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Testing the Role of Multicopy Plasmids in the Evolution of Antibiotic Resistance
09:00

Testing the Role of Multicopy Plasmids in the Evolution of Antibiotic Resistance

Published on: May 2, 2018

Stability of cefdinir (C1-983, FK482) to extended-spectrum plasmid-mediated beta-lactamases

D J Payne1, S G Amyes

  • 1Department of Medical Microbiology, Medical School, University of Edinburgh.

Journal of Medical Microbiology
|February 1, 1993
PubMed

Insights

This study investigated the stability of cefdinir against 15 extended-spectrum beta-lactamases (ESBLs). Cefdinir demonstrated greater stability than cefuroxime and cefixime but was less stable than ceftazidime against specific enzymes.

Area of Science:

  • Microbiology
  • Biochemistry
  • Pharmacology

Background:

  • Extended-spectrum beta-lactamases (ESBLs) are enzymes produced by bacteria that confer resistance to beta-lactam antibiotics.
  • Plasmid-encoded ESBLs are a significant challenge in treating bacterial infections.
  • Understanding the hydrolysis kinetics of different beta-lactam antibiotics by various ESBLs is crucial for guiding antimicrobial therapy.

Purpose of the Study:

  • To determine the hydrolysis kinetics (Vmax, Km, Vmax/Km) of cefdinir and other beta-lactam antibiotics by purified ESBLs.
  • To compare the stability of cefdinir against a panel of 15 ESBLs and the narrow-spectrum beta-lactamase TEM-1.
  • To evaluate the relative resistance of cefdinir, cefuroxime, cefixime, and ceftazidime to hydrolysis by these enzymes.

Main Methods:

  • Purification of fourteen plasmid-encoded extended-spectrum beta-lactamases from clinical isolates of Escherichia coli.
  • Enzymatic assays to determine Vmax, Km, and Vmax/Km for ampicillin, carbenicillin, cephaloridine, cephalexin, cefuroxime, cefixime, cefdinir, ceftazidime, and cefotaxime using eight ESBLs and TEM-1.
  • Determination of relative hydrolysis rates for the remaining six ESBLs using the same panel of antibiotics.

Main Results:

  • Cefdinir exhibited Vmax/Km or relative hydrolysis rates equal to or lower than ampicillin, cephaloridine, cephalexin, and cefotaxime across all tested enzymes.
  • Cefdinir demonstrated greater stability against the 15 ESBLs compared to cefuroxime and cefixime.
  • Ceftazidime showed higher stability than cefdinir against eight of the tested ESBLs.

Conclusions:

  • Cefdinir possesses a favorable stability profile against a broad range of extended-spectrum beta-lactamases compared to cefuroxime and cefixime.
  • Ceftazidime remains a more robust option against certain ESBL-producing bacteria.
  • These findings contribute to understanding antibiotic resistance mechanisms and inform clinical decisions for treating infections caused by ESBL-producing Enterobacteriaceae.

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