Incidence of Breakthrough Invasive Fungal Infections While on Micafungin for Antifungal Prophylaxis in Pediatric Hematopoietic Cell Transplant Patients

Abstract

Introduction Pediatric hematopoietic cell transplant (HCT) patients are at significant risk for invasive fungal infections (IFIs). IFIs are life threatening for HCT patients. Due to its tolerability and lack of drug interactions, micafungin is utilized as primary antifungal prophylaxis (PAP) in the peri-transplant period. In 2012, we created a micafungin dosing protocol for pediatric patients based on the most current literature at that time. Objectives Our primary endpoint was to determine the prevalence of breakthrough IFIs in pediatric HCT patients after initiating PAP according to this institutional micafungin dosing protocol. The secondary endpoint was to evaluate the incidence of adverse effects (AEs). Methods Retrospective analyses of our institution's electronic records were performed to quantify the incidence of breakthrough IFIs in pediatric HCT patients who received micafungin for PAP according to institutional protocol between July 2012 and Dec 2017. Micafungin Pediatric Dosing Guidelines. PAP for HCT Results A total of 300 pediatric HCT patients were included in the analysis. All patients were neutrophil engrafted by Day +30. All patients started micafungin PAP prior to conditioning and continued through Day +100. Of the 300 patients, 50% converted to voriconazole, 30% remained on micafungin, 20% converted to fluconazole and 10% received amphotericin B. Per the European Organization for Research and Treatment of Cancer (EORTC) IFI Criteria Classification, 10 patients (3.1%) developed an IFI. Eight cases (2.6%) were classified as proven and 2 cases (0.7%) were probable. Pathogens identified were Candida parapsilosis (5/8 cases), Rhizopus (1 case), Candida krusei (1 case) and one case had both Mucormycosis and Rhizopus. The infection source was blood in 6/8 cases, wound (1 case) and sinuses/brain (1 case). Seven of eight patients with ‘proven' IFI died. Two deaths were directly associated with IFI (C. parapsilosis and mucormycosis); other deaths were attributed to bacterial infection (3), pulmonary hemorrhage or underlying disease. For the entire study group, approximately 8%, 5.7% and 1.7% had Grade 2, 3 and 4 hepatotoxicity, respectively (CTCAE grading criteria). Most patients with Grade 3 or 4 were noted to have moderate to severe Veno-Occlusive Disease or other primary disease processes so the events were likely not related to micafungin. Conclusions The micafungin dosing protocol for pediatric HCT patients has shown to be efficacious with very few documented breakthrough IFI over a five year study period. Additionally, micafungin was well tolerated at these doses with few treatment-related and/or low grade AEs.