Treatment of invasive fungal infections in clinical practice: a multi-centre survey on customary dosing, treatment indications, efficacy and safety of voriconazole

Abstract

Invasive fungal infections are frequent and often deadly complications in patients with malignant hematological diseases. Voriconazole is a third generation triazole antifungal with broad activity against most clinically relevant fungal pathogens. Clinical practice often deviates from insights gained from controlled randomized trials. We conducted a multi-centre survey to evaluate efficacy, safety, treatment indications and dosing of voriconazole outside clinical trials. Patients receiving voriconazole were documented via electronic data capturing. An analysis was conducted after submission of 100 episodes from September 2004 to November 2005. Voriconazole was administered for suspected or proven invasive fungal infection (IFI) (57%), as empirical treatment in patients with fever of unknown origin (21%) and secondary (19%) as well as primary (3%) prophylaxis of IFI. Investigators’ assessment of fungal infection often diverted from EORTC/MSG 2002 criteria. A favorable response was reported in 61.4% for suspected or proven IFI and 52.4% for empirical treatment. Mortality was 15%, 26.7% of which was attributable to IFI. Breakthrough fungal infections occurred in four (21.1%) patients with voriconazole as secondary prophylaxis. Toxicity and adverse events comprised elevated liver enzymes and visual disturbances. Although indications frequently deviated from clinical evidence and legal approval, voriconazole showed efficacy and safety, comparable to major controlled clinical trials. Data from this survey demonstrate the difficulty of putting drugs to their approved use in IFI.