Pre-emptive diagnosis and treatment of fungal infections--evaluation of a single-centre policy

Abstract

Invasive fungal disease (IFD) remains a significant cause of mortality in haematology patients. Management strategies range from empiric therapy to pre-emptive approaches. Prophylaxis with mould-active agents has been evaluated, but the optimal strategy remains unclear. We present here a retrospective analysis of the pre-emptive strategy implemented at our institution. We analysed 348 consecutive neutropenic episodes in 234 patients. The main elements of our pre-emptive strategy included twice-weekly Galactomannan testing and weekly computed tomography (CT) scan. Antifungal prophylaxis usually consisted of fluconazole (400 mg once weekly). Antifungal treatment was started if criteria for IFD (including possible) were fulfilled. Along with the incidence of antifungal treatment and IFD, we also analysed the adherence to the strategy. Adherence was good but suboptimal with 81% of CT scans having been performed at an interval of 10 days or less. Concerning antifungal treatment, in 56 episodes the patient was receiving a mould-active agent as secondary prophylaxis. Antifungal treatment was started during 39% of the remaining episodes. In all, 109 cases of IFD were diagnosed, 51 being probable or proven. Forty-nine patients died before day 100, IFD directly caused or contributed to death in six patients. Two cases of IFD were diagnosed post-mortem and were missed by our pre-emptive strategy. Our pre-emptive strategy is feasible and safe with an acceptable rate of IFD and associated mortality, while avoiding anti-fungal treatment in a significant proportion of patients. The exact role of pre-emptive treatment compared with systematic mould-active prophylaxis can only be determined in a well-designed randomized trial.