Standards of CARE: what is considered 'best practice' for the management of invasive fungal infections? A haematologist's and a mycologist's perspective.

Patients at risk of, or diagnosed with, an invasive fungal infection benefit from an early antifungal intervention. Different strategies have been explored, each with particular strengths and weaknesses. The use of broad-spectrum antifungal prophylaxis seems logical, but selective use is important given its potential for major collateral damage, including interference with diagnostic assays, selection of resistance, toxicity and drug interactions. Hence, anti-mould prophylaxis should be restricted to well-defined high-risk groups. An empirical approach is still widely applied but incurs the clinical and cost penalties associated with overtreatment. Nowadays there is a growing interest in delaying antifungal treatment until an invasive fungal infection is highly suspected ('pre-emptive' management) or confirmed, prompted by the development of more-sensitive diagnostic techniques. While pre-emptive treatment looks appealing, the necessary monitoring and detailed treatment algorithms can be rather complex and often require a multidisciplinary effort. This article aims to bring together different perspectives on 'best practice' for the management of invasive fungal infections, using haematology patients as a model.

Phase 1b study of new posaconazole tablet for prevention of invasive fungal infections in high-risk patients with neutropenia.

Posaconazole tablets, a new oral formulation of posaconazole, can be effective when given as antifungal prophylaxis to neutropenic patients at high risk for invasive fungal infection (e.g., those with acute myelogenous leukemia or myelodysplastic syndrome). Such effectiveness might be specifically important to patients with poor oral intake because of nausea, vomiting, or chemotherapy-associated mucositis. This was a prospective, global study in high-risk patients to characterize the pharmacokinetics and safety profile of posaconazole tablets and to identify the dose of posaconazole tablets that would provide exposure within a predefined range of exposures (steady-state average concentration [area under the concentration-time curve/24 h] of ≥500 ng/ml and ≤2,500 ng/ml in >90% of patients). The study evaluated two sequential dosing cohorts: 200 mg posaconazole once daily (n = 20) and 300 mg posaconazole once daily (n = 34) (both cohorts had a twice-daily loading dose on day 1) taken without regard to food intake during the neutropenic period for ≤28 days. The exposure target was reached (day 8) in 15 of 19 (79%) pharmacokinetic-evaluable patients taking 200 mg posaconazole once daily and in 31 of 32 (97%) patients taking 300 mg posaconazole once daily; 300 mg posaconazole once daily achieved the desired exposure target. Posaconazole tablets were generally well tolerated in high-risk neutropenic patients. (This study has been registered at ClinicalTrials.gov under registration no. NCT01777763.).