From the Guidelines
Carbapenemase enzymes are classified into four molecular classes: A, B, C, and D, based on the Ambler classification system, with Class A including KPC, Class B including metallo-β-lactamases (MBLs) like NDM, VIM, and IMP, and Class D including OXA-48-like enzymes. The Ambler classification system is crucial for guiding treatment approaches, as different classes of enzymes confer variable susceptibility profiles 1.
Key Characteristics of Each Class
- Class A carbapenemases, such as KPC, utilize a serine residue at their active site and are inhibited by certain β-lactamase inhibitors 1.
- Class B carbapenemases, or metallo-β-lactamases (MBLs), including NDM, VIM, and IMP, require zinc ions for their activity and are not inhibited by traditional β-lactamase inhibitors but rather by metal chelators 1.
- Class D carbapenemases, primarily OXA-type enzymes like OXA-48, also use serine at their active site but have distinct inhibition profiles 1.
Clinical Importance
Understanding the Ambler classification is vital for selecting appropriate antimicrobial therapy, as the effectiveness of different inhibitors varies among the classes 1. For instance, newer β-lactamase inhibitors can target specific classes, highlighting the need for rapid testing to identify the carbapenemase type and guide therapy 1. Rapid testing strategies are strongly recommended to identify specific carbapenemases and guide antibiotic therapy, especially considering the impact of timely initiation of active antibiotic therapy on patient outcomes 1.
From the Research
Molecular Classification of Carbapenemase Enzymes
The molecular classification of carbapenemase enzymes is based on the Ambler classification system, which categorizes these enzymes into four main classes: A, B, C, and D.
- Class A carbapenemases are serine-based enzymes that hydrolyze penicillins, classical cephalosporins, monobactam, and imipenem and meropenem 2.
- Class B enzymes are metallo-beta-lactamases that contain zinc in the active site and hydrolyze all beta-lactams with the exception of aztreonam 3, 4.
- Class D carbapenemases are also serine-based enzymes and consist of OXA-type beta-lactamases frequently detected in Acinetobacter baumannii 3, 4.
Characteristics of Carbapenemase Classes
The characteristics of each carbapenemase class are distinct and include:
- Class A carbapenemases: inhibited by clavulanate and tazobactam, and can be encoded by both chromosomal and plasmid-mediated genes 2.
- Class B carbapenemases: the most clinically significant carbapenemases, and have been reported worldwide with their genes being plasmid- and integron-located 3.
- Class D carbapenemases: compromise the efficacy of imipenem and meropenem significantly, and are being increasingly reported, mostly in Acinetobacter baumannii 3.
Clinical Significance of Carbapenemases
The clinical significance of carbapenemases lies in their ability to hydrolyze a broad variety of beta-lactams, including carbapenems, cephalosporins, penicillin, and aztreonam, making them a major concern for treating serious infections 5, 6.
- The emergence of carbapenemase-producing bacteria has limited the options for treatment, and the dissemination of these enzymes across different bacterial groups has raised concerns over their prevalence and the need for public health measures to control their propagation 5.