title: Evaluation of antifungal combinations of nystatin-intralipid against Aspergillus terreus using checkerboard and disk diffusion methods.
abstract: OBJECTIVE
  The objective of this study was to evaluate the efficacy of combinations of nystatin-intralipid, found previously to be more active than nystatin, with antifungals of different mode of activity, against Aspergillus terreus.
  
  
  METHODS
  Antifungal activity of combinations of nystatin-intralipid with voriconazole, caspofungin, terbinafine or 5-fluorocytosine were evaluated by the checkerboard and disk diffusion methods. The results were compared to those obtained with nystatin.
  
  
  RESULTS
  The combination of nystatin-intralipid with caspofungin exhibited better antifungal activity than each drug alone and resulted in a synergistic interaction in three out of six tested strains of A. terreus. No such effect was obtained with Nystatin and caspofungin. Nystatin-intralipid or nystatin with voriconazole yielded indifferent interactions. When nystatin-intralipid was combined with terbinafine, a strong antagonism was produced in all six A. terreus strains. This effect was observed both by checkerboard and disk diffusion methods. In contrast no interaction or only slight antagonism was observed in the combination of nystatin with terbinafine. Disk diffusion method revealed similar inhibition zones when disks impregnated with 5-fluorocytosine were placed on plain, nystatin-intralipid or nystatin containing agar plates.
  
  
  CONCLUSIONS
  Among four tested combinations, only combination of nytatin-intralipid with caspofungin, a representative of the echinocandin class of antifungals, resulted in synergistic interaction. Antagonism obtained by combining nystatin-intralipid with terbinafine can be explained by existence of hydrophobic interaction between these two compounds interfering with their antifungal action. The fact that nystatin-intralipid and nystatin interact differently with other antifungals, may indicate differences in their mechanisms of activity.
authors: Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, 69978 Tel Aviv, Israel; City of Hope, Beckman Research Institute, Department of Immunology, Duarte, California, USA.
authors: R
authors: R
authors: Semis
authors: Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, 69978 Tel Aviv, Israel.
authors: M
authors: M
authors: Nahmias
authors: Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, 69978 Tel Aviv, Israel.
authors: S
authors: S
authors: Lev
authors: Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, 69978 Tel Aviv, Israel.
authors: M
authors: M
authors: Frenkel
authors: Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, 69978 Tel Aviv, Israel. Electronic address: segale@post.tau.ac.il.
authors: E
authors: E
authors: Segal
mesh_terms: D000935:Antifungal Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001230:Aspergillus / Q000187:drug effects* / Q000254:growth & development; D000077336:Caspofungin; D004338:Drug Combinations; D054714:Echinocandins / Q000008:administration & dosage / Q000494:pharmacology; D004655:Emulsions / Q000008:administration & dosage / Q000494:pharmacology; D005437:Flucytosine / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D055666:Lipopeptides; D008826:Microbial Sensitivity Tests / Q000379:methods; D009281:Naphthalenes / Q000008:administration & dosage / Q000494:pharmacology; D009761:Nystatin / Q000008:administration & dosage / Q000494:pharmacology*; D010743:Phospholipids / Q000008:administration & dosage / Q000494:pharmacology*; D013024:Soybean Oil / Q000008:administration & dosage / Q000494:pharmacology*; D000077291:Terbinafine; D065819:Voriconazole / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D000935:Antifungal Agents; D004338:Drug Combinations; D054714:Echinocandins; D004655:Emulsions; D055666:Lipopeptides; D009281:Naphthalenes; D010743:Phospholipids; C545823:soybean oil, phospholipid emulsion; D009761:Nystatin; D013024:Soybean Oil; D005437:Flucytosine; D000077336:Caspofungin; D000077291:Terbinafine; D065819:Voriconazole
keywords: Antifungal combinations; Aspergillus terreus; Checkerboard assay; Combinaisons antifongiques; Disk-diffussion assay; Méthode de la diffusion par disque; Méthode du damier; Nystatin-Intralipid; Nystatine-intralipide