RRC ID 52825
Author Reichert-Lima F, Busso-Lopes AF, Lyra L, Peron IH, Taguchi H, Mikami Y, Kamei K, Moretti ML, Schreiber AZ.
Title Evaluation of antifungal combination against Cryptococcus spp.
Journal Mycoses
Abstract The second cause of death among systemic mycoses, cryptococcosis treatment represents a challenge since that 5-flucytosine is not currently available in Brazil. Looking for alternatives, this study evaluated antifungal agents, alone and combined, correlating susceptibility to genotypes. Eighty Cryptococcus clinical isolates were genotyped by URA5 gene restriction fragment length polymorphism. Antifungal susceptibility was assessed following CLSI-M27A3 for amphotericin (AMB), 5-flucytosine (5FC), fluconazole (FCZ), voriconazole (VRZ), itraconazole (ITZ) and terbinafine (TRB). Drug interaction chequerboard assay evaluated: AMB + 5FC, AMB + FCZ, AMB + TRB and FCZ + TRB. Molecular typing divided isolates into 14 C. deuterogattii (VGII) and C. neoformans isolates were found to belong to genotype VNI (n = 62) and VNII (n = 4). C. neoformans VNII was significantly less susceptible than VNI (P = 0.0407) to AMB; C. deuterogattii was significantly less susceptible than VNI and VNII to VRZ (P < 0.0001). C. deuterogattii was less susceptible than C. neoformans VNI for FCZ (P = 0.0170), ITZ (P < 0.0001) and TRB (P = 0.0090). The combination FCZ + TRB showed 95.16% of synergistic effect against C. neoformans genotype VNI isolates and all combinations showed 100% of synergism against genotype VNII isolates, suggesting the relevance of cryptococcal genotyping as it is widely known that the various genotypes (now species) have significant impact in antifungal susceptibilities and clinical outcome. In difficult-to-treat cryptococcosis, terbinafine and different antifungal combinations might be alternatives to 5FC.
Volume 59(9)
Pages 585-93
Published 2016-9
DOI 10.1111/myc.12510
PMID 27135278
MeSH Amphotericin B / pharmacology Antifungal Agents / pharmacology* Brazil Cryptococcosis / microbiology* Cryptococcus / classification Cryptococcus / drug effects* Cryptococcus / genetics Cryptococcus neoformans / drug effects* Cryptococcus neoformans / genetics Drug Combinations Drug Synergism Fluconazole / pharmacology Flucytosine / pharmacology Genotype Humans Itraconazole / pharmacology Microbial Sensitivity Tests Molecular Typing Naphthalenes / pharmacology Polymorphism, Restriction Fragment Length Voriconazole / pharmacology
IF 2.793
Resource
Pathogenic microorganisms