title: In vitro synergistic interaction between amphotericin B and pentamidine against Scedosporium prolificans.
abstract: To develop new approaches for the treatment of invasive infections caused by Scedosporium prolificans, the in vitro interaction between amphotericin B and pentamidine against 30 clinical isolates was evaluated using a checkerboard microdilution method based on the National Committee for Clinical Laboratory Standards M38-P guidelines. The interaction between the drugs was analyzed using fractional inhibitory concentration index (FICI) analysis and response surface modeling. Amphotericin B alone was inactive against all the isolates. The geometric mean MIC for pentamidine was 57 micro g/ml (range, 8 to 256 micro g/ml; MIC at which 50% of the isolates tested were inhibited [MIC(50)], 64 micro g/ml; MIC(90), 128 micro g/ml). The combination was synergistic against 28 of 30 isolates (93.3%) by FICI analysis and 30 of 30 (100%) by response surface modeling analysis. Antagonism was not observed.
authors.affiliation: Department of Medical Microbiology, University Medical Center Nijmegen, The Netherlands.
authors.forename: Javier
authors.initials: J
authors.lastname: Afeltra
authors.forename: Eric
authors.initials: E
authors.lastname: Dannaoui
authors.forename: Jacques F G M
authors.initials: JF
authors.lastname: Meis
authors.forename: Juan L
authors.initials: JL
authors.lastname: Rodriguez-Tudela
authors.forename: Paul E
authors.initials: PE
authors.lastname: Verweij
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D004357:Drug Synergism; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000379:methods; D008954:Models, Biological; D010419:Pentamidine / Q000494:pharmacology*; D021681:Scedosporium / Q000187:drug effects*
chemical_list: D000935:Antifungal Agents; D010419:Pentamidine; D000666:Amphotericin B