A NEW TIME-KILL METHOD OF ASSESSING THE RELATIVE EFFICACY OF ANTIMICROBIAL AGENTS ALONE AND IN COMBINATION DEVELOPED USING A REPRESENTATIVEBETA-LACTAM, AMINOGLYCOSIDE AND FLUOROQUINOLONE

A time-kill curve employing nine sampling times over 6 h was used to p rovide data which were then used to develop a theoretical (best-fit) c urve. From the theoretical curve parameters describing the rate of kil l (alpha), time from addition of antibiotic to initiation of killing ( d) and a function of the degree of killing observed (Y-m/Y-o) were def ined. The area-under-the-curve (AUC) was calculated from the theoretic al curve. The variability of each parameter was assessed using a theor etical curve to fit the data from experiments done on three occasions and in triplicate. In terms of the parameters alpha, d, Y-m/Y-o and AU C, no synergy was demonstrated with combinations of piperacillin/tazob actam plus ciprofloxacin or gentamicin when compared with single antib iotics. The AUC represents the best summary parameter of a time-kill c urve but should be supported by other parameters describing the best-f it curve.