Efficacy and safety of micafungin as an empirical therapy for invasive fungal infections in patients with hematologic disorders: a multicenter, prospective study

Abstract

This study was conducted as a prospective, multicenter trial to evaluate the efficacy and safety of micafungin as an empirical therapy for suspected invasive fungal infections (IFIs), including febrile neutropenia (FN), and to evaluate the usefulness of β-D: -glucan (BG) and Aspergillus galactomannan (GM) antigen in patients with hematologic diseases. A total of 121 patients were enrolled and assessed for safety, and 119 were examined for clinical efficacy. The main underlying diseases were acute myeloid leukemia (38.0%), acute lymphoblastic leukemia (18.2%), and malignant lymphoma (18.2%). The median initial daily dose and duration of micafungin treatment were 150 mg/day and 13 days, respectively. The overall response rate for suspected IFIs (n = 119), based on four composite endpoints, including baseline IFI, breakthrough IFIs (proven and probable), survival, and premature discontinuation, was 79.0%. In addition, the response rate for FN (n = 81), based on these four endpoints as well as defervescence during neutropenia, was 39.5%. Breakthrough IFIs (proven, probable, and possible) occurred in five patients during micafungin treatment. All of these patients were positive for either BG or GM before the breakthrough IFIs. The incidence of adverse events (AEs) associated with micafungin was 10.7% and most were mild. The majority of AEs were liver dysfunction. These results indicate the effectiveness and safety of micafungin as an empirical therapy for suspected IFIs, including FN, and the usefulness of monitoring both BG and GM to detect breakthrough IFIs.

Efficacy and Tolerability of Micafungin Monotherapy for Candidemia and Deep-Seated Candidiasis in Adults with Cancer

“…We studied the efficacy and tolerability of micafungin in cancer patients with candidemia or deep-seated candidiasis. The overall clinical response rate (81% [95% CI, 71 to 91%]) was comparable to those in two previous randomized controlled trials (74.0% and 71.2%) (4, 5), a contemporary study of micafungin treatment of patients with hematological malignancies (79%) (11), and previously published data on caspofungin (70.4% and 83.1%) (7,8). Notably, we did not find significant effects of high micafungin doses on response rates or 30-day mortality rates, which agrees with previous results (6).…”

Efficacy and safety of micafungin versus extensive azoles in the prevention and treatment of invasive fungal infections for neutropenia patients with hematological malignancies: A meta-analysis of randomized controlled trials

“…The US Food and Drug Administration (FDA) approved MCFG for anti-fungal prophylaxis during the pre-engraftment phase in patients undergoing hematopoietic stem cell transplantation (SCT). The Infectious Diseases Society of America (IDSA) guidelines also recommend MCFG as an alternative prophylactic drug to treat IA [16]. …”

Activity of a Long-Acting Echinocandin, Rezafungin, and Comparator Antifungal Agents Tested against Contemporary Invasive Fungal Isolates (SENTRY Program, 2016 to 2018)

“…Other potential drawbacks of the available echinocandins for clinical application are the use of a fixed dose irrespective of body size or species susceptibility (S) and emerging resistance mediated by mutations in the fks genes (15,17). It has been suggested that underdosing of echinocandins, coupled with poor penetration to certain body sites, may partially account for the emerging echinocandin resistance (15,18,19). An echinocandin that could be safely administered at higher doses to ensure optimal pharmacokinetic (PK) and pharmacodynamic (PD) features and target attainment may facilitate outpatient therapy, reduce the hospital stay, and possibly delay or prevent the development of echinocandin resistance, thus becoming an important step toward improving the ability to effectively manage candidemia and IC (15,20).…”