Time-survival studies for quantifying effects of azlocillin and tobramycin on Pseudomonas aeruginosa

Abstract

Time-survival studies were conducted to estimate the effects of azlocillin and tobramycin on Pseudomonas aeruginosa NCIMB 8295 (in the exponential phase of growth) at concentrations ranging from one-quarter to twice the MIC. The effects of the individual agents and their combinations were determined by measuring the viable counts (CFU per milliliter) over a 24-h period. The typical pattern observed from the plot of the logarithm of the CFU per milliliter against time was an initial rapid killing; this was followed by a period of stasis and regrowth. Initial rates of killing by tobramycin were concentration dependent, whereas this was not the case with azlocillin. From the time-survivor plots, the area under the curve for viable bacteria was also calculated. It offered a useful method of interpreting the results of time-kill studies, taking the overall pattern of killing and regrowth into consideration. The area under the curve for viable bacteria was concentration dependent for both antibiotics. A 2(2) factorial experimental design was used to analyze the joint effects of azlocillin and tobramycin. In such a factorial experiment, an interaction between two factors, in this case, azlocillin and tobramycin concentrations, is shown by a change in the slope of the plot when the concentration of the interactant is changed. Analysis of variance showed that the combination was synergistic at low concentrations, but this was not significant when the concentration of either interactant was increased.