scholarly journals Inhaled Voriconazole for Prevention of Invasive Pulmonary Aspergillosis

2009 ◽  
Vol 53 (6) ◽  
pp. 2613-2615 ◽  
Author(s):  
Justin A. Tolman ◽  
Nathan P. Wiederhold ◽  
Jason T. McConville ◽  
Laura K. Najvar ◽  
Rosie Bocanegra ◽  
...  
Keyword(s):  
Invasive Aspergillosis ◽  
Aspergillus Fumigatus ◽  
Amphotericin B ◽  
Murine Model ◽  
Invasive Pulmonary Aspergillosis ◽  
Invasive Disease ◽  
Pulmonary Aspergillosis ◽  
Drug Concentrations ◽  
Intravenous Formulation

ABSTRACT Targeted airway delivery of antifungals as prophylaxis against invasive aspergillosis may lead to high lung drug concentrations while avoiding toxicities associated with systemically administered agents. We evaluated the effectiveness of aerosolizing the intravenous formulation of voriconazole as prophylaxis against invasive pulmonary aspergillosis caused by Aspergillus fumigatus in an established murine model. Inhaled voriconazole significantly improved survival and limited the extent of invasive disease, as assessed by histopathology, compared to control and amphotericin B treatments.

scholarly journals Novel Inhalational Murine Model of Invasive Pulmonary Aspergillosis

2004 ◽  
Vol 48 (5) ◽  
pp. 1908-1911 ◽  
Author(s):  
Donald C. Sheppard ◽  
Gunter Rieg ◽  
Lisa Y. Chiang ◽  
Scott G. Filler ◽  
John E. Edwards ◽  
...  
Keyword(s):  
Invasive Aspergillosis ◽  
Amphotericin B ◽  
Murine Model ◽  
Human Disease ◽  
Invasive Pulmonary Aspergillosis ◽  
Cortisone Acetate ◽  
Pulmonary Aspergillosis ◽  
Aerosol Chamber ◽  
Novel Model

ABSTRACT We developed a novel model of invasive aspergillosis (IA) that recapitulates human disease. Mice were immunosuppressed with cyclophosphamide and cortisone acetate and then infected in an aerosol chamber. This procedure reproducibly delivered 1 × 103 to 3 × 103 conidia to the lungs. Lethal pulmonary IA developed over 2 weeks and was prevented by amphotericin B.

scholarly journals Posaconazole Prophylaxis in Experimental Azole-Resistant Invasive Pulmonary Aspergillosis

2014 ◽  
Vol 59 (3) ◽  
pp. 1487-1494 ◽  
Author(s):  
Seyedmojtaba Seyedmousavi ◽  
Johan W. Mouton ◽  
Willem J. G. Melchers ◽  
Paul E. Verweij
Keyword(s):  
Invasive Aspergillosis ◽  
Aspergillus Fumigatus ◽  
Murine Model ◽  
Pulmonary Infection ◽  
Invasive Pulmonary Aspergillosis ◽  
Clinical Isolates ◽  
Wild Type ◽  
Breakthrough Infection ◽  
Pulmonary Aspergillosis ◽  
Content Type

ABSTRACTWe investigated the efficacy of posaconazole prophylaxis in preventing invasive aspergillosis due to azole-resistantAspergillus fumigatusisolates. Using a neutropenic murine model of pulmonary infection, posaconazole prophylaxis was evaluated using three isogenic clinical isolates, with posaconazole MICs of 0.063 mg/liter (wild type), 0.5 mg/liter (F219I mutation), and 16 mg/liter. A fourth isolate harboring TR34/L98H (MIC of 0.5 mg/liter) was also tested. Posaconazole prophylaxis was effective inA. fumigatuswith posaconazole MICs of ≤0.5 mg/liter, where 100% survival was reached. However, breakthrough infection was observed in mice infected with the isolate for which the posaconazole MIC was >16 mg/liter.

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.

scholarly journals Efficacy of Ambruticin Analogs in a Murine Model of Invasive Pulmonary Aspergillosis

2006 ◽  
Vol 50 (10) ◽  
pp. 3464-3466 ◽  
Author(s):  
Lisa Y. Chiang ◽  
Daniele E. Ejzykowicz ◽  
Zong-Qiang Tian ◽  
Leonard Katz ◽  
Scott G. Filler
Keyword(s):  
Antifungal Activity ◽  
Mouse Model ◽  
Invasive Aspergillosis ◽  
Murine Model ◽  
Antifungal Agents ◽  
Invasive Pulmonary Aspergillosis ◽  
Vehicle Control ◽  
Pulmonary Aspergillosis

ABSTRACT Ambruticins are a family of polyketides. The antifungal activity of an ambruticin, KOSN-2079, was tested in the mouse model of invasive aspergillosis. KOSN-2079 significantly reduced pulmonary fungal burdens and improved survival over that with the vehicle control. These results support the continued development of ambruticins as antifungal agents.

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.

scholarly journals Efficacy of Single-Dose Liposomal Amphotericin B or Micafungin Prophylaxis in a Neutropenic Murine Model of Invasive Pulmonary Aspergillosis

2008 ◽  
Vol 52 (11) ◽  
pp. 4178-4180 ◽  
Author(s):  
Russell E. Lewis ◽  
Nathaniel D. Albert ◽  
Dimitrios P. Kontoyiannis
Keyword(s):  
Body Weight ◽  
Amphotericin B ◽  
Murine Model ◽  
Liposomal Amphotericin ◽  
Invasive Pulmonary Aspergillosis ◽  
Liposomal Amphotericin B ◽  
Potential Utility ◽  
Pulmonary Aspergillosis ◽  
Fungal Burden ◽  
Animal Survival

ABSTRACT In a neutropenic murine model of invasive pulmonary aspergillosis, prophylaxis with single doses of liposomal amphotericin B or micafungin at ≥5 mg/kg of body weight improved animal survival and suppressed the lung fungal burden for up to 7 days after infection, demonstrating the potential utility of infrequent dosing with these antifungals.

scholarly journals Efficacy of 2-(3,4-Dimethyl-2,5-Dihydro-1H-Pyrrole-2-yl)-1-Methylethyl Pentanoate in a Murine Model of Invasive Aspergillosis

2005 ◽  
Vol 49 (10) ◽  
pp. 4365-4367 ◽  
Author(s):  
Rajesh Dabur ◽  
S. K. Diwedi ◽  
V. Yadav ◽  
V. Mishra ◽  
Rambir Singh ◽  
...  
Keyword(s):  
Body Weight ◽  
Survival Rate ◽  
Invasive Aspergillosis ◽  
Aspergillus Fumigatus ◽  
Amphotericin B ◽  
Murine Model ◽  
Antifungal Compound ◽  
Dose Dependent

ABSTRACT 2-(3,4-Dimethyl-2,5-dihydro-1H-pyrrole-2-yl)-1-methylethyl pentanoate, an antifungal compound, was found to be nontoxic to RAW cells up to a concentration of 312.5 μg/ml, whereas amphotericin B was lethal to all cells at 37.5 μg/ml. The treatment of Aspergillus fumigatus-infected mice with a dose of 200.0 mg of compound/kg of body weight increased their survival rate by 60%, with a decrease in CFU in organ tissues. The protection afforded by the compound against experimental aspergillosis was found to be dose dependent.

scholarly journals Pretreatment with Empty Liposomes Attenuates the Immunopathology of Invasive Pulmonary Aspergillosis in Corticosteroid-Immunosuppressed Mice

2006 ◽  
Vol 51 (3) ◽  
pp. 1078-1081 ◽  
Author(s):  
Russell E. Lewis ◽  
Georgios Chamilos ◽  
Randall A. Prince ◽  
Dimitrios P. Kontoyiannis
Keyword(s):  
Body Weight ◽  
Antifungal Activity ◽  
Amphotericin B ◽  
Murine Model ◽  
Liposomal Amphotericin ◽  
Invasive Pulmonary Aspergillosis ◽  
Pulmonary Aspergillosis ◽  
Amphotericin B Deoxycholate ◽  
Immunomodulatory Properties ◽  
Immunosuppressed Mice

ABSTRACT In a nonneutropenic murine model of invasive pulmonary aspergillosis, pretreatment with empty liposomes (E-lipo) was nearly as effective as 10 mg/kg of body weight liposomal amphotericin B and superior to 1 mg/kg amphotericin B deoxycholate. The beneficial immunomodulatory properties of E-lipo appear to compensate for their lack of direct antifungal activity.

scholarly journals Pharmacodynamic Activity of Amphotericin B Deoxycholate Is Associated with Peak Plasma Concentrations in a Neutropenic Murine Model of Invasive Pulmonary Aspergillosis

2006 ◽  
Vol 50 (2) ◽  
pp. 469-473 ◽  
Author(s):  
Nathan P. Wiederhold ◽  
Vincent H. Tam ◽  
Jingduan Chi ◽  
Randall A. Prince ◽  
Dimitrios P. Kontoyiannis ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Invasive Pulmonary Aspergillosis ◽  
Dose Fractionation ◽  
Pharmacokinetic Analysis ◽  
Pulmonary Aspergillosis ◽  
Fungal Burden ◽  
Drug Concentrations ◽  
Amphotericin B Deoxycholate

ABSTRACT We conducted a dose fractionation study of neutropenic, corticosteroid-immunosuppressed mice to characterize the pharmacodynamic/pharmacokinetic (PK/PD) parameter most closely associated with amphotericin B (AMB) efficacy in the treatment of invasive pulmonary aspergillosis. Pharmacokinetic parameter estimates were determined by a nonparametric population pharmacokinetic analysis of plasma drug concentrations following single intraperitoneal doses (0.25, 1.0, and 3.0 mg/kg of body weight) of amphotericin B deoxycholate. Three dosage groups (0.5, 0.75, and 1.0 mg/kg) fractionated into three dosing intervals (every 8 h [q8h], q24h, or q72h) were tested to discriminate between the PK/PD parameters (the ratio of maximum concentration of drug in serum [C max]/MIC, the ratio of area under the concentration-time curve/MIC, and percentage of time above MIC) most closely associated with AMB efficacy over a range of clinically achievable exposures in humans. The efficacy of each regimen was determined by quantitative PCR and survival. Reductions in pulmonary fungal burden and improvements in survival were maximized at the highest peak plasma concentrations in each of the dosage groups. Reductions in pulmonary fungal burden and increased survival were most closely associated with C max/MIC, with maximal activity occurring as the C max/MIC approached 2.4. In our model, C max/MIC is the PK/PD parameter most closely associated with efficacy in the treatment of invasive pulmonary aspergillosis. These data predict that less frequently administered, higher dosages of AMB would optimize efficacy.

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