Abstract
Optimal dosing of β-lactam antibiotics in critically ill patients is a challenge given the unpredictable pharmacokinetic profile of this patient population. Several studies have shown intermittent dosing to often yield inadequate drug concentrations. Continuous dosing is an attractive alternative from a pharmacodynamic point of view. This study evaluated whether, during continuous dosing, piperacillin concentrations reached and maintained a pre-defined target in critically ill patients. Adult patients treated with piperacillin by continuous dosing in the intensive care unit of a university medical centre in The Netherlands were prospectively studied. Total and unbound piperacillin concentrations drawn at fixed time points throughout the entire treatment course were determined by liquid chromatography-tandem mass spectrometry. A pharmacokinetic combined target of a piperacillin concentration ≥80 mg/L, reached within 1 h of starting study treatment AND maintained throughout the treatment course, was set. Eighteen patients were analysed. The median duration of monitored piperacillin treatment was 60 h (interquartile range, 33-96 h). Of the 18 patients, 5 (27.8 %) reached the combined target; 15 (83.3%) reached and maintained a less strict target of >16 mg/L. In this patient cohort, this dosing schedule was insufficient to reach the pre-defined target. Depending on which target is to be met, a larger initial cumulative dose is desirable, combined with therapeutic drug monitoring.
Original language | English |
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Pages (from-to) | 68-73 |
Number of pages | 6 |
Journal | International journal of antimicrobial agents |
Volume | 50 |
Issue number | 1 |
Early online date | 10-May-2017 |
DOIs | |
Publication status | Published - Jul-2017 |
Keywords
- EFFICACY
- PHARMACODYNAMICS
- INTENSIVE-CARE-UNIT
- CONTINUOUS VENOVENOUS HEMOFILTRATION
- ILL PATIENTS
- CONTINUOUS-INFUSION
- SEVERE SEPSIS
- SEPTIC SHOCK
- PHARMACOKINETICS
- TAZOBACTAM
- beta-Lactam
- Critical care
- Continuous dosing
- Piperacillin