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A multicenter study on the effect of continuous hemodiafiltration intensity on antibiotic pharmacokinetics.

ABSTRACT: Continuous renal replacement therapy (CRRT) may alter antibiotic pharmacokinetics and increase the risk of incorrect dosing. In a nested cohort within a large randomized controlled trial, we assessed the effect of higher (40 mL/kg per hour) and lower (25 mL/kg per hour) intensity CRRT on antibiotic pharmacokinetics.We collected serial blood samples to measure ciprofloxacin, meropenem, piperacillin-tazobactam, and vancomycin levels. We calculated extracorporeal clearance (CL), systemic CL, and volume of distribution (Vd) by non-linear mixed-effects modelling. We assessed the influence of CRRT intensity and other patient factors on antibiotic pharmacokinetics.We studied 24 patients who provided 179 pairs of samples. Extracorporeal CL increased with higher-intensity CRRT but the increase was significant for vancomycin only (mean 28 versus 22 mL/minute; P?=?0.0003). At any given prescribed CRRT effluent rate, extracorporeal CL of individual antibiotics varied widely, and the effluent-to-plasma concentration ratio decreased with increasing effluent flow. Overall, systemic CL varied to a greater extent than Vd, particularly for meropenem, piperacillin, and tazobactam, and large intra-individual differences were also observed. CRRT dose did not influence overall (systemic) CL, Vd, or half-life. The proportion of systemic CL due to CRRT varied widely and was high in some cases.In patients receiving CRRT, there is great variability in antibiotic pharmacokinetics, which complicates an empiric approach to dosing and suggests the need for therapeutic drug monitoring. More research is required to investigate the apparent relative decrease in clearance at higher CRRT effluent rates.ClinicalTrials.gov NCT00221013. Registered 14 September 2005.

SUBMITTER: Roberts DM

PROVIDER: S-EPMC4404619 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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A multicenter study on the effect of continuous hemodiafiltration intensity on antibiotic pharmacokinetics.

Roberts Darren M DM Liu Xin X Roberts Jason A JA Nair Priya P Cole Louise L Roberts Michael S MS Lipman Jeffrey J Bellomo Rinaldo R

Critical care (London, England) 20150313

<h4>Introduction</h4>Continuous renal replacement therapy (CRRT) may alter antibiotic pharmacokinetics and increase the risk of incorrect dosing. In a nested cohort within a large randomized controlled trial, we assessed the effect of higher (40 mL/kg per hour) and lower (25 mL/kg per hour) intensity CRRT on antibiotic pharmacokinetics.<h4>Methods</h4>We collected serial blood samples to measure ciprofloxacin, meropenem, piperacillin-tazobactam, and vancomycin levels. We calculated extracorporea ...[more]

PMID: 25881576

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Project description:Poststroke guidelines recommend moderate-intensity, continuous aerobic training (MCT) to improve aerobic capacity and mobility after stroke. High-intensity interval training (HIT) has been shown to be more effective than MCT among healthy adults and people with heart disease. However, HIT and MCT have not been compared previously among people with stroke.The purpose of this study was to assess the feasibility and justification for a definitive randomized controlled trial (RCT) comparing HIT and MCT in people with chronic stroke.A preliminary RCT was conducted.The study was conducted in a cardiovascular stress laboratory and a rehabilitation research laboratory.Ambulatory people at least 6 months poststroke participated.Both groups trained 25 minutes, 3 times per week, for 4 weeks. The HIT strategy involved 30-second bursts at maximum-tolerated treadmill speed alternated with 30- to 60-second rest periods. The MCT strategy involved continuous treadmill walking at 45% to 50% of heart rate reserve.Measurements included recruitment and attendance statistics, qualitative HIT acceptability, adverse events, and the following blinded outcome variables: peak oxygen uptake, ventilatory threshold, metabolic cost of gait, fractional utilization, fastest treadmill speed, 10-Meter Walk Test, and Six-Minute Walk Test.During the 8-month recruitment period, 26 participants consented to participate. Eighteen participants were enrolled and randomly assigned to either the HIT group (n=13) or the MCT group (n=5). Eleven out of the 13 HIT group participants attended all sessions. Participants reported that HIT was acceptable and no serious adverse events occurred. Standardized effect size estimates between groups were moderate to very large for most outcome measures. Only 30% of treadmill speed gains in the HIT group translated into overground gait speed improvement.The study was not designed to definitively test safety or efficacy.Although further protocol optimization is needed to improve overground translation of treadmill gains, a definitive RCT comparing HIT and MCT appears to be feasible and warranted.

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A multicenter study on the effect of continuous hemodiafiltration intensity on antibiotic pharmacokinetics.

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A multicenter study on the effect of continuous hemodiafiltration intensity on antibiotic pharmacokinetics.

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