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Association between augmented renal clearance, antibiotic exposure and clinical outcome in critically ill septic patients receiving high doses of β-lactams administered by continuous infusion: a prospective observational study.

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 <4 × MIC 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<4×MIC was 12%, with a significant association with CLCr (P <0.0001). A threshold of CLCr ≥ 170 mL/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<4×MIC. Mean CLCr values ≥170 mL/min were significantly associated with subexposure<4xMIC [OR = 10.1 (2.4-41.6); P = 0.001]. Patients with subexposure<4×MIC presented higher rates of therapeutic failure [OR = 6.3 (1.2-33.2); P = 0.03]. Mean CLCr values ≥170 mL/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.

journal_name

Int J Antimicrob Agents

journal_title

International journal of antimicrobial agents

authors

Carrié C,Petit L,d'Houdain N,Sauvage N,Cottenceau V,Lafitte M,Foumenteze C,Hisz Q,Menu D,Legeron R,Breilh D,Sztark F

doi

10.1016/j.ijantimicag.2017.11.013

subject

Has Abstract

pub_date

2018-03-01 00:00:00

pages

443-449

issue

eissn

0924-8579

issn

1872-7913

pii

S0924-8579(17)30430-2

journal_volume

pub_type

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Association between augmented renal clearance, antibiotic exposure and clinical outcome in critically ill septic patients receiving high doses of β-lactams administered by continuous infusion: a prospective observational study.