Empirical versus Preemptive Antifungal Therapy for High-Risk, Febrile, Neutropenic Patients: A Randomized, Controlled Trial. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America [Clin Infect Dis] Journal article | | Title | Empirical versus Preemptive Antifungal Therapy for High-Risk, Febrile, Neutropenic Patients: A Randomized, Controlled Trial. | | Author(s) | Cordonnier C, Pautas C, Maury S, Vekhoff A, Farhat H, Suarez F, Dhédin N, Isnard F, Ades L, Kuhnowski F, Foulet F, Kuentz M, Maison P, Bretagne S, Schwarzinger M | | Institution | Hematology and 2Parasitology-Mycology Departments, and 3Unité de Recherche Clinique, Henri Mondor Teaching Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP) and Paris 12 University, Créteil, 4Hematology Department, Hotel Dieu Teaching Hospital, 5Hematology Department, Necker Teaching Hospital, 6Hematology Department, Pitié-Salpêtriêre Teaching Hospital, 7Hematology Department, Saint-Antoine Teaching Hospital, and 8Hematology Department, Cochin Teaching Hospital, AP-HP, and 9INSERM, Unité de Recherche en Santé (UMR-S) 707, and 10Université Pierre et Marie Curie, Université Paris 6, UMR-S 707, Paris, 11Hematology Department, André Mignot Hospital, Le Chesnay, and 12Hematology Department, Avicenne Teaching Hospital, Bobigny, France. | | Source | Clin Infect Dis 2009 Mar 12. | | Abstract | Background. Empirical antifungal therapy is the standard of care for neutropenic patients with hematological malignancies who remain febrile despite broad-spectrum antibacterial treatment. Recent diagnostic improvements may ensure the early diagnosis of potentially invasive fungal disease. Reserving antifungals for this stage may achieve similar survival rates and reduce treatment toxicity and costs. Methods. In this multicenter, open-label, randomized noninferiority trial, we compared an empirical antifungal strategy with a preemptive one. Empirical treatment was defined as antibacterial treatment of patients who have persistent or recurrent fever. Preemptive treatment was defined as treatment of patients who have clinical, imaging, or galactomannan-antigen-assay evidence suggesting fungal disease. First-line antifungal treatment was amphotericin B deoxycholate (1 mg/kg/day) or liposomal amphotericin (3 mg/kg/day), depending on daily renal function. The primary efficacy outcome was the proportion of patients alive at 14 days after recovery from neutropenia.
Results. The median duration of neutropenia (neutrophil count, <500 cells/mm(3)) for the 293 patients enrolled was 18 days (range, 5-69 days). By intention-to-treat analysis, survival was 97.3% with empirical treatment and 95.1% with preemptive treatment. The lower 95% confidence limit for the difference in mortality was -5.9%, which was within the noninferiority margin of -8%. Probable or proven invasive fungal infections were more common among patients who received preemptive treatment than among patients who received empirical treatment (13 of 143 vs. 4 of 150; [Formula: see text]), and most infections occurred during induction therapy (12 of 73 patients in the preemptive treatment group vs. 3 of 78 patients in the empirical treatment group were infected during induction therapy; [Formula: see text]). Preemptive treatment did not decrease nephrotoxicity but decreased costs of antifungal therapy by 35%.
Conclusions. Preemptive treatment increased the incidence of invasive fungal disease, without increasing mortality, and decreased the costs of antifungal drugs. Empirical treatment may provide better survival rates for patients receiving induction chemotherapy. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19281327 |
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