title: [In vitro interaction studies of azithromycin and dihydroartemisinin in Plasmodium falciparum isolates from Bangladesh].
abstract: 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.
authors.affiliation: Department of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna, Austria.
authors.forename: Matthias G
authors.initials: MG
authors.lastname: Vossen
authors.forename: Rashidul
authors.initials: R
authors.lastname: Haque
authors.forename: Peter
authors.initials: P
authors.lastname: Starzengruber
authors.forename: Wasif Ali
authors.initials: WA
authors.lastname: Khan
authors.forename: Kamala
authors.initials: K
authors.lastname: Thriemer
authors.forename: Aung Swi Prue
authors.initials: AS
authors.lastname: Marma
authors.forename: Selim
authors.initials: S
authors.lastname: Akther
authors.forename: Mark
authors.initials: M
authors.lastname: Fukuda
authors.forename: Harald
authors.initials: H
authors.lastname: Noedl
mesh_terms: 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
chemical_list: D037621:Artemisinins; C039060:artenimol; D017963:Azithromycin