The inoculum effect of antibiotics against CTX-M-extended-spectrum β-lactamase-producing Escherichia coli

Background: Questions remain regarding the use of the cephalosporins to treat infections caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli. For example, should ceftazidime or cefepime be used to treat infections with CTX-M ESBL-producing organisms with low MICs (minimum inhibitory concentrations), according to the new Clinical and Laboratory Standards Institute's (CLSI) recommendations for susceptibility testing? Some studies have reported that in vitro MICs of cephalosporins increase as the inoculum increases, which is the inoculum effect; however, most of the enzymes studied were SHV and TEM. In this study, we aimed to investigate the inoculum effect on ceftazidime, cefepime and four other beta-lactam agents against CTX-M-ESBLs-producing Escherichia coli. Methods: Antibiotic susceptibilities were determined using broth microdilution MIC methodology according to the CLSI recommended with standard and 100-fold-higher inocula. Results: An inoculum effect on meropenem and cefminox was not detected. The size of the inoculum affected piperacillin/tazobactam activity against only 4 strains, all CTX-M-14 genotypes. The inoculum size affected the activity of ceftazidime, cefepime and cefotaxime against 35%, 85%, 100% of strains, respectively. Among the strains with an inoculum effect, CTX-M-14 was the most common ESBL genotype. Conclusions: These findings suggest that meropenem is the most active compound against serious infections caused by Escherichia coli producing ESBLs. Cefminox and piperacillin-tazobactam exhibit strong activity against many strains. Until further studies are performed, clinicians should be aware that third- and fourth-generation cephalosporins (such as ceftazidime and cefepime) are not reliable for serious infections even though in vitro tests indicate susceptibility.