scholarly journals Posaconazole Prophylaxis in Experimental Systemic Zygomycosis

2006 ◽  
Vol 51 (1) ◽  
pp. 73-77 ◽  
Author(s):  
Francesco Barchiesi ◽  
Elisabetta Spreghini ◽  
Alfredo Santinelli ◽  
Annette W. Fothergill ◽  
Eleonora Pisa ◽  
...  
Keyword(s):  
Body Weight ◽  
Amphotericin B ◽  
Rhizopus Oryzae ◽  
Systemic Infection ◽  
Drug Efficacy ◽  
Antifungal Drugs ◽  
Active Infection ◽  
Absidia Corymbifera ◽  
The Brain

ABSTRACT Three isolates of zygomycetes belonging to two different genera (Rhizopus oryzae and Absidia corymbifera) were used to produce a systemic infection in neutropenic mice. On days −2 and −1 and at 2 h prior to infection, the mice received either posaconazole (POS) at doses ranging from 20 to 80 mg/kg of body weight/day or amphotericin B (AMB) at 1 mg/kg/day. Antifungal drug efficacy was assessed by determination of the prolongation of survival, determination of the percentage of infected organs (brain, lung, spleen, and kidney), and histological examination for the number of infection foci and their sizes in brain and kidney tissues. AMB significantly prolonged the survival of mice infected with all isolates. POS significantly prolonged the survival of mice infected with zygomycetes. Cultured organs from mice infected with R. oryzae were all positive, while treated mice challenged with A. corymbifera generally showed lower percentages of infected organs compared with the percentages for the controls. Zygomycete isolates established an active infection (the presence of hyphae) in the brains and the kidneys of all controls. In mice challenged with R. oryzae, both antifungal drugs were effective at reducing the number and the size of infection foci in the kidneys. Only AMB reduced the numbers, but not the sizes, of infection foci in the brain. Finally, both drugs significantly reduced the numbers and the sizes of infection foci in both tissues of mice infected with A. corymbifera. Our data suggest that prophylaxis with POS has some potential to prevent zygomycosis.

scholarly journals Treatment of Murine Fusariosis with SCH 56592

1999 ◽  
Vol 43 (3) ◽  
pp. 589-591 ◽  
Author(s):  
M. Lozano-Chiu ◽  
S. Arikan ◽  
V. L. Paetznick ◽  
E. J. Anaissie ◽  
D. Loebenberg ◽  
...  
Keyword(s):  
Body Weight ◽  
Amphotericin B ◽  
Fusarium Solani ◽  
Antifungal Agent ◽  
Systemic Infection ◽  
Immunocompetent Mice ◽  
Systemic Infections ◽  
Organ Clearance

ABSTRACT Doses of 10 to 100 mg of the azole antifungal agent SCH 56592/kg of body weight/day were studied in immunocompetent mice as therapy for systemic infection by Fusarium solani. Treatment was begun 1 h after intravenous infection and continued daily for 4 or 13 doses. Prolongation of survival and organ clearance were dependent on both the dose and the duration of SCH 56592 therapy, with the best results seen at 50 and 100 mg/kg/day. The results at the highest doses of SCH 56592 used (50 or 100 mg/kg/day) were comparable to those obtained with amphotericin B at 1 mg/kg/day. SCH 56592 has potential for therapy of systemic infections caused byF. solani.

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 Albaconazole (UR-9825) in Treatment of Disseminated Scedosporium prolificans Infection in Rabbits

2003 ◽  
Vol 47 (6) ◽  
pp. 1948-1951 ◽  
Author(s):  
Javier Capilla ◽  
Clara Yustes ◽  
Emili Mayayo ◽  
Belkys Fernández ◽  
Montserrat Ortoneda ◽  
...  
Keyword(s):  
Body Weight ◽  
Amphotericin B ◽  
Rabbit Model ◽  
Systemic Infection ◽  
Control Group ◽  
Scedosporium Prolificans ◽  
Tissue Burden

ABSTRACT There are no effective therapeutics for treating invasive Scedosporium prolificans infections. Doses of 15, 25, and 50 mg/kg of body weight/day for the new triazole albaconazole (ABC) were evaluated in an immunocompetent rabbit model of systemic infection with this mold. Treatments were begun 1 day after challenge and given for 10 days. ABC at any dose was more effective than amphotericin B (AMB) at 0.8 mg/kg/day at clearing S. prolificans from tissue (P < 0.007). The percentages of survival at 25 mg of ABC/kg/day were similar to those obtained with AMB. Rabbits showed 100% survival when they were treated with 50 mg of ABC per kg (P < 0.0001 versus control group), and only this dosage was able to reduce tissue burden significantly in the five organs studied, i.e., spleen, kidneys, liver, lungs, and brain.

scholarly journals Antifungal Therapy in a Murine Model of Disseminated Infection by Cryptococcus gattii

2010 ◽  
Vol 54 (10) ◽  
pp. 4074-4077 ◽  
Author(s):  
Enrique Calvo ◽  
F. Javier Pastor ◽  
M. Mar Rodríguez ◽  
Isabel Pujol ◽  
Josep Guarro
Keyword(s):  
Body Weight ◽  
Brain Tissue ◽  
Amphotericin B ◽  
Murine Model ◽  
Systemic Infection ◽  
Cryptococcus Gattii ◽  
Pulmonary Cryptococcosis ◽  
Fungistatic Activity ◽  
Fungal Load ◽  
Tissue Burden

ABSTRACT We have evaluated the efficacy of posaconazole (PSC), voriconazole (VRC), and amphotericin B (AMB) in a murine model of systemic infection by Cryptococcus gattii using immunocompromised animals and three clinical strains of the fungus. AMB was the most effective drug in prolonging the survival of mice and also in reducing tissue burden in all organs tested. To a lesser degree, VRC at 60 mg/kg of body weight in lung tissue and PSC at 40 mg/kg also in spleen demonstrated good efficacy in reducing the fungal load. The PSC and VRC levels in serum and brain tissue, determined by an agar diffusion bioassay method at 4 h after the last dose of the therapy, were above the corresponding MIC values. However, these drugs were not able to reduce the fungal load in brain tissue. Our results demonstrated that PSC and, to a lesser degree, VRC, have fungistatic activity and potential for the treatment of human pulmonary cryptococcosis.

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.

Comparison of Fungizone, Amphotec, AmBisome, and Abelcet for Treatment of Systemic Murine Cryptococcosis

1998 ◽  
Vol 42 (4) ◽  
pp. 899-902 ◽  
Author(s):  
Karl V. Clemons ◽  
David A. Stevens
Keyword(s):  
Body Weight ◽  
Cryptococcus Neoformans ◽  
Amphotericin B ◽  
Rank Order ◽  
Yeast Cells ◽  
Treatment Regimens ◽  
Equal Dose ◽  
The Brain ◽  
All Treatment ◽  
Better Than

ABSTRACT Three lipid-based formulations of amphotericin B have been approved for use in various countries. The aim of this study was to compare Amphotec (ABCD; Sequus), AmBisome (AmBi; Nexstar), Abelcet (ABLC; The Liposome Co.), and conventional deoxycholate amphotericin B (Fungizone; Bristol Meyers Squibb) for the treatment of experimental systemic cryptococcosis. A model was established in 10-week-old female CD-1 mice by intravenous (i.v.) injection of 6.25 × 105 viableCryptococcus neoformans yeast cells. Therapy began 4 days later, with i.v. administration three times per week for 2 weeks. Mice received either no treatment, 1 mg of Fungizone per kg of body weight, or 1, 5, or 10 mg of ABCD, AmBi, or ABLC per kg. Ninety percent of control mice died between days 15 and 34. All treatment regimens except ABLC at 1 mg/kg prolonged survival compared with no treatment (P < 0.01 to 0.001). All mice receiving 5 or 10 mg of ABCD or AmBi per kg and 90% of mice given 10 mg of ABLC per kg survived, whereas ≤50% of those given other treatment regimens survived. Fungizone was the least effective of the four formulations, with 5 or 10 mg of ABCD, AmBi, or ABLC per kg resulting in a significantly better outcome than Fungizone (P < 0.001). Among the three formulations, ABCD and AmBi were equally effective, both being better than ABLC at equal 5- or 10-mg/kg doses (P < 0.001). Comparison of residual infectious burdens in various organs showed that each drug had some dose-responsive efficacy in three or more organs at escalating doses. In the brain, ABCD or AmBi at 5 or 10 mg/kg or ABLC at 10 mg/kg was more effective than Fungizone at 1 mg/kg or no treatment, while ABCD or AmBi at 1 mg/kg was as effective as ABLC at 10 mg/kg. Similar results were obtained for the kidneys and lungs. In the spleen, ABCD at 10 mg/kg cured all mice of infection and was superior to all other regimens. In the liver, AmBi at 5 mg/kg was superior to an equal dose of ABCD or ABLC. Overall, the efficacies of ABCD and AmBi were equal to that of Fungizone at 1 mg/kg and were about 10-fold better than that of ABLC, particularly in the brain; a comparative rank order of efficacies was ABCD ≅ AmBi > ABLC ≫ Fungizone. This is the first study that compared all four amphotericin B formulations.

scholarly journals Activity of Posaconazole in Treatment of Experimental Disseminated Zygomycosis

2003 ◽  
Vol 47 (11) ◽  
pp. 3647-3650 ◽  
Author(s):  
Eric Dannaoui ◽  
Jacques F. G. M. Meis ◽  
David Loebenberg ◽  
Paul E. Verweij
Keyword(s):  
Amphotericin B ◽  
Dose Response ◽  
Rhizopus Oryzae ◽  
Rhizopus Microsporus ◽  
Disseminated Infection ◽  
Absidia Corymbifera ◽  
Beneficial Effects ◽  
Clear Dose Response ◽  
Dose Response Effect ◽  
Partial Activity

ABSTRACT Three isolates of zygomycetes were used to produce a disseminated infection in nonimmunocompromised mice. Against all zygomycete strains, amphotericin B significantly prolonged survival. Itraconazole was inactive against Rhizopus microsporus and Rhizopus oryzae but was partially active against Absidia corymbifera. Posaconazole had no beneficial effects against R. oryzae but showed partial activity against A. corymbifera. Posaconazole had a clear dose-response effect against R. microsporus.

scholarly journals Posaconazole Combined with Amphotericin B, an Effective Therapy for a Murine Disseminated Infection Caused by Rhizopus oryzae

2008 ◽  
Vol 52 (10) ◽  
pp. 3786-3788 ◽  
Author(s):  
M. Mar Rodríguez ◽  
Carolina Serena ◽  
Marçal Mariné ◽  
F. Javier Pastor ◽  
Josep Guarro
Keyword(s):  
Body Weight ◽  
Amphotericin B ◽  
Murine Model ◽  
Rhizopus Oryzae ◽  
Effective Therapy ◽  
Prolonged Survival ◽  
Low Doses ◽  
Disseminated Infection ◽  
Tissue Burden

ABSTRACT In a murine model of disseminated zygomycosis, low doses of amphotericin B (0.3 mg/kg body weight/day) combined with posaconazole (40 mg/kg/day) prolonged survival and reduced tissue burden with respect to that of controls and that of both drugs administered alone. Results were similar to those obtained with amphotericin B given alone at 0.8 mg/kg/day.

scholarly journals Evaluation of the Efficacies of Amphotericin B, Posaconazole, Voriconazole, and Anidulafungin in a Murine Disseminated Infection by the Emerging Opportunistic Fungus Sarocladium (Acremonium)kiliense

2013 ◽  
Vol 57 (12) ◽  
pp. 6265-6269 ◽  
Author(s):  
Fabiola Fernández-Silva ◽  
Javier Capilla ◽  
Emilio Mayayo ◽  
Deanna A. Sutton ◽  
Pilar Hernández ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Survival Rates ◽  
Systemic Infection ◽  
Serum Levels ◽  
Antifungal Drugs ◽  
Content Type ◽  
Animal Survival ◽  
Fungal Load ◽  
High Mics

ABSTRACTWe evaluated and compared the efficacies of different antifungal drugs againstSarocladium kiliense(formerlyAcremonium kiliense), a clinically relevant opportunistic fungus, in a murine model of systemic infection. Three clinical strains of this fungus were tested, and the therapy administered was as follows: posaconazole at 20 mg/kg of body weight (twice daily), voriconazole at 40 mg/kg, anidulafungin at 10 mg/kg, or amphotericin B at 0.8 mg/kg. The efficacy was evaluated by prolonged animal survival, tissue burden reduction, and (1→3)-β-d-glucan serum levels. In general, the four antifungal drugs showed high MICs and poorin vitroactivity. The efficacy of the different treatments was only modest, since survival rates were never higher than 40% and no drug was able to reduce fungal load in all the organs for the three strains tested. Posaconazole, in spite of its high MICs (≥16 μg/ml), showed the highest efficacy. The (1→3)-β-d-glucan serum levels were equally reduced by all drugs evaluated.

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