{
  "abstract": "Background and Importance Triazole antifungals are broad-spectrum drugs used in children from 2-years-old for treating severe fungal infections and as prophylaxis in high risk haematopoietic stem cell transplant recipients. Their pharmacokinetics show significant variability, especially in paediatric patients, due to factors like bodyweight and immature liver function, underscoring the need for individualised dosing in this population.Aim and Objectives To describe the pharmacokinetic variability of azole antifungals in paediatric patients monitored in tertiary care hospitals, analysing the impact of therapeutic drug monitoring.Material and Methods Descriptive, retrospective, multicentre study including paediatric patients treated with antifungal agents who had plasma concentrations measured between February 2020-August 2025.Trough plasma concentrations were measured at steady state using high performance liquid chromatography with ultraviolet detection (HPLC-UV).Therapeutic ranges: voriconazole=1.5-5.5µg/mL, isavuconazole=2-5 µg/mL.Collected Data: Gender, age, underlying pathology, type of treatment (empirical, targeted, or prophylaxis), infection treated, presence of isolates (MIC), treatment toxicity, liver function, levels, pharmacist recommendations, physician acceptance.Results Plasma concentrations were determined in 94 samples from 31 patients, 65.38% girls, median age 11 (6–12) years and mainly haematological underlying conditions (80.8%). Voriconazole accounted for 84.04% (N=79) of the samples and isavuconazole 15.96% (N=15). There were no posaconazole samples. Empirical treatments represented 74.5%, targeted 24.5%, and prophylaxis 1.1%. Type of infections: respiratory 81.9%, systemic 6.4%, neurological 5.3%, among others. Aspergillus was most frequently isolated (A.flavus N=3, A.fumigatus N=9, A.terreus N=5), followed by Candida (C.guillermondii N=4, C.krusei N=2), with all isolates being sensitive to treatment.For voriconazole, median concentration was 1.28 (0.42-3.03) µg/mL, with 44.3% (35) being subtherapeutic, 44.3% (35) within range, and 11.4% (9) supratherapeutic levels. Of those out-of-range, levels were re-requested in 78.43%, and 73,68% were brought into range and 26,3% were discontinuation.44% of supratherapeutic levels presented adverse effects (visual disturbances, hypertransaminasemia), which resolved upon reaching therapeutic range, except for one discontinuation.For isavuconazole, median concentration was 2.08 (1.59-3.04) µg/mL, 86.7% (13) within range, 6.7% (1) subtherapeutic, and 6.7% (1) supratherapeutic. Both children with out-of-range levels had their dosing regimen adjusted, achieving adequate levels in next determination.Conclusion and Relevance Voriconazole shows significant pharmacokinetic variability, with more than 50% of plasma levels outside the therapeutic range. This highlights the crucial importance of pharmacokinetic monitoring to reach therapeutic ranges and ensure the effectiveness and safety of treatments in severe paediatric conditions.Conflict of Interest No conflict of interest",
  "authors": [
    {
      "affiliations": [
        "Hospital Universitario Virgen Macarena, Hospital Pharmacy, Seville, Spain"
      ],
      "name": "L Amaro"
    },
    {
      "affiliations": [
        "Hospital Universitario Virgen Macarena, Hospital Pharmacy, Seville, Spain"
      ],
      "name": "C Moya-Mangas"
    },
    {
      "affiliations": [
        "Hospital Universitario Virgen Macarena, Hospital Pharmacy, Seville, Spain"
      ],
      "name": "J Cordero-Ramos"
    },
    {
      "affiliations": [
        "Hospital Universitario Virgen Macarena, Hospital Pharmacy, Seville, Spain"
      ],
      "name": "V Merino-Bohórquez"
    }
  ],
  "title": "4CPS-012 Therapeutic drug monitoring of azole antifungals in the paediatric population in tertiary care hospitals",
  "uid": "d315da58-70a9-5722-9420-53dcdb918d78"
}