RESUMEN
Invasive candidiasis is rare in children after the neonatal period, but can occur in children with (secondary) immunodeficiency with a damaged gastrointestinal or skin barrier, or when receiving antibiotics. A 10-month-old girl was diagnosed as suffering from cystic fibrosis (CF) when showing failure to thrive, pulmonary symptoms and hypoproteinaemia. At that time, Candida albicans was identified from blood culture and treated intravenously with liposomal amphotericin B for 13 days. Six weeks later, the girl presented with osteoarticular infection of the left knee caused by C. albicans. The infection showed insufficient response to therapy with liposomal amphotericin B, but the patient recovered after therapy with fluconazole and flucytosine. Follow-up over 4 years revealed no sequelae. In conclusion, invasive Candida infections may occur in patients with CF, and preventive measures might be considered in patients at risk. In the case of an invasive infection, prolonged treatment with a combination of antifungal drugs may be required.
Asunto(s)
Candida albicans/aislamiento & purificación , Candidiasis Invasiva/diagnóstico , Candidiasis Invasiva/patología , Fibrosis Quística/complicaciones , Osteoartritis/diagnóstico , Osteoartritis/patología , Anfotericina B/administración & dosificación , Antifúngicos/administración & dosificación , Candidemia/complicaciones , Candidemia/tratamiento farmacológico , Candidiasis Invasiva/microbiología , Femenino , Fluconazol/administración & dosificación , Flucitosina/administración & dosificación , Humanos , Lactante , Osteoartritis/microbiología , Resultado del TratamientoAsunto(s)
Fibrosis Quística/complicaciones , Diabetes Mellitus/etiología , Prueba de Tolerancia a la Glucosa , Hipoglucemia/fisiopatología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Femenino , Humanos , Hipoglucemia/complicaciones , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
Tobramycin and colistin represent 2 standard antimicrobial agents in the treatment of cystic fibrosis (CF) patients who are chronically colonized with Pseudomonas aeruginosa. In this study, we determined the rate of resistance to tobramycin and colistin in 1844 isolates of P. aeruginosa obtained from 22 CF patients under alternate therapy with inhaled tobramycin and colistin. Resistance to tobramycin was observed in 27.5% of isolates. In contrast, all isolates were susceptible to colistin. Molecular typing of selected isolates suggested that only 1 clone occurred over time in each patient. To conclude, resistance to tobramycin in P. aeruginosa isolates from CF patients under antimicrobial therapy may occur while colistin resistance remains uncommon.
Asunto(s)
Antibacterianos/farmacología , Colistina/farmacología , Fibrosis Quística/complicaciones , Farmacorresistencia Bacteriana , Infecciones por Pseudomonas/microbiología , Pseudomonas aeruginosa/efectos de los fármacos , Tobramicina/farmacología , Adulto , Técnicas de Tipificación Bacteriana , Enfermedad Crónica , Análisis por Conglomerados , Fibrosis Quística/tratamiento farmacológico , Dermatoglifia del ADN , Femenino , Genotipo , Humanos , Masculino , Infecciones por Pseudomonas/tratamiento farmacológico , Pseudomonas aeruginosa/clasificación , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/aislamiento & purificaciónRESUMEN
BACKGROUND: The ifosfamide metabolite chloroacetaldehyde had been made responsible for side effects only. We found in previous studies a strong cytotoxicity on human MX-1 tumor cells and xenografts in nude mice. Chloroacetaldehyde is supposed to act via alkylation or by inhibition of mitochondrial oxidative phosphorylation with decrease of ATP. The aim of this study was to further elucidate chloroacetaldehyde's mode of action. METHODS: MX-1 breast carcinoma cells were measured for ATP-content after exposure to chloroacetaldehyde. Further, the effect of chloroacetaldehyde on DNA-synthesis and its potency of causing strand-breaks or cross-links were investigated by bromodeoxyuridine-incorporation, comet-assay and a DNA interstrand cross-linking-assay. RESULTS: Chloroacetaldehyde in high concentrations induces a reduction of ATP-levels when anaerobic glycolysis is blocked by oxamate and reduces the bromodeoxyuridine-incorporation to 46.3% after 4 h when used in IC(50) concentrations (7.49 mumol/l). In addition we observed DNA single strand-breaks in MX-1 cells treated with chloroacetaldehyde visible in the Comet assay, but no DNA-cross-linking by comet assay and cross-linking assay. CONCLUSION: In summary, our results show that chloroacetaldehyde influences the oxidative phosphorylation in mitochondria, however, this is observed only in high concentrations and is not of clinical relevance because the tumor cells regenerate ATP by anaerobic glycolysis. Nevertheless, chloroacetaldehyde causes DNA-strand-breaks and strong inhibition of DNA-synthesis.