title: Does consistent piperacillin dosing result in consistent therapeutic concentrations in critically ill patients? A longitudinal study over an entire antibiotic course.
abstract: Piperacillin plasma concentrations are known to vary between critically ill patients. However, there are no comprehensive data on the variability of antibiotic concentrations within the same patient. The purpose of this study was to investigate the adequacy of dosing during an entire 7-day antibiotic course and to investigate the variability in antibiotic trough concentrations both between patients and within the same patient. Piperacillin trough concentrations were measured daily in critically ill patients with normal renal function. The drug assay was performed using UPLC-MS/MS. The pharmacokinetic/pharmacodynamic target was 100% fT>MIC of the Pseudomonas aeruginosa EUCAST breakpoint. Within- and between-patient variability were calculated as percent coefficient of variation (CV). Eleven patients treated for pneumonia were included in this nested prospective observational cohort study. The median (range) age was 67 (18-79) years, weight was 75 (57-90)kg and BMI was 23.5 (22.3-26.4). The median (range) creatinine clearance on Day 1 of antibiotic treatment was 102 (62-154)mL/min. Trough concentrations were variable, ranging from 4.9 mg/L to 98.0 mg/L. A median CV of 40% for within-patient variability and 57% for between-patient variability was found. Within-patient variability was inversely correlated with SOFA score (R = 0.65, P = 0.027) and APACHE II score on admission (R = 0.73, P = 0.009). In conclusion, piperacillin concentrations varied widely both between patients and within the same patient. Within-patient variability was inversely correlated with disease severity. Consistent dosing of piperacillin/tazobactam does not result in consistent piperacillin concentrations throughout the entire treatment period.
authors.affiliation: Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, De Pintelaan 185, Ghent 9000, Belgium; Department of Critical Care Medicine, Ghent University Hospital, De Pintelaan 185, Ghent 9000, Belgium. Electronic address: mieke.carlier@ugent.be.
authors.forename: Mieke
authors.initials: M
authors.lastname: Carlier
authors.affiliation: Department of Critical Care Medicine, Ghent University Hospital, De Pintelaan 185, Ghent 9000, Belgium.
authors.forename: Sofie
authors.initials: S
authors.lastname: Carrette
authors.affiliation: Department of Laboratory Medicine, Ghent University Hospital, De Pintelaan 185, Ghent 9000, Belgium.
authors.forename: Veronique
authors.initials: V
authors.lastname: Stove
authors.affiliation: Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, De Pintelaan 185, Ghent 9000, Belgium; Department of Laboratory Medicine, Ghent University Hospital, De Pintelaan 185, Ghent 9000, Belgium.
authors.forename: Alain G
authors.initials: AG
authors.lastname: Verstraete
authors.affiliation: Department of Critical Care Medicine, Ghent University Hospital, De Pintelaan 185, Ghent 9000, Belgium.
authors.forename: Jan J
authors.initials: JJ
authors.lastname: De Waele
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid; D015331:Cohort Studies; D003422:Critical Care / Q000379:methods; D016638:Critical Illness; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D010878:Piperacillin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D010949:Plasma / Q000737:chemistry*; D011446:Prospective Studies; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D053719:Tandem Mass Spectrometry; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D010878:Piperacillin
keywords: Biological variation; ICU; PK/PD; TDM; β-Lactams