THERAPEUTIC DRUG MONITORING (TDM) OF TRIAZOLES (ISAVUCONAZOLE) AND THE USE OF SERUM 1,3-BETA-D-GLUCAN IN PATIENTS WITH INVASIVE FUNGAL DISEASES

Abstract 1 Isavuconazole is the first-line treatment for invasive aspergillosis. As most patients in large studies reached therapeutic levels (>1 mg/L), therapeutic drug monitoring (TDM) is not considered necessary. Low levels were reported in some critically ill patients admitted to the intensive care unit (ICU). We aimed to compare the levels of isavuconazole in critically ill patients and those in non-critically ill patients. The data from all patients treated with standard-dose isavuconazole between 1 January 2019 and 26 October 2022 were retrospectively analyzed. The following data were collected: TDM results from the first 30 days of therapy, ward of admission, demographic and clinical characteristics, continuous renal replacement therapy, extracorporeal membrane oxygenation, and co-administered medications. In this study, 72 patients (median age 65 years) and 188 TDM measurements were collected from 188 participants. 33 patients (45.8%) were ICU patients (3 also had haematological disorders); 39 (54.2%) were non-ICU patients, of whom 31 also had haematological disorders. The mean isavuconazole blood level in all patients was 3.33 ± 2.26 mg/L. ICU patients had significantly lower levels than the non-ICU population: mean 2.02 ± 1.22 versus 4.15 ± 2.31 mg/L (P < 0.001). The rates of subtherapeutic levels were significantly higher among ICU patients compared with the non-ICU population: all determinations <2 mg/L in 33.3% versus 7.7%, and all determinations <1 mg/L in 12.1% versus 0%, respectively. Admission to the ICU, BMI >25 kg/m2, a bilirubin level >1.2 mg/dL, and the absence of haematological disorders were all associated with lower isavuconazole levels. In conclusion, the isavuconazole blood levels of ICU patients were significantly lower than those of non-ICU patients. To evaluate the efficacy of isavuconazole, TDM should be performed in ICU patients.