title: Synergysm of voriconazole or itraconazole with other antifungal agents against species of Fusarium.
abstract: BACKGROUND
  Infections caused by Fusarium are difficult to treat because these fungi show in vitro and in vivo resistance to practically all the antifungal agents available, which explains the high mortality rates. An attempt to overcome fungal resistance is the combination of antifungal agents, especially those with different mechanisms of action.
  
  
  OBJECTIVE
  Evaluate the in vitro interactions of combinations of voriconazole or itraconazole with other antifungal agents against 32 isolates of Fusarium spp.: Fusarium chlamydosporum, Fusarium oxysporum, Fusarium proliferatum and Fusarium solani.
  
  
  METHODS
  Drug interactions were assessed by a checkerboard microdilution method that also included the determination of the MIC of each drug alone according to CLSI (Clinical and Laboratory Standards Institute) document M38-A2, 2008.
  
  
  RESULTS
  The best combinations were voriconazole+terbinafine which showed synergism against 84% of Fusarium strains. Other synergistic combinations were voriconazole+itraconazole (50%), voriconazole+fluconazole (50%), voriconazole+miconazole (38%), voriconazole+flucytosine (22%) and voriconazole+ketoconazole (25%). The synergisms observed with itraconazole combinations were itraconazole+terbinafine (25%) and itraconazole+flucytosine (9.37%). The antagonisms observed were: voriconazole+fluconazole (3%) and itraconazole+flucytosine (12.5%).
  
  
  CONCLUSIONS
  The synergism showed by voriconazole+terbinafine was remarkable. To better elucidate the potential usefulness of our findings, new in vivo and in vitro studies deserve be performed.
authors: Pharmaceuthic Sciences Postgraduate Program, Universidade Federal de Santa Maria (UFSM), Santa Maria, Rio Grande do Sul State, Brazil; Department of Microbiology and Parasitology, Universidade Federal de Santa Maria (UFSM), Santa Maria, Rio Grande do Sul State, Brazil.
authors: Tatiana B
authors: TB
authors: Spader
authors: Tarcieli P
authors: TP
authors: Venturini
authors: Luana
authors: L
authors: Rossato
authors: Laura B
authors: LB
authors: Denardi
authors: Patricia B
authors: PB
authors: Cavalheiro
authors: Sonia A
authors: SA
authors: Botton
authors: Janio M
authors: JM
authors: Santurio
authors: Sydney Hartz
authors: SH
authors: Alves
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D025141:Drug Resistance, Fungal; D004357:Drug Synergism; D005437:Flucytosine / Q000494:pharmacology; D005670:Fusarium / Q000145:classification / Q000187:drug effects*; D017964:Itraconazole / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009281:Naphthalenes / Q000494:pharmacology; D013045:Species Specificity; D000077291:Terbinafine; D065819:Voriconazole / Q000494:pharmacology*
chemical_list: D000935:Antifungal Agents; D009281:Naphthalenes; D017964:Itraconazole; D005437:Flucytosine; D000077291:Terbinafine; D065819:Voriconazole
keywords: Antifungal agents; Fusarium spp.; Fármacos antimicóticos; Sensibilidad; Sinergia; Susceptibility; Synergism; Voriconazol; Voriconazole