We described bacterial killing and resistance emergence at various fixed concentrations of meropenem and piperacillin/tazobactam against Pseudomonas aeruginosa and Escherichia coli. Time-kill studies were conducted utilizing nine isolates and a large range of concentrations. Within each strain and antibiotic, initial killing was similar, with concentrations ≥2×MIC. At many (strain-specific) concentrations causing substantial initial killing, regrowth occurred at 24-48h. For remaining concentrations, growth typically remained suppressed (<5-log10 cfu/mL). The concentrations of meropenem required to suppress regrowth ranged from 2-8×MIC for P. aeruginosa and 2-64×MIC for E. coli. For piperacillin/tazobactam, the equivalent concentrations ranged from 8-16×MIC for P. aeruginosa and 4-16×MIC for E. coli. The number of less-susceptible bacteria increased with rising concentrations before decreasing at even higher concentrations. Suppression of regrowth and resistance was substantially improved with higher concentrations (typically ≥8×MIC), suggesting a benefit of higher β-lactam concentrations beyond those required for maximum initial killing.
Keywords: Bacterial killing; In vitro studies; Resistance; beta-Lactam antibiotics.
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