Pharmacodynamic effects of antibiotics on growing and nongrowing bacteria

Sammanfattning: The main objective of this thesis was to study antibiotic effects on nongrowing baCteria and to study the development of resistance in Staphylococcus epidermidis, a bacterium which is often found in biofilm infections. The antibiotic effect on biofilm infections is generally weak, which probably is due to decreased growth rate of the bacteria. The effects of antibiotics on growing and nongrowing bacteria were studied with pharmacodynamic parameters. One of these parameters is postantibiotic effect (PAE). The conventional PAE measurement is performed with viable count. Viable counting is very laborious, which is why other methods have been used. However, the results may differ from those obtained with the viable count method for determining PAE. In this study effective regrowth time (ERT) and control-related effective regrowth time (CERT) were shown to be independent of the method used for bacterial quantification. With CERT and PAE it possible to study antibiotic effects on nongrowing and growing bacteria.CERT and PAE of amikacin, ciprofloxacin, and imipenem were investigated on growing and nongrowing Escherichia coli and Pseudonumas aeruginosa. All drugs had long CERT and PAE on growing bacteria. Arnikacin and ciprofloxacin, but not imipenem had long CERT and PAE on nongrowing bacteria.Amikacin, imipenem, ofloxacin, rifampicin, and vancomycin induced CERT and PAE on growing S. epidermidis, and imipenem combination with amikacin or vancomycin had a synergistic CERT and PAE in these cultures. Only rifampicin or antibiotic combinations containing rifampicin were effective against nongrowing S. epidermidis. There was no synergistic CERT or PAE on nongrowing bacteria.Selection and regrowth of highly rifampicin resistant S. epidermidis, which was present at a frequency of 10·7 in the initial inoculum, were seen when the bacteria were in~ubated with rifampicin at a high inoculum. Rifampicin combined with high concentrations of amikacin or ofloxacin prevents selection and regrowth of rifampicin resistant bacteria.

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