scholarly journals Activity of voriconazole (UK-109,496) against clinical isolates of Aspergillus species and its effectiveness in an experimental model of invasive pulmonary aspergillosis.

1997 ◽  
Vol 41 (3) ◽  
pp. 696-698 ◽  
Author(s):  
M Murphy ◽  
E M Bernard ◽  
T Ishimaru ◽  
D Armstrong
Keyword(s):  
Body Weight ◽  
Experimental Model ◽  
Antifungal Agent ◽  
Invasive Pulmonary Aspergillosis ◽  
Clinical Isolates ◽  
Aspergillus Species ◽  
Pulmonary Aspergillosis

Voriconazole, a new azole antifungal agent, showed potent activity against clinical isolates of Aspergillus spp. in vitro. For A. fumigatus, the MIC range was < 0.03 to 0.5 microgram/ml and the MIC at which 90% of isolates are inhibited was 0.25 microgram/ml. In an experimental model of invasive pulmonary aspergillosis which mimics infection in humans, oral voriconazole at dosages of 30 mg/kg of body weight per day significantly delayed or prevented mortality.

scholarly journals EDTA as an Adjunct Antifungal Agent for Invasive Pulmonary Aspergillosis in a Rodent Model

2006 ◽  
Vol 50 (5) ◽  
pp. 1823-1827 ◽  
Author(s):  
Ray Hachem ◽  
Paul Bahna ◽  
Hend Hanna ◽  
L. Clifton Stephens ◽  
Issam Raad
Keyword(s):  
Body Weight ◽  
Antifungal Agent ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Invasive Pulmonary Aspergillosis ◽  
Pulmonary Aspergillosis ◽  
Lipid Complex ◽  
Optimal Dosing ◽  
Amphotericin B Lipid Complex ◽  
Severe Lung

ABSTRACT Rats immunosuppressed by the administration of cyclophosphamide and cortisone acetate and then infected with Aspergillus fumigatus were treated with an antifungal drug, EDTA, or a combination of one of the antifungal agents, amphotericin B lipid complex (ABLC; 5 mg/kg of body weight/day for 7 days), and EDTA (30 mg/kg/day for 7 days). The mortality rate was reduced, the duration of survival was increased, fewer A. fumigatus organisms were recovered from the lungs, and less-severe lung lesions were seen histopathologically in the rats receiving the combination treatment than in the rats receiving either an antifungal agent or EDTA alone. Further studies regarding the mechanisms of EDTA and its interactions with ABLC are warranted, and further studies are needed to more fully examine the safety, tolerance, and optimal dosing of EDTA in the treatment of this and other fungal infections.

Effect of direct infusion of antifungal agent on invasive pulmonary aspergillosis in a patient with acute leukemia

2002 ◽  
Vol 8 (1) ◽  
pp. 106-108 ◽  
Author(s):  
Kazunori Nakase ◽  
Akira Yazaki ◽  
Hiroshi Shiku ◽  
Sigehisa Tamaki ◽  
Motoaki Tanigawa ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Antifungal Agent ◽  
Invasive Pulmonary Aspergillosis ◽  
Direct Infusion ◽  
Pulmonary Aspergillosis

scholarly journals Detection of Aspergillus Species DNA in Serum Samples of the Patients with Non-Invasive Pulmonary Aspergillosis

1997 ◽  
Vol 71 (3) ◽  
pp. 255-259 ◽  
Author(s):  
Atsuro HASHIMOTO ◽  
Yuriko YAMAKAMI ◽  
Shunji MIZUNOE ◽  
Eiji YAMAGATA ◽  
Hiroshi NAGAOKA ◽  
...  
Keyword(s):  
Invasive Pulmonary Aspergillosis ◽  
Aspergillus Species ◽  
Serum Samples ◽  
Pulmonary Aspergillosis ◽  
Non Invasive

scholarly journals Long-Circulating Immunoliposomal Amphotericin B against Invasive Pulmonary Aspergillosis in Mice

1998 ◽  
Vol 42 (1) ◽  
pp. 40-44 ◽  
Author(s):  
Takakazu Otsubo ◽  
Kazuo Maruyama ◽  
Shigefumi Maesaki ◽  
Yoshitsugu Miyazaki ◽  
Eitaro Tanaka ◽  
...  
Keyword(s):  
Body Weight ◽  
Polyethylene Glycol ◽  
Amphotericin B ◽  
Marked Reduction ◽  
Survival Rates ◽  
Invasive Pulmonary Aspergillosis ◽  
Intravenous Dose ◽  
Pharmacokinetic Studies ◽  
Pulmonary Aspergillosis ◽  
Liposome Surface

ABSTRACT We investigated the efficacy of long-circulating immunoliposomal amphotericin B (AmB) against invasive pulmonary aspergillosis in mice using three types of liposomal AmB: conventional liposomal AmB (AmBisome), a long-circulating liposomal AmB and prepared by coating the liposome surface with polyethylene glycol (PEG; PEG-L-AmB), long-circulating immunoliposomal AmB (34A-PEG-L-AmB). The survival rates for mice with invasive pulmonary aspergillosis treated with an intravenous dose of 2 mg of AmBisome, PEG-L-AmB, or 34A-PEG-L-AmB per kg of body weight were 16.7, 83.3, and 100%, respectively. Treatment with 34A-PEG-L-AmB produced a marked reduction in the number ofAspergillus fumigatus organisms in the lungs. Pharmacokinetic studies showed the presence of high AmB concentrations in the plasma of mice treated with PEG-L-AmB (40.8 μg/ml) and in the lungs of mice treated with 34A-PEG-L-AmB (42.3 μg/g). We conclude that 34A-PEG-L-AmB, a long-circulating immunoliposomal AmB, is a promising form of AmB against invasive pulmonary aspergillosis.

scholarly journals Accelerated Metabolism of Voriconazole and Its Partial Reversal by Cimetidine

2009 ◽  
Vol 53 (4) ◽  
pp. 1712-1714 ◽  
Author(s):  
Brad Moriyama ◽  
Jason Elinoff ◽  
Robert L. Danner ◽  
Juan Gea-Banacloche ◽  
Gennethel Pennick ◽  
...  
Keyword(s):  
Body Weight ◽  
Cytochrome P450 ◽  
Enzyme Inhibitor ◽  
Invasive Pulmonary Aspergillosis ◽  
Cytochrome P450 Enzyme ◽  
Pulmonary Aspergillosis ◽  
P450 Enzyme ◽  
Partial Reversal

ABSTRACT We report a case of accelerated metabolism of voriconazole during therapy for invasive pulmonary aspergillosis, resulting in subtherapeutic levels. Target voriconazole levels were restored with high dosages of voriconazole (up to 40 mg/kg of body weight/day) and the addition of cimetidine as a cytochrome P450 enzyme inhibitor.

scholarly journals Pharmacokinetics and Pharmacodynamics of Amphotericin B Deoxycholate, Liposomal Amphotericin B, and Amphotericin B Lipid Complex in an In Vitro Model of Invasive Pulmonary Aspergillosis

2010 ◽  
Vol 54 (8) ◽  
pp. 3432-3441 ◽  
Author(s):  
Jodi M. Lestner ◽  
Susan J. Howard ◽  
Joanne Goodwin ◽  
Lea Gregson ◽  
Jayesh Majithiya ◽  
...  
Keyword(s):  
Confocal Microscopy ◽  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
Invasive Pulmonary Aspergillosis ◽  
Host Cells ◽  
Pulmonary Aspergillosis ◽  
Lipid Complex ◽  
Amphotericin B Deoxycholate ◽  
Amphotericin B Lipid Complex

ABSTRACT The pharmacodynamic and pharmacokinetic (PK-PD) properties of amphotericin B (AmB) formulations against invasive pulmonary aspergillosis (IPA) are not well understood. We used an in vitro model of IPA to further elucidate the PK-PD of amphotericin B deoxycholate (DAmB), liposomal amphotericin B (LAmB) and amphotericin B lipid complex (ABLC). The pharmacokinetics of these formulations for endovascular fluid, endothelial cells, and alveolar cells were estimated. Pharmacodynamic relationships were defined by measuring concentrations of galactomannan in endovascular and alveolar compartments. Confocal microscopy was used to visualize fungal biomass. A mathematical model was used to calculate the area under the concentration-time curve (AUC) in each compartment and estimate the extent of drug penetration. The interaction of LAmB with host cells and hyphae was visualized using sulforhodamine B-labeled liposomes. The MICs for the pure compound and the three formulations were comparable (0.125 to 0.25 mg/liter). For all formulations, concentrations of AmB progressively declined in the endovascular fluid as the drug distributed into the cellular bilayer. Depending on the formulation, the AUCs for AmB were 10 to 300 times higher within the cells than within endovascular fluid. The concentrations producing a 50% maximal effect (EC50) in the endovascular compartment were 0.12, 1.03, and 4.41 mg/liter for DAmB, LAmB, and ABLC, respectively, whereas, the EC50 in the alveolar compartment were 0.17, 7.76, and 39.34 mg/liter, respectively. Confocal microscopy suggested that liposomes interacted directly with hyphae and host cells. The PK-PD relationships of the three most widely used formulations of AmB differ markedly within an in vitro lung model of IPA.

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