#78: Use of Isavuconazonium for Treatment Of Invasive Fungal Infection in Immunocompromised Pediatric Patients. (26th March 2021)

• Record Type: Journal Article
• Authors: Mohandas, Sindhu; Mongkolrattanothai, Kanokporn; Stach, Leslie; Orbach, Regina; Neely, Michael
• Is Part Of: Journal of the Pediatric Infectious Diseases Society. Volume 10(2021)Supplement 1
• Page Start: S2
• Page End: S2
• Publication Date: 2021-03-26
• Subjects: Communicable diseases in children -- Periodicals; Children -- Diseases -- Periodicals; 618.929
• DOI: 10.1093/jpids/piaa170.006
• Languages: English
• ISSNs: 2048-7193

Abstract

Abstract: Background: Isavuconazole (ISZ), dosed as the pre-drug isavuconazonium (ISM), is active against a wide variety of clinically important fungal pathogens. ISM is approved for the treatment of invasive aspergillosis and mucormycosis in adults ≥18 years of age. We present our experience with ISM to treat proven or probable fungal infection in immunocompromised pediatric patients. Methods: Retrospective review of patients who received ISM at our institution between April 2016 and April 2019, we abstracted demographic information, primary diagnosis, indication for ISM therapy, ISZ serum concentrations if available, and outcomes. Results: Of 14 patients who received ISM, 11 were ≤18 years of age (range 6–18 years). Underlying conditions included leukemia ( n = 7), lymphoma ( n = 1), post BMT ( n = 1), diabetes ( n = 1), and cardiac transplant ( n = 1). Nine (82%) had proven invasive fungal infection (IFI) with aspergillosis ( n = 2), zygomycosis ( n = 3), mixed aspergillosis and zygomycosis ( n = 2), mixed Rhizopus and Scedosporium ( n = 1), and pathology only ( n = 1) and 2 had probable IFI. Five of these 11 patients received combination ISM and liposomal amphotericin initially and the other 6 received liposomal amphotericin with or without other azoles prior to changing to ISM monotherapy. This was followed by monotherapy with ISM in 10 patients after a mean of 26 days (range 6–63) and continued dual therapy in the one. ISM dosing was 10 mg/kg q8h on days 1 and 2, followed by q24 thereafter, up to a maximum of 372 mg/dose. There were 19 measured ISZ serum concentrations obtained from 8 patients after >1 week of verified inpatient dosing, ranging from 1.0 to 7.5 mg/L, above the MIC in all cases when known. Three (27%) patients died of underlying non-mycological causes, 1 (9%) died of progressive scedosporiosis, and 7 (64%) improved. ISM was well tolerated with no dose-limiting, drug-related toxicities noted. Conclusions: ISM is a well-tolerated therapeutic option in pediatric patients at risk for or with invasive mycosis. Only 1 of our 11 patients died from progressive fungal disease.