RESUMEN
We have evaluated the in vitro activity of caspofungin against 36 wild-type strains of Candida parapsilosis sensu stricto using 3 techniques: broth microdilution, disk diffusion, and the determination of minimal fungicidal concentration (MFC). The first 2 methods showed a good in vitro activity of caspofungin, but the MFCs were ≥2 dilutions above their corresponding MICs. In a murine model of disseminated infection, we evaluated the efficacy of caspofungin at 5 mg/kg against 8 strains of C. parapsilosis representing different degrees of in vitro susceptibility (0.12-1 µg/mL). All the isolates responded to treatment and (1â3)-ß-D-glucan levels were reduced in all the cases; however, the study revealed differences among isolates, since caspofungin reduced the tissue burden of mice infected with isolates with MICs ≤0.5 µg/mL but was less effective against those with MICs of 1 µg/mL.
Asunto(s)
Candida/efectos de los fármacos , Candidiasis/tratamiento farmacológico , Equinocandinas/farmacología , Equinocandinas/uso terapéutico , Animales , Candidiasis/microbiología , Caspofungina , Recuento de Colonia Microbiana , Modelos Animales de Enfermedad , Lipopéptidos , Masculino , Ratones , Pruebas de Sensibilidad Microbiana , Proteoglicanos , Resultado del Tratamiento , beta-Glucanos/sangreRESUMEN
We evaluated the efficacy of voriconazole against nine strains of Aspergillus terreus with different MICs (0.12 to 4 µg/ml) by using a murine model. Markers of efficacy included survival, tissue burden, galactomannan antigenemia, and drug serum levels. Voriconazole was especially effective in prolonging survival and reducing the fungal load in infections by strains that showed MICs that were less than or equal to the epidemiological cutoff value (1 µg/ml). In vitro data might be useful for predicting the outcome of A. terreus infections.
Asunto(s)
Antifúngicos/farmacología , Aspergilosis/tratamiento farmacológico , Aspergillus/efectos de los fármacos , Pirimidinas/farmacología , Triazoles/farmacología , Anfotericina B/farmacología , Animales , Aspergilosis/inmunología , Aspergilosis/microbiología , Aspergilosis/mortalidad , Aspergillus/crecimiento & desarrollo , Aspergillus/aislamiento & purificación , Farmacorresistencia Fúngica/efectos de los fármacos , Galactosa/análogos & derivados , Masculino , Mananos/antagonistas & inhibidores , Mananos/inmunología , Ratones , Pruebas de Sensibilidad Microbiana , Pronóstico , Análisis de Supervivencia , VoriconazolRESUMEN
We have determined the in vitro activity of amphotericin B (AMB) and posaconazole (PSC) against Saksenaea vasiformis using broth microdilution and disk diffusion methods and determined the minimal fungicidal concentration (MFC). PSC was found to have the greatest in vitro activity in all cases and was the most efficacious in prolonging survival and reducing the fungal load in an immunocompetent murine model of disseminated infection caused by four strains of the fungus.
Asunto(s)
Antifúngicos/uso terapéutico , Modelos Animales de Enfermedad , Mucorales/patogenicidad , Mucormicosis/tratamiento farmacológico , Mucormicosis/microbiología , Mucormicosis/patología , Triazoles/uso terapéutico , Anfotericina B/farmacología , Anfotericina B/uso terapéutico , Animales , Antifúngicos/farmacología , Masculino , Ratones , Pruebas de Sensibilidad Microbiana , Resultado del Tratamiento , Triazoles/farmacologíaRESUMEN
The in vitro susceptibility of 17 strains of Mucor circinelloides to amphotericin B and posaconazole was ascertained by using broth microdilution and disk diffusion methods and by determining the minimal fungicidal concentration (MFC). We evaluated the efficacy of posaconazole at 40 mg/kg of body weight/day and amphotericin B at 0.8 mg/kg/day in a neutropenic murine model of disseminated infection by M. circinelloides by using 6 different strains tested previously in vitro. In general, most of the posaconazole MICs were within the range of susceptibility or intermediate susceptibility, while the small inhibition zone diameters (IZDs) were indicative of nonsusceptibility for all isolates tested. The MFCs were ≥ 3 dilutions higher than the corresponding MICs. In contrast, amphotericin B showed good activity against all of the strains tested regardless of the method used. The in vivo studies demonstrated that amphotericin B was effective in prolonging survival and reducing the fungal load. Posaconazole showed poor in vivo efficacy with no correlation with the MIC values. The results suggested that posaconazole should be used with caution in the treatment of infections caused by Mucor circinelloides or by strains of Mucor not identified to the species level.
Asunto(s)
Anfotericina B/uso terapéutico , Mucor/efectos de los fármacos , Mucormicosis/tratamiento farmacológico , Neutropenia/tratamiento farmacológico , Triazoles/uso terapéutico , Anfotericina B/administración & dosificación , Animales , Antifúngicos/administración & dosificación , Antifúngicos/uso terapéutico , Encéfalo/efectos de los fármacos , Encéfalo/microbiología , Modelos Animales de Enfermedad , Farmacorresistencia Fúngica , Riñón/efectos de los fármacos , Riñón/microbiología , Masculino , Ratones , Pruebas de Sensibilidad Microbiana , Mucor/fisiología , Mucormicosis/complicaciones , Mucormicosis/microbiología , Mucormicosis/mortalidad , Neutropenia/complicaciones , Neutropenia/microbiología , Neutropenia/mortalidad , Especificidad de la Especie , Tasa de Supervivencia , Insuficiencia del Tratamiento , Triazoles/administración & dosificaciónRESUMEN
We have evaluated the in vitro activity of anidulafungin (AFG) against 31 strains of Candida parapsilosis sensu stricto by using broth microdilution, disk diffusion, and minimal fungicidal concentration (MFC) determination procedures. The two first methods showed a high level of activity of the drug, while MFCs were 1 to 5 dilutions higher than their corresponding MICs. To assess if MICs were predictive of in vivo outcomes, six strains representing different AFG MICs (0.12 to 2 µg/ml) were tested in a murine model of disseminated infection treated with different doses of the drug (1, 5, or 10 mg/kg of body weight). AFG was able to prolong the survival of mice infected with all the strains tested but was able to reduce the tissue burden of those mice infected only with the strains that showed the lowest MIC (0.12 µg/ml).
Asunto(s)
Antifúngicos/uso terapéutico , Candida/efectos de los fármacos , Candida/patogenicidad , Candidiasis/sangre , Candidiasis/tratamiento farmacológico , Equinocandinas/uso terapéutico , Mananos/sangre , beta-Glucanos/sangre , Anidulafungina , Animales , Estimación de Kaplan-Meier , Masculino , Ratones , Pruebas de Sensibilidad MicrobianaRESUMEN
Posaconazole (PSC) is an antifungal drug recommended as an alternative for the treatment of invasive aspergillosis in patients who are refractory or intolerant to primary antifungal therapy. We have evaluated the in vitro activity of PSC against 21 strains of the Aspergillus terreus complex using both broth microdilution and disk diffusion (Neo Sensitabs) methods. PSC showed the same high level of activity against all the strains with the two in vitro methods used. We developed a murine model of disseminated infection to evaluate the efficacy of PSC at 5, 10, or 20 mg/kg of body weight twice a day by using 6 different strains chosen randomly. PSC showed good efficacy, especially at 20 mg/kg, as measured by prolonged survival, tissue burden reduction, histopathology, and lowered galactomannan levels. The PSC levels in serum on the fourth day of treatment were higher than the MICs for the strains tested.