RESUMEN
The genera Acremonium and Sarocladium comprise a high diversity of morphologically and genetically related fungi generally found in the environment, although a few species, mainly Sarocladium kiliense and Acremonium egyptiacum, can also be involved in many human infections. Clinical management of opportunistic infections caused by these fungi is very complex, since their correct identification is unreliable, and they generally show poor antifungal response. More than 300 clinical cases involving a broad range of Acremonium/Sarocladium infections have so far been published, and with this review we aim to compile and provide a detailed overview of the current knowledge on Acremonium/Sarocladium human infections in terms of presentation, diagnosis, treatments and prognoses. We also aim to summarise and discuss the data currently available on their antifungal susceptibility, emphasising the promising results obtained with voriconazole as well as their impact in terms of animal infections.
Asunto(s)
Hypocreales , Micosis , Infecciones Oportunistas , Acremonium/clasificación , Acremonium/efectos de los fármacos , Acremonium/aislamiento & purificación , Acremonium/patogenicidad , Animales , Antifúngicos/uso terapéutico , Artritis/tratamiento farmacológico , Artritis/microbiología , Sangre/microbiología , Infecciones del Sistema Nervioso Central/tratamiento farmacológico , Infecciones del Sistema Nervioso Central/microbiología , Dermatomicosis/tratamiento farmacológico , Farmacorresistencia Fúngica , Endocarditis/tratamiento farmacológico , Endocarditis/microbiología , Infecciones del Ojo/tratamiento farmacológico , Infecciones del Ojo/microbiología , Humanos , Hypocreales/clasificación , Hypocreales/efectos de los fármacos , Hypocreales/aislamiento & purificación , Hypocreales/patogenicidad , Infecciones Fúngicas Invasoras/tratamiento farmacológico , Infecciones Fúngicas Invasoras/patología , Micetoma/tratamiento farmacológico , Micosis/tratamiento farmacológico , Micosis/patología , Micosis/veterinaria , Onicomicosis/tratamiento farmacológico , Onicomicosis/microbiología , Infecciones Oportunistas/tratamiento farmacológico , Infecciones Oportunistas/patología , Infecciones Oportunistas/veterinaria , Osteomielitis/tratamiento farmacológico , Osteomielitis/microbiología , Peritonitis/tratamiento farmacológico , Peritonitis/microbiología , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Infecciones del Sistema Respiratorio/microbiología , Voriconazol/uso terapéuticoRESUMEN
BACKGROUND: The incidence of systemic infections by Saccharomyces cerevisiae has increased in recent years, especially among immunocompromised patients. Amphotericin B, voriconazole or echinocandins have been used with favorable outcome against systemic infections by this fungus. However, clinical experience is limited and no in vivo studies have been conducted. AIMS: We evaluated the in vitro activity of nine antifungal compounds against S.cerevisiae and the in vivo efficacy of those three antifungals showing the highest in vitro activity by using a murine model of systemic infection. METHODS: Minimal inhibitory concentrations (MICs) were determined by the microdilution method against three strains of S. cerevisiae. After intravenous infection with 5×107 CFUs, animals received liposomal amphotericin B (5mg/kg), voriconazole (25mg/kg) or anidulafungin (5mg/kg). Treatment efficacy was assessed by determining of CFUs/g in liver, kidney, brain, lung and spleen. RESULTS: 5-Fluorocytosine was the most in vitro active compound followed by amphotericin B, voriconazole and anidulafungin. The in vivo study showed that liposomal amphotericin B was the most effective drug driving highest fungal clearance. CONCLUSIONS: All treatments reduced the fungal load in comparison to the control group, being liposomal amphotericin B the most effective drug followed by anidulafungin and finally voriconazole.
Asunto(s)
Anfotericina B/farmacología , Anfotericina B/uso terapéutico , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Equinocandinas/farmacología , Equinocandinas/uso terapéutico , Micosis/tratamiento farmacológico , Saccharomyces cerevisiae/efectos de los fármacos , Voriconazol/farmacología , Voriconazol/uso terapéutico , Animales , Modelos Animales de Enfermedad , Humanos , Masculino , Ratones , Pruebas de Sensibilidad MicrobianaRESUMEN
Cryptococcus albidus and Cryptococcus laurentii are uncommon species of this genus that in recent decades have increasingly caused opportunistic infections in humans, mainly in immunocompromised patients; the best therapy for such infection being unknown. Using a murine model of systemic infection by these fungi, we have evaluated the efficacy of amphotericin B (AMB) at 0.8 mg/kg, administered intravenously, fluconazole (FLC) or voriconazole (VRC), both administered orally, at 25 mg/kg and the combination of AMB plus VRC against three C. albidus and two C. laurentii strains. All the treatments significantly reduced the fungal burden in all the organs studied. The combination showed a synergistic effect in the reduction in fungal load, working better than both monotherapies. The histopathological study confirmed the efficacy of the treatments.
Asunto(s)
Antifúngicos/uso terapéutico , Criptococosis/tratamiento farmacológico , Criptococosis/microbiología , Cryptococcus/efectos de los fármacos , Administración Intravenosa , Administración Oral , Anfotericina B/uso terapéutico , Animales , Criptococosis/sangre , Modelos Animales de Enfermedad , Sinergismo Farmacológico , Quimioterapia Combinada , Fluconazol/uso terapéutico , Huésped Inmunocomprometido , Pulmón/microbiología , Ratones , Pruebas de Sensibilidad Microbiana , Bazo/microbiología , Voriconazol/uso terapéuticoRESUMEN
Background: Scedosporiosis is associated with a mortality rate of up to 90% in patients suffering from disseminated infections. Recommended first-line treatment is voriconazole, but epidemiological cut-off values and clinical breakpoints have not been determined. Objectives: To correlate voriconazole treatment response in mice suffering from disseminated scedosporiosis with MIC values determined using CLSI broth microdilution, Etest (bioMérieux) and disc diffusion. Methods: Voriconazole MICs for 31 Scedosporium apiospermum strains were determined using CLSI broth microdilution, Etest and disc diffusion. Groups of mice were challenged intravenously with 1 out of 16 S. apiospermum strains (voriconazole CLSI broth microdilution MIC range: 0.125-8.0 mg/L) and treated with 40 mg/kg voriconazole orally by gavage once daily. Efficacy of voriconazole was evaluated by a statistically significant ( P < 0.05) reduction in fungal burden in brain. Results: A categorical agreement of 90.4% was reached for CLSI broth microdilution and disc diffusion and of 93.6% for CLSI broth microdilution and Etest. Correlation of CLSI MICs and in vivo outcome was good, as mice challenged with strains with an MIC ≤2 mg/L responded to voriconazole therapy in 92.3% and those challenged with strains with an MIC ≥4 mg/L responded to voriconazole therapy in 33.3%. Conclusions: CLSI broth microdilution and Etest deliver comparable results that enable a prediction of in vivo outcome. Our results suggest that voriconazole is able to reduce fungal burden in the brain of 92.3% of all mice challenged with strains with voriconazole CLSI MICs ≤2 mg/L, while mice challenged with strains with CLSI MICs ≥4 mg/L showed limited response to voriconazole treatment.
Asunto(s)
Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Micosis/tratamiento farmacológico , Scedosporium/efectos de los fármacos , Voriconazol/farmacología , Voriconazol/uso terapéutico , Animales , Antifúngicos/administración & dosificación , Encéfalo/efectos de los fármacos , Encéfalo/microbiología , Humanos , Ratones , Pruebas de Sensibilidad Microbiana , Micosis/sangre , Micosis/microbiología , Valor Predictivo de las Pruebas , Voriconazol/administración & dosificaciónRESUMEN
In this study, 27 clinical isolates of Candida glabrata with voriconazole (VRC) minimum inhibitory concentrations (MICs) ranging from ≤0.03 µg/mL to 8 µg/mL were tested to determine whether in vitro data are predictive of in vivo efficacy. The efficacy of VRC administered at 40 mg/kg was assayed in a neutropenic murine model of disseminated infection by C. glabrata. The reduction in fungal tissue burden in the kidneys was used as a marker of treatment efficacy. VRC reduced the fungal tissue burden in mice infected with strains that had MICs below the epidemiological cut-off value (ECV) of 0.25 µg/mL. Variable efficacy of VRC was obtained when the MIC equalled the ECV, and VRC was ineffective when the MIC exceeded the ECV. These results suggest that the use of in vitro data could be useful to predict the outcome for infections by this fungus.
Asunto(s)
Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Candida glabrata/efectos de los fármacos , Candidiasis/tratamiento farmacológico , Voriconazol/farmacología , Voriconazol/uso terapéutico , Animales , Recuento de Colonia Microbiana , Modelos Animales de Enfermedad , Riñón/microbiología , Masculino , Ratones , Pruebas de Sensibilidad Microbiana , Resultado del TratamientoRESUMEN
Candida kefyr is an emerging pathogen able to cause disseminated infection, especially in immunocompromised patients. Although guidelines for the treatment of invasive candidiasis have been published, no specific recommendations against C. kefyr are available. We determine the in vitro killing activity of amphotericin B (AMB), fluconazole (FLC) and caspofungin (CFG) as well as their efficacy in a murine model of systemic infection by two C. kefyr strains. Time-kill curves of AMB, FLC and CFG were determined in final volumes of 10 ml containing the assayed drugs ranged from 0.03 to 32 µg ml-1 at different time points and efficacy of the drugs was evaluated in a systemic model of candidiasis, conducted in immunosuppressed mice, through survival, (1â3)-ß-D-glucan levels in serum and fungal load in kidneys. AMB and CFG showed fungicidal and FLC fungistatic activity against both isolates. The three drugs were able to reduce fungal burden in kidneys and (1â3)-ß-D-glucan concentration in serum of infected mice, with CFG showing the highest efficacy, followed by FLC. In conclusion, CFG showed efficacy over AMB and FLC against the systemic candidiasis by C. kefyr. The established epidemiological cut-off for anidulafungin seems the best indicator of outcome for echinocandins.
Asunto(s)
Anfotericina B/administración & dosificación , Antifúngicos/administración & dosificación , Candida/efectos de los fármacos , Candidiasis Invasiva/tratamiento farmacológico , Equinocandinas/administración & dosificación , Fluconazol/administración & dosificación , Lipopéptidos/administración & dosificación , Anfotericina B/farmacología , Animales , Antifúngicos/farmacología , Caspofungina , Recuento de Colonia Microbiana , Modelos Animales de Enfermedad , Equinocandinas/farmacología , Fluconazol/farmacología , Riñón/microbiología , Lipopéptidos/farmacología , Masculino , Ratones , Pruebas de Sensibilidad Microbiana , Viabilidad Microbiana/efectos de los fármacos , Proteoglicanos , Análisis de Supervivencia , Resultado del Tratamiento , beta-Glucanos/sangreRESUMEN
We evaluated the combination of posaconazole with amphotericin B in vitro and in a murine model of systemic infections caused by Sporothrix brasiliensis and Sporothrix schenckii sensu stricto. In vitro data 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.
Asunto(s)
Anfotericina B/uso terapéutico , Antifúngicos/uso terapéutico , Sporothrix/efectos de los fármacos , Esporotricosis/tratamiento farmacológico , Triazoles/uso terapéutico , Animales , Farmacorresistencia Fúngica Múltiple , Quimioterapia Combinada , Ratones , Pruebas de Sensibilidad Microbiana , Sporothrix/patogenicidadRESUMEN
Background. Candida guilliermondii has been recognized as an emerging pathogen showing a decreased susceptibility to fluconazole and considerably high echinocandin MICs. Aims. Evaluate the in vitro activity of anidulafungin in comparison to amphotericin B and fluconazole against different isolates of C. guilliermondii, and their efficacy in an immunosuppressed murine model of disseminated infection. Methods. The in vitro susceptibility of four strains against amphotericin B, fluconazole and anidulafungin was performed by using a reference broth microdilution method and time-kill curves. The in vivo efficacy was evaluated by determination of fungal load reduction in kidneys of infected animals receiving deoxycholate AMB at 0,8 mg/kg i.v., liposomal amphotericin B at 10 mg/kg i.v., fluconazole at 50 mg/kg, or anidulafungin at 10 mg/kg. Results. Amphotericin B and anidulafungin showed fungicidal activity, while fluconazole was fungistatic for all the strains. In the murine model, liposomal amphotericin B at 10 mg/kg/day was effective in reducing the tissue burden in kidneys of mice infected with any of the tested strains. However, amphotericin B, anidulafungin and fluconazole were only effective against those strains showing low MIC values. Conclusions. Liposomal amphotericin B showed the higher activity and efficacy against the two strains of C. guilliermondii, in contrast to the poor effect of fluconazole and anidulafungin. Further studies with more isolates of C. guilliermondii representing a wider range of MICs should be carried out to assess whether there is any relationship between MIC values and anidulafungin efficacy (AU)
Antecedentes. Candida guilliermondii es un patógeno emergente, con reducida sensibilidad al fluconazol y a las equinocandinas. Objetivos. Evaluar la actividad in vitro de la anidulafungina, en comparación con la de la anfotericina B y el fluconazol, frente a C. guilliermondii y su eficacia en un modelo animal de infección diseminada. Métodos. La sensibilidad in vitro se valoró mediante microdilución en caldo y curvas de mortalidad. La eficacia in vivo se evaluó mediante la determinación de la carga fúngica en riñón de ratones inmunosuprimidos con infección diseminada por C. guilliermondii tratados con anfotericina B desoxicolato (0.8 mg/kg i.v.), anfotericina B liposomal (10 mg/kg i.v.), fluconazol (50 mg/kg) o anidulafungina (10 mg/kg). Resultados. La anfotericina B y la anidulafungina mostraron actividad fungicida, mientras que el fluconazol fue fungistático frente a todas las cepas. En el modelo murino, la anfotericina B liposomal redujo para todas las cepas la carga fúngica en riñones, mientras que la anfotericina B desoxicolato, la anidulafungina y el fluconazol fueron efectivas solo en aquellos animales infectados con las cepas de menor valor de concentración mínima inhibitoria (CMI). Conclusiones. La anfotericina B liposomal mostró la mayor actividad y eficacia frente a C. guilliermondii, en contraste con el limitado efecto del fluconazol y de la anidulafungina. Se necesitan estudios que incluyan cepas con un rango más amplio de CMI que permitan determinar la relación entre la actividad in vitro y la eficacia de la anidulafungina (AU)
Asunto(s)
Animales , Masculino , Femenino , Ratones , Candida , Candida/aislamiento & purificación , Candida/metabolismo , Antifúngicos/metabolismo , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Modelos Animales , Ácido Desoxicólico/uso terapéutico , Resultado del Tratamiento , Evaluación de Eficacia-Efectividad de Intervenciones , Pruebas de Sensibilidad Microbiana/métodos , Sensibilidad y Especificidad , Fluconazol/metabolismo , Fluconazol/farmacocinética , Fluconazol/uso terapéutico , Anfotericina B/uso terapéuticoRESUMEN
BACKGROUND: Candida guilliermondii has been recognized as an emerging pathogen showing a decreased susceptibility to fluconazole and considerably high echinocandin MICs. AIMS: Evaluate the in vitro activity of anidulafungin in comparison to amphotericin B and fluconazole against different isolates of C. guilliermondii, and their efficacy in an immunosuppressed murine model of disseminated infection. METHODS: The in vitro susceptibility of four strains against amphotericin B, fluconazole and anidulafungin was performed by using a reference broth microdilution method and time-kill curves. The in vivo efficacy was evaluated by determination of fungal load reduction in kidneys of infected animals receiving deoxycholate AMB at 0,8 mg/kg i.v., liposomal amphotericin B at 10 mg/kg i.v., fluconazole at 50 mg/kg, or anidulafungin at 10 mg/kg. RESULTS: Amphotericin B and anidulafungin showed fungicidal activity, while fluconazole was fungistatic for all the strains. In the murine model, liposomal amphotericin B at 10 mg/kg/day was effective in reducing the tissue burden in kidneys of mice infected with any of the tested strains. However, amphotericin B, anidulafungin and fluconazole were only effective against those strains showing low MIC values. CONCLUSIONS: Liposomal amphotericin B showed the higher activity and efficacy against the two strains of C. guilliermondii, in contrast to the poor effect of fluconazole and anidulafungin. Further studies with more isolates of C. guilliermondii representing a wider range of MICs should be carried out to assess whether there is any relationship between MIC values and anidulafungin efficacy.
Asunto(s)
Anfotericina B/farmacología , Antifúngicos/farmacología , Candida/efectos de los fármacos , Candidiasis Invasiva/tratamiento farmacológico , Equinocandinas/farmacología , Fluconazol/farmacología , Anidulafungina , Animales , Antifúngicos/uso terapéutico , Candida/aislamiento & purificación , Candidiasis Invasiva/etiología , Candidiasis Invasiva/microbiología , Enfermedades Transmisibles Emergentes/microbiología , Evaluación Preclínica de Medicamentos , Riñón/microbiología , Masculino , Ratones , Pruebas de Sensibilidad Microbiana , Neutropenia/complicaciones , Distribución Aleatoria , Especificidad de la EspecieRESUMEN
Despite the use of recommended therapies, invasive infections by Aspergillus terreus show a poor response. For years, investigative studies on the failure of therapy of fungal infections have focused on in vitro susceptibility data. However, it is well known that low minimum inhibitory concentrations (MICs) are not always predictive of response to therapy despite a correct dosage schedule. Many experimental and clinical studies have tried to establish a relationship between MICs and outcome in serious fungal infections but have come to contradictory and even surprising conclusions. The success or failure of treatment is determined by many factors, including the in vitro susceptibility of the causative fungal isolate, the pharmacokinetics/pharmacodynamics of the drug used for treatment, pharmacokinetic variability in the population, and the underlying disease that patients suffer. To try to understand this poor response to treatment, available data on the in vitro susceptibility of A. terreus, the experimental and clinical response to amphotericin B, triazoles and echinocandins, and the pharmacokinetics/pharmacodynamics of these antifungals have been reviewed. Of special interest are the fungistatic activites of these drugs against A. terreus and the high interpatient variability of serum drug levels observed in therapy based on triazoles, which make monitoring of infected patients necessary.
Asunto(s)
Anfotericina B/uso terapéutico , Antifúngicos/uso terapéutico , Aspergilosis/tratamiento farmacológico , Aspergillus/efectos de los fármacos , Equinocandinas/uso terapéutico , Triazoles/uso terapéutico , Anfotericina B/farmacocinética , Anfotericina B/farmacología , Antifúngicos/farmacocinética , Antifúngicos/farmacología , Aspergilosis/microbiología , Equinocandinas/farmacocinética , Equinocandinas/farmacología , Humanos , Pruebas de Sensibilidad Microbiana , Suero/química , Resultado del Tratamiento , Triazoles/farmacocinética , Triazoles/farmacologíaRESUMEN
We evaluated the in vitro killing activity of voriconazole (VRC) and posaconazole (PSC) against two clinical isolates of Candida guilliermondii. The two drugs showed fungistatic activity against both isolates and were effective in reducing kidney fungal burden in a neutropenic murine model of disseminated candidiasis in infected mice. PSC was significantly more effective than VRC against one of the strains. The serum levels of PSC and VRC were above the corresponding MICs for these isolates.
Asunto(s)
Antifúngicos/farmacología , Azoles/farmacología , Candida/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Triazoles/farmacología , Voriconazol/farmacologíaRESUMEN
OBJECTIVES: Scedosporium infections are associated with high therapeutic failure rates. Combination therapy may be an alternative approach to improve outcome. The in vitro and in vivo efficacy of micafungin plus posaconazole or plus voriconazole was investigated herein. METHODS: Scedosporium boydii (nâ=â17) and Scedosporium apiospermum (nâ=â26) were tested using the chequerboard method according to CLSI M38-A2 guidelines and the fractional inhibitory concentration index (FICI) was evaluated. In vivo outcome of micafungin plus posaconazole or micafungin plus voriconazole against two isolates of each of the mentioned species was evaluated in a well-established, immunocompromised, haematogenous murine model of systemic scedosporiosis. Survival and tissue burden in kidneys and brain were investigated. RESULTS: The FICI category of 'no interaction' was most frequent, while 'synergism' or 'antagonism' was rarely observed. FICI failed to predict the in vivo outcome of both combinatorial treatment strategies. In vivo outcome was strain-dependent rather than species-dependent, even though effects on fungal tissue burden were more pronounced for S. boydii. Both combinations improved survival significantly when compared with untreated controls and micafungin monotherapy. Voriconazole and posaconazole did not differ in their efficacy and micafungin failed to be effective. Combinations were by trend better than voriconazole and posaconazole as single therapy, but statistically significant differences were lacking. CONCLUSIONS: No benefit of the azole/echinocandin combination was found when compared with voriconazole and posaconazole monotherapies. FICI failed to predict the outcome of in vivo drug combinations in the murine study.
Asunto(s)
Antifúngicos/administración & dosificación , Equinocandinas/administración & dosificación , Lipopéptidos/administración & dosificación , Micosis/tratamiento farmacológico , Scedosporium/efectos de los fármacos , Triazoles/administración & dosificación , Animales , Quimioterapia Combinada , Masculino , Micafungina , Ratones , Pruebas de Sensibilidad Microbiana/métodos , Micosis/mortalidad , Distribución Aleatoria , Scedosporium/aislamiento & purificaciónRESUMEN
It has been argued that the in vitro activity of caspofungin (CSP) is not a good predictor of the outcome of echinocandin treatment in vivo. We evaluated the in vitro activity of CSP and the presence of FKS mutations in the hot spot 1 (HS1) region of the FKS1 and FKS2 genes in 17 Candida glabrata strains with a wide range of MICs. The efficacy of CSP against systemic infections from each of the 17 strains was evaluated in a murine model. No HS1 mutations were found in the eight strains showing MICs for CSP of ≤ 0.5 µg/ml, but they were present in eight of the nine strains with MICs of ≥ 1 µg/ml, i.e., three in the FKS1 gene and five in the FKS2 gene. CSP was effective for treating mice infected with strains with MICs of ≤ 0.5 µg/ml, showed variable efficacy in animals challenged with strains with MICs of 1 µg/ml, and did not work in those with strains with MICs of >1 µg/ml. In addition, mutations, including one reported for the first time, were found outside the HS1 region in the FKS2 gene of six strains with different MICs, but their presence did not influence drug efficacy. The in vitro activity of CSP was compared with that of another echinocandin, anidulafungin, suggesting that the MICs of both drugs, as well as mutations in the HS1 regions of the FKS1 and FKS2 genes, are predictive of outcome.
Asunto(s)
Antifúngicos/farmacología , Candida glabrata/efectos de los fármacos , Candidiasis/tratamiento farmacológico , Equinocandinas/farmacología , Proteínas Fúngicas/genética , Glucosiltransferasas/genética , Mutación/fisiología , Animales , Candida glabrata/genética , Candidiasis/microbiología , Caspofungina , Farmacorresistencia Fúngica/genética , Riñón/microbiología , Lipopéptidos , Masculino , Ratones , Pruebas de Sensibilidad Microbiana , Tasa de SupervivenciaRESUMEN
The in vitro activities of fluconazole (FLC), amphotericin B (AmB) and caspofungin (CSP) were evaluated against three isolates of Candida lusitaniae using time-kill curves. AmB showed in vitro fungicidal activity, whilst FLC and CSP exerted mainly strain-dependent fungistatic activity. The in vivo efficacies of the three drugs were evaluated in a murine model of disseminated infection. The doses administered were FLC 50 mg/kg/day, AmB 0.8 mg/kg/day and CSP 5 mg/kg/day. All three drugs were able to reduce the fungal burden in the kidneys of infected mice, with AmB showing the highest efficacy, followed by CSP. At least in this model, FLC, AmB and CSP are good candidates for treating invasive infections by C. lusitaniae.
Asunto(s)
Anfotericina B/uso terapéutico , Antifúngicos/uso terapéutico , Candida/efectos de los fármacos , Candidiasis/tratamiento farmacológico , Equinocandinas/uso terapéutico , Fluconazol/uso terapéutico , Animales , Candidiasis/microbiología , Caspofungina , Recuento de Colonia Microbiana , Modelos Animales de Enfermedad , Riñón/microbiología , Lipopéptidos , Masculino , Ratones , Pruebas de Sensibilidad Microbiana , Resultado del TratamientoAsunto(s)
Acremonium/efectos de los fármacos , Antifúngicos/farmacología , Farmacorresistencia Fúngica/genética , Acremonium/crecimiento & desarrollo , Acremonium/aislamiento & purificación , Anfotericina B/farmacología , Anidulafungina , Combinación de Medicamentos , Interacciones Farmacológicas , Equinocandinas/farmacología , Humanos , Pruebas de Sensibilidad Microbiana , Naftalenos/farmacología , Pirimidinas/farmacología , Terbinafina , Triazoles/farmacología , VoriconazolRESUMEN
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
We developed a murine model of systemic sporotrichosis by using three strains of each of the two commonest species causing sporotrichosis, i.e., Sporothrix schenckii sensu stricto and Sporothrix 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.
Asunto(s)
Antifúngicos/uso terapéutico , Hígado/microbiología , Sporothrix/efectos de los fármacos , Esporotricosis/tratamiento farmacológico , Triazoles/uso terapéutico , Administración Oral , Anfotericina B/administración & dosificación , Anfotericina B/uso terapéutico , Animales , Antifúngicos/administración & dosificación , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Histocitoquímica , Hígado/efectos de los fármacos , Masculino , Ratones , Pruebas de Sensibilidad Microbiana , Especificidad de la Especie , Sporothrix/fisiología , Esporotricosis/microbiología , Esporotricosis/mortalidad , Esporotricosis/patología , Tasa de Supervivencia , Resultado del Tratamiento , Triazoles/administración & dosificaciónRESUMEN
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.