Summary
Thein vitro activity of clarithromycin alone and in combination with its primary human metabolite, 14-hydroxy-clarithromycin, was determined against 203 strains ofHaemophilus influenzae. Microdilution broth MICs and MBCs of both clarithromycin and 14-hydroxy-clarithromycin were determined. The clarithromycin MIC50 was 4 mg/l and the MIC90 was 8 mg/l. The hydroxy metabolite was 2–4-fold more active with an MIC50 and MIC90 of 2 mg/l. The MBCs were equal to the MICs. The microbicidal effect of combinations of clarithromycin and 14-hydroxy-clarithromycin was tested using a microdilution checkerboard technique and the fractional inhibitory index was calculated. The combination was additive in 92% and synergistic in 8% of all strains ofH. influenzae tested; no antagonism was found. The results were independent of the site of isolation of the strain or presence of β-lactamase. These findings suggest the potential clinical utility of clarithromycin for the treatment ofH. influenzae infections.
Zusammenfassung
DieIn-vitro-Aktivität von Clarithromycin allein und in Kombination mit seinem primären Metaboliten beim Menschen, 14-hydroxy-Clarithromycin, wurde bei 203 Stämmen vonHaemophilus influenzae geprüft. Für Clarithromycin wie seinen 14-hydroxy-Metaboliten wurden die MHK-und MBK- Werte mit der Mikrodilutions-Methode in Bouillon bestimmt. Die MHK50 von Clarithromycin betrug 4 mg/l, die MHK90 8% mg/l. Für den Hydroxy-Metaboliten ergab sich eine 2–4-fach höhere Aktivität mit MHK50- und MHK90-Werten von 2 mg/l. Die MBK-Werte waren mit den MHK-Werten identisch. Mit der Checkerboard-Methode wurde die mikrobizide Wirkung von Kombinationen aus Clarithromycin und 14-hydroxy-Clarithromycin bestimmt und der fraktionierte Hemmquotient berechnet. Für 92% aller Teststämme war die Wirkung der Kombination additiv, für acht synergistisch. Es fand sich kein Antagonismus. Die Ergebnisse waren unabhängig von der Isolations-Lokalisation oder der Anwesenheit von β-Laktamase. Diese Befunde lassen annehmen, daß Clarithromycin für die Behandlung vonH. influenzae-Infektionen geeignet ist.
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Bergeron, M.G., Bernier, M. & L'Ecuyer, J. In vitro activity of clarithromycin and its 14-hydroxy-metabolite against 203 strains ofHaemophilus influenzae . Infection 20, 164–167 (1992). https://doi.org/10.1007/BF01704612
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DOI: https://doi.org/10.1007/BF01704612