Fluconazole levels in serum and cerebrospinal fluid according to daily dosage in patients with cryptococcosis and other fungal infections

ABSTRACT Fluconazole is extensively used for the treatment of candidiasis and cryptococcosis. Among other factors, successful treatment is related to appropriate fluconazole levels in blood and cerebrospinal fluid. In the present study, fluconazole levels were determined in 15 patients, 14 of whom had AIDS and 13 had neurocryptococcosis. The only selection criterion was treatment with fluconazole, which was performed with a generic or similar form of the drug. Fluconazole level was determined by high performance liquid chromatography and the susceptibility profile of Cryptococcus spp. isolated from the patients was assessed by broth microdilution. Blood and cerebrospinal fluid fluconazole levels were found to be related to the fluconazole daily dose, and exceeded the minimum inhibitory concentration of this antifungal for the Cryptococcus spp. isolates. A good correlation was observed between serum and cerebrospinal fluid drug concentration. In conclusion, treatment with non-original fluconazole under usual medical practice conditions results in appropriate blood and cerebrospinal fluid levels of the drug for inhibiting Cryptococcus spp. susceptible to this antifungal drug. The relatively common failures of neurocryptococcosis treatment appear not to be due to insufficient fluconazole levels in the cerebrospinal fluid, especially with the use of daily doses of 400-800 mg.

Fatal Peripheral Candidal Suppurative Thrombophlebitis in a Postoperative Patient

We report a case of fatal fungal peripheral suppurative thrombophlebitis, caused by Candida albicans, which was disseminated to the blood, lungs, eyes, and spine. Clinical suspicion and aggressive management are important in managing fungal peripheral suppurative thrombophlebitis. Early clinical suspicion is important in managing fungal peripheral suppurative thrombophlebitis, and radical excision of the affected veins, recognition of metastatic foci, and use of systemic antifungal agents are essential to avoid septic shock and death.

Change in distribution & antifungal susceptibility of Candida species isolated from candidaemia cases in a tertiary care centre during 1996-2000.

BACKGROUND & OBJECTIVES: As a marked increase in the number of patients with candidaemia was reported in the first half (1991-1995) of the last decade at the Postgraduate Institute of Medical Education & Research, Chandigarh, India, the present study was aimed at determining further change if any, in the incidence and distribution of Candida species and their antifungal resistance pattern during the second half (1996-2000) of the same decade. METHODS: The patients with candidaemia were studied to determine the frequency of candidaemia and Candida species isolated during 1996-2000. One hundred Candida strains other than Pichia anomala (C. pelliculosa) were randomly selected from those isolates to evaluate antifungal susceptibility pattern against amphotericin B, 5-fluorocytosine, ketoconazole, fluconazole and itraconazole. The results were compared with our previous study. RESULTS: An increase in the number of patients with candidaemia was observed during 1996 (538) and 1997 (421) compared to 1998-2000 due to P. anomala outbreak. With the control of the outbreak, a substantial decrease in the incidence of candidaemia was observed from 1998 (251 in 1998, 122 in 1999 and 165 in 2000). A higher isolation of non-C. albicans Candida species (89.8%) was observed, with C. tropicalis being the most common (541, 36.1%) agent. No major change in the isolation rate of other non-C. albicans Candida species (C. guilliermondii, C. krusei, C. glabrata and C. parapsilosis) was observed. An emergence of resistance to amphotericin B in 15.4 per cent C. albicans, 8.1 per cent C. tropicalis and 33.3 per cent C. krusei strains was observed. An increase in resistance to ketoconazole (from 0% to 13%) and 5-fluorocytosine (from 1% to 8%) and a decrease to fluconazole (from 13% to 6%) were observed. Resistance to itraconazole was observed in 17 per cent of Candida strains by broth macro-dilution method. INTERPRETATION & CONCLUSION: A change in the isolation of Candida species was observed i.e. in the incidence and isolation of non-C. albicans Candida species. Emergence of resistance to amphotericin B and increase of resistance to most other antifungals are cause for concern.

Candidemias: aspectos preditivos da infecção em crianças hospitalizadas / Candidemia: predictors factors of infection in hospitalized children

As infecções fúngicas, em particular aquelas causadas por Candida spp, têm aumentado na população pediátrica hospitalizada e submetida a procedimentos de risco, determinando alta letalidade. O objetivo desse estudo foi caracterizar a população de crianças com diagnóstico de candidemia hospitalar num hospital pediátrico em São Paulo no período de janeiro de 1994 a dezembro de 1997, e identificar os fatores de risco para essa doença, através de um estudo caso-controle pareado. Quarenta crianças com cultura positiva para Candida spp foram identificadas e um controle (sem candidemia) foi selecionado para cada caso. A idade das crianças variou de dois dias a 14 anos e mais de metade dos casos (52,5 por cento) tinha idade inferior a seis meses. Além da C. albicans, foram isoladas C. tropicalis, C. parapsilosis, C. krusei e C. guilliermondi. A letalidade global foi de 57,5 por cento entre os casos e de 2,5 por cento nos controles. A analise univariada revelou 11 procedimentos de risco para a candidemia hospitalar: uso de cateter venoso (OR=17,00), sonda nasogástrica (OR=6,50), ventilação mecânica (OR=5,67), utilização de mais de cinco antibióticos na internação (OR=10,00), transfusão sanguínea (OR=5,00), permanência em UTI (OR=4,50), uso de vancomicina (OR=19,00), imipenem (OR=14,00), ceftazidime (OR=5,66), cefotaxime (OR=3,75) e metronidazol (OR=5,00). Para obter-se fatores provavelmente preditores para a infecção, inclui-se na análise, as variáveis clínicas e laboratoriais estatisticamente significativas encontradas: a presença de febre (OR=7,00), hepatomegalia (OR=4,00), candidíase oral e/ou perineal (OR=3,50), leucocitose (OR=4,25) e plaquetopenia (OR=18,70). Considerando-se o tamanho da amostra pareada, para a análise multivariada, obteve-se duas variáveis preditoras para a infecção fúngica, a saber: a presença de candidemia oral e/ou perineal (OR=4,29) e a utilização de cinco ou mais antimicrobianos (OR=11,32)

Obtención, caracterización de antígenos y evaluación de la tÚcnica de inmunotransferencia para la detección de candidiasis sistémica / Obtention, characterization of antigens and evaluation of the immunotransfer technique for the detection of systemic candidiasis

A culture media containing peptone, glucose, yeast extract and serum was evaluated to promote the development of the mycelium formation in Candida albicans and it was compared with the commercial media Tc 199. No significant difference was found between them. Somatic antigens characterized by PAGE-SDS were obtained from yeast and mycelial forms. Proteins reported as having high diagnostic value were expressed in both antigens. It was determined by immunotransference that the antigenic proteins predominating in the mycelium formation had molecular weights of 19, 21, 27 and 57 Kda. The immunotransference was standardized for detecting antibodies in patients with systemic candidiasis. 24 positive sera were evaluated by this technique and it was compared with the ELISA technique, which proved to be more sensitive and less specific. The most recognized proteins were those of 136 and 21 Kda and the complex from 42 to 45 Kda.

Estudio serológico en pacientes con candidiasis / Serological studies on patients with candidiasis

Se presentan los resultados serológicos obtenidos al estandarizar la prueba de contrainmunoelectroforesis y compararls con la dobleinmunodifusión, para detedtat anticuerpos anti-candida albicans. Se utilizaron antígenos comerciales y de producción nacional, simultáneamente. El elavorado en nuestro país manisfestó una reactividad idéntica a la de los reactivos comerciales utilizados. Las pruebas serlógicas comparadas ofrecieron el 100 por ciento de coincidencia en los resultados positivos y negativos. Se evidenciaron las ventajas de rapidez de la contraimunoelectroforesis. El 24 por ciento de los pacientes con evidencias clinicomicólogicas de candidiasis profunda mostró resultados serológicos positivos, lo cual coincidió en su mayoría, con cultivos positivos procedentes de esputo. En los pacientes con candidiasis superficiales y resto del grupo control, no se detectó presencia de anticuerpos anti-candida albicans

Sensibilidad in vitro de candia parapsilosis frente a anfotericina B, fluconazol, itraconazol y ketoconazol / In vitro antifungal susceptibility to amphotericin B, fluconazole, itraconazole and ketoconazole, of candida parapsilosis

Se determinó la sensibilidad in vitro a anfotericina B, fluconazol, itraconazol y ketoconazol de 60 aislamientos de candida parapsilosis procedentes de muestras de pacientes asistidos en el Hospital Universitario de Canarias. Se utilizó un micrométodo de dilución en caldos de YNB enriquecido y tamponado a pH7. Los resultados muestran que la mayor sensibilidad la presentaron frente a ketoconazol (M.G. (media geométrica) 0.06 *g/ml, rango *0.05-3.125 *g/ml), seguido por itraconazol (M.G. 0.11 *g/ml, rango *0.05-3.125 *g/ml) y anfotericina B (M.G. 0.43 *g/ml, rango *0.05-1.56 *g/ml). C. parapsilosis mostró mayor resistencia frente a fluconazol (M.G. 1.65 *g/ml, rango *0.05-25 *g/ml). La actividad de los cuatro antifúngicos sistémicos ensayados frente a C. parapsilosis es buena, solamente en el caso del fluconazol se encontró un 5%de cepas resistentes