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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
A multicenter study on the effect of continuous hemodiafiltration intensity on antibiotic pharmacokinetics
Critical Care, Volume 19, No. 1, Article 84, Year 2015
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Description
Introduction: 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. Methods: 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. Results: 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. Conclusions: 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. © Roberts et al.; licensee BioMed Central.
Authors & Co-Authors
Roberts, Darren M.
Australia, Brisbane
Royal Brisbane and Women's Hospital
Liu, Xin
Australia, Woolloongabba
Princess Alexandra Hospital
Australia, Adelaide
University of South Australia
Australia, Woodville South
The Queen Elizabeth Hospital, North Western Adelaide Health Service
Roberts, Jason A.
Australia, Brisbane
Royal Brisbane and Women's Hospital
Cole, Louise
Australia, Penrith
Nepean Hospital
Roberts, Michael S.
Australia, Woolloongabba
Princess Alexandra Hospital
Australia, Adelaide
University of South Australia
Australia, Woodville South
The Queen Elizabeth Hospital, North Western Adelaide Health Service
Lipman, Jeffrey
Australia, Brisbane
Royal Brisbane and Women's Hospital
Bellomo, Rinaldo
Australia, Melbourne
Austin Health
Statistics
Citations: 105
Authors: 7
Affiliations: 7
Identifiers
Doi:
10.1186/s13054-015-0818-8
ISSN:
13648535
Research Areas
Health System And Policy
Study Design
Cohort Study
Study Approach
Quantitative