[In vitro interaction studies of azithromycin and dihydroartemisinin in Plasmodium falciparum isolates from Bangladesh].
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.
Vossen
Matthias G
MG
Department of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna, Austria.
Haque
Rashidul
R
Starzengruber
Peter
P
Khan
Wasif Ali
WA
Thriemer
Kamala
K
Marma
Aung Swi Prue
AS
Akther
Selim
S
Fukuda
Mark
M
Noedl
Harald
H
D000818:Animals; D037621:Artemisinins / Q000008:administration & dosage*; D017963:Azithromycin / Q000008:administration & dosage*; D001459:Bangladesh; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006801:Humans; D007928:Lethal Dose 50; D016778:Malaria, Falciparum / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000469:parasitology*; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000502:physiology*; D015996:Survival Rate; D016896:Treatment Outcome
D037621:Artemisinins; C039060:artenimol; D017963:Azithromycin