Killing of Escherichia coli by beta-lactams at different inocula.
Escherichia coli is a common pathogen implicated in intra-abdominal infections; a heavy bacterial burden is often encountered, and the clinical utility of beta-lactams may be limited by the inoculum effect. We examined the impact of a high inoculum on the bactericidal activity of various beta-lactams against E. coli. Two wild-type, an extended-spectrum beta-lactamase-producing, and a plasmid-mediated AmpC-producing strains, were used. Clinically achievable concentrations of piperacillin/tazobactam, ceftriaxone, and ertapenem were investigated. Viable bacterial burden was serially determined for 24 h by quantitative culture. All 3 beta-lactams demonstrated significant killing against the standard inoculum (10(5) CFU/mL) of susceptible strains. However, the activity of piperacillin/tazobactam was drastically reduced with 10(8) CFU/mL of bacteria. Ertapenem was the least affected by the inoculum effect in all strains. Our results suggest that different beta-lactam subclasses have a distinct killing profile against a dense E. coli population. Comparative in vivo/clinical investigations are warranted to validate our findings.
Tam
Vincent H
VH
University of Houston College of Pharmacy, TX 77030, USA. vtam@uh.edu
Ledesma
Kimberly R
KR
Chang
Kai-Tai
KT
Wang
Tsai-Ying
TY
Quinn
John P
JP
D000900:Anti-Bacterial Agents; D002443:Ceftriaxone / Q000494:pharmacology; D015169:Colony Count, Microbial; D000077727:Ertapenem; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D050296:Microbial Viability / Q000187:drug effects*; D010397:Penicillanic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D010878:Piperacillin / Q000494:pharmacology; D000077725:Piperacillin, Tazobactam Drug Combination; D013997:Time Factors; D001618:beta-Lactamases / Q000096:biosynthesis; D047090:beta-Lactams / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D047090:beta-Lactams; D000077725:Piperacillin, Tazobactam Drug Combination; D002443:Ceftriaxone; D010397:Penicillanic Acid; D001618:beta-Lactamases; D000077727:Ertapenem; D010878:Piperacillin