Methods
Using an electronic medical record report in Epic, we identified children aged 0 to 18 years who switched from one triazole antifungal to a different triazole while an inpatient at a tertiary referral pediatric hospital, The Royal Children’s Hospital Melbourne (RCH), Australia over a five-year period (Nov 2016 to Oct 2021). Children were included if they had: received ≥48 hours of antifungal therapy with the first triazole; had abnormal liver function tests (LFTs) consistent with Common Terminology Criteria for Adverse Events (CTCAE)5 Grade 2 liver injury or above prior to switching triazole antifungals; the first triazole antifungal was assessed as a possible or probable cause of the LFT abnormality as per the Naranjo criteria by a paediatric clinical pharmacologist (AG)6; the child received the second triazole antifungal within 48 hours of cessation of the first drug and the abnormal LFTs improved after the switch. Children were included only if the results of their LFTs were available at baseline (prior to azole therapy), at the end of their first triazole antifungal course, and within 2 to 14 days after the antifungal switch and end of therapy.
Clinical data on patient demographics, medical comorbidities, antifungal agents received, and other hepatotoxic medications administered were collected. Concomitant hepatotoxic medications and the probability of effect on deranged LFTs were identified as per LiverTox7. Ethics approval was obtained from RCH human research ethics committee (HREC 76476).