Our objective was to evaluate the maximum tolerated dose of caspofungin for invasive aspergillosis (IA).Invasive aspergillosis (IA) remains an important cause of infectious morbidity and mortality in immunocompromised patients. It is the most common invasive fungal disease (IFD) in patients with hematological malignancies (5). Current first-line therapies with liposomal amphotericin B and voriconazole fail in approximately 50% of patients. With 12-week mortality rates as high as 28%, new approaches are urgently needed (7, 12).High-dose liposomal amphotericin B (i.e., 10 mg/kg per day for the first 2 weeks of treatment) did not yield better outcomes than a standard dose of 3 mg/kg per day but resulted in higher rates of renal adverse events (AEs) (7). Dose escalation of voriconazole is not pursued due to the nonlinear disposition of the compound and a narrow therapeutic window. Antifungal combination therapy is another attractive strategy, but it has yet to be proven superior to monotherapy (22).Caspofungin is generally well tolerated and exhibits favorable pharmacokinetic properties (21). Unlike the triazoles, it is not metabolized through the cytochrome P450 enzyme system (11). The drug had excellent efficacy and safety results in clinical trials of candidiasis (1,17,23,24) and was effective as salvage therapy for IA after amphotericin B or itraconazole proved ineffective or toxic (15), and a large-scale study in neutropenic patients with persistent fever demonstrated an efficacy similar to that of liposomal amphotericin B but improved tolerability (26). Two recently published trials investigated the caspofungin standard maintenance doses of 50 mg once a day (QD) for first-line treatment of IA and yielded response rates of 33 and 42% (13, 25). While these response rates were below the expected outcomes (7, 12), they have been attributed to the severely ill patient groups enrolled in these trials and the rigorous enforcement of the EORTC/MSG
• CT evaluation offers good prediction of outcome for invasive pulmonary aspergillosis. • Predictive capability exceeds galactomannan, blood counts, and lesion count. • Any progression between day 7 and day 14 constitutes a high-risk scenario.
In this controlled prospective study, fungal spores were collected from homes of neutropenic patients. Cases were defined as patients with probable or proven controls as patients with no invasive pulmonary aspergillosis, while patients with possible disease were evaluated as a third group. Forty patients were enrolled and returned questionnaires on high-risk activities and mould exposure. A. fumigatus was detected in concentrations of 0 to 76 cfu/m(3) in every home. A. terreus was detected in nine (18%) homes. Mean Aspergillus spp. cfu/m(3) according to EORTC criteria were: proven/probable IA (15 patients) - 36; possible IA (12 patients) - 42; no IA (13 patients) - 42. Of the seven patients with self-reported moulded walls at home, four had probable and three had possible aspergillosis; the risk ratio of developing IA was 1.65 (95% CI: 1.25-2.17). In conclusion self-reported domestic mould exposure was associated with a high incidence of IA and may be a feasible tool for identifying high-risk patients. There was no correlation between domestic ambient-air spore counts and IA.
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