Interaction of aminoglycosides and cephalosporins against Pseudomonas aeruginosa. Correlation between interaction index and killing curve

Abstract

Three multiresistant clinical isolates of Pseudomonas aeruginosa were evaluated, by the chequerboard and the killing curve methods, for in-vitro synergy between cephalosporins and aminoglycosides. The killing-curve method was standardized to give results comparable with those obtained with the chequerboard test (FIC index). This was achieved with combinations showing synergy by chequerboard (FIC ≤0.75) by using in the killing curves subinhibitory concentrations: half the MIC in single antibiotic assay and one eighth the MIC in the combinations. For combinations that showed indifference by chequerboard (FIC = 1) half the MIC was used for antibiotics alone and in combination. For the antagonistic combinations by chequerboard (FIC> 2) concentrations equal to the MIC were used with single antibiotics and combinations in the killing curve experiments. Prediction of killing curve results could then be obtained with the FIC index. The killing curve results could not be explained by pH changes or inactivation of the antibiotics.