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).