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Antimicrobial Agents and Chemotherapy, October 1999, p. 2463-2467, Vol. 43, No. 10
0066-4804/99/$04.00+0

Safety and Efficacy of Multilamellar Liposomal Nystatin against Disseminated Candidiasis in Persistently Neutropenic Rabbits

Andreas H. Groll,1 Vidmantas Petraitis,1 Ruta Petraitiene,1 Aida Field-Ridley,1 Myrna Calendario,1 John Bacher,2 Stephen C. Piscitelli,3 and Thomas J. Walsh1,*

Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute,1 Surgery Branch, Veterinary Resources Services, National Center for Research Resources,2 and Pharmacokinetics Research Laboratory, Pharmacy Department, Warren Grant Magnuson Clinical Center,3 National Institutes of Health, Bethesda, Maryland 20892

Received 7 April 1999/Returned for modification 3 June 1999/Accepted 28 July 1999

The activity of liposomal nystatin (L-Nys) against subacute disseminated candidiasis was investigated in persistently neutropenic rabbits. Antifungal therapy was administered for 10 days starting 24 h after intravenous inoculation of 103 blastoconidia of Candida albicans. Responses to treatment were assessed by the quantitative clearance of the organism from blood and tissues. Treatments consisted of L-Nys at dosages of 2 and 4 mg/kg of body weight/day (L-Nys2 and L-Nys4, respectively) amphotericin B deoxycholate at 1 mg/kg/day (D-AmB), and fluconazole at 10 mg/kg/day (Flu). All treatments were given intravenously once daily. Compared to the results for untreated but infected control animals, treatment with L-Nys2, L-Nys4, D-AmB, and Flu resulted in a significant clearance of the residual burden of C. albicans from the kidney, liver, spleen, lung, and brain (P < 0.0001 by analysis of variance). When the proportion of animals infected at at least one of the five tissue sites studied was evaluated, a dose-dependent response to treatment with L-Nys was found (P < 0.05). Compared to D-AmB-treated rabbits, mean serum creatinine and blood urea nitrogen levels at the end of therapy were significantly lower in animals treated with L-Nys2 (P < 0.001) and L-Nys4 (P < 0.001 and P < 0.01, respectively). L-Nys was less nephrotoxic than conventional amphotericin B and had dose-dependent activity comparable to that of amphotericin B for the early treatment of subacute disseminated candidiasis in persistently neutropenic rabbits.

* Corresponding author. Mailing address: Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Building 10, Rm. 13N240, 10, Center Dr., Bethesda, MD 20892. Phone: (301) 402-0023. Fax: (301) 402-0575. E-mail: walsht{at}mail.nih.gov.

Antimicrobial Agents and Chemotherapy, October 1999, p. 2463-2467, Vol. 43, No. 10
0066-4804/99/$04.00+0


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