In-vivo assessment of in-vitro killing patterns of Pseudomonas aeruginosa.

Time-kill curves of Pseudomonas aeruginosa exposed to gentamicin or ticarcillin in vitro were correlated with time-kill curves obtained with various dosage schedules of the same study drugs in granulocytopenic mice. An instantaneous, fast and drug-dependent killing pattern was found in vitro with gentamicin. This pattern corresponded to bacterial killing in vivo which was clearly dependent on peak drug levels. In contrast, slow bacterial killing with little relationship to concentration was found in vitro with ticarcillin and proved to correlate with an antibacterial effect in vivo seen at trough levels. We conclude that in-vitro time-kill curves of antimicrobial agents may be predictive for optimizing dosage regimens in vivo.