RUIJGROK EJ, VULTO AG, VERBRUGH HA, VAN ETTEN EW; Interscience Conference on Antimicrobial Agents and Chemotherapy.
Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 1999 Sep 26-29; 39: 582 (abstract no. 2007).
Erasmus Univ. Med. Ctr., Rotterdam, NETHERLANDS.
BACKGROUND: As it is known from clinical practice that treatment of invasive pulmonary aspergillosis in immunocompromised patients often fails, prevention of this serious infection is desirable. Local treatment via nebulization of amphotericin B (AMB) directly targets the lungs and may be attractive as a prophylactic measure. We determined the pulmonary disposition and the prophylactic efficacy of nebulized Fungizone (AMB desoxycholate, AMB-DOC) and nebulized AmBisome (liposomal AMB, L-AMB) in a model of severe invasive aspergillosis in leukopenic rats.METHODS: For determination of pulmonary concentrations of AMB, AMB-DOC or L-AMB was nebulized in healthy rats (female, RP-strain, SPF). At different times after nebulization, lungs were removed and AMB was analyzed by HPLC. For the efficacy studies, rats were immune suppressed with cyclophosphamide and the left lung was inoculated with 1.5x10[5] conidia Aspergillus fumigatus. Untreated control rats died between 4 and 9 days after inoculation. Treatment consisted of a single dose of nebulized AMB-DOC or L-AMB (60 min, nebulizer reservoir concentration 2 and 4 mg/ml, respectively) and was given at 2 h, 24 h, 48 h, 72 h, 96 h or 7 days before inoculation. Survival was monitored up to 12 days after inoculation.RESULTS: Maximal concentration of AMB in lungs after nebulization of AMB-DOC or L-AMB was 22.2 and 24.6 microg/g, respectively. AMB was cleared slowly from the lungs in both cases (t[1/2][beta ] > 20 days). Survival was prolonged after administration of either nebulized AMB-DOC or L-AMB in all prophylactic regimens as compared to controls (p<0.05, log rank test). There seemed to be a slight difference, in favour of L-AMB, between the two products in the duration of protection.CONCLUSION: Prophylaxis with a single-dose of either nebulized AMB-DOC or L-AMB is effective in prolonging survival in invasive pulmonary aspergillosis in leukopenic rats, even when given 7 days before fungal inoculation.
Publication Types:
Keywords:
- AmBisome
- Amphotericin B
- Animals
- Aspergillosis
- Aspergillosis, Allergic Bronchopulmonary
- Aspergillus fumigatus
- Deoxycholic Acid
- Drug Combinations
- Female
- Humans
- Immunocompromised Host
- Influenza, Human
- Liposomes
- Lung
- Lung Diseases, Fungal
- Muridae
- Nebulizers and Vaporizers
- Rats
- amphotericin B-deoxycholate
- immunology
Other ID:
UI: 102246862
From Meeting Abstracts