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114 Hollander and Mouton55Δ log CFU/ml31-1-3R 2 = 0.5233Δ log CFU/ml31-1-3R 2 = 0.5652-5-50 1 23log 10 AUC FIC-0.5 0.0 0.5 1.0 1.5log 10 C MAX-FIC53R 2 = 0.534453R 2 = 0.6821Δ log CFU/ml1-1-3Δ log CFU/ml1-1-3-5-50 25 50 75 1000 25 50 75 100%T >MIC-COMBI%T >FICIFIGURE 4 Correlation between PDI based on FIC combi and MIC combi and efficacy, expressed asdCFU/mL. Abbreviations: FIC, fractional inhibitory concentration; MIC, minimal inhibitoryconcentration.The efficacy in vivo itself poses even more problems. Basically, two outcomeparameters are being used. One is survival analysis and the other is CFU counts.The problem in the studies using survival analysis is that usually only one or atmost two strains are tested. The advantage is that some form of statistical analysisis usually performed on outcome, for instance, Fisher tests or, in more recentstudies, survival analysis. Table 3 shows a summary of the results obtained bysurvival analysis. Although the majority of the in vitro results are concordant withthe in vivo outcome, it must be borne in mind that in most cases, strains wereselected to perform animal experiments, usually based on in vitro synergism.Conclusions drawn from these studies may thus be highly biased. Studies usingCFU counts as an end point usually yield much more information, mainly becauseof the quantity of strains tested, but basically suffer from the same drawbacks astime-kill curves in vitro in that different definitions are being used and thus maylead to conflicting interpretations (95). The major conclusions from the survivalstudies is that although interaction itself is usually described by the survivalanalysis, this is more mechanism based and the prediction from the in vitro test isat most indicative because of the small number of strains tested. The results ofin vivo time-kill curves should be viewed with some caution (Table 4). Ideally thesame strain should be tested in more than one experimental system.A pharmacodynamic analysis on the interaction between drugs in vivo wasperformed by Mouton et al. (65). Although the primary objective of that study wasto show that the effect of the antimicrobials during combination therapy correlated