A new time-kill method of assessing the relative efficacy of antimicrobial agents alone and in combination developed using a representative beta-lactam, aminoglycoside and fluoroquinolone

J Antimicrob Chemother. 1996 Aug;38(2):193-203. doi: 10.1093/jac/38.2.193.


A time-kill curve employing nine sampling times over 6 h was used to provide data which were then used to develop a theoretical (best-fit) curve. From the theoretical curve parameters describing the rate of kill (alpha), time from addition of antibiotic to initiation of killing (d) and a function of the degree of killing observed (Ym/Yo) were defined. The area-under-the-curve (AUC) was calculated from the theoretical curve. The variability of each parameter was assessed using a theoretical curve to fit the data from experiments done on three occasions and in triplicate. In terms of the parameters alpha, d, Ym/Yo and AUC, no synergy was demonstrated with combinations of piperacillin/tazobactam plus ciprofloxacin or gentamicin when compared with single antibiotics. The AUC represents the best summary parameter of a time-kill curve but should be supported by other parameters describing the best-fit curve.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acinetobacter / drug effects
  • Ciprofloxacin / administration & dosage
  • Ciprofloxacin / pharmacology*
  • Citrobacter freundii / drug effects
  • Drug Therapy, Combination / pharmacology*
  • Enterobacteriaceae / drug effects
  • Gentamicins / administration & dosage
  • Gentamicins / pharmacology*
  • Microbial Sensitivity Tests*
  • Models, Biological
  • Penicillanic Acid / administration & dosage
  • Penicillanic Acid / analogs & derivatives*
  • Penicillanic Acid / pharmacology
  • Piperacillin / administration & dosage
  • Piperacillin / pharmacology*
  • Serratia marcescens / drug effects
  • Tazobactam


  • Gentamicins
  • Ciprofloxacin
  • Penicillanic Acid
  • Tazobactam
  • Piperacillin