scholarly journals Liposomal Amphotericin B, and Not Amphotericin B Deoxycholate, Improves Survival of Diabetic Mice Infected with Rhizopus oryzae

2003 ◽  
Vol 47 (10) ◽  
pp. 3343-3344 ◽  
Author(s):  
Ashraf S. Ibrahim ◽  
Valentina Avanessian ◽  
Brad Spellberg ◽  
John E. Edwards
Keyword(s):  
Overall Survival ◽  
Body Weight ◽  
Amphotericin B ◽  
Murine Model ◽  
Liposomal Amphotericin ◽  
Rhizopus Oryzae ◽  
Liposomal Amphotericin B ◽  
High Dose ◽  
Diabetic Mice ◽  
Amphotericin B Deoxycholate

ABSTRACT The efficacies of liposomal amphotericin B (LAmB) and amphotericin B deoxycholate (AmB) were compared in a diabetic murine model of hematogenously disseminated Rhizopus oryzae infection. At 7.5 mg/kg of body weight twice a day (b.i.d.), LAmB significantly improved overall survival compared to the rates of survival in both untreated control mice (P = 0.001) and mice treated with 0.5 mg of AmB per kg b.i.d. (P = 0.047). These data indicate that high-dose LAmB is more effective than AmB in treating murine disseminated zygomycosis.

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 Comparative Pharmacodynamics of Amphotericin B Lipid Complex and Liposomal Amphotericin B in a Murine Model of Pulmonary Mucormycosis

2009 ◽  
Vol 54 (3) ◽  
pp. 1298-1304 ◽  
Author(s):  
Russell E. Lewis ◽  
Nathan D. Albert ◽  
Guangling Liao ◽  
Jingguo Hou ◽  
Randall A. Prince ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Murine Model ◽  
Liposomal Amphotericin ◽  
Rhizopus Oryzae ◽  
Tissue Concentration ◽  
Liposomal Amphotericin B ◽  
Tissue Concentrations ◽  
Lipid Complex ◽  
Pulmonary Mucormycosis ◽  
Amphotericin B Lipid Complex

ABSTRACT We compared the kinetics of amphotericin B (AMB) lung accumulation and fungal clearance by liposomal amphotericin B (L-AMB) and amphotericin B lipid complex (ABLC) in a neutropenic murine model of invasive pulmonary mucormycosis (IPM). Immunosuppressed BALB/c mice were inoculated with 1 × 106 Rhizopus oryzae spores and administered L-AMB or ABLC at daily intravenous doses of 1, 5, or 10 mg/kg of body weight for 5 days starting 12 h after infection. At a dose of 10 mg/kg/day, both L-AMB and ABLC were effective at reducing the R. oryzae lung fungal burden and achieved lung tissue concentrations exceeding the isolate mean fungicidal concentration (MFC) of 8 μg/ml by 72 h. When ABLC was dosed at 5 mg/kg/day, the ABLC-treated animals had significantly higher AMB lung concentrations than the L-AMB treated animals at 24 h (6.64 and 1.44 μg/g, respectively; P = 0.013) and 72 h (7.49 and 1.03 μg/g, respectively; P = 0.005), and these higher concentrations were associated with improved fungal clearance, as determined by quantitative real-time PCR (mean conidial equivalent of R. oryzae DNA per lung, 4.44 ± 0.44 and 6.57 ± 0.74 log10, respectively; P < 0.001). Analysis of the AMB tissue concentration-response relationships revealed that the suppression of R. oryzae growth in the lung required tissue concentrations that approached the MFC for the infecting isolate (50% effective concentration, 8.19 μg/g [95% confidence interval, 2.81 to 18.1 μg/g]). The rates of survival were similar in the animals treated with L-AMB and ABLC at 10 mg/kg/day. These data suggest that higher initial doses may be required during L-AMB treatment than during ABLC treatment of experimental IPM.

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 Virulence and Experimental Treatment of Trichoderma longibrachiatum, a Fungus Refractory to Treatment

2016 ◽  
Vol 60 (8) ◽  
pp. 5029-5032 ◽  
Author(s):  
Katihuska Paredes ◽  
Javier Capilla ◽  
Emilio Mayayo ◽  
Josep Guarro
Keyword(s):  
Amphotericin B ◽  
High Resistance ◽  
Murine Model ◽  
Liposomal Amphotericin ◽  
Experimental Treatment ◽  
Liposomal Amphotericin B ◽  
Antifungal Compounds ◽  
Content Type ◽  
Trichoderma Longibrachiatum ◽  
Amphotericin B Deoxycholate

ABSTRACTDifferent inocula ofTrichoderma longibrachiatumwere tested in a murine model, and only the highest one (1 × 107CFU/animal) killed all of the mice at day 15 postinfection, with spleen and liver the most affected organs. The efficacies of amphotericin B deoxycholate, liposomal amphotericin B, voriconazole, and micafungin were evaluated in the same model, with very poor results. Our study demonstrated the low virulence but high resistance to antifungal compounds of this fungus.

scholarly journals Activity of a new liposomal formulation of amphotericin B against two strains of Leishmania infantum in a murine model.

1997 ◽  
Vol 41 (8) ◽  
pp. 1731-1734 ◽  
Author(s):  
M Paul ◽  
R Durand ◽  
H Fessi ◽  
D Rivollet ◽  
R Houin ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Murine Model ◽  
Leishmania Infantum ◽  
Liposomal Amphotericin ◽  
Liposomal Formulation ◽  
Liposomal Amphotericin B ◽  
Control Group ◽  
Conventional Drug ◽  
Amphotericin B Deoxycholate ◽  
Different Strains

The efficacy of a new liposomal formulation of amphotericin B was compared to that of amphotericin B deoxycholate (Fungizone) in a murine model of visceral leishmaniasis induced by Leishmania infantum. Median effective doses (ED50) were determined with two different strains: strain 1 was obtained from an untreated patient, and strain 2 was obtained from a patient who had received 12.5 g of amphotericin B over 3 years. BALB/c mice were infected intravenously on day 0 with promastigotes and then treated on days 14, 16, and 18 (strain 1) or on days 21, 23, and 25 (strain 2) with the liposomal formulation of amphotericin B (five doses were tested for each strain: 0.05, 0.1, 0.5, 0.8, and 3 mg/kg of body weight) or with conventional amphotericin B (four doses were tested for each strain: 0.05, 0.1, 0.5, and 0.8 mg/kg). Mice in the control group received normal saline solution. The liposomal amphotericin B formulation was about three times more active than the conventional drug against both strains. ED50 of the liposomal formulation were 0.054 (strain 1) and 0.194 (strain 2) mg/kg. ED50 of conventional amphotericin B were 0.171 (strain 1) and 0.406 (strain 2) mg/kg. Determination of drug tissular levels, 3 days after the last drug administration, showed a drug accumulation in hepatic and splenic tissues much higher after administration of liposomal amphotericin B than after conventional amphotericin B. A lack of toxicity was noted in all groups treated with the liposomal formulation.

scholarly journals 1554. Nebulized Liposomal Amphotericin B for Treatment of Murine Pulmonary Mucormycosis

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S567-S568
Author(s):  
Adilene Sandoval ◽  
Jill Adler-Moore
Keyword(s):  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
Rhizopus Oryzae ◽  
Liposomal Amphotericin B ◽  
High Dose ◽  
Spore Viability ◽  
Drug Levels ◽  
Pulmonary Mucormycosis ◽  
Life Threatening

Abstract Background Pulmonary mucormycosis, a life-threatening infection of immunocompromised individuals, can have a 95% mortality rate, even with treatment. Intravenous (IV) liposomal amphotericin B (AmBisomeâ, AmBi) is used to treat the infection, but rapid growth of the pathogen can limit the drug’s effectiveness. In the present study we investigated whether nebulized (nebz) AmBi could improve treatment outcome using a neutropenic murine model of pulmonary mucormycosis. Methods Rhizopus oryzae (ATCC MYA4621) was grown on Potato Dextrose Agar for 3–7 days, followed by spore harvesting, and determination of spore viability. Male ICR mice were immunosuppressed with 200 mg/kg of cyclophosphamide d-2, d0, d+2, d+4, and d0 challenged intranasally with 1 × 106 spores. In Study 1, mice (n = 16 mice/gp) were given AmBi at 7.5 or 10 mg/kg IV for 6 days, or nebz AmBi for 20 minutes (1.33 mg/mL AmBi in reservoir) for 4 days. In Study 2, 16 mice/gp were given AmBi at 15 mg/kg IV for 6 days or nebz AmBi for 7 days. PBS was the control. Lungs and kidneys were collected d+6 to determine drug concentration by a bioassay (n = 7–8 mice/gp) and morbidity (n = 8 mice/gp) monitored to d+21. Results In Study 1, survival was significantly better with nebz AmBi for 4 days (50%) or 10 mg/kg IV AmBi (33%) vs. 7.5 mg/kg IV AmBi (0%) (P < 0.003). In Study 2 with 13% survival in the PBS mice, 7 days of nebz AmBi produced 100% survival and 15 mg/kg IV AmBi gave 83% survival (P < 0.02 vs. PBS), underscoring the need for more intensive treatments. In Study 2, we also observed that average lung drug levels with nebz AmBi were significantly lower (3 μg/g lung) than with 15mg/kg AmBi IV (19 μg/g lung) (P = 0.003), even though both treatments were comparably effective. Kidney drug levels with 15 mg/kg AmBi IV were 13 μg/g and in comparison, nebz AmBi produced no detectable drug. Conclusion Daily nebulization of AmBi for one week or a high dose of IV AmBi at 15 mg/kg for 6 days protected the mice from severe pulmonary mucormycosis caused by R. oryzae, delivering effective drug levels to the lungs. The IV treatment yielded elevated levels of drug in the kidneys, while nebulization with AmBi produced no detectable drug in the kidneys. This indicated that nebz AmBi would be a less nephrotoxic, but still very effective route for drug delivery. Disclosures All authors: No reported disclosures.

High-dose Weekly Liposomal Amphotericin B Antifungal Prophylaxis in Patients Undergoing Liver Transplantation

2015 ◽  
Vol 99 (4) ◽  
pp. 848-854 ◽  
Author(s):  
Maddalena Giannella ◽  
Giorgio Ercolani ◽  
Francesco Cristini ◽  
Mariacristina Morelli ◽  
Michele Bartoletti ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
Antifungal Prophylaxis ◽  
Liposomal Amphotericin B ◽  
High Dose

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.

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