NAKAJIMA M, TAMADA S, YOSHIDA K, WAKAI Y, NAKAI T, IKEDA F, GOTO T, NIKI Y, MATSUSHIMA T; Interscience Conference on Antimicrobial Agents and Chemotherapy.

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2000 Sep 17-20; 40: 387.

Div. Respiratory Diseases, Dept. Internal Med., Kawasaki Med. Shc., Kurashiki, Japan

FK463 has been demonstrated to have efficacy against invasive pulmonary aspergillosis in experimental murine and rabbit models. In this study, we report pathological findings in the murine invasive pulmonary aspergillosis model induced by intranasal inoculation with A. fumigatus IFM40836 on immunosuppressed mice (subcutaneouslly hydrocortisone), using FK463, amphotericin B (AmB) and combination (FK463 and AmB) therapy. Medication was performed once a day intravenously with FK463 (0.5, 1 and 2 mg/kg), AmB (0.25 and 0.5 mg/kg) and a combination of FK463 and AmB at 1 and 0.25 mg/kg or 2 and 0.5 mg/kg. The MICs of FK463 and AmB against A. fumigatus IFM40836 were 0.0156 microg/mL and 2 microg/mL, respectively, using the M27-A microdilution method. Survival rate at 6 days was 61.5 % with FK463 (1 mg/kg), 53.8 % with AmB (0.25 mg/kg) and 100 % with FK463 (1 mg/kg) + AmB (0.25 mg/kg). Pathological examination of lungs revealed invasive pulmonary aspergillosis in the control group. In control mice at 3 days after inoculation, hyphae were growing in the bronchial (bronchiolar) lumina and wall, along with neutrophilic infiltration and macrophages. At 6 days after inoculation, hyphae infected into the alveoli. All control mice died within 10 days. With the FK463 or AmB groups, hyphae were growing in the bronchi at 6 days. On the other hand, the FK463 and AmB combination groups at both doses showed tissue reactions, such as fibroblast proliferation, organizing pneumonia and bronchiolitis obliterans organizing pneumonia without hyphal growth at 6 days. Comparing the three groups, pathological findings in the combination group were more favorable than in the FK463 or AmB groups. These findings correlated with survival rate.KEYWORDS: Combination therapy; FK463; Pathological study

Publication Types:

• Meeting Abstracts

Keywords:

• Amphotericin B
• Animals
• Aspergillosis, Allergic Bronchopulmonary
• Disease Models, Animal
• Humans
• Lipoproteins
• Lung
• Lung Diseases, Fungal
• Mice
• Microbial Sensitivity Tests
• Models, Biological
• Peptides, Cyclic
• Rabbits
• diagnosis
• micafungin
• therapy

Other ID:

• GWAIDS0010308

UI: 102247806

From Meeting Abstracts