title: Potential factors for inadequate voriconazole plasma concentrations in intensive care unit patients and patients with hematological malignancies.
abstract: Voriconazole plasma concentrations (VPCs) vary widely, and concentrations outside the therapeutic range are associated with either worse outcome in invasive aspergillosis (IA) or increased toxicity. The primary goal of this cohort study conducted in a real-life setting was to identify potential factors associated with inadequate VPCs in ICU patients and patients with hematological malignancies. Within a period of 12 months, trough VPCs were obtained and analyzed with high-performance liquid chromatography, and the adequate range was defined as 1.5 to 5.5 mg/liter. VPCs of <1.5 mg/liter were defined as low, whereas VPCs of >5.5 mg/liter were defined as potentially toxic. A total of 221 trough VPCs were obtained in 61 patients receiving voriconazole, and 124/221 VPCs (56%) were found to be low. Multivariate analysis revealed that low VPCs were significantly associated with clinical failure of voriconazole, prophylactic use, younger age, underlying hematological malignancy, concomitant proton pump inhibitor (PPI) (pantoprazole was used in 88% of the patients), and absence of side effects. Low VPCs remained an independent predictor of clinical failure of voriconazole. The defined adequate range was reached in 79/221 (36%) VPCs. In 18 samples (8%), potentially toxic levels were measured. Multivariate analysis revealed higher body mass index (BMI), absence of hematological malignancy, therapeutic application, and diarrhea as factors associated with potentially toxic VPCs. Neurotoxic adverse events occurred in six patients and were mostly associated with VPCs in the upper quartile of our defined adequate range. In conclusion, potential factors like younger age, prophylaxis, underlying hematological malignancy, BMI, and concomitant PPI should be considered within the algorithm of voriconazole treatment.
authors: Division of Pulmonology, Department of Internal Medicine, Medical University of Graz, Graz, Austria. martin.hoenigl@medunigraz.at
authors: Martin
authors: M
authors: Hoenigl
authors: Wiebke
authors: W
authors: Duettmann
authors: Reinhard B
authors: RB
authors: Raggam
authors: Katharina
authors: K
authors: Seeber
authors: Katharina
authors: K
authors: Troppan
authors: Sonja
authors: S
authors: Fruhwald
authors: Florian
authors: F
authors: Prueller
authors: Jasmin
authors: J
authors: Wagner
authors: Thomas
authors: T
authors: Valentin
authors: Ines
authors: I
authors: Zollner-Schwetz
authors: Albert
authors: A
authors: Wölfler
authors: Robert
authors: R
authors: Krause
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000935:Antifungal Agents / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use; D001228:Aspergillosis / Q000097:blood / Q000188:drug therapy*; D015992:Body Mass Index; D015331:Cohort Studies; D016903:Drug Monitoring; D005260:Female; D019337:Hematologic Neoplasms / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011743:Pyrimidines / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use; D016896:Treatment Outcome; D014230:Triazoles / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use; D065819:Voriconazole; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D065819:Voriconazole
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