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“Background: Invasive candidiasis is a leading cause of morbidity and mortality in critically ill infants. Prompt administration of fluconazole and achievement of the therapeutic target (area under the curve 0 to 24 hours > 400 mg*h/L) improve outcomes in candidemic patients. A loading dose of fluconazole is advised for older patients but has not been evaluated in infants. We sought to determine the pharmacokinetics and safety of a fluconazole loading dose in infants at risk for invasive fungal infection.
Methods: We enrolled 10 hospitalized infants < 60 days old with suspected systemic fungal infection in this open-label study; 9 received a 25-mg/kg
fluconazole loading dose followed by a maintenance dose of
12 mg/kg every 24 hours for 4 additional days. Plasma samples were obtained following the loading and steady-state doses (doses 3-5). We used a 1-compartment PCI32765 model to fit the data to estimate pharmacokinetic indices.
Results: Data from 57 drug concentrations obtained from 8 infants (median postnatal age, 16 days [interquartile range, 13-32] and median gestational age, 37 weeks [35-38]) showed that the median fluconazole SIS3 area under the curve 0 to 24 hours (mg*h/L) in this population was 479 (347-496). Of the 8 infants who received the loading dose, 5 (63%) achieved the therapeutic target on the first day of dosing, and all infants achieved a fluconazole 24-hour trough concentration > 8 mu g/mL. No adverse events were thought to be related to fluconazole
therapy.
Conclusions: A loading dose of fluconazole (25 mg/kg) was safe in this small cohort of young infants and achieved the therapeutic target more rapidly than traditional dosing.”
“The pathogenic yeast Candida dubliniensis is increasingly reported as a cause of systemic fungal infections. We compared the virulence of 9 clinical bloodstream isolates of C. dubliniensis with 3 C. albicans isolates in a murine model of invasive candidiasis. Quantification of organisms ACY-241 manufacturer and inflammatory changes in kidneys of infected animals were evaluated in a blinded, systematic manner. Average 7-day mortality among animals infected with C. dubliniensis was 21.0% (33/157 animals; range for strains: 0-57.1%); and with C. albicans 23.2%, (23/99 animals; range for strains: 6.7-85.0%) (p 0.65). Greater strain variation was noted within species than between the two species. Both species comprised strains of either high or low virulence, and six of the nine C. dubliniensis strains showed negligible virulence. Colony counts determined on samples from liver and kidneys did not differ between species. According to histopathological analysis, C. dubliniensis produced significantly lower levels of hyphae than C. albicans (p <0.001). Candida albicans caused a greater inflammatory response in kidneys (p <0.