SHV-type extended-spectrum beta-lactamase production is associated with Reduced cefepime susceptibility in

Dóra Szabó1, Robert A Bonomo, Fernanda Silveira

  • 1Division of Infectious Diseases, University of Pittsburgh, Pittsburgh, PA 15213, USA.

Insights

Cefepime effectiveness against Enterobacter cloacae is challenged by extended-spectrum beta-lactamases (ESBLs). Many ESBL-producing strains show high cefepime resistance, potentially misclassified as susceptible by current guidelines.

Area of Science:

  • Microbiology
  • Infectious Diseases
  • Pharmacology

Background:

  • Cefepime is a fourth-generation cephalosporin antibiotic.
  • Enterobacter cloacae is an opportunistic pathogen.
  • Extended-spectrum beta-lactamases (ESBLs) confer resistance to beta-lactam antibiotics.

Purpose of the Study:

  • To investigate the prevalence and characteristics of ESBL production in Enterobacter cloacae bloodstream isolates.
  • To evaluate the in vitro susceptibility of these isolates to cefepime.
  • To assess the reliability of phenotypic ESBL detection methods.

Main Methods:

  • PCR amplification of bla genes to detect ESBLs.
  • Determination of minimum inhibitory concentrations (MICs) for cefepime.
  • Comparison of cefepime MICs with Clinical and Laboratory Standards Institute (CLSI) breakpoints.

Main Results:

  • One-third of E. cloacae isolates produced SHV-type ESBLs, often alongside AmpC hyperproduction and TEM-1.
  • ESBL-producing strains exhibited significantly higher cefepime MICs (MIC(90) = 64 µg/ml) compared to non-producers (MIC(90) = 0.5 µg/ml).
  • Two-thirds of ESBL-producing isolates were misclassified as susceptible to cefepime using current CLSI breakpoints.

Conclusions:

  • The emergence of ESBLs in E. cloacae compromises cefepime efficacy.
  • Current cefepime breakpoints may overestimate susceptibility in ESBL-producing strains.
  • Reevaluation of cefepime pharmacokinetic/pharmacodynamic (PK/PD) parameters and clinical breakpoints for E. cloacae is warranted.

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