Microbial pharmacodynamics of piperacillin in neutropenic mice of systematic infection due toPseudomonas aeruginosa
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Mathematical solutions for two possible pharmacodynamic interactions (linear nonsaturable and nonlinear saturable) between antibiotics and microorganisms derived from the incorporation of clinically relevant antibiotic dosage regimens such as single bolus dosing, multiple doses, and constant infusion at steady state have been obtained. It is concluded that the saturable nonlinear interaction model between the tested antibiotic and microorganism appears appropriate. The model and its derived equations are capable of describing in vivobacterial growth of P. aeruginosaafter single bolus dosing and multiple doses of piperacillin as described by a linear one-compartment pharmacokinetic model. The activity of piperacillin against P. aeruginosain the neutropenic mouse systemic infection model can be described by an equation with three dynamic parameters: the bacterial growth rate constant k app ,0.02345min−1, the bacterial killing rate constant k′ kill ,0.02623 min−1, and the Michaelis-Menten type saturation constant Km, 0.05467 μg/ml. The concept and derived equations for the optimal dosing interval and minimum critical concentration are of clinical importance for the proper selection of antibiotic dosage regimens.
Key wordsmicrobial pharmacodynamics linear nonsaturable model nonlinear saturable model antibiotic dosage regimen piperacillin Pseudomonas aeruginosa systemic infection neutropenic mouse
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- 5.M. Gibaldi and D. Perrier.Pharmacokinetics, 2nd ed., Marcel Dekker. New York, 1982, pp. 221–269.Google Scholar
- 7.E. R. Garrett. Kinetics of antimicrobial action.Scand. J. Infect. Dis. 14(suppl.):54–85 (1978).Google Scholar
- 12.D. Lewis, D. Reeves, B. Wiedemann, and S. Zinner (eds).Methodology and evaluation of in vitro models of antimicrobial chemotherapy. Proceedings of a joint meeting held in Bad Honnef (Bonn). March 1984.J. Antimicrob. Chemother. (Suppl. A) (1985).Google Scholar
- 23.J. Zhi. Pharmacodynamic modeling of antimicrobial activity: piperacillin versusPseudomonas aeruginosa Ph. D. dissertation, University of Connecticut, 1987.Google Scholar
- 24.R. Cleeland and E. Grunberg. Laboratory evaluation of new antibioticsin vitro and in experimental animal infections. In V. Lorian (ed.)Antibiotics in Laboratory Medicine. 2nd ed., Williams & Wilkins, Baltimore, 1986, pp. 825–876.Google Scholar
- 25.C. M. Metzler, G. L. Elfring, and A. J. McEwen. A package of computer program for pharmacokinetic modeling.Biometrics. September 1974, p. 562.Google Scholar
- 26.S. Bolton.Pharmaceutical Statistics, Marcel Dekker, New York, 1986, p. 156.Google Scholar