Variability of antibiotic trough concentrations in critically ill patients receiving renal replacement therapy: A pragmatic, multi-national observational study
Refereed conference paper presented and published in conference proceedings

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Achieving appropriate blood antibiotic concentrations is important to optimise the treatment of sepsis and improve mortality. We tested the hypothesis that the prescription of renal replacement therapy (RRT), and antibiotics in ICU is highly variable, and resultant antibiotic blood concentrations are unlikely to consistently meet appropriate therapeutic targets.
Prospective, observational, multi-national, pharmacokinetic study in 26 intensive care units. Antibiotic dosing and RRT prescription were determined by individual unit protocols. Patient demographic, RRT and clinical data and trough antibiotic concentrations of meropenem, piperacillin-tazobactam, vancomycin, and linezolid were evaluated. Beta lactam therapeutic target concentrations were established; high (4xMIC) and low (1xMIC) for common gram-negative bacteria in ICU. Vancomycin target concentrations were; high (>=20 mg/L) and low (>=15 mg/L), according to current guidelines.
384 patients were enrolled from 26 ICUs. Patients received meropenem (n=187); piperacillin (n=160); tazobactam (n=101); vancomycin (n=60); and linezolid (n=6), providing 514 trough concentrations. Linezolid trough concentrations were not evaluated because of small numbers. We observed a wide variability in patient illness severity, antibiotic dosing regimens prescribed for all antibiotics, as well as in the modality and prescribing practices for RRT. A wide range of trough concentrations was observed (Figure 1). Trough concentrations failed to meet higher and lower therapeutic targets in 26%, 36%, 72%, and 4%, 4%, and 55% of patient samples for meropenem, piperacillin and vancomycin, respectively.
Current antibiotic dosing and RRT prescribing practices result in antibiotic concentrations that fail to meet therapeutic targets in many patients. Individualised antibiotic dosing, using algorithms derived from an understanding of PK and practice variability, supported by therapeutic drug monitoring, are needed to improve the adequacy and consistency of blood antibiotic concentrations in critically ill patients requiring RRT.
Acceptance Date16/12/2018
All Author(s) ListJoynt GM, Choi GYS, Roberts JA, Lipman J, Lee A, SMARRT study group
Name of Conference20th Congress of APACCM and ASM of HKSCCM 2018
Start Date of Conference15/12/2018
End Date of Conference16/12/2018
Place of ConferenceHong Kong
Country/Region of ConferenceHong Kong
Proceedings TitleCritical Care and Shock
Volume Number22
Issue Number1
Pages69 - 69
LanguagesEnglish-United States
KeywordsPharmacokinetics, antibiotic dosing, meropenem, piperacillin, vancomycin

Last updated on 2019-02-07 at 16:00