Aspergillus fumigatus AB16.2 and AB16.4 are laboratory-selected isolates (derived from ATCC 208996) that show reduced in vitro susceptibility (MIC Â³ 8 mg/ml) to amphotericin B. To study the in vitro and in vivo correlation of amphotericin B resistance in A. fumigatus we investigated the susceptibility of AB16.4 to conventional amphotericin B (AMB) using a murine pulmonary aspergillosis model. Six-week old DBA/2J female mice (20-23 gram) were immunosuppressed by three consecutive subcutaneous injections of cortisone acetate (250 mg/kg) on day -3, -1 and 1 where day 0 was the day of infection. The immunosuppressed animals (30 animals/group) were challenged with 1x 106 conidia/mouse prepared from the susceptible parent ATCC 208996 or AB16.4. Antifungal treatment was initiated on day 1 (AMB 2 mg/kg/day; i.p.) and continued for 5 days. The effectiveness of the antifungal treatment with AMB was evaluated by the fungal burden in the lungs of infected animals. A comparison of the fungal burden of the animals infected with the susceptible parent ATCC 208996 (30862 Â± 17092 CFU/lung) to that obtained for animals infected with the resistant mutant AB16.4 (17025 Â± 5866 CFU/lung) showed no significant difference (p = 0.23) suggesting that the drug-resistant mutant is equally efficient to produce pulmonary aspergillosis in mouse. The fungal burden in the lungs of animals infected with the drug-susceptible parent but not treated (controls) was 30862 Â± 17092 CFU/lung whereas that of the animals treated with AMB was 5969 Â± 8029 CFU/lung resulting in 81% reduction (p = 0.05). On the other hand, the fungal burdens in the lungs of control and AMB-treated animals infected with the resistant isolate AB16.4 were 17025 Â± 5866 and 13514 Â± 6642 CFU/lung. No significant reduction of CFU/lung occurred (p = 0.58) with AMB treatment. These results show good in vitro/in vivo correlation with AMB-susceptible and -resistant strains of A. fumigatus.
Full conference title:
42nd Interscience Conference on Antimicrobial Agents and Chemotherapy
- ICAAC 42nd