In:
Mycoses, Wiley, Vol. 60, No. 11 ( 2017-11), p. 728-735
Kurzfassung:
Although anti‐fungal triazoles are dosed orally or systemically for Aspergillus fumigatus infection, systemic adverse events and limited exposure of the lung cavity would make a topical treatment for the lung an attractive option. In this study, we examined the effects of intranasally dosed posaconazole on survival rates and biomarkers in A. fumigatus (itraconazole susceptible: ATCC 13073 [Af]; or resistant: NCPF 7100 [AfR]) infected, temporarily neutropenic A/J mice. Once daily treatment produced a dose‐dependent improvement of survival of Af‐infected mice ( ED 50 : 0.019 mg/mouse [approx. 0.755 mg/kg, in]), similar to its potency ( ED 50 : 0.775 mg/kg, po) after once daily oral dosing. For AfR infection, either intranasal or oral posaconazole was largely ineffective on survival, although the highest dose of intranasal treatment (0.35 mg/mouse) achieved 75% survival rate. Early intervention (treated on days 0, 1, 2 and 3 postinfection) and late intervention (treated on days 1, 2 and 3) with intranasal posaconazole (0.014‐0.35 mg/mouse) demonstrated potent inhibition of lung fungal load and galactomannan levels in both bronchoalveolar lavage fluid ( BALF ) and serum as well as inflammatory cells, IFN ‐γ, IL ‐17 and malondialdehyde ( MDA ) in BALF . Thus, posaconazole when dosed intranasally once daily showed an improvement of survival equivalent to or better than oral treatment, and produced potent inhibition of fungal load and biomarkers.
Materialart:
Online-Ressource
ISSN:
0933-7407
,
1439-0507
DOI:
10.1111/myc.2017.60.issue-11
Sprache:
Englisch
Verlag:
Wiley
Publikationsdatum:
2017
ZDB Id:
2020780-3