Summary
The effect of decreasing concentrations of azlocillin and sisomicin onPseudomonas aeruginosa was examined. Logarithmically growing bacterial cultures were incubated in an ultrafiltration cell, and after adding the antibiotics, the culture medium was diluted every 20 min without any decrease in cell density. The turn-over of medium resulted in the elimination of azlocillin with a half-life of 75 min. This simulated serum kineticsin vivo. When testing sisomicin, small amounts of this agent were added during every dilution step to achieve a half-life of 120 min. Growth conditions were comparable in all experiments. The simultaneous combination of azlocillin and sisomicin resulted in strong synergism as assessed by higher killing rates and more prolonged growth inhibition of surviving bacteria. Comparable results were observed when both drugs were added at intervals of 40 min. When applied at intervals of 120 min, the combined effect of azlocillin and sisomicin was reduced, but still superior to the effect of double the concentration of each compound alone. Thus, neither pre-treatment with azlocillin nor with sisomicin impaired the antibacterial activity of the combination partner. This seems to be of clinical importance since the agents may be administered at different times during combined therapy.
Zusammenfassung
Untersucht wurde die Wirkung abnehmender Konzentrationen von Azlocillin und Sisomicin aufPseudomonas aeruginosa. Nach Zugabe der Wirkstoffe zu einer logarithmisch wachsenden Bakterienkultur in einer Ultrafiltrationszelle wurde das Kulturmedium alle 20 min ohne Ausschwemmung von Keimen verdünnt. Durch den Austausch des Mediums wurde Azlocillin entsprechend derin vivo beobachteten Serumkinetik mit einer Halbwertszeit von 75 min eliminiert. Bei Prüfung von Sisomicin wurden geringe Mengen dieses Wirkstoffes bei jedem Verdünnungsschritt ergänzt, um eine Halbwertszeit von 120 min zu erzielen. In allen Versuchsansätzen herrschten vergleichbare Wachstumsbedingungen. Gleichzeitige Kombination von Azlocillin und Sisomicin führte zu einem starken Synergismus, der sich in höheren Abtötungsraten und länger anhaltender Wachstumshemmung der überlebenden Keime äußerte. Vergleichbare Ergebnisse wurden beobachtet, wenn beide Wirkstoffe im Abstand von 40 min zugesetzt wurden. Ein zeitlicher Abstand von 120 min führte zu einer Abschwächung des synergistischen Effektes, doch übertraf die Kombination in ihrer Wirkung noch immer die jeweils doppelten Konzentrationen der Einzelsubstanzen. Somit führte weder eine Vorbehandlung mit Azlocillin noch mit Sisomicin zu einer Beeinträchtigung der antibakteriellen Wirksamkeit des Kombinationspartners. Dies scheint von klinischer Bedeutung, da die Wirkstoffe bei kombinierter Therapie zu verschiedenen Zeitpunkten verabreicht werden können.
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Haller, I. Combined action of decreasing concentrations of azlocillin and sisomicin on pseudomonas aeruginosa as assessed in a dynamic in vitro model. Infection 10 (Suppl 3), S229–S233 (1982). https://doi.org/10.1007/BF01640679
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DOI: https://doi.org/10.1007/BF01640679