In vitro interaction between cefepime and amoxicillin-clavulanate against extended-spectrum β-lactamase-producing Escherichia coli.

We read with interest the article by Chopra et al. (1) suggesting that empirical therapy with cefepime for bloodstream infections due to extended-spectrum-lactamase (ESBL)-producing Enterobacteriaceae is associated with excess mortality. The effectiveness of cefepime would be compromised by ESBL production, resulting in higher MICs (2, 3). Several beta-lactamase inhibitors (including clavulanate) are active against ESBLs, and this property forms the basis for in vitro screening of Gram-negative bacteria for these enzymes. Combining clavulanate with oxy-imino-cephalosporins that have relatively low MICs despite ESBL production may provide an alternative to penem use (4). We tested the combination of cefepime and amoxicillinclavulanate (AC) in vitro, by comparison with the ceftazidime-AC combination, against 63 previously characterized ESBL-expressing Escherichia coli isolates collected from 2009 to 2011 (5). In addition, as cefepime is relatively resistant to degradation by AmpC -lactamase, we tested these combinations against 11 E. coli strains with constitutively overexpressed or plasmid-mediated AmpC -lactamase production and ESBLs (Table 1). We used the disk diffusion method and Clinical and Laboratory Standards Institute (CLSI) guidelines. Isolates were screened for ESBL production by the double-disk synergy test of cefotaxime, ceftazidime, cefepime (30 g), and AC disks on Muller-Hinton agar. AmpC producers were subjected to the double-disk synergy test on cloxacillin-containing MuellerHinton agar (6). Multiplex PCR was used to characterize -lactamase genes, including blaCTX-M, blaSHV, blaTEM, blaOXA-1, blaCMY, and blaDHA, using previously described methods and primers, followed by sequencing (7). The MICs of cefepime, ceftazidime, and AC were determined by the Etest method (AB bioMérieux, Solna, Sweden). The Etest has also been used to