High-dose induction liposomal amphotericin B followed by de-escalation is effective in experimental Aspergillus terreus pneumonia
| Autor: | Guangling Liao, Randall A. Prince, Dimitrios P. Kontoyiannis, Weiqun Wang, Russell E. Lewis, Nathaniel P. Albert |
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| Přispěvatelé: | R. E. Lewi, N. P. Albert, G. Liao, W. Wang, R. A. Prince, D. P. Kontoyiannis |
| Rok vydání: | 2013 |
| Předmět: |
Microbiology (medical)
Antifungal Agents Neutropenia Cyclophosphamide Pharmacology Mice Pharmacokinetics Amphotericin B medicine Animals Pharmacology (medical) Aspergillus terreus liposomal amphotericin B Mice Inbred BALB C biology business.industry biology.organism_classification medicine.disease bacterial infections and mycoses Survival Analysis Aspergillus terreu Pneumonia Disease Models Animal Infectious Diseases Aspergillus Treatment Outcome Pharmacodynamics Immunology Administration Intravenous Female Pulmonary Aspergillosis Cortisone business medicine.drug |
| Zdroj: | The Journal of antimicrobial chemotherapy. 68(5) |
| ISSN: | 1460-2091 |
| Popis: | Received 15 October 2012; returned 21 November 2012; revised 7 December 2012; accepted 13 December 2012 Objectives: Aspergillus terreus is considered to be resistant to amphotericin B (AMB). However, it is unknown whether higher daily doses of liposomal AMB (L-AMB) can overcome this resistance in vivo. We evaluated the efficacy and total lung homogenate AMB concentrations of escalating intravenous doses of L-AMB (3‐20 mg/kg daily) versus an induction-de-escalation dosing strategy (10 mg/kg/day ×3 days, then 3 mg/kg/ day) in an experimental neutropenic murine model of A. terreus pneumonia. Methods: BALB/c mice were rendered neutropenic with cyclophosphamide and administered cortisone acetate prior to intranasal inoculation (3.5×10 6 conidia) with A. terreus (Etest MIC 8 mg/L). Mice were then treated with L-AMB regimens for 5‐7 days. The efficacy was assessed by animal survival and quantitative PCR lung fungal burden. Total AMB lung homogenate concentrations were determined by HPLC. Results: Compared with untreated controls, 10 mg/kg/day L-AMB prolonged survival (mean .7 versus 3‐4 days, P,0.003) and reduced A. terreus lung fungal burden (median log10 conidial DNA 5.0 versus 6.7, P,0.05). Daily L-AMB regimens .10 mg/kg/day were associated with poorer survival and higher lung fungal burden. The induction-de-escalation strategy of 10 mg/kg/day ×3 days followed by 3 mg/kg/day was as effective as 10 mg/kg daily dosing, and resulted in higher mean AMB lung homogenate concentrations compared with a continuous 10 mg/ kg regimen (23.2+6.7 versus 16.4+4.4 mg/g, P¼0.09). Conclusions: A high-dose induction-de-escalation L-AMB dosing strategy was an effective treatment for experimental A. terreus pneumonia in neutropenic mice. |
| Databáze: | OpenAIRE |
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