Intravenous itraconazole compared with liposomal amphotericin B as empirical antifungal therapy in patients with neutropaenia and persistent fever
Open Access
- 1 August 2020
- Vol. 63 (8), 794-801
- https://doi.org/10.1111/myc.13100
Abstract
Background Fungal infections are a major complication of neutropaenia following chemotherapy. Their early diagnosis is difficult, and empirical antifungal treatment is widely used, and uses of less toxic drugs that reduce breakthrough infection are required. Objective We conducted a multicentre, open-label, randomised, non-inferiority trial to compare the safety and efficacy of intravenous itraconazole (ivITCZ) and liposomal amphotericin B (LAmB) as empirical antifungal therapy in patients with haematological malignancies with neutropaenia and persistent fever. Methods Patients with haematological malignancies who developed fever refractory to broad-spectrum antibacterial agents under neutropaenia conditions were enrolled. Patients were randomised for treatment with LAmB (3.0 mg/kg/d) or ivITCZ (induction: 400 mg/d, maintenance: 200 mg/d). Results Observed overall favourable response rates of 17/52 (32.7%) and 18/50 (36.0%) in the LAmB and ivITCZ groups, with a model-based estimate of a 4% difference (90% CI, -12% to 20%), did not fulfil the statistical non-inferiority criterion. In the LAmB group, there were two cases of breakthrough infection and five cases of probable invasive fungal disease, whereas in the itraconazole group, neither breakthrough infection nor probable invasive fungal disease occurred. Patients in the ivITCZ group had significantly fewer grade 3-4 hypokalaemia-related events than LAmB group patients (P < .01). The overall incidence of adverse events tended to be lower in the ivITCZ group (P = .07). Conclusion ivITCZ showed similar efficacy and safety as LAmB as empirical antifungal therapy in haematological malignancy patients with febrile neutropaenia, although the small sample size and various limitations prevented demonstration of its non-inferiority.This publication has 19 references indexed in Scilit:
- Revised Definitions of Invasive Fungal Disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus GroupClinical Infectious Diseases, 2008
- Breakthrough Trichosporonosis in Patients with Hematologic Malignancies Receiving MicafunginClinical Infectious Diseases, 2006
- In Vitro Susceptibilities of Clinical Isolates of Candida Species, Cryptococcus neoformans , and Aspergillus Species to Itraconazole: Global Survey of 9,359 Isolates Tested by Clinical and Laboratory Standards Institute Broth Microdilution MethodsJournal of Clinical Microbiology, 2005
- Zygomycosis after Prolonged Use of Voriconazole in Immunocompromised Patients with Hematologic Disease: Attention RequiredClinical Infectious Diseases, 2005
- Caspofungin versus Liposomal Amphotericin B for Empirical Antifungal Therapy in Patients with Persistent Fever and NeutropeniaThe New England Journal of Medicine, 2004
- Invasive Zygomycosis in Hematopoietic Stem Cell Transplant Recipients Receiving Voriconazole ProphylaxisClinical Infectious Diseases, 2004
- Breakthrough Zygomycosis after Voriconazole Treatment in Recipients of Hematopoietic Stem-Cell TransplantsThe New England Journal of Medicine, 2004
- Breakthrough Trichosporonosis in a Bone Marrow Transplant Recipient Receiving Caspofungin AcetateClinical Infectious Diseases, 2002
- Emerging Fungal Pathogens in Immunocompromised Patients: Classification, Diagnosis, and ManagementClinical Infectious Diseases, 1993
- Infections with Aspergillus SpeciesClinical Infectious Diseases, 1993