PMC:7306567 / 16239-17641 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7306567","sourcedb":"PMC","sourceid":"7306567","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7306567","text":"Treatment options and challenges for IAPA in the ICU\nFirst-line treatment options for IPA include voriconazole and isavuconazole [35, 43]. Other options include echinocandins in combination with anti-mold azoles, and liposomal amphotericin B (L-AmB) in regions with high rates of azole-resistant A. fumigatus, although clinical data with L-AmB in ICU patients are limited [43, 44]. Achieving adequate drug exposure is challenging in ICU patients with multiple factors contributing to pharmacokinetic variability. Unlike L-AmB and the echinocandins, drug interactions are clinically relevant for the azoles and pharmacogenetic factors are important in inter-individual drug exposure variability [45]. The impact of therapeutic drug monitoring (TDM) for voriconazole shows a clear relation between exposure and both efficacy and toxicity. Target plasma trough voriconazole concentrations of ≥ 1.5–2 mg/L are associated with near-maximal clinical response in treatment of IA with a wild-type phenotype [46–51], with higher exposures (\u003e 5.5 mg/L) increasing the risk of (neuro)toxicity. Higher trough concentrations (\u003e 2 mg/L) are recommended for treatment of pathogens with elevated MICs (e.g., \u003e 0.25 mg/L) [52]. For isavuconazole, there is no robust target plasma concentration, and the population average exposure of participants that demonstrated a favorable response (2–4 mg/L) is commonly used 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