Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8738628 | International Journal of Antimicrobial Agents | 2018 | 29 Pages |
Abstract
This study assessed whether augmented renal clearance (ARC) impacts negatively on antibiotic concentrations and clinical outcomes in patients treated by high-dose β-lactams administered continuously. Over a 9-month period, all critically ill patients without renal impairment treated by one of the monitored β-lactams for a documented infection were eligible. During the first 3 days of antibiotic therapy, every patient underwent 24-h CLCr measurements and therapeutic drug monitoring. The main outcome was the rate of β-lactam underdosing, defined as a free drug concentration <4âÃâMIC of the known pathogen. Secondary outcomes were rates of subexposure for β-lactams and therapeutic failure. The performance of CLCr in predicting underdosing was assessed by a ROC curve, and multivariable logistic regression was performed to determine risk factors for subexposure and therapeutic failure. A total of 79 patients were included and 235 samples were analysed. The rate of underdosing<4ÃMIC was 12%, with a significant association with CLCr (Pâ<0.0001). A threshold of CLCrââ¥â170âmL/min had a sensitivity and specificity of 0.93 (95% CI 0.77-0.99) and 0.65 (95% CI 0.58-0.71) for predicting β-lactam underdosing<4ÃMIC. Mean CLCr values â¥170âmL/min were significantly associated with subexposure<4xMIC [ORâ=â10.1 (2.4-41.6); Pâ=â0.001]. Patients with subexposure<4ÃMIC presented higher rates of therapeutic failure [ORâ=â6.3 (1.2-33.2); Pâ=â0.03]. Mean CLCr values â¥170âmL/min remain a risk factor for subexposure to β-lactams despite high doses of β-lactams administered continuously. β-Lactam subexposure was associated with higher rates of therapeutic failure in septic critically ill patients.
Related Topics
Life Sciences
Immunology and Microbiology
Applied Microbiology and Biotechnology
Authors
Cédric Carrié, Laurent Petit, Nicolas d'Houdain, Noemie Sauvage, Vincent Cottenceau, Melanie Lafitte, Cecile Foumenteze, Quentin Hisz, Deborah Menu, Rachel Legeron, Dominique Breilh, Francois Sztark,