scholarly journals Effects of Double and Triple Combinations of Antifungal Drugs in a Murine Model of Disseminated Infection by Scedosporium prolificans

2009 ◽  
Vol 53 (5) ◽  
pp. 2153-2155 ◽  
Author(s):  
M. Mar Rodríguez ◽  
Enrique Calvo ◽  
Carolina Serena ◽  
Marçal Mariné ◽  
F. Javier Pastor ◽  
...  

ABSTRACT We have evaluated the efficacies of micafungin, amphotericin B, and voriconazole, alone and in double and triple combinations, in a murine model of systemic infection by Scedosporium prolificans. Micafungin combined with voriconazole or amphotericin B was the most effective, these being the only treatments able to prolong survival and to reduce the fungal load in the kidneys and brain. Triple combinations of these drugs did not improve the results obtained with double combinations.

2009 ◽  
Vol 54 (2) ◽  
pp. 919-923 ◽  
Author(s):  
Enrique Calvo ◽  
F. Javier Pastor ◽  
M. Mar Rodríguez ◽  
Emilio Mayayo ◽  
Valentina Salas ◽  
...  

ABSTRACT We have evaluated the efficacy of posaconazole, amphotericin B, and itraconazole in a murine model of disseminated infection by Fonsecaea monophora. Of these three antifungal drugs tested, posaconazole prolonged survival significantly and reduced the fungal load in most of the organs tested. Bioassay studies demonstrated the relationship between posaconazole levels and dose escalation in serum and brain tissue. Posaconazole may have a clinical role in the treatment of disseminated infections by F. monophora.


2010 ◽  
Vol 54 (10) ◽  
pp. 4074-4077 ◽  
Author(s):  
Enrique Calvo ◽  
F. Javier Pastor ◽  
M. Mar Rodríguez ◽  
Isabel Pujol ◽  
Josep Guarro

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.


2013 ◽  
Vol 57 (12) ◽  
pp. 6265-6269 ◽  
Author(s):  
Fabiola Fernández-Silva ◽  
Javier Capilla ◽  
Emilio Mayayo ◽  
Deanna A. Sutton ◽  
Pilar Hernández ◽  
...  

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.


2003 ◽  
Vol 47 (6) ◽  
pp. 1948-1951 ◽  
Author(s):  
Javier Capilla ◽  
Clara Yustes ◽  
Emili Mayayo ◽  
Belkys Fernández ◽  
Montserrat Ortoneda ◽  
...  

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.


2005 ◽  
Vol 49 (11) ◽  
pp. 4757-4759 ◽  
Author(s):  
Marçal Mariné ◽  
Carolina Serena ◽  
Belkys Fernández-Torres ◽  
F. Javier Pastor ◽  
Josep Guarro

ABSTRACT We compared the efficacies of amphotericin B, fluconazole, flucytosine, and micafungin in a systemic murine infection by three isolates of Candida glabrata. Amphotericin B showed the best results, although none of the drugs dramatically reduced mortality or tissue burden in liver or spleen.


1999 ◽  
Vol 43 (5) ◽  
pp. 1256-1257 ◽  
Author(s):  
J. Guarro ◽  
I. Pujol ◽  
E. Mayayo

ABSTRACT In the treatment of disseminated Fusarium infections, amphotericin B either alone or in combination with flucytosine and rifampin is the drug therapy most frequently used. The efficacy of these antifungal drugs was evaluated in a murine disseminated-infection model, with five strains of Fusarium solani. All the treatments were clearly ineffective.


2008 ◽  
Vol 52 (10) ◽  
pp. 3786-3788 ◽  
Author(s):  
M. Mar Rodríguez ◽  
Carolina Serena ◽  
Marçal Mariné ◽  
F. Javier Pastor ◽  
Josep Guarro

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.


2013 ◽  
Vol 57 (9) ◽  
pp. 4540-4542 ◽  
Author(s):  
Marcelo Sandoval-Denis ◽  
F. Javier Pastor ◽  
Javier Capilla ◽  
Josep Guarro

ABSTRACTThe combination of amphotericin B at a suboptimal dose (0.3 mg/kg) with voriconazole has shown efficacy in prolonging survival and reducing tissue burden in a murine model of disseminated infection by an isolate ofAspergillus fumigatusthat had showed a poorin vivoresponse to the azole. The efficacy of the combined treatment was higher than that obtained with amphotericin B at 0.8 mg/kg.


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