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Intracellular bactericidal activity of fosfomycin against staphylococci: A comparison with other antibiotics

Intrazelluläre bakterizide Aktivität von Fosfomycin gegen Staphylokokken: Ein Vergleich mit anderen Antibiotika

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Summary

The intracellular bactericidal activity of fosfomycin was compared to that of other anti-staphylococcal agents. Two staphylococcal strains (one isolate ofStaphylococcus aureus and one isolate ofStaphylococcus epidermidis) were incubatedin vitro with human granulocytes isolated from volunteers. After phagocytosis and removal of residual extracellular bacteria, the cells were resuspended in the presence of clinically relevant concentrations of fosfomycin, teicoplanin, vancomycin and rifampin. The number of bacteria surviving intracellularly was determined by colony counts after osmotic lysis of the granulocytes at different time intervals. Incubation with fosfomycin resulted in a mean reduction of intracellular bacteria by approximately two logs of ten within 18 h for both staphylococcal strains. Although less effective than rifampin, fosfomycin showed a significantly higher intracellular activity than the glycopeptide antibiotics in this model.

Zusammenfassung

Die intrazelluläre bakterizide Aktivität von Fosfomycin wurde mit derjenigen anderer staphylokokkenwirksamer Antibiotika verglichen. Zwei klinische Staphylokokkenisolate (je ein Stamm vonStaphylococcus aureus undStaphylococcus epidermidis) wurden hierzu mit humanen Granulozyten, die von gesunden freiwilligen Spendern isoliert wurden,in vitro inkubiert. Nach einer initialen Phagozytosephase und anschließender Entfernung extrazellulär verbliebener Bakterien wurden die Zellen in frischem Medium nachinkubiert, das klinisch relevante Konzentrationen von Fosfomycin, Teicoplanin, Vancomycin beziehungsweise Rifampicin enthielt. Nach verschiedenen Zeitintervallen wurden die Zellen osmotisch lysiert und die Anzahl intrazellulär überlebender Staphylokokken durch Koloniezählung ermittelt. In Gegenwart von Fosfomycin wurde die Anzahl vitaler intrazellulärer Keime innerhalb von 18 Stunden um circa 2 Zehnerpotenzen reduziert. Obwohl weniger aktiv als Rifampicin, zeigte Fosfomycin im vorliegenden Modell eine deutlich bessere intrazelluläre Bakterizidie als die beiden Glykopeptide.

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Dedicated to Prof. Dr.Meta Alexander, former head of the Dept. of Infectious Diseases, Klinikum Rudolf Virchow/Charlottenburg, on the occasion of her retirement.

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Trautmann, M., Meincke, C., Vogt, K. et al. Intracellular bactericidal activity of fosfomycin against staphylococci: A comparison with other antibiotics. Infection 20, 350–354 (1992). https://doi.org/10.1007/BF01710683

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