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.
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.
MacGowan
A P
AP
Bristol Centre for Antimicrobial Research & Evaluation, Southmead Health Services NHS Trust, UK.
Wootton
M
M
Hedges
A J
AJ
Bowker
K E
KE
Holt
H A
HA
Reeves
D S
DS
D000150:Acinetobacter / Q000187:drug effects; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000494:pharmacology*; D016971:Citrobacter freundii / Q000187:drug effects; D004359:Drug Therapy, Combination / Q000494:pharmacology*; D004755:Enterobacteriaceae / Q000187:drug effects; D005839:Gentamicins / Q000008:administration & dosage / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D010397:Penicillanic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D010878:Piperacillin / Q000008:administration & dosage / Q000494:pharmacology*; D012706:Serratia marcescens / Q000187:drug effects; D000078142:Tazobactam
D005839:Gentamicins; D002939:Ciprofloxacin; D010397:Penicillanic Acid; D000078142:Tazobactam; D010878:Piperacillin