Delay of antifungal therapy influences the outcome of invasive aspergillosis in experimental models of infection

Autor: Francesco Barchiesi, Gianfranco Greganti, Daniele Giannini, Tommasina Biscotti, Esther Manso, Alfredo Santinelli
Rok vydání: 2016
Předmět:
0301 basic medicine
Microbiology (medical)
medicine.medical_specialty
Antifungal Agents
Time Factors
030106 microbiology
Colony Count
Microbial
Microbial Sensitivity Tests
Early Therapy
Aspergillosis
Gastroenterology
Aspergillus fumigatus
Efficacy
Echinocandins
Lipopeptides
Mice
03 medical and health sciences
0302 clinical medicine
Amphotericin B
Internal medicine
medicine
Animals
Pharmacology (medical)
030212 general & internal medicine
Intensive care medicine
Lung
Invasive Pulmonary Aspergillosis
Pharmacology
Kidney
biology
business.industry
Micafungin
bacterial infections and mycoses
medicine.disease
biology.organism_classification
Survival Analysis
Disease Models
Animal
Regimen
Treatment Outcome
Infectious Diseases
medicine.anatomical_structure
Drug Therapy
Combination
Female
business
medicine.drug
Zdroj: Journal of Antimicrobial Chemotherapy. 71:2230-2233
ISSN: 1460-2091
0305-7453
DOI: 10.1093/jac/dkw111
Popis: OBJECTIVES The aim of the present study was to evaluate the effects of delayed antifungal therapy on the outcome of invasive aspergillosis due to Aspergillus fumigatus in experimental models of infection. METHODS A clinical isolate of A. fumigatus susceptible to amphotericin B (MIC 0.5 mg/L) and micafungin [minimum effective concentration (MEC) 0.03 mg/L] was used in all experiments. Two models of infection were investigated in immunosuppressed mice: disseminated infection and pulmonary infection. Twenty-four hours (early therapy) and 48 h (delayed therapy) post-infection, the mice were given vehicle, liposomal amphotericin B, micafungin or liposomal amphotericin B plus micafungin (combination). Drug efficacy was assessed by either survival or tissue burden experiments. RESULTS In disseminated infection, any drug regimen given early significantly prolonged survival. When therapy was delayed, only micafungin and the combination were effective. In pulmonary infection, although there was a trend towards a prolongation of survival of mice treated early with liposomal amphotericin B, only the combination was effective. Similarly, when therapy was delayed, only the combination was effective. In disseminated infection, any drug regimen given early was effective at reducing the cfu in kidney tissue. In pulmonary infection, only liposomal amphotericin B and the combination given early were effective at reducing the cfu in lung tissue. Conversely, when therapy was delayed, no regimen was effective at reducing the tissue burden, regardless of the type of infection. CONCLUSIONS Our data indicate that delayed initiation of antifungal therapy is deleterious in experimental models of invasive aspergillosis. A combination regimen seems to have some advantages over a single-drug approach when the therapy is started late.
Databáze: OpenAIRE
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