scholarly journals Prophylactic efficacy of single dose pulmonary administration of amphotericin B inhalation powder in a guinea pig model of invasive pulmonary aspergillosis

2012 ◽  
Vol 67 (4) ◽  
pp. 970-976 ◽  
Author(s):  
W. R. Kirkpatrick ◽  
L. K. Najvar ◽  
A. C. Vallor ◽  
N. P. Wiederhold ◽  
R. Bocanegra ◽  
...  
Keyword(s):  
Single Dose ◽  
Guinea Pig ◽  
Amphotericin B ◽  
Invasive Pulmonary Aspergillosis ◽  
Pig Model ◽  
Pulmonary Aspergillosis ◽  
Prophylactic Efficacy ◽  
Pulmonary Administration ◽  
Guinea Pig Model ◽  
Inhalation Powder

scholarly journals Efficacy of the Investigational Echinocandin ASP9726 in a Guinea Pig Model of Invasive Pulmonary Aspergillosis

2015 ◽  
Vol 59 (5) ◽  
pp. 2875-2881 ◽  
Author(s):  
Nathan P. Wiederhold ◽  
Laura K. Najvar ◽  
Satoru Matsumoto ◽  
Rosie A. Bocanegra ◽  
Monica L. Herrera ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Quantitative Pcr ◽  
Guinea Pigs ◽  
Plasma Concentrations ◽  
Invasive Pulmonary Aspergillosis ◽  
Pig Model ◽  
Pulmonary Aspergillosis ◽  
Content Type ◽  
Fungal Burden ◽  
Guinea Pig Model

ABSTRACTASP9726 is an investigational echinocandin within vitroactivity againstAspergillusspecies. We evaluated the pharmacokinetics and efficacy of this agent in an established guinea pig model of invasive pulmonary aspergillosis. ASP9726 plasma concentrations were measured in guinea pigs administered either a single dose or multiple doses of this agent at 2.5, 5, and 10 mg/kg of body weight/day by subcutaneous injection. Immunosuppressed guinea pigs were inoculated withA. fumigatusAF293, and ASP9726 (2.5, 5, and 10 mg/kg/day), voriconazole (10 mg/kg by oral gavage twice daily), or caspofungin (3 mg/kg/day by intraperitoneal injection) was administered for 8 days. Changes in fungal burden were measured by enumerating CFU and by quantitative PCR of specimens from within the lungs, as well as by analysis of serum (1→3)-β-d-glucan and galactomannan. Lung histopathology was also evaluated. ASP9726 plasma concentrations increased in a dose-proportional manner, and the drug was well tolerated at each dose. Each dose of ASP9726, voriconazole, and caspofungin significantly reduced pulmonary fungal burden as measured by quantitative PCR and by determining (1→3)-β-d-glucan and galactomannan levels, but only voriconazole significantly reduced numbers of CFU. ASP9726 at 5 mg/kg also significantly improved survival. Histopathology demonstrated morphological changes in hyphae in animals exposed to ASP9726 and caspofungin, consistent with the activities of the echinocandins. These results suggest that ASP9726 may be efficacious for the treatment of invasive pulmonary aspergillosis.

scholarly journals Comparison of Lateral Flow Technology and Galactomannan and (1→3)-β-d-Glucan Assays for Detection of Invasive Pulmonary Aspergillosis

2009 ◽  
Vol 16 (12) ◽  
pp. 1844-1846 ◽  
Author(s):  
Nathan P. Wiederhold ◽  
Christopher R. Thornton ◽  
Laura K. Najvar ◽  
William R. Kirkpatrick ◽  
Rosie Bocanegra ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Invasive Aspergillosis ◽  
Pulmonary Disease ◽  
Invasive Pulmonary Aspergillosis ◽  
Lateral Flow ◽  
Pig Model ◽  
Pulmonary Aspergillosis ◽  
Lateral Flow Device ◽  
Flow Device ◽  
Guinea Pig Model

ABSTRACT We compared a lateral flow device to galactomannan and (1→3)-β-d-glucan assays to detect invasive aspergillosis in an established guinea pig model of pulmonary disease. The lateral flow device became positive earlier (day 3) than the (1→3)-β-d-glucan and galactomannan assays (day 5), with all samples positive by each assay on day 7.

scholarly journals Sequential or Combination Antifungal Therapy with Voriconazole and Liposomal Amphotericin B in a Guinea Pig Model of Invasive Aspergillosis

2006 ◽  
Vol 50 (4) ◽  
pp. 1567-1569 ◽  
Author(s):  
William R. Kirkpatrick ◽  
Brent J. Coco ◽  
Thomas F. Patterson
Keyword(s):  
Guinea Pig ◽  
Invasive Aspergillosis ◽  
Amphotericin B ◽  
Antifungal Therapy ◽  
Liposomal Amphotericin ◽  
Pig Model ◽  
Liposomal Amphotericin B ◽  
Guinea Pig Model

ABSTRACT We evaluated combinations of voriconazole (VRC) and liposomal amphotericin B (L-AMB) in a guinea pig invasive aspergillosis model. Simultaneous VRC and L-AMB was most effective, although VRC monotherapy was also effective. These regimens as well as sequential L-AMB followed by VRC were more effective than L-AMB alone or VRC followed by L-AMB.

scholarly journals Efficacy of Voriconazole in a Guinea Pig Model of Disseminated Invasive Aspergillosis

2000 ◽  
Vol 44 (10) ◽  
pp. 2865-2868 ◽  
Author(s):  
William R. Kirkpatrick ◽  
Robert K. McAtee ◽  
Annette W. Fothergill ◽  
Michael G. Rinaldi ◽  
Thomas F. Patterson
Keyword(s):  
Guinea Pig ◽  
Invasive Aspergillosis ◽  
Amphotericin B ◽  
Pig Model ◽  
Treatment Regimens ◽  
Guinea Pig Model

ABSTRACT Voriconazole (VRC) was evaluated in an immunosuppressed-guinea pig model of invasive aspergillosis. VRC was more effective than amphotericin B or similar doses of itraconazole in the clearance ofAspergillus from tissues. VRC treatment regimens improved survival and significantly reduced tissue colony counts compared with those of controls.

scholarly journals Efficacy of Voriconazole in a Guinea Pig Model of Invasive Trichosporonosis

2006 ◽  
Vol 50 (6) ◽  
pp. 2240-2243 ◽  
Author(s):  
Carolina Serena ◽  
Félix Gilgado ◽  
Marçal Mariné ◽  
F. Javier Pastor ◽  
Josep Guarro
Keyword(s):  
Body Weight ◽  
Guinea Pig ◽  
Amphotericin B ◽  
Guinea Pigs ◽  
Systemic Infection ◽  
Pig Model ◽  
Trichosporon Asahii ◽  
Tissue Burden ◽  
Guinea Pig Model

ABSTRACT We have evaluated the efficacy of voriconazole (VRC) in a systemic infection by Trichosporon asahii in immunosuppressed guinea pigs. VRC was more effective than amphotericin B in prolonging survival and reducing tissue burden. The best results were obtained with VRC at 10 mg/kg of body weight/day.

scholarly journals Efficacy of prophylactic aerosol amphotericin B lipid complex in a rat model of pulmonary aspergillosis.

1997 ◽  
Vol 41 (2) ◽  
pp. 259-261 ◽  
Author(s):  
C E Cicogna ◽  
M H White ◽  
E M Bernard ◽  
T Ishimura ◽  
M Sun ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Rat Model ◽  
Parent Compound ◽  
Invasive Pulmonary Aspergillosis ◽  
Transplant Recipients ◽  
Pulmonary Aspergillosis ◽  
Lipid Complex ◽  
Prophylactic Efficacy ◽  
Similar Dose ◽  
Amphotericin B Lipid Complex

Invasive pulmonary aspergillosis remains an important cause of morbidity and mortality among transplant recipients and patients receiving cancer chemotherapy. The lipid-associated formulation of amphotericin B (AmB), AmB lipid complex (ABLC), was evaluated for its prophylactic efficacy when it was administered as an aerosol in a rat model of pulmonary aspergillosis. Aerosol ABLC (aero-ABLC), in doses from 0.4 to 1.6 mg/kg of body weight given 2 days before infection, significantly delayed mortality compared to the mortality of rats given placebo (P < 0.001). At day 10 postinfection, 50% of rats in the 0.4-mg/kg group and 75% of rats in the 1.6-mg/kg group were alive, while all control animals had died. In a second trial aero-ABLC was more effective than an equivalent dose of aerosol AmB (aero-AmB) in prolonging survival, with 100% survival at day 14 postinfection in the ABLC group, compared to 62.5% survival in the AmB group. Mean concentrations of AmB in lungs were 3.7 times higher at day 1 (P < 0.002) and almost six times higher at day 7 (P < 0.001) after treatment with aero-ABLC than after treatment with a similar dose of aero-AmB. We conclude that aero-ABLC provided higher and more prolonged levels of the parent compound in the lungs than aero-AmB and was more effective in delaying mortality from aspergillosis in this model.

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