Post-Exposure Effects of Cefepime and Cefpirome on Isogenic Escherichia coli Hosts Producing SHV-Extended-Spectrum β-Lactamases

Abstract

Persistent suppression of bacterial growth after short antimicrobial exposure is called postantibiotic effect (PAE). By definition, there should be no subinhibitory concentrations of antimicrobial agent left when the postantibiotic effect starts. However, if subinhibitory concentrations are maintained after removing the antibiotic, the recovery period of the treated cultures is markedly prolonged. This is defined as postantibiotic-sub-MIC-effect (PA-SME). The aim of this study was to determine the PAE and PA-SME of cefpirome and cefepime on isogenic Escherichia coli strains producing SHV-2, SHV-5, and SHV-12 extended spectrum β-lactamases (ESBL) compared to a non-ESBL E. coli strain. It was hypothesized that the presence of an ESBL would hydrolyze the cephalosporin molecule before it exerted a toxic effect on the bacterial cell and thus shorten the duration of PA-SME. Cefpirome and cefepime had no PAE against ESBL producing E. coli or it was of a short duration and present only at high antibiotic concentrations, but exposure to subinhibitory concentration of those antibiotics in the PA (postantibiotic) phase resulted in a significant delay of regrowth. The effect was more pronounced with higher concentrations of antibiotics, and uninfluenced by the type of enzyme and the antibiotic. The present study shows that the presence of subinhibitory concentrations of cefepime and cefpirome in the medium after exposure to suprainhibitory concentrations results in a significant delay of regrowth of both ESBL-positive and - negative E. coli strains. The production of SHV-2, SHV-5 and SHV-12 ESBLs did not shorten the duration of the PA-SME.