Early Empiric Antifungal Treatment of Infections in Neutropenic Patients with Hematological Malignancies Comparing Fluconazole with Amphotericin B and 5-Flucytosine

Intensification of chemotherapy in patients with hematological malignancies has improved prognosis with regard to the underlying disease. Despite advances in supportive care and antibiotic therapy, prolonged periods of neutropenia constitute the most important risk factor for opportunistic infections, especially for those of fungal origin [1-4]. Granulocyte counts of less than 0,1 x 109 /1 and duration of more than one week predispose about 85% of the patients to infectious complications [5,6]. Because of the high mortality, empiric strategies have been introduced [7-11]. Results of the first German multicenter study of the Paul-Ehrlich-Society [7], showed that infections during the early phase of neutropenia were predominantly caused by gram-positive pathogens. In contrast the longer the neutropenic period the higher was the incidence of fungal infections. This correlated with the result, that after nonresponse to the first line empiric antibiotic therapy the response rate improved more by adding amphotericin B than by change of the antibiotic regimen. In addition, especially patients suffering from pneumonia—half of those caused by fungi—had a worse outcome. So it appears reasonable to not only apply empiric antibiotic therapy but also empiric antifungal treatment at an early stage. So we conducted a prospective randomized study to compare the toxicity and efficacy of fluconazole and amphotericinB/5-flucytosine in neutropenic patients and stratified patients according to fever of unknown origin (FUO) or documented or highly suspected fungal infection.