Effect of inoculum size on the antibacterial activity of cefpirome and cefepime against Klebsiella pneumoniae strains producing SHV extended-spectrum β-lactamases

Abstract

Objective. To determine the effects of varying inoculum size on in vitro susceptibility of SHV extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae isolates to cefepime and cefpirome compared to previously established cephalosporins and aztreonam. Methods. Antibiotic susceptibilities were determined by disk diffusion test, the MIC broth microdilution method, and time-kill studies with two different inocula of 105 and 107 CFU/mL. The strains were classified into four groups acccording to the type of β-lactamase they produce: SHV-2, SHV-5, SHV-12, and ESBL-negative klebsiellae. Results. The antibacterial activities of cefpirome and cefepime were comparable to that of cefotaxime, but were significantly greater than those of ceftazidime and aztreonam. An inoculum effect was detected for all broad-spectrum cephalosporins, but it was more pronounced with cefpirome and cefepime compared to older cephalosporins. The disk diffusion test proved to be not sensitive enough for the detection of an inoculum effect, particularly for cefepime. Conclusions. The present study found that most SHV-producing klebsiellae have MICs of cefpirome that imply susceptibility at the moderate inoculum size, in spite of the fact that, according to the NCCLS, all ESBL producers should be considered resistant to all cephalosporins, independent of MIC values. With a high inoculum, most of the strains seemed to be resistant to both antibiotics. Furthermore, the bactericidal activities of cefpirome and cefepime against isogenic Escherichia coli strains producing SHV-2, SHV-4 and SHV-5 β-lactamases, respectively, were also inoculum dependent. Bactericidal activity against SHV-4 and SHV-5 β-lactamase producers was obtained only at the moderate inoculum, whereas the SHV-2 β-lactamase producer was efficiently killed with both antibiotics, regardless of the inoculum size.