Variability of antibiotic concentrations in critically ill patients receiving continuous renal replacement therapy: A multicentre pharmacokinetic study

Roberts, Darren M., Roberts, Jason A., Roberts, Michael S., Liu, Xin, Nair, Priya, Cole, Louise, Lipman, Jeffrey, Bellomo, Rinaldo and on behalf of the RENAL Replacement Therapy Study Investigators (2012) Variability of antibiotic concentrations in critically ill patients receiving continuous renal replacement therapy: A multicentre pharmacokinetic study. Critical Care Medicine, 40 5: 1523-1528. doi:10.1097/CCM.0b013e318241e553


Author Roberts, Darren M.
Roberts, Jason A.
Roberts, Michael S.
Liu, Xin
Nair, Priya
Cole, Louise
Lipman, Jeffrey
Bellomo, Rinaldo
on behalf of the RENAL Replacement Therapy Study Investigators
Total Author Count Override 8
Title Variability of antibiotic concentrations in critically ill patients receiving continuous renal replacement therapy: A multicentre pharmacokinetic study
Journal name Critical Care Medicine   Check publisher's open access policy
ISSN 0090-3493
1530-0293
Publication date 2012-05
Sub-type Article (original research)
DOI 10.1097/CCM.0b013e318241e553
Volume 40
Issue 5
Start page 1523
End page 1528
Total pages 6
Place of publication Baltimore MD, United States
Publisher Lippincott Williams & Wilkins
Collection year 2013
Language eng
Formatted abstract
Objectives: In critically ill patients receiving continuous renal replacement therapy, we aimed to assess the variability of antibiotic trough concentrations, the influence of effluent flow rates on such concentrations, and the incidence of suboptimal antibiotic dosage.

Design: Prospective, observational, multicenter, pharmacokinetic study.

Setting: Four tertiary intensive care units within the multicenter RENAL randomized controlled trial of continuous renal replacement therapy intensity.

Patients: Twenty-four critically ill adult patients with acute kidney injury receiving ciprofloxacin, meropenem, piperacillin/tazobactam, or vancomycin during continuous renal replacement therapy.

Interventions: We obtained trough blood samples and measured antibiotic concentrations.

Measurements and Main Results:
We obtained data from 40 dosing intervals and observed wide variability in trough concentrations (6.7-fold for meropenem, 3.8-fold for piperacillin, 10.5-fold for tazobactam, 1.9-fold for vancomycin, and 3.9-fold for ciprofloxacin). The median (interquartile range) trough concentrations (mg/L) for meropenem was 12.1 (7.8–18.4), 105.0 (74.4–204.0)/3.8 (3.4–21.8) for piperacillin/tazobactam, 12.0 (9.8–16.0) for vancomycin, and 3.7 (3.0–5.6) for ciprofloxacin. Overall, 15% of dosing intervals did not meet predetermined minimum therapeutic target concentrations, 40% did not achieve the higher target concentration, and, during 10% of dosing intervals, antibiotic concentrations were excessive. No difference, however, was found between patients on the basis of the intensity of continuous renal replacement therapy; this effect may have been obscured by differences in dosing regimens, time off the filter, or altered pharmacokinetics.

Conclusions: There is significant variability in antibiotic trough concentrations in critically ill patients receiving continuous renal replacement therapy, which did not only appear to be influenced by effluent flow rate. Here, empirical dosing of antibiotics failed to achieve the target trough antibiotic concentration during 25% of the dosing intervals.

Keyword Antibiotic
Critically ill patient
Dialysis
Pharmacodynamics
Pharmacokinetics
Therapeutic drug monitoring
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Medicine Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 71 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 80 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Mon, 28 May 2012, 23:40:10 EST by System User on behalf of School of Medicine