Aerosolized Itraconazole (ITZ) as Prophylaxis Against Invasive Pulmonary Aspergillosis (IPA) Due to Aspergillus Fumigatus.

C. A. ALVAREZ 1,2, N. P. WIEDERHOLD1,2, J. T. MCCONVILLE 1, J. I. PETERS 2, L. K. NAJVAR 2, J. R. GRAYBILL 2, D. MARKS 2, R. L. TALBERT 1,2, D. S. BURGESS 1,2, R. BOCANEGRA 2, K. P. JOHNSTON 1, R. O. WILLIAMS III 1;

Author address: 

1Univ. of Texas Coll. of Pharmacy, Austin, TX, 2Univ. of Texas Hlth.Sci. Ctr., San Antonio, TX.

Abstract: 

Background: Prophylactic strategies against IPA are often limited by drug toxicities and drug interactions. Targeted airway delivery of antifungals to the lungs may avoid these pitfalls. We evaluated the effectiveness of an aerosolized nanostructured formulation of ITZ produced by spray freezing into liquid (SFL) as prophylaxis against IPA caused by A. fumigatus. Methods: Immunocompromised Balb/C mice (20 per group per arm) received either ITZ by oral gavage (Sporanox Oral Liquid [SOL] 30 mg/kg TID) or by aerosolization (SFL 30 mg/kg via 20 minute aerosolizations, or control, BID). Dosing began 2 days prior to pulmonary inoculation with A. fumigatus 293 (ITZ MIC 0.25 mcg/mL) and continued for 7 days post-inoculation. In the fungal burden arm, mice were euthanized and lungs harvested for CFU enumeration and quantitative PCR (conidial equivalents [CE]) one day after discontinuation of therapy, and changes in lung histopathology were assessed. In the survival arm, mice were monitored over a 5 day period following discontinuation of therapy and survival was assessed by Kaplan-Meier analysis. Results: SFL survival (35%) was significantly greater compared to control (10%; p
2006

abstract No: 

M-1688

Full conference title: 

46th Interscience Conference on Antimicrobial Agents and Chemotherapy
    • ICAAC 46th