BECKER MJ, DE MARIE S, FENS MH, VERBRUGH HA, BAKKER-WOUDENBERG IA; Interscience Conference on Antimicrobial Agents and Chemotherapy.
Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2000 Sep 17-20; 40: 386.
Erasmus Med. Ctr. Rotterdam, Rotterdam, The Netherlands
BACKGROUND: As seen in patients with invasive pulmonary aspergillosis, in our rat model the efficacy of AmBisome treatment regimes remains suboptimal. To investigate whether this is the result of low bio-availability of amphotericin B, Fungizone was added to AmBisome in different regimes.METHODS: Groups of neutropenic rats with left-sided invasive pulmonary aspergillosis received anti-fungal treatment, starting when hyphal growth was established (16 h after fungal inoculation). Mortality rates and levels of circulating galactomannan were assessed. 10-day-treatment regimes included: 1) Fungizone 1 mg/kg o.d. (n= 25); 2) AmBisome 10 mg/kg o.d. (n= 25); 3) AmBisome 10 mg/kg o.d. combined with a single dose of Fungizone 1 mg/kg at day 1 (n= 27); 4) AmBisome 10 mg/kg o.d. combined with 1 mg/kg Fungizone at day 1, 3 and 5 (n= 9); 28 control rats received no treatment.RESULTS: 96% of untreated rats died before day 11. All treatment regimes significantly increased survival compared to untreated controls and significantly suppressed levels of circulating galactomannan. Addition of a single dose of Fungizone 1 mg/kg to the AmBisome 10 mg/kg o.d. regimen at day 1 significantly increased survival compared to AmBisome alone (P< 0.03) and to Fungizone o.d. alone (P< 0.01). Additions of multiple doses Fungizone 1 mg/kg to AmBisome 10 mg/kg o.d. did not improve survival compared to AmBisome alone.CONCLUSIONS: Addition of one single dose of Fungizone to AmBisome at the start of treatment was the only treatment regime that improved Therapeutic efficacy compared to AmBisome alone. Prolonged survival time was correlated with low levels of circulating galactomannan.KEYWORDS: Aspergillosis; Galactomannan
Publication Types:
Keywords:
- AmBisome
- Amphotericin B
- Animals
- Antifungal Agents
- Aspergillosis
- Aspergillosis, Allergic Bronchopulmonary
- Humans
- Influenza, Human
- Mannans
- Miconazole
- Rats
- galactomannan
Other ID:
UI: 102247804
From Meeting Abstracts