Summary
In recent clinical trials acithromycin in combination with artemisinin derivatives proved to be a promising combination therapy with indifferent to synergistic interaction. The aim of the present study was the assessment of optimal combination ratios for dihydroartemisinin and azithromycin for the treatment of uncomplicated falciparum malaria. The study was conducted in Bandarban, in Southeastern Bangladesh. Plasmodium falciparum isolates collected as part of a clinical trial were cultured for 72 hours. Samples were analyzed using the HRP2 drug sensitivity assay in fixed combinations and checkerboard assays. An indifferent mode of interaction was found for the 1 : 500 combination of dihydroartemisinine and azithromycin. The sum fractional inhibitory concentrations (SFICs) at IC95 ranged from 0.89 to 1.16 for combination ratios of 1 : 500 and 1 : 5000, respectively. A trend towards lower SFICs was observed with rising inhibitory concentrations (i.e. at IC90 and IC95). Correlation analysis suggests a different mode of action for azithromycin as compared to traditional antimalarials.
Zusammenfassung
In jüngsten klinischen Studien erwies sich Azithromycin in Kombination mit Artemisininderivaten als vielversprechende Kombination für die Behandlung der unkomplizierten falciparum Malaria mit in-differenter bis synergistischer Interaktion. Das Ziel der vorliegenden Studie war die Ermittlung von optimalen Wirkstoffverhältnissen für Azithromycin und Dihydroartemisinin für die Behandlung der unkomplizierten falciparum Malaria. Die Plasmodium falciparum Isolate wurden im Rahmen einer klinischen Studie in der MARIB Feldstation im Bandarban Sadar Hospital, im Südosten Bangladeshs gewonnen und für 72 Stunden kultiviert. Die Analyse erfolgte mittels des HRP2 Medikamentensensibilitätstest. Die Auswertung der Daten ergab eine im Großen und Ganzen indifferente Interaktion für Dihydroartemisinin in Kombination mit Azithromycin mit einem optimalen Konzentrationsverhältnis bei einem Mischungsverhältnis von etwa 1 : 500. Die summarischen fraktionellen Hemmkonzentrationen (SFICs) lagen bei 95 prozentiger Hemmung zwischen 0,89 und 1,16 für die Mischverhältnisse 1 : 500 und 1 : 5000. Ein deutlicher Trend zu niedrigeren SFICs zeigte sich bei höheren Hemmkonzentrationen. Die Korrelationsanalyse legt für Azithromycin einen von den bisher verwendeten Therapeutika unterschiedlichen Wirkmechanismus nahe.
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Vossen, M., Haque, R., Starzengruber, P. et al. In vitro Interaktionsstudien mit Azithromycin und Dihydroartemisinin in Plasmodium falciparum Isolaten aus Bangladesh. Wien Klin Wochenschr 119 (Suppl 3), 71–75 (2007). https://doi.org/10.1007/s00508-007-0863-7
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DOI: https://doi.org/10.1007/s00508-007-0863-7