymes confers variable susceptibility profiles that require different treatment strategies.
From the Research
Molecular Classification of Carbapenemase Enzymes
The molecular classification of carbapenemase enzymes can be categorized into two main systems:
- Ambler classification
- Bush Jacoby Classification
Ambler Classification
The Ambler classification system categorizes carbapenemases into four molecular classes:
- Class A: includes chromosomally-encoded and clavulanic acid-inhibited IMI, NMC-A, and SME, as well as plasmid-encoded KPC enzymes and GES-type enzymes 2
- Class B: comprises metallo-beta-lactamases, mostly of the IMP and VIM series, which are the most clinically significant carbapenemases 2, 3
- Class D: includes OXA-48-like beta-lactamases, which are being increasingly reported, mostly in Acinetobacter baumannii, and compromise the efficacy of imipenem and meropenem significantly 2, 4
Bush Jacoby Classification
There is limited information available on the Bush Jacoby Classification system in the provided studies. However, the Ambler classification system is widely used to categorize carbapenemases into different molecular classes. Some studies have evaluated the performance of assays in detecting carbapenemase activity and characterizing the carbapenemase class according to the Ambler classification 5, 6. For example, the mCIMplus assay can detect carbapenemase activity within 8 hours and characterize the carbapenemase class within 20 hours, with a sensitivity of 99.3% at 8 hours and 98.5% at 20 hours 6.
Key Points
- The Ambler classification system is widely used to categorize carbapenemases into different molecular classes.
- Class A, B, and D carbapenemases are the most commonly reported classes.
- The mCIMplus assay can detect carbapenemase activity and characterize the carbapenemase class according to the Ambler classification.
- The detection of carbapenemase activity and characterization of the carbapenemase class can guide antimicrobial therapy and facilitate infection control measures 6.