scholarly journals Efficacy of Posaconazole in Murine Experimental Sporotrichosis

2012 ◽  
Vol 56 (5) ◽  
pp. 2273-2277 ◽  
Author(s):  
Fabiola Fernández-Silva ◽  
Javier Capilla ◽  
Emilio Mayayo ◽  
Josep Guarro

ABSTRACTWe developed a murine model of systemic sporotrichosis by using three strains of each of the two commonest species causing sporotrichosis, i.e.,Sporothrix schenckiisensu stricto andSporothrix brasiliensis, in order to evaluate the efficacy of posaconazole (PSC). The drug was administered at a dose of 2.5 or 5 mg/kg of body weight twice a day by gavage, and one group was treated with amphotericin B (AMB) as a control treatment. Posaconazole, especially at 5 mg/kg, showed good efficacy against all the strains tested, regardless of their MICs, as measured by prolonged survival, tissue burden reduction, and histopathology.

2015 ◽  
Vol 59 (8) ◽  
pp. 5018-5021 ◽  
Author(s):  
Débora Nunes Mario ◽  
Josep Guarro ◽  
Janio Morais Santurio ◽  
Sydney Hartz Alves ◽  
Javier Capilla

ABSTRACTWe evaluated the combination of posaconazole with amphotericin Bin vitroand in a murine model of systemic infections caused bySporothrix brasiliensisandSporothrix schenckiisensu stricto.In vitrodata demonstrated a synergistic effect, and although posaconazole alone was effective against sporotrichosis, efficacy in terms of survival and burden reduction was increased with the combination. This combination might be an option against disseminated sporotrichosis, especially when itraconazole or amphotericin B at optimal doses are contraindicated.


2015 ◽  
Vol 60 (1) ◽  
pp. 296-300 ◽  
Author(s):  
Adela Martin-Vicente ◽  
Javier Capilla ◽  
Josep Guarro

ABSTRACTAspergillus fumigatusis the main mold causing invasive fungal infection that shows high mortality rates. Therapeutic failure and the increase in drug resistance make it necessary to explore alternative treatments for this infection. We have evaluated the efficacy of amphotericin B at 0.8 mg/kg or 0.3 mg/kg of body weight combined with 40 mg/kg of posaconazole against threeA. fumigatusisolates in a murine model of disseminated infection. The combination of the polyene and the azole led to a greater increase in survival and a significantly greater reduction in tissue burden than monotherapies.


2017 ◽  
Vol 61 (10) ◽  
Author(s):  
A. Espinel-Ingroff ◽  
D. P. B. Abreu ◽  
R. Almeida-Paes ◽  
R. S. N. Brilhante ◽  
A. Chakrabarti ◽  
...  

ABSTRACT Clinical and Laboratory Standards Institute (CLSI) conditions for testing the susceptibilities of pathogenic Sporothrix species to antifungal agents are based on a collaborative study that evaluated five clinically relevant isolates of Sporothrix schenckii sensu lato and some antifungal agents. With the advent of molecular identification, there are two basic needs: to confirm the suitability of these testing conditions for all agents and Sporothrix species and to establish species-specific epidemiologic cutoff values (ECVs) or breakpoints (BPs) for the species. We collected available CLSI MICs/minimal effective concentrations (MECs) of amphotericin B, five triazoles, terbinafine, flucytosine, and caspofungin for 301 Sporothrix schenckii sensu stricto, 486 S. brasiliensis, 75 S. globosa, and 13 S. mexicana molecularly identified isolates. Data were obtained in 17 independent laboratories (Australia, Europe, India, South Africa, and South and North America) using conidial inoculum suspensions and 48 to 72 h of incubation at 35°C. Sufficient and suitable data (modal MICs within 2-fold concentrations) allowed the proposal of the following ECVs for S. schenckii and S. brasiliensis, respectively: amphotericin B, 4 and 4 μg/ml; itraconazole, 2 and 2 μg/ml; posaconazole, 2 and 2 μg/ml; and voriconazole, 64 and 32 μg/ml. Ketoconazole and terbinafine ECVs for S. brasiliensis were 2 and 0.12 μg/ml, respectively. Insufficient or unsuitable data precluded the calculation of ketoconazole and terbinafine (or any other antifungal agent) ECVs for S. schenckii, as well as ECVs for S. globosa and S. mexicana. These ECVs could aid the clinician in identifying potentially resistant isolates (non-wild type) less likely to respond to therapy.


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.


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.


2003 ◽  
Vol 47 (10) ◽  
pp. 3343-3344 ◽  
Author(s):  
Ashraf S. Ibrahim ◽  
Valentina Avanessian ◽  
Brad Spellberg ◽  
John E. Edwards

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.


Author(s):  
Conchita Toriello ◽  
Carolina Brunner-Mendoza ◽  
Estela Ruiz-Baca ◽  
Esperanza Duarte-Escalante ◽  
Amelia Pérez-Mejía ◽  
...  

Abstract Sporotrichosis is an endemic mycosis caused by the species of the Sporothrix genus, and it is considered one of the most frequent subcutaneous mycoses in Mexico. This mycosis has become a relevant fungal infection in the last two decades. Today, much is known of its epidemiology and distribution, and its taxonomy has undergone revisions. New clinical species have been identified and classified through molecular tools, and they now include Sporothrix schenckii sensu stricto, Sporothrix brasiliensis, Sporothrix globosa, and Sporothrix luriei. In this article, we present a systematic review of sporotrichosis in Mexico that analyzes its epidemiology, geographic distribution, and diagnosis. The results show that the most common clinical presentation of sporotrichosis in Mexico is the lymphocutaneous form, with a higher incidence in the 0–15 age range, mainly in males, and for which trauma with plants is the most frequent source of infection. In Mexico, the laboratory diagnosis of sporotrichosis is mainly carried out using conventional methods, but in recent years, several researchers have used molecular methods to identify the Sporothrix species. The treatment of choice depends mainly on the clinical form of the disease, the host’s immunological status, and the species of Sporothrix involved. Despite the significance of this mycosis in Mexico, public information about sporotrichosis is scarce, and it is not considered reportable according to Mexico’s epidemiological national system, the “Sistema Nacional de Vigilancia Epidemiológica.” Due to the lack of data in Mexico regarding the epidemiology of this disease, we present a systematic review of sporotrichosis in Mexico, between 1914 and 2019, that analyzes its epidemiology, geographic distribution, and diagnosis.


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.


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