Therapeutic Drug Monitoring of Fluconazole in Critically Ill Patients

Author(s):  
2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Alan Abdulla ◽  
Puck van den Broek ◽  
Tim M.J. Ewoldt ◽  
Anouk E. Muller ◽  
Henrik Endeman ◽  
...  

2018 ◽  
Vol 4 (5) ◽  
pp. 166-174
Author(s):  
Nora J mabelis ◽  
Kimberly N. Shudofsky ◽  
Joost J. van Raaij ◽  
Sjoerd D. Meenks ◽  
Thomas Havenith ◽  
...  

Antibiotics ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1452
Author(s):  
Schrader Nikolas ◽  
Riese Thorsten ◽  
Kurlbaum Max ◽  
Meybohm Patrick ◽  
Kredel Markus ◽  
...  

Therapeutic drug monitoring (TDM) is increasingly relevant for an individualized antibiotic therapy and subsequently a necessary tool to reduce multidrug-resistant pathogens, especially in light of diminishing antimicrobial capabilities. Critical illness is associated with profound pharmacokinetic and pharmacodynamic alterations, which challenge dose finding and the application of particularly hydrophilic drugs such as β-lactam antibiotics. Methods: Implementation strategy, potential benefit, and practicability of the developed standard operating procedures were retrospectively analyzed from January to December 2020. Furthermore, the efficacy of the proposed dosing target of piperacillin in critically ill patients was evaluated. Results: In total, 160 patients received piperacillin/tazobactam therapy and were subsequently included in the study. Of them, 114 patients received piperacillin/tazobactam by continuous infusion and had at least one measurement of piperacillin serum level according to the standard operating procedure. In total, 271 measurements were performed with an average level of 79.0 ± 46.0 mg/L. Seventy-one piperacillin levels exceeded 100 mg/L and six levels were lower than 22.5 mg/L. The high-level and the low-level group differed significantly in infection laboratory parameters (CRP (mg/dL) 20.18 ± 11.71 vs. 5.75 ± 5.33) and renal function [glomerular filtration rate (mL/min/1.75 m2) 40.85 ± 26.74 vs. 120.50 ± 70.48]. Conclusions: Piperacillin levels are unpredictable in critically ill patients. TDM during piperacillin/tazobactam therapy is highly recommended for all patients. Although our implementation strategy was effective, further strategies implemented into the daily clinical workflow might support the health care staff and increase the clinicians’ alertness.


2019 ◽  
Vol 41 (1) ◽  
pp. 29-37 ◽  
Author(s):  
Sophie Neugebauer ◽  
Christina Wichmann ◽  
Sibylle Bremer-Streck ◽  
Stefan Hagel ◽  
Michael Kiehntopf

2021 ◽  
Vol 50 (1) ◽  
pp. 437-437
Author(s):  
Christina Rose ◽  
Michelle Miller ◽  
Kazumi Morita ◽  
Sheriff Gbadamosi ◽  
Kerry Mohrien

2020 ◽  
Vol 65 (3) ◽  
Author(s):  
Indy Sandaradura ◽  
Jessica Wojciechowski ◽  
Deborah J. E. Marriott ◽  
Richard O. Day ◽  
Sophie Stocker ◽  
...  

ABSTRACT Fluconazole has been associated with higher mortality compared with the echinocandins in patients treated for invasive candida infections. Underexposure from current fluconazole dosing regimens may contribute to these worse outcomes, so alternative dosing strategies require study. The objective of this study was to evaluate fluconazole drug exposure in critically ill patients comparing a novel model-optimized dose selection method with established approaches over a standard 14-day (336-h) treatment course. Target attainment was evaluated in a representative population of 1,000 critically ill adult patients for (i) guideline dosing (800-mg loading and 400-mg maintenance dosing adjusted to renal function), (ii) guideline dosing followed by therapeutic drug monitoring (TDM)-guided dose adjustment, and (iii) model-optimized dose selection based on patient factors (without TDM). Assuming a MIC of 2 mg/liter, free fluconazole 24-h area under the curve (fAUC24) targets of ≥200 mg · h/liter and <800 mg · h/liter were used for assessment of target attainment. Guideline dosing resulted in underexposure in 21% of patients at 48 h and in 23% of patients at 336 h. The TDM-guided strategy did not influence 0- to 48-h target attainment due to inherent procedural delays but resulted in 37% of patients being underexposed at 336 h. Model-optimized dosing resulted in ≥98% of patients meeting efficacy targets throughout the treatment course, while resulting in less overexposure compared with guideline dosing (7% versus 14%) at 336 h. Model-optimized dose selection enables fluconazole dose individualization in critical illness from the outset of therapy and should enable reevaluation of the comparative effectiveness of this drug in patients with severe fungal infections.


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