SHV-type extended-spectrum beta-lactamase production is associated with reduced cefepime susceptibility in Enterobacter cloacae

Cefepime is a potentially useful antibiotic for treatment of infections with Enterobacter cloacae. However, in our institution the MIC,, for E. cloacae bloodstream isolates is 1.6 mu g/ml. PCR amplification of bla genes revealed that one-third (15145) of E. cloacae bloodstream isolates produced SRV-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 >= 2 mu g/ml. The MIC90 for cefepime for ESBL-producing strains was 64 mu g/ml, while for non-ESBL producers it was 0.5 mu g/ml. Using current Clinical and Laboratory Standards Institute breakpoints for cefepime, two thirds (10115) 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.