scholarly journals Effect of amphotericin B treatment on kinetics of cytokines and parameters of fungal load in neutropenic rats with invasive pulmonary aspergillosis

2003 ◽  
Vol 52 (3) ◽  
pp. 428-434 ◽  
Author(s):  
M. J. Becker
Keyword(s):  
Amphotericin B ◽  
Invasive Pulmonary Aspergillosis ◽  
Pulmonary Aspergillosis ◽  
Fungal Load ◽  
Kinetics Of

scholarly journals The Initial 96 Hours of Invasive Pulmonary Aspergillosis: Histopathology, Comparative Kinetics of Galactomannan and (1→3)-β-d-Glucan, and Consequences of Delayed Antifungal Therapy

2010 ◽  
Vol 54 (11) ◽  
pp. 4879-4886 ◽  
Author(s):  
William W. Hope ◽  
Vidmantas Petraitis ◽  
Ruta Petraitiene ◽  
Tamarra Aghamolla ◽  
John Bacher ◽  
...  
Keyword(s):  
Monte Carlo ◽  
Monte Carlo Simulations ◽  
Amphotericin B ◽  
Antifungal Therapy ◽  
Time Course ◽  
Invasive Pulmonary Aspergillosis ◽  
Rabbit Model ◽  
Pulmonary Aspergillosis ◽  
Lung Weight ◽  
Kinetics Of

ABSTRACT Acute invasive pulmonary aspergillosis is a rapidly progressive and frequently lethal infection. Relatively little is known about early events in the pathogenesis and relationship between the cell wall biomarkers galactomannan and (1→3)-β-d-glucan. The consequences of delayed antifungal therapy are also poorly defined. A persistently neutropenic rabbit model of invasive pulmonary aspergillosis was used to describe the histopathology of early invasive pulmonary aspergillosis and the kinetics of galactomannan and (1→3)-β-d-glucan. The time course of both molecules was mathematically modeled by using a population methodology, and Monte Carlo simulations were performed. The effect of progressive delay in the administration of amphotericin B deoxycholate 1 mg/kg at 24, 48, 72, and 96 h postinoculation on fungal burden, lung weight, pulmonary infarct score, and survival was determined. Histopathology showed phagocytosis of conidia by pulmonary alveolar macrophages at 4 h postinoculation. At 12 to 24 h, there was a progressive focal inflammatory response with conidial germination and hyphal extension. Subsequently, hyphae invaded into the contiguous lung. Galactomannan and (1→3)-β-d-glucan had similar trajectories, and both exhibited considerable interindividual variability, which was reflected in Monte Carlo simulations. Concentrations of both molecules began to rise <24 h postinoculation before pulmonary hemorrhagic infarction was present. Delays of 72 and 96 h in the administration of amphotericin B resulted in fungal burdens and lung weights that were indistinguishable from those of controls, respectively. Galactomannan and (1→3)-β-d-glucan have similar kinetics and are comparable biomarkers of early invasive pulmonary aspergillosis. Antifungal treatment at ≥48 h postinoculation is associated with suboptimal therapeutic outcomes.

scholarly journals Comparative Analysis of Amphotericin B Lipid Complex and Liposomal Amphotericin B Kinetics of Lung Accumulation and Fungal Clearance in a Murine Model of Acute Invasive Pulmonary Aspergillosis

2007 ◽  
Vol 51 (4) ◽  
pp. 1253-1258 ◽  
Author(s):  
Russell E. Lewis ◽  
Guangling Liao ◽  
Jinggou Hou ◽  
Georgios Chamilos ◽  
Randall A. Prince ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
Invasive Pulmonary Aspergillosis ◽  
Drug Distribution ◽  
Pulmonary Aspergillosis ◽  
Tissue Concentrations ◽  
Lipid Complex ◽  
Fungal Burden ◽  
Amphotericin B Lipid Complex ◽  
Kinetics Of

ABSTRACT The reformulation of amphotericin B (AMB) into a lipid complex (AMB lipid complex [ABLC]) or liposomal carrier (liposomal AMB [L-AMB]) changes the rate and extent of drug distribution to the lung. The importance of pharmacokinetic differences among the various lipid AMB formulations in the treatment of invasive pulmonary aspergillosis (IPA) remains unknown. We compared the kinetics of AMB lung accumulation and fungal clearance of ABLC- and L-AMB-treated mice with acute IPA. BALB/c mice were immunosuppressed with cyclophosphamide and cortisone before intranasal inoculation with 1.5 × 106 Aspergillus fumigatus 293 conidia. ABLC or L-AMB was administered in daily intravenous doses (1, 5, or 10 mg/kg of body weight), starting 12 h after infection and continuing until day 5. At predetermined times (0, 24, 72, and 120 h), mice were euthanized, and lungs were harvested for determinations of lung fungal burdens (quantitative PCR) and total AMB lung tissue concentrations. Both ABLC and L-AMB were effective at reducing lung fungal burdens at doses of ≥5 mg/kg/day. Clearance of A. fumigatus during the first 24 h was associated with AMB tissue concentrations of >4 μg/g. At 5 mg/kg/day, ABLC produced a more rapid fungal clearance than did L-AMB, but at the end of therapy, fungal burden reductions were similar for both formulations and were not improved with higher dosages. These data suggest that ABLC delivers active AMB to the lung more rapidly than does L-AMB, resulting in faster Aspergillus clearance in an experimental model of IPA. However, pharmacodynamic differences between the two formulations were less apparent when mice were dosed at 10 mg/kg/day.

scholarly journals Efficacy of Nebulized Liposomal Amphotericin B in Treatment of Experimental Pulmonary Aspergillosis

2005 ◽  
Vol 49 (7) ◽  
pp. 3028-3030 ◽  
Author(s):  
Joan Gavaldà ◽  
María-Teresa Martín ◽  
Pedro López ◽  
Xavier Gomis ◽  
José-Luís Ramírez ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Murine Model ◽  
Liposomal Amphotericin ◽  
Invasive Pulmonary Aspergillosis ◽  
Liposomal Amphotericin B ◽  
Pulmonary Aspergillosis ◽  
Lower Lung

ABSTRACT The efficacy of therapeutic aerosolized amphotericin B (AMB) was studied in a steroid-immunosuppressed murine model of invasive pulmonary aspergillosis. Nebulized liposomal AMB can be a valid approach to the treatment of this infection, with subjects showing significantly improved survival relative to that of subjects given intravenous deoxycholate AMB, as well as lower lung weights and pulmonary glucosamine levels.

Fungal Lung Infections Treated by 5 Flucytosine

1982 ◽  
Vol 27 (3) ◽  
pp. 244-246
Author(s):  
R. P. Symonds ◽  
A. G. Robertson ◽  
L. M. Stewart ◽  
G. Boyd
Keyword(s):  
Amphotericin B ◽  
Invasive Pulmonary Aspergillosis ◽  
Pulmonary Aspergillosis ◽  
Lung Infections

5 Flucytosine was used successfully to treat two patients with pulmonary candidiasis and, in combination with Amphotericin B, one patient with invasive pulmonary aspergillosis.

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.

Aerosol amphotericin B inhalations for prevention of invasive pulmonary aspergillosis in neutropenic cancer patients

1995 ◽  
Vol 71 (6) ◽  
pp. 287-291 ◽  
Author(s):  
G. F. Behre ◽  
S. Schwartz ◽  
K. Lenz ◽  
W.-D. Ludwig ◽  
H. Wandt ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Amphotericin B ◽  
Invasive Pulmonary Aspergillosis ◽  
Pulmonary Aspergillosis

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.

Successfully treated invasive pulmonary aspergillosis in a patient with diabetic ketoacidosis

Open Medicine ◽  
2013 ◽  
Vol 8 (5) ◽  
pp. 685-688
Author(s):  
Ryo Kumagai ◽  
Gen Ohara ◽  
Shinya Sato ◽  
Kunihiko Miyazaki ◽  
Katsunori Kagohashi ◽  
...  
Keyword(s):  
Early Intervention ◽  
Invasive Aspergillosis ◽  
Diabetic Ketoacidosis ◽  
Amphotericin B ◽  
Early Treatment ◽  
Liposomal Amphotericin ◽  
Invasive Pulmonary Aspergillosis ◽  
Full Recovery ◽  
Liposomal Amphotericin B ◽  
Pulmonary Aspergillosis

AbstractWe report herein a case of diabetic ketoacidosis associated with invasive aspergillosis that was successfully treated with liposomal amphotericin-B (L-AMB). Early intervention after confirming the diagnosis of invasive pulmonary aspergillosis is very important, and initiating early treatment with L-AMB can lead to a full recovery.

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