RESUMEN
Coccidioidomycosis caused by Coccidioides immitis or Coccidioides posadasii is a rare infectious disease except in endemic regions. In this report the third documented imported case of coccidioidomycosis in Turkey was presented. A thirty-year-old male patient was admitted to our hospital with fever and purulent drainage from his chest tube. He had worked in Arizona, USA, until 4 months before this presentation. While in Arizona, he experienced cough and hemoptysis and was diagnosed as pulmonary coccidioidomycosis. He was treated with itraconazole for two months and he had no symptoms for 3 years. He then returned to Turkey and 2 months after his return to Turkey, he was admitted to another hospital in Istanbul with dyspnea and diagnosed as hydro-pneumothorax, and pleural fluid obtained from the inserted chest tube was found to be purulent. One gram of BID amoxicillin-clavulanate was given. Physical examination on admission revealed a purulent drainage on the right side chest tube, a temperature of 38.5°C and decreased breath sounds on the right lung. Piperacillin-tazobactam 3 x 4.5 g intravenous and fluconazole 400 mg intravenous once daily were started. Human immunodeficiency virus test was negative. Gram-negative diplococci and rods, gram-positive cocci and septate hyphae were seen in the Gram stain of his pleural fluid. Pleural fluid culture revealed Moraxella catarrhalis after 24 hours incubation and a mold after 72 hours of incubation. Anti-coccidioidal antibodies were found positive in a titer of 1/2. Hydro-pneumothorax, atelectasis and a 3 mm nodules in the right lung were seen in his thorax CT. The patient's pleural fluid and the culture plates were sent to the Public Health Institute of Turkey, Mycology Reference Laboratory (PHIT-MRL), with a clinical suspicion of coccidioidomycosis. The specimen and plates were submitted to the PHIT-MRL Bio Safety Level-3 laboratory for mycological evaluation. The microscopic examination of 15% KOH preparations of pleural fluid specimens revealed septate hyphae which appear to be in the early stages of forming arthroconidia. The pleural fluid culture grew buff-white coloured colonies with aerial hyphae, which were suspected of being a Coccidioides spp. The strain was identified as C.immitis/posadasii by direct microscopy and culture, and subsequently confirmed by the FDA-approved DNA probe. DNA sequence analysis of the ITS and D1/D2 rDNA regions confirmed the isolate to be C.posadasii species [ITS 100% match to GenBank Accession No. AB232901 (630/630 base pair match), and D1/D2 100% match to GenBank Accession No. AB232884 (617/617 base pair match)]. ITS1 and ITS2 barcode analysis also confirmed the species to be C.posadasii, which is the species endemic in Arizona. Susceptibility testing was performed according to Clinical and Laboratory Standards Institute M38-A2 guidelines in the Fungus Testing Laboratory of the University of Texas Health Science Center at San Antonio and minimal inhibitory concentration values were; 0.125 µg/ml for amphotericin B, posaconazole and voriconazole, 0.5 µg/ml for itraconazole and 8 µg/ml for fluconazole. He had decortication of the pleura and was discharged from hospital after six weeks treatment with intravenous fluconazole which was continued orally for one year. Anti-coccidioidal antibodies were negative after two months of treatment. The patient is currently asymptomatic. The presented case is the third case reported from Turkey and provides additional contribution to the existing literature with regard to the appearance of arthroconidium, which is the unusual hyphal form, instead of the expected spherules in the infected tissue.
Asunto(s)
Antifúngicos/uso terapéutico , Coccidioides/aislamiento & purificación , Coccidioidomicosis/microbiología , Adulto , Combinación Amoxicilina-Clavulanato de Potasio/farmacología , Combinación Amoxicilina-Clavulanato de Potasio/uso terapéutico , Antifúngicos/farmacología , Arizona , Coccidioides/efectos de los fármacos , Coccidioides/crecimiento & desarrollo , Coccidioidomicosis/tratamiento farmacológico , Fluconazol/farmacología , Fluconazol/uso terapéutico , Humanos , Itraconazol/farmacología , Itraconazol/uso terapéutico , Masculino , Ácido Penicilánico/análogos & derivados , Ácido Penicilánico/farmacología , Ácido Penicilánico/uso terapéutico , Piperacilina/farmacología , Piperacilina/uso terapéutico , Combinación Piperacilina y Tazobactam , Pleura/microbiología , Recurrencia , Esporas Fúngicas/efectos de los fármacos , Esporas Fúngicas/crecimiento & desarrollo , Esporas Fúngicas/aislamiento & purificación , Viaje , TurquíaRESUMEN
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
Ustilago, a common fungal parasite of grains, is infrequently isolated as a pathogen in humans. We describe a case of Ustilago echinata infection following an open distal tibia fracture, review the current literature of this genus as a cause of invasive fungal infection in humans, and discuss management issues.
Asunto(s)
Antifúngicos/uso terapéutico , Fracturas Abiertas/microbiología , Micosis/tratamiento farmacológico , Tibia/lesiones , Ustilago/efectos de los fármacos , Ustilago/aislamiento & purificación , Adulto , Secuencia de Bases , ADN de Hongos/genética , Humanos , Masculino , Artes Marciales , Pruebas de Sensibilidad Microbiana , Micosis/microbiología , Análisis de Secuencia de ADN , Tibia/microbiología , Ustilago/clasificación , Ustilago/genética , Adulto JovenRESUMEN
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
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
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
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 determined the in vitro activities of amphotericin B (AMB), voriconazole, posaconazole (PSC), itraconazole (ITC), ravuconazole, terbinafine, and caspofungin against five strains of Cunninghamella bertholletiae and four of Cunninghamella echinulata. The best activity was shown by terbinafine against both species (MIC range = 0.3 to 0.6 µg/ml) and PSC against Cunninghamella bertholletiae (MIC = 0.5 µg/ml). We have also evaluated the efficacies of PSC, ITC, and AMB in neutropenic and diabetic murine models of disseminated infection by Cunninghamella bertholletiae. PSC at 40, 60, or 80 mg/kg of body weight/day was as effective as AMB at 0.8 mg/kg/day in prolonging survival and reducing the fungal tissue burden in neutropenic mice. PSC at 80 mg/kg/day was more effective than AMB at 0.8 mg/kg/day in reducing the fungal load in brain and lung of diabetic mice. Histological studies revealed an absence of fungal elements in organs of mice treated with either AMB at 0.8 mg/kg/day or PSC at 60 or 80 mg/kg/day in both models. ITC showed limited efficacy in both models. PSC could be a therapeutic option for the treatment of systemic infections caused by Cunninghamella bertholletiae.
Asunto(s)
Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Cunninghamella/efectos de los fármacos , Mucormicosis/tratamiento farmacológico , Anfotericina B/farmacología , Anfotericina B/uso terapéutico , Animales , Caspofungina , Cunninghamella/patogenicidad , Diabetes Mellitus Experimental , Equinocandinas/farmacología , Equinocandinas/uso terapéutico , Itraconazol/farmacología , Itraconazol/uso terapéutico , Lipopéptidos , Masculino , Ratones , Pruebas de Sensibilidad Microbiana , Mucormicosis/microbiología , Pirimidinas/farmacología , Pirimidinas/uso terapéutico , Tiazoles/farmacología , Triazoles/farmacología , Triazoles/uso terapéutico , VoriconazolRESUMEN
Scedosporium spp. are increasingly recognized as causes of resistant life-threatening infections in immunocompromised patients. Scedosporium spp. also cause a wide spectrum of conditions, including mycetoma, saprobic involvement and colonization of the airways, sinopulmonary infections, extrapulmonary localized infections, and disseminated infections. Invasive scedosporium infections are also associated with central nervous infection following near-drowning accidents. The most common sites of infection are the lungs, sinuses, bones, joints, eyes, and brain. Scedosporium apiospermum and Scedosporium prolificans are the two principal medically important species of this genus. Pseudallescheria boydii, the teleomorph of S. apiospermum, is recognized by the presence of cleistothecia. Recent advances in molecular taxonomy have advanced the understanding of the genus Scedosporium and have demonstrated a wider range of species than heretofore recognized. Studies of the pathogenesis of and immune response to Scedosporium spp. underscore the importance of innate host defenses in protection against these organisms. Microbiological diagnosis of Scedosporium spp. currently depends upon culture and morphological characterization. Molecular tools for clinical microbiological detection of Scedosporium spp. are currently investigational. Infections caused by S. apiospermum and P. boydii in patients and animals may respond to antifungal triazoles. By comparison, infections caused by S. prolificans seldom respond to medical therapy alone. Surgery and reversal of immunosuppression may be the only effective therapeutic options for infections caused by S. prolificans.
Asunto(s)
Micetoma , Scedosporium , Administración por Inhalación , Animales , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Artritis/microbiología , Biodiversidad , Enfermedades Óseas Infecciosas/microbiología , Infecciones Fúngicas del Sistema Nervioso Central/microbiología , Infecciones Fúngicas del Ojo/microbiología , Humanos , Huésped Inmunocomprometido , Inmunosupresores/uso terapéutico , Pruebas de Sensibilidad Microbiana , Micetoma/diagnóstico , Micetoma/epidemiología , Micetoma/microbiología , Micetoma/terapia , Filogenia , Infecciones del Sistema Respiratorio/microbiología , Scedosporium/clasificación , Scedosporium/efectos de los fármacos , Scedosporium/patogenicidad , Scedosporium/fisiologíaRESUMEN
We evaluated the in vitro susceptibilities of 217 zygomycetes to amphotericin B, ketoconazole, fluconazole, itraconazole, voriconazole, posaconazole, caspofungin, and flucytosine. The significant in vitro activity of posaconazole against several species appears to support its reported clinical efficacy. Decreased susceptibility to amphotericin B was noted with Cunninghamella bertholletiae.
Asunto(s)
Antifúngicos/uso terapéutico , Mucormicosis/tratamiento farmacológico , Anfotericina B/uso terapéutico , Caspofungina , Equinocandinas , Fluconazol/uso terapéutico , Flucitosina/uso terapéutico , Humanos , Técnicas In Vitro , Itraconazol/uso terapéutico , Cetoconazol/uso terapéutico , Lipopéptidos , Pruebas de Sensibilidad Microbiana , Péptidos Cíclicos/uso terapéutico , Pirimidinas/uso terapéutico , Triazoles/uso terapéutico , VoriconazolRESUMEN
Aspergillus terreus is an uncommon but emerging fungal pathogen, which causes lethal infections that are often refractory to amphotericin B (AmB). In comparison to Aspergillus fumigatus, A. terreus was resistant to the in vitro fungicidal effects of safely achievable concentrations of AmB. These in vitro findings correlated directly with resistance of A. terreus to AmB in experimental invasive pulmonary aspergillosis. Residual fungal pulmonary burden and galactomannan antigenemia demonstrated persistent infection, despite therapy with deoxycholate AmB or liposomal AmB. By comparison, posaconazole and itraconazole resolved GM antigenemia, reduced residual fungal burden, and improved survival. There were no differences in phagocytic host response to A. terreus versus A. fumigatus; however, the rate of conidial germination of A. terreus was slower. The strain of A. terreus with the highest minimum inhibitory and minimum lethal concentration of AmB also had the lowest membrane ergosterol content. The hyphae of A. terreus in vivo displayed distinctive aleurioconidia, which may be a practical microscopic feature for rapid preliminary diagnosis.