From the Guidelines
Class C beta-lactamases in the Ambler classification are chromosomally encoded cephalosporinases that belong to the serine beta-lactamase group, and the most effective treatment option for infections caused by these enzymes is ceftazidime-avibactam, as it restores the antibacterial activity of ceftazidime against Ambler class A, class C, and some class D enzymes 1.
Characteristics of Class C Beta-Lactamases
Class C enzymes have a serine residue at their active site and are characterized by their ability to hydrolyze cephalosporins more efficiently than penicillins. These enzymes are typically resistant to beta-lactamase inhibitors like clavulanic acid, sulbactam, and tazobactam, making infections caused by organisms producing these enzymes more challenging to treat. Common examples include AmpC beta-lactamases found in organisms like Enterobacter species, Citrobacter freundii, and Pseudomonas aeruginosa.
Treatment Options
When treating infections caused by AmpC-producing organisms, carbapenems (like meropenem or imipenem) are often effective, as they remain stable against Class C hydrolysis. Cefepime may also be effective in some cases due to its rapid penetration through porins and relative stability against these enzymes. However, the use of ceftazidime-avibactam has been shown to be effective in treating infections caused by Class C beta-lactamases, including those producing AmpC enzymes 1. Additionally, meropenem-vaborbactam and imipenem-cilastatin-relebactam have also been recommended as treatment options for CRE-BSI, although the evidence is limited 1.
Key Considerations
Understanding the characteristics of Class C beta-lactamases is crucial for appropriate antibiotic selection in clinical practice. The use of rapid testing strategies to identify specific carbapenemases and guide antibiotic therapy is strongly recommended, as it can improve patient outcomes by allowing for early initiation of active antibiotic therapy 1. In summary, the treatment of infections caused by Class C beta-lactamases requires a thorough understanding of the characteristics of these enzymes and the use of effective antibiotic therapies, such as ceftazidime-avibactam.
From the Research
Ambler Classification of Beta-Lactamase Genes - Class C
- The Ambler classification is a system used to categorize beta-lactamase enzymes based on their molecular structure 2.
- Class C beta-lactamases, also known as AmpC beta-lactamases, are a type of enzyme that can hydrolyze a wide range of beta-lactam antibiotics, including cephalosporins and penicillins 2.
- AmpC beta-lactamases are typically encoded on the chromosomes of many Enterobacteriaceae, but can also be plasmid-mediated, allowing them to spread to other bacteria 2.
- The production of AmpC beta-lactamases can be inducible or constitutive, resulting in different resistance phenotypes 3, 4.
- Inducible AmpC producers, such as Enterobacter spp., may appear susceptible to third-generation cephalosporins, but can easily yield mutants that are resistant to these drugs, resulting in treatment failures 3, 4.
Treatment Options for AmpC-Producing Enterobacterales
- Carbapenems are often considered the preferred option for treating severe infections caused by AmpC-producing Enterobacterales, especially when adequate source control is not achieved 5, 3, 4.
- Cefepime is also supported by substantial clinical evidence as an effective carbapenem-sparing option for treating AmpC-producing Enterobacterales 6, 3, 4.
- However, the use of cefepime may be associated with a higher risk of neurological adverse events compared to carbapenems 6.
- Other treatment options, such as piperacillin/tazobactam, may also be effective, but the risk of derepression and emergence of resistance during treatment is a concern 4.
Diagnostic Issues and Epidemiological Impact
- The diagnosis of AmpC-producing Enterobacterales can be challenging, and techniques to identify these isolates are still evolving and not yet optimized for the clinical laboratory 2.
- AmpC-producing Enterobacterales are a major threat to human health, particularly in healthcare-associated infections, and can cause a wide range of infections, including bloodstream infections and pneumonia 3, 4.