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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.
Abstract:
Cefepime is a potentially useful antibiotic for treatment of infections with Enterobacter cloacae. However, in our institution the MIC(90) for E. cloacae bloodstream isolates is 16 microg/ml. PCR amplification of bla genes revealed that one-third (15/45) of E. cloacae bloodstream isolates produced SHV-type extended-spectrum beta-lactamases (ESBLs) in addition to hyperproduction of AmpC-type beta-lactamases. The majority (11/15) of ESBL producers also produced the TEM-1 beta-lactamase. The SHV types included SHV-2, -5, -7, -12, -14, and -30. All but two of the ESBL-producing E. cloacae isolates, but none of the non-ESBL-producing strains, had MICs of cefepime of >or=2 microg/ml. The MIC(90) for cefepime for ESBL-producing strains was 64 mug/ml, while for non-ESBL producers it was 0.5 microg/ml. Using current Clinical and Laboratory Standards Institute breakpoints for cefepime, two thirds (10/15) of ESBL-producing isolates would have been regarded as susceptible to cefepime. Phenotypic ESBL detection methods were generally unreliable with these E. cloacae isolates. Based on these results, pharmacokinetic, pharmacodynamic, and clinical reevaluation of cefepime breakpoints for E. cloacae may be prudent.
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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