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The Use of a β-lactamase-based Conductimetric Biosensor Assay to Detect Biomolecular Interactions
Published on: February 1, 2018
Detection of plasmid-mediated class C beta-lactamases
1Division of Infectious Diseases, University of Pittsburgh Medical Center, Falk Medical Building Suite 3A, 3601 Fifth Avenue, Pittsburgh, PA 15213, USA.
Abstract:
Plasmid-mediated class C beta-lactamases are reported from Enterobacteriaceae with increasing frequency. They likely originate from chromosomal AmpC of certain Gram-negative bacterial species and subsequently are mobilized onto transmissible plasmids. There are reports of unfavorable clinical outcomes in patients infected with these organisms and treated with broad-spectrum cephalosporins. However, unlike class A extended-spectrum beta-lactamases (ESBLs), no screening and confirmatory tests have been uniformly established for strains that produce class C beta-lactamases. Reduced susceptibility to cefoxitin is a sensitive but not specific indicator of class C beta-lactamase production. Simple confirmatory tests including tests using boronic acid compounds as specific class C beta-lactamase inhibitors have recently been developed. Their utilization will enable clinical microbiology laboratories to report those strains producing plasmid-mediated class C beta-lactamases as being resistant to all broad-spectrum cephalosporins, thus allowing physicians to prescribe appropriate antimicrobial therapy.
Insights
Plasmid-mediated class C beta-lactamases are emerging in Enterobacteriaceae, leading to treatment challenges. New tests using boronic acid inhibitors can now reliably detect these enzymes, guiding appropriate antimicrobial therapy.
Area of Science:
- Microbiology
- Antimicrobial Resistance
- Clinical Diagnostics
Background:
- Increasing prevalence of plasmid-mediated class C beta-lactamases (pC-beta-Ls) in Enterobacteriaceae.
- These enzymes, often derived from chromosomal AmpC, are linked to poor clinical outcomes with broad-spectrum cephalosporins.
- Lack of standardized screening and confirmatory tests for pC-beta-Ls, unlike for ESBLs.
Purpose of the Study:
- To address the need for reliable detection of plasmid-mediated class C beta-lactamases.
- To evaluate simple confirmatory tests for identifying these resistance mechanisms.
- To facilitate accurate reporting of resistance to guide antimicrobial therapy.
Main Methods:
- Review of existing literature on class C beta-lactamases and their detection.
- Discussion of cefoxitin susceptibility as a preliminary indicator.
- Highlighting the development and utility of boronic acid-based inhibitor tests.
Main Results:
- Plasmid-mediated class C beta-lactamases are a growing clinical concern.
- Cefoxitin resistance is a sensitive but non-specific marker for class C beta-lactamase production.
- Boronic acid-based tests offer a simple and specific method for confirmation.
Conclusions:
- Newly developed boronic acid inhibitor tests enable accurate identification of pC-beta-Ls.
- Effective laboratory reporting of pC-beta-L-producing strains is crucial.
- Accurate detection allows for appropriate antimicrobial selection, improving patient outcomes.
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