7fd9f42e145ef52ca50e1a5ec06f9ed5 pmc_34200506.pdf 5fd4f7bdfce79e3ddf26a069dc19321921776e0d pmc_34200506.pdf d41575fc3effe5735046a3a9f74fa3dab16a5eb6b800075d8022ad80392c9e33 pmc_34200506.pdf Title: Voriconazole Use in Children: Therapeutic Drug Monitoring and Control of Inflammation as Key Points for Optimal Treatment Subject: Voriconazole plasma concentrations (PC) are highly variable, particularly in children. Dose recommendations in 2–12-year-old patients changed in 2012. Little data on therapeutic drug monitoring (TDM) after these new recommendations are available. We aimed to evaluate voriconazole monitoring in children with invasive fungal infection (IFI) after implementation of new dosages and its relationship with safety and effectiveness. A prospective, observational study, including children aged 2–12 years, was conducted. TDM was performed weekly and doses were changed according to an in-house protocol. Effectiveness, adverse events, and factors influencing PC were analysed. A total of 229 PC from 28 IFI episodes were obtained. New dosing led to a higher rate of adequate PC compared to previous studies; still, 35.8% were outside the therapeutic range. In patients aged < 8 years, doses to achieve therapeutic levels were higher than recommended. Severe hypoalbuminemia and markedly elevated C-reactive protein were related to inadequate PC. Therapeutic PC were associated with drug effectiveness and safety. Higher doses in younger patients and a dose adjustment protocol based on TDM should be considered. Voriconazole PC variability has decreased with current updated recommendations, but it remains high and is influenced by inflammatory status. Additional efforts to control inflammation in children with IFI should be encouraged. Keywords: paediatric fungal infections; antifungal treatment; therapeutic drug monitoring; voriconazole; children; inflammation Author: José María Valle-T-Figueras, Berta Renedo Miró, Maria Isabel Benítez Carabante, Cristina Díaz-de-Heredia, Jaume Vima Bofarull, Natalia Mendoza-Palomar, Maria Teresa Martín-Gómez and Pere Soler-Palacín Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Tue Jun 8 14:02:16 2021 CEST ModDate: Tue Jun 8 14:05:07 2021 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 17 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 569102 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- PSUYZB+VnURWPalladioL Type 1 Custom yes yes no 10 0 YVVBUE+URWPalladioL-Ital Type 1 Custom yes yes no 15 0 OXRYUI+URWPalladioL-Bold Type 1 Custom yes yes no 20 0 TIUXMW+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 XWOCXD+VnURWPalladioL-Bold Type 1 Custom yes yes no 28 0 BSDWLC+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 37 0 LUDWNL+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 40 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 62 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 66 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 70 0 IKKWKP+CMSY10 Type 1 Builtin yes yes no 85 0 MOSBKF+URWPalladioL-BoldItal Type 1 Custom yes yes no 98 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-10-02 03:12:39 CEST RepresentationInformation: pmc_34200506.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2023-03-31 12:14:18 CEST Size: 569102 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 429 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Materials and Methods Destination: section.2 Children: Item: Title: Ethics Destination: subsection.2.1 Item: Title: Inclusion Criteria Destination: subsection.2.2 Item: Title: Procedures Destination: subsection.2.3 Item: Title: Data Collection and Definitions Destination: subsection.2.4 Item: Title: Statistical Analysis Destination: subsection.2.5 Item: Title: Results Destination: section.3 Children: Item: Title: Characteristics of Patients and Invasive Fungal Infections Destination: subsection.3.1 Item: Title: Therapeutic Drug Monitoring Destination: subsection.3.2 Item: Title: Effectiveness Destination: subsection.3.3 Item: Title: Safety Destination: subsection.3.4 Item: Title: Discussion Destination: section.4 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: section.5 Info: Title: Voriconazole Use in Children: Therapeutic Drug Monitoring and Control of Inflammation as Key Points for Optimal Treatment Author: José María Valle-T-Figueras, Berta Renedo Miró, Maria Isabel Benítez Carabante, Cristina Díaz-de-Heredia, Jaume Vima Bofarull, Natalia Mendoza-Palomar, Maria Teresa Martín-Gómez and Pere Soler-Palacín Subject: Voriconazole plasma concentrations (PC) are highly variable, particularly in children. Dose recommendations in 2 12-year-old patients changed in 2012. Little data on therapeutic drug monitoring (TDM) after these new recommendations are available. We aimed to evaluate voriconazole monitoring in children with invasive fungal infection (IFI) after implementation of new dosages and its relationship with safety and effectiveness. A prospective, observational study, including children aged 2 12 years, was conducted. TDM was performed weekly and doses were changed according to an in-house protocol. Effectiveness, adverse events, and factors influencing PC were analysed. A total of 229 PC from 28 IFI episodes were obtained. New dosing led to a higher rate of adequate PC compared to previous studies; still, 35.8% were outside the therapeutic range. In patients aged < 8 years, doses to achieve therapeutic levels were higher than recommended. Severe hypoalbuminemia and markedly elevated C-reactive protein were related to inadequate PC. Therapeutic PC were associated with drug effectiveness and safety. Higher doses in younger patients and a dose adjustment protocol based on TDM should be considered. Voriconazole PC variability has decreased with current updated recommendations, but it remains high and is influenced by inflammatory status. Additional efforts to control inflammation in children with IFI should be encouraged. 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