Pharmacodynamics of beta-lactam antibiotics. Studies on the paradoxical and postantibiotic effects in vitro and in an animal model

Scandinavian Journal of Infectious Diseases. Supplementum
I Odenholt-Tornqvist

Abstract

The pharmacodynamics of antibiotics, i.e. the rate of killing and the time before regrowth of surviving bacteria, may be important factors for determination of the dosage interval. In the present study the effect of protein binding, antibiotic concentrations, bacterial growth phase and bacterial inoculum on the rate of bacterial killing was investigated. The postantibiotic effect (PAE) was also studied in vitro and in vivo. The killing rate of S. aureus did not differ when the bacteria were exposed to the same free concentrations of dicloxacillin in medium with and without albumin. Protein binding per se did thus not diminish the bactericidal activity. A paradoxically reduced bactericidal effect was noted when S. aureus was exposed to high concentrations of dicloxacillin, cloxacillin and benzylpenicillin. For determination of PAE of imipenem on Ps. aeruginosa, counts of viable bacteria were compared with assay of bacterial intracellular ATP. Both methods demonstrated a PAE for the strains tested at an inoculum of 10(6) cfu/ml. At an inoculum of 10(8) cfu/ml no PAE was found, which coincided with a lack of bactericidal effect. Both the PAE and the bactericidal effect were restored with aeration of the cultures, indicating insuff...Continue Reading

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