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Pharmacokinetic and pharmacodynamic parameters for antimicrobial effects of cefotaxime and amoxicillin in an in vitro kinetic model
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
2001 In: Antimicrobial Agents and Chemotherapy, Vol. 45, no 9, 2436-2440 p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
2001. Vol. 45, no 9, 2436-2440 p.
URN: urn:nbn:se:uu:diva-90206OAI: oai:DiVA.org:uu-90206DiVA: diva2:162481
Available from: 2003-03-19 Created: 2003-03-19Bibliographically approved
In thesis
1. Biological and Pharmacological Factor that Influence the Selection of Antibiotic Resistance
Open this publication in new window or tab >>Biological and Pharmacological Factor that Influence the Selection of Antibiotic Resistance
2003 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Antibiotic treatment causes an ecological disturbance on the human microflora. Four commensal bacteria: E. coli, enterococci, a-streptococci and coagulase-negative staphylococci, from patients with extensive, high antibiotic usage were investigated with regard to resistance pattern and mutation frequency. Among 193 investigated strains it was found that high antibiotic usage selected for resistant bacteria and enriched for bacteria with a small but significantly increased mutation frequency.

The relative biological fitness cost of resistance in Staphylococcus epidermidis was assessed in a human in vivo model where the indigenous flora was present. In vitro data of the bacterial growth rate correlated well to in vivo fitness assayed in the competition experiments on skin.

An in vitro kinetic model was shown to be a useful tool to establish the pharmacokinetic and pharmacodynamic (PK/PD) indices for efficacy of antibiotics. It was confirmed that the time, when the concentration exceeds the minimal inhibitory concentration (MIC), correlates with efficacy for b-lactam antibiotics. To achieve maximal killing for penicillin-resistant pneumococci, with an MIC of 2 mg/L, the peak concentration was also of importance.

Suboptimal dosing regimen facilitates selection of resistance. Penicillin-resistant pneumococci were easily selected in a mixed population with penicillin-sensitive, -intermediate and -resistant pneumococci in an in vitro kinetic model. The selection of the resistant strain was prevented when the benzylpenicillin concentration exceeded the MIC for approximately 50% of 24 h.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2003. 49 p.
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1228
Microbiology, Human microflora, antibiotic resistance, selection, mutation frequency, biological fitness, pharmacokinetics, pharmacodynamics, β-lactam antibiotics, suboptimal dosing regimen, Mikrobiologi
National Category
Research subject
Clinical Bacteriology
urn:nbn:se:uu:diva-3355 (URN)91-554-5549-2 (ISBN)
Public defence
2003-04-11, Hörsalen, Klinisk mikrobiologi, Uppsala, 13:15
Available from: 2003-03-19 Created: 2003-03-19 Last updated: 2013-09-16Bibliographically approved

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