RESUMEN
BACKGROUND: A retrospective study on the epidemiology of fungaemia due to yeasts of medical importance at the Hospital Nacional de Pediatría Prof. Dr. J. Garrahan, Buenos Aires was conducted between September 2001 and September 2003. OBJECTIVES: To learn the distribution of yeast species and to evaluate their in vitro antifungal susceptibility profile. METHODS: The minimum inhibitory concentration (MIC) was determined according to the CLSI M27-A2 procedure, and time kill curves against amphotericin B were also performed. RESULTS-CONCLUSIONS: The species isolated were Candida parapsilosis (32.6% of isolates); Candida albicans (26.5%), Candida tropicalis (24.5%), and other yeasts (16.4%). Candida isolates were susceptible to the antifungals evaluated, but amphotericin B-tolerant isolates were detected using time kill curves.
Asunto(s)
Fungemia/epidemiología , Adolescente , Niño , Preescolar , Femenino , Fungemia/microbiología , Hospitales Pediátricos , Humanos , Lactante , Masculino , Estudios RetrospectivosRESUMEN
Tinea capitis is an infection caused by dermatophytes of the genera Microsporum and Trichophyton, and constitutes a major health problem in Argentina. The aim of the present study was to find out the incidence of those etiological agents and the therapeutic response in patients attending a High-Complexity Paediatric Hospital within a two-year period. A total of 98 tinea capitis were diagnosed, 13 of which were Celsus kerion. Microsporum canis was isolated in 61.28%. The range of values for minimum inhibitory concentrations were >32, 0.06-4; <0.015-2; <0.015-0.25; 0.13-8; 0.06-128 microg/mL for fluconazole itraconazole, voriconazole, terbinafine, ketoconazole and griseofulvin, respectively.
Asunto(s)
Hospitales Pediátricos/estadística & datos numéricos , Tiña del Cuero Cabelludo/epidemiología , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Argentina/epidemiología , Niño , Preescolar , Femenino , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Microsporum/aislamiento & purificación , Estudios Prospectivos , Tiña del Cuero Cabelludo/tratamiento farmacológico , Tiña del Cuero Cabelludo/microbiología , Trichophyton/aislamiento & purificación , Población UrbanaRESUMEN
The in vitro activities of amphotericin B (AMB), itraconazole (ITC), voriconazole (VCZ) and terbinafine (TBF) alone and in the combinations AMB+VCZ, TBF+ITC and TBF+VCZ were evaluated against 29 clinical isolates of Fusarium spp. (15 Fusarium solani, 7 Fusarium oxysporum, 2 Fusarium decemcellulare, 2 Fusarium dimerum and 3 other Fusarium spp.). Minimum inhibitory concentrations were determined using the method of the Clinical and Laboratory Standards Institute and the interaction activity was calculated using the fractional inhibitory concentration index. The four antifungal drugs tested alone showed very limited activity against most of the isolates. In contrast, the combination TBF+VCZ showed synergy for 21 isolates. The combination AMB+VCZ showed synergism for only five strains. No interaction or antagonism was observed among the remaining strains. TBF+ITC showed no interaction for 18 strains. The in vitro antifungal activity of the drugs alone and in combination varied for different species. These results corroborate previous in vitro studies in which the combination TBF+VCZ showed synergy against Fusarium spp., although further studies are needed to elucidate its potential usefulness for therapy.
Asunto(s)
Antifúngicos/farmacología , Fusarium/efectos de los fármacos , Anfotericina B/farmacología , Interacciones Farmacológicas , Fusarium/aislamiento & purificación , Fusarium/patogenicidad , Humanos , Itraconazol/farmacología , Pruebas de Sensibilidad Microbiana , Naftalenos/farmacología , Pirimidinas/farmacología , Terbinafina , Triazoles/farmacología , VoriconazolRESUMEN
An efficient microwave-assisted synthesis of new (Z)-5-arylidenerhodanines under solvent-free conditions is described and their in vitro antifungal activity was evaluated following the CLSI (formerly NCCLS) guidelines against a panel of both standardized and clinical opportunistic pathogenic fungi. An analysis of the structure-activity relationship (SAR) along with computational studies showed that the most active compounds (F- and CF(3)-substituted rhodanines) possess high logP values and low polarizability. Mechanism-based assays suggest that active compounds neither would bind to ergosterol nor would produce a damage to the fungal membrane.
Asunto(s)
Antifúngicos/síntesis química , Antifúngicos/farmacología , Hongos Mitospóricos/efectos de los fármacos , Rodanina , Levaduras/efectos de los fármacos , Antifúngicos/efectos de la radiación , Simulación por Computador , Diseño de Fármacos , Pruebas de Sensibilidad Microbiana , Microondas , Estructura Molecular , Rodanina/análogos & derivados , Rodanina/síntesis química , Rodanina/farmacología , Sensibilidad y Especificidad , Estereoisomerismo , Relación Estructura-ActividadRESUMEN
The physiological patterns, the sequence polymorphisms of the internal transcriber spacer (ITS), and intergenic spacer regions (IGS) of the rRNA genes and the antifungal susceptibility profile were evaluated for their ability to identify Trichosporon spp. and their specificity for the identification of 49 clinical isolates of Trichosporon spp. Morphological and biochemical methodologies were unable to differentiate among the Trichosporon species. ITS sequencing was also unable to differentiate several species. However, IGS1 sequencing unambiguously identified all Trichosporon isolates. Following the results of DNA-based identification, Trichosporon asahii was the species most frequently isolated from deep sites (15 of 25 strains; 60%). In the main, other Trichosporon species were recovered from cutaneous samples. The majority of T. asahii, T. faecale, and T. coremiiforme clinical isolates exhibited resistance in vitro to amphotericin B, with geometric mean (GM) MICs >4 mug/ml. The other species of Trichosporon did not show high MICs of amphotericin B, and GM MICs were <1 mug/ml. Azole agents were active in vitro against the majority of clinical strains. The most potent compound in vitro was voriconazole, with a GM MIC =0.14 mug/ml. The sequencing of IGS correctly identified Trichosporon isolates; however, this technique is not available in many clinical laboratories, and strains should be dispatched to reference centers where these complex methods are available. Therefore, it seems to be more practical to perform antifungal susceptibility testing of all isolates belonging to Trichosporon spp., since correct identification could take several weeks, delaying the indication of an antifungal agent which exhibits activity against the infectious strain.
Asunto(s)
ADN Intergénico , ADN Espaciador Ribosómico , Polimorfismo Genético , Trichosporon/clasificación , Trichosporon/genética , Trichosporon/fisiología , Anfotericina B/farmacología , Antifúngicos/farmacología , Argentina/epidemiología , ADN de Hongos/análisis , ADN de Hongos/genética , ADN Intergénico/análisis , ADN Intergénico/genética , ADN Ribosómico/análisis , ADN Ribosómico/genética , ADN Espaciador Ribosómico/análisis , ADN Espaciador Ribosómico/genética , Susceptibilidad a Enfermedades , Farmacorresistencia Fúngica/genética , Humanos , Pruebas de Sensibilidad Microbiana , Filogenia , ARN de Hongos/análisis , ARN de Hongos/genética , ARN Ribosómico/análisis , ARN Ribosómico/genética , Estudios Retrospectivos , Análisis de Secuencia de ADN , España/epidemiología , Trichosporon/efectos de los fármacos , Trichosporon/crecimiento & desarrollo , Trichosporon/aislamiento & purificaciónRESUMEN
Five sequential Cryptococcus neoformans isolates recovered from an AIDS patient with recurrent meningitis were analyzed. Four isolates were fluconazole susceptible, while the fifth isolate developed fluconazole resistance. Analysis of the 14-alpha lanosterol demethylase gene (ERG11) showed a point mutation in the resistant strain responsible for the amino acid substitution G484S.
Asunto(s)
Antifúngicos/farmacología , Cryptococcus neoformans/efectos de los fármacos , Sistema Enzimático del Citocromo P-450/genética , Farmacorresistencia Fúngica/genética , Fluconazol/farmacología , Meningitis Criptocócica/microbiología , Oxidorreductasas/genética , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Adulto , Secuencia de Aminoácidos , Sustitución de Aminoácidos , Clonación Molecular , Genotipo , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Datos de Secuencia Molecular , Plásmidos , Mutación Puntual/genética , Recurrencia , Esterol 14-DesmetilasaRESUMEN
The aim of this study was to identify retrospectively trends in species distribution and susceptibility patterns of Candida species causing bloodstream infections in 99 medical centres (55 in Spain and 44 in Argentina) from 1996 to 1999. A total of 744 Candida isolates were sent to the mycology reference laboratories during the study period (514 to the Spanish laboratory and 230 to the Argentinian laboratory). Candida non-albicans strains caused more episodes of fungaemia than Candida albicans isolates in both Spain and Argentina. C. albicans was isolated in 30.2% (155/514) and 40.9% (94/230) of episodes in Spain and in Argentina, respectively. In addition, Candida parapsilosis was the second most commonly isolated pathogen (36.4%). Candida tropicalis caused 13.7% of infections and Candida glabrata 7.4%. The amphotericin B MIC was Asunto(s)
Antifúngicos/farmacología
, Candida/efectos de los fármacos
, Argentina
, Candida/aislamiento & purificación
, Candida/metabolismo
, Distribución de Chi-Cuadrado
, Humanos
, Pruebas de Sensibilidad Microbiana/métodos
, Pruebas de Sensibilidad Microbiana/estadística & datos numéricos
, Estudios Retrospectivos
, España
RESUMEN
A bloodstream infection due to Candida haemulonii afflicting a patient with fever and a medical history of megaloblastic anemia is reported. The clinical isolate was misidentified by the API 20C and VITEK identification systems. The results of susceptibility tests showed that the MIC of amphotericin B for C. haemulonii was 4 microg/ml. Additional susceptibility testing procedures based on the use of antibiotic medium 3 and Iso-Sensitest broth were performed, and killing curves were determined. Two collection strains of C. haemulonii were employed as controls. The three isolates exhibited resistance to amphotericin B in vitro regardless of the antifungal susceptibility testing method employed. In addition, the MICs of fluconazole for the three isolates were high. Further studies are needed in order to ascertain whether this species exhibits innate or acquired resistance to amphotericin B and other antifungal agents.