title: Activity of an Intralipid formulation of nystatin in murine systemic candidiasis.
abstract: Since nystatin (NYT) is used only topically owing to its toxicity upon systemic administration, a study was initiated aiming to develop a formulation of NYT that could be used systemically against invasive mycoses. The present research is a continuation of previous in vitro investigation of the antifungal effect of nystatin-Intralipid (NYT-IL) against Candida, exploring its in vivo activity. NYT-IL was tested in murine systemic candidiasis induced in naïve as well as cyclophosphamide-immunosuppressed female ICR mice. The infection was assessed by survival rate (SR), mean survival time (MST) and qualitative and quantitative fungal organ colonisation. Mice were treated by intravenous administration of various doses of NYT-IL for 5 consecutive days starting either 24h or 48 h after the initiation of infection. The experiments showed that NYT-IL is therapeutically effective in the murine candidiasis model. NYT-IL was found to be less toxic in vivo than NYT and therefore higher doses of NYT-IL could be used. The efficacy of NYT-IL was expressed in treated naïve and immunosuppressed mice by increased SR, prolonged MST and reduced fungal organ colonisation. Early initiation of treatment increased efficacy. In summary, the Intralipid formulation of NYT can be administered parenterally and is effective against systemic experimental Candida infection.
authors.affiliation: Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: R
authors.initials: R
authors.lastname: Semis
authors.forename: S
authors.initials: S
authors.lastname: Mendlovic
authors.forename: I
authors.initials: I
authors.lastname: Polacheck
authors.forename: E
authors.initials: E
authors.lastname: Segal
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D002177:Candidiasis / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000473:pathology; D015169:Colony Count, Microbial; D003520:Cyclophosphamide / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004339:Drug Compounding; D016503:Drug Delivery Systems; D004655:Emulsions / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D005217:Fat Emulsions, Intravenous / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D016867:Immunocompromised Host / Q000502:physiology; D007166:Immunosuppressive Agents / Q000276:immunology; D051379:Mice; D008813:Mice, Inbred ICR; D009761:Nystatin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D010743:Phospholipids / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D013024:Soybean Oil / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000935:Antifungal Agents; D004655:Emulsions; D005217:Fat Emulsions, Intravenous; D007166:Immunosuppressive Agents; D010743:Phospholipids; C545823:soybean oil, phospholipid emulsion; D009761:Nystatin; D013024:Soybean Oil; D003520:Cyclophosphamide