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Antibacterial activity and kill kinetics of amoxicillin-clavulanic acid combinations against Escherichia coli and Klebsiella aerogenes

Antibakterielle Aktivität und Bakterizidiekinetik von Amoxicillin-Clavulansäure-Kombinationen gegen Escherichia coli und Klebsiella aerogenes

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Summary

Combinations of amoxicillin and clavulanic acid were tested against 11Escherichia coli strains and fiveKlebsiella aerogenes strains. Apart from oneE. coli, the strains were highly resistant to amoxicillin due to beta-lactamase production. Synergy was demonstrated in all strains by agar dilution. Synergy was detected against the beta-lactamase-producing strains under simulatedin vivo conditions with constantly decreasing concentrations simulatingin vivo pharmacokinetics. The correlation between antibacterial activity determined by minimum inhibitory concentrations and bacterial kill kinetics in thein vivo simulation model was acceptable. A higher bacterial kill rate was observed when the antibiotic dosage was increased beyond the minimum concentration where an antibacterial effect was seen; this was not demonstrable by traditional agar dilution tests. In combination, a greater relative amount of amoxicillin compared to clavulanic acid allows a reduction in the total amount of antimicrobial agents with the same degree of antibacterial activity.

Zusammenfassung

Kombinationen von Amoxicillin und Clavulansäure wurden auf ihre Wirksamkeit gegen 11Escherichia coli-und fünfKlebsiella aerogenes-Stämme geprüft. Mit Ausnahme einesE. coli-Stammes waren alle Stämme infolge Beta-Laktamasebildung hochresistent gegenüber Amoxicillin. Für alle Stämme wurde mit Agar-Dilutionsverfahren ein Synergismus nachgewiesen. Der Synergismus gegen Beta-Laktamase-produzierende Stämme war unter simuliertenIn vivo-Bedingungen bei Nachahmung derIn vivo-Pharmakokinetik mit ständig abnehmenden Konzentrationen nachzuweisen. Die Korrelation zwischen der mit Hilfe der minimalen Hemmkonzentrationen bestimmten und über Bakterizidiekinetik imIn-vivo-Simulationsmodell ermittelten antibakteriellen Aktivität war akzeptabel. Die Erhöhung der Bakterizidierate bei Erhöhung der Antibiotikadosis über die minimale Hemmkonzentration hinaus läßt sich in den gebräuchlichen Agar-Dilutionsverfahren nicht nachweisen. Wenn die relative Menge von Amoxicillin in der Kombination größer ist als diejenige von Clavulansäure, läßt sich die Gesamtmenge der antimikrobiellen Substanzen bei gleichbleibender antibakterieller Aktivität reduzieren.

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Authors and Affiliations

  1. Vaccine Department, National Institute of Public Health, Oslo, Norway

    J. E. Fuglesang

  2. Department of Microbiology, Institute of Pharmacy, University of Oslo, Oslo, Norway

    T. Bergan

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  1. J. E. Fuglesang
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  2. T. Bergan
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Fuglesang, J.E., Bergan, T. Antibacterial activity and kill kinetics of amoxicillin-clavulanic acid combinations against Escherichia coli and Klebsiella aerogenes. Infection 11, 329–335 (1983). https://doi.org/10.1007/BF01641359

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