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 less than or equal to 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 greater than 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.

Activities of Piperacillin, Ceftazidime, Cefepime and Cefpirome against <i>Pseudomonas aeruginosa</i> Strains with Intrinsic Ticarcillin Resistance

“…The recently devel oped cephalosporins, cefepime and cefpi rome, behaved much like piperacillin and cef tazidime. Previous studies on the bactericidal activity of P-laetams against ticarcillin-resistant strains were performed with p-lactamaseproducing strains [15,16], or did not specify the resistance mechanism [13,14,17]. Our results show that increased intrinsic resis tance does not significantly alter the bacteri cidal activity of piperacillin, ceftazidime, ce fepime or cefpirome.…”

“…It is ex plained neither by the selection of resistant bacteria nor by antibiotic inactivation [17], and could be due to the formation of aggre gates that adhere to the glass surface and release cells into the medium [19], The use of small-diameter glass test tubes instead of flasks and constant shaking in our experiment did not prevent regrowth, but it was less marked at higher concentrations of the antibi otic. According to Gwynn et al [19], it can be prevented by coating the interior of the vessel with silicone.…”

“…However, the bac tericidal activities of these four agents are similar, and do not appear to be impaired by this resistance mechanism. Further studies are needed to determine whether the synergis tic effect of P-lactam-aminoglycoside combi nations against ticarcillin-susceptible strains [12,13,17,18] is fully maintained against intrinsically ticarcillin-resistant strains.…”

Comparison of two techniques for measurement of in vitro killing kinetics of five antibiotics againstPseudomonas aeruginosa

“…However, this finding should not be generalized. Regrowth in killing curves has been observed by others (12,16,20), prompting several different hypotheses: aggregate formation (9), mutant selection (21) antibiotic inactivation (22) and inoculum effect (7). Thus, the MIC of an agent is not predictive of bactericidal effect.…”