Activity of aminocandin (IP960) compared with amphotericin B and fluconazole in a neutropenic murine model of disseminated infection caused by a fluconazole-resistant strain of Candida tropicalis

2005 ◽  
Vol 56 (3) ◽  
pp. 590-593 ◽  
Author(s):  
Peter A. Warn ◽  
Andrew Sharp ◽  
Graham Morrissey ◽  
David W. Denning
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.


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.


2005 ◽  
Vol 49 (2) ◽  
pp. 497-502 ◽  
Author(s):  
Carolina Serena ◽  
F. Javier Pastor ◽  
Félix Gilgado ◽  
Emilio Mayayo ◽  
Josep Guarro

ABSTRACT Using a murine model of disseminated infection caused by Trichosporon asahii, we have evaluated the efficacies of amphotericin B (AMB; 1 mg/kg of body weight/day), fluconazole (FLC; 20 mg/kg/twice a day), and micafungin (MFG; 5 mg/kg/twice a day). We tested these drugs alone and in combination (MFG with AMB and MFG with FLC). MFG with AMB showed a synergistic effect and demonstrated a higher degree of efficacy in prolonging survival and reducing the kidney fungal burden than either agent alone. The combination MFG with FLC was able to reduce significantly the kidney fungal burden in comparison to that achieved with either drug administered alone.


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.


1995 ◽  
Vol 39 (4) ◽  
pp. 924-929 ◽  
Author(s):  
J R Graybill ◽  
L K Najvar ◽  
J D Holmberg ◽  
M F Luther

D0870 is a recently developed triazole with characteristics of a broad spectrum of activity and slow clearance by nonrenal mechanisms. Herein we have evaluated the efficacy of D0870, alone and combined with flucytosine, in a murine model of disseminated Candida tropicalis infection. Four isolates of C. tropicalis were evaluated. Two were highly susceptible in vitro to fluconazole, and two were resistant to fluconazole. All were highly susceptible to flucytosine and D0870. Animals were pretreated with 5-fluorouracil 1 day before infection because C. tropicalis has reduced virulence in immunocompetent mice. This was done to render them neutropenic for > 10 days. Mice were infected intravenously and treated orally with D0870 or fluconazole, alone or combined with flucytosine. Survival and tissue burden of the spleen and kidneys were used to evaluate the efficacy of antifungal therapy. Fluconazole was less effective for treatment of resistant C. tropicalis than susceptible C. tropicalis. D0870 was more potent than fluconazole and was effective in fluconazole-resistant isolates. Flucytosine was consistently effective when used alone but did not consistently add to the benefit of D0870 or fluconazole. D0870 has potential in treatment of candidiasis caused by C. tropicalis, including fluconazole-resistant isolates.


2015 ◽  
Vol 59 (7) ◽  
pp. 4289-4292 ◽  
Author(s):  
Sofia Costa-de-Oliveira ◽  
Isabel M. Miranda ◽  
Ana Silva-Dias ◽  
Ana P. Silva ◽  
Acácio G. Rodrigues ◽  
...  

ABSTRACTCandida albicansis the most prevalent cause of fungemia worldwide. Its ability to develop resistance in patients receiving azole antifungal therapy is well documented. In a murine model of systemic infection, we show that ibuprofen potentiates fluconazole antifungal activity against a fluconazole-resistant strain, drastically reducing the fungal burden and morbidity. The therapeutic combination of fluconazole with ibuprofen may constitute a new approach for the management of antifungal therapeutics to reverse the resistance conferred by efflux pump overexpression.


2000 ◽  
Vol 44 (10) ◽  
pp. 2664-2671 ◽  
Author(s):  
P. A. Warn ◽  
J. Morrissey ◽  
C. B. Moore ◽  
D. W. Denning

ABSTRACT We compared four doses of amphotericin B lipid complex (ABLC) with three doses of fluconazole in temporarily neutropenic mice in a murine model of disseminated candidiasis due to four different isolates ofCandida tropicalis. The mice were infected with a 90% lethal dose of four strains of C. tropicalis for which the fluconazole MICs ranged from 1 to >125 mg/liter 3 days after receiving 200 mg of cyclophosphamide/kg of body weight. Treatment was started 18 h after infection and lasted for 7 days. ABLC (1, 2, 5, and 10 mg/kg) was administered once a day intravenously, fluconazole was administered by oral gavage once daily (25 and 50 mg/kg/day) or twice daily (125 mg/kg). MICs determined in five different ways with 24- and 48-h endpoints were also compared. The overall survival rates were controls, 14%; fluconazole, 64%; and ABLC, 82%. Treatment with ABLC at 2 to 10 mg/kg increased survival compared to controls (P = <0.0001) and was also superior to fluconazole at 25 and 50 mg/kg (P = 0.006). In the fluconazole-resistant C. tropicalis model (MIC, 128 μg/ml), ABLC at 2 to 10 mg/kg was superior to fluconazole at 250 mg/kg and ABLC at 10 mg/kg was superior to all fluconazole doses (P = <0.05). Fluconazole at 250 mg/kg daily was superior to both 25 and 50 mg/kg at reducing mortality with most isolates. ABLC was superior to fluconazole (P = <0.01), and fluconazole at 250 mg/kg was superior to fluconazole at both 25 and 50 mg/kg (P = 0.02) in all models at reducing C. tropicalis counts in the kidneys. Neither drug consistently sterilized the brain or kidneys. A 48-h endpoint reading with the NCCLS susceptibility testing microtiter variation overestimates resistance to fluconazole. ABLC is an effective treatment for fluconazole-resistant C. tropicalis at all doses tested.


2009 ◽  
Vol 53 (4) ◽  
pp. 1705-1708 ◽  
Author(s):  
Mery Ruíz-Cendoya ◽  
Marçal Mariné ◽  
M. M. Rodríguez ◽  
Josep Guarro

ABSTRACT We have evaluated and compared the efficacies of high doses of amphotericin B (AMB; 3 mg/kg of body weight/day), voriconazole (60 mg/kg), and posaconazole (PSC; 100 mg/kg) alone and combined in a murine model of disseminated infection by Fusarium oxysporum. The combination of AMB with PSC showed the best results, prolonging the survival of mice and reducing their organ fungal loads. This combination might constitute a therapeutic option for those infections where monotherapies fail.


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