title: Pharmacokinetics of an extended 4-hour infusion of piperacillin-tazobactam in critically ill patients undergoing continuous renal replacement therapy.
abstract: OBJECTIVE
  To evaluate the pharmacokinetic and pharmacodynamic profiles of piperacillin-tazobactam administered as a 4-hour infusion in critically ill patients undergoing continuous renal replacement therapy (CRRT).
  
  
  METHODS
  Prospective, observational, pharmacokinetic study.
  
  
  METHODS
  Intensive care unit of a tertiary care hospital in Montréal, Canada.
  
  
  METHODS
  Twenty critically ill adults who were undergoing continuous venovenous hemodiafiltration and receiving a 4-hour infusion of piperacillin 4 g-tazobactam 0.5 g every 8 hours for a documented or suspected infection.
  
  
  METHODS
  Blood samples were collected every hour over an 8-hour dosing interval. Prefilter and postfilter blood samples, and effluent and urine samples were also collected.
  
  
  RESULTS
  The primary outcome was the proportion of patients who achieved an unbound piperacillin plasma concentration above a target minimum inhibitory concentration (MIC) of 64 mg/L (MIC that inhibits 90% of isolates for Pseudomonas aeruginosa) for at least 50% of the dosing interval; 18 (90%) of the 20 patients achieved this outcome. In all patients, the free piperacillin concentrations were above the Pseudomonas aeruginosa breakpoint of 16 mg/L for the entire time interval. Regarding piperacillin pharmacokinetic parameters, the median (interquartile range) minimum unbound plasma concentration was 65.15 mg/L (51.30-89.30), maximum unbound plasma concentration was 141.3 mg/L (116.75-173.90), sieving coefficient was 0.809 (0.738-0.938), total clearance was 65.82 ml/minute (53.79-102.87), and renal clearance was 0.16 ml/minute (0.05-3.04). The median CRRT dose was 32.0 ml/kg/h (25.0-39.8).
  
  
  CONCLUSIONS
  Administration of a 4-hour infusion of piperacillin-tazobactam was associated with a favorable pharmacodynamic profile in patients undergoing CRRT. Concentrations associated with maximal activity were attained in our patients.
authors.affiliation: Pharmacy Department, Hôpital Maisonneuve-Rosemont, Montreal, Quebec, Canada.
authors.forename: Don-Kelena
authors.initials: DK
authors.lastname: Awissi
authors.affiliation: Pharmacy Department, Hôpital Maisonneuve-Rosemont, Montreal, Quebec, Canada.
authors.forename: Annie
authors.initials: A
authors.lastname: Beauchamp
authors.affiliation: Pharmacy Department, Hôpital Maisonneuve-Rosemont, Montreal, Quebec, Canada.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Hébert
authors.affiliation: Pharmacy Department, Hôpital Maisonneuve-Rosemont, Montreal, Quebec, Canada.
authors.forename: Viviane
authors.initials: V
authors.lastname: Lavigne
authors.affiliation: Pharmacy Department, Hôpital Maisonneuve-Rosemont, Montreal, Quebec, Canada.
authors.forename: Danya Lucia
authors.initials: DL
authors.lastname: Munoz
authors.affiliation: Pharmacy Department, Hôpital Maisonneuve-Rosemont, Montreal, Quebec, Canada.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Lebrun
authors.affiliation: Pharmacy Department, Hôpital Maisonneuve-Rosemont, Montreal, Quebec, Canada.
authors.forename: Michel
authors.initials: M
authors.lastname: Savoie
authors.affiliation: Pharmacy Department, Hôpital Maisonneuve-Rosemont, Montreal, Quebec, Canada.
authors.forename: Mylène
authors.initials: M
authors.lastname: Fagnan
authors.affiliation: Biochemistry Department, Hôpital Maisonneuve-Rosemont, Montreal, Quebec, Canada.
authors.forename: Julie
authors.initials: J
authors.lastname: Amyot
authors.affiliation: Biochemistry Department, Hôpital Maisonneuve-Rosemont, Montreal, Quebec, Canada.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Tétreault
authors.affiliation: Biochemistry Department, Hôpital Maisonneuve-Rosemont, Montreal, Quebec, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Robitaille
authors.affiliation: Faculty of Pharmacy, Université de Montréal, Montreal, Quebec, Canada.
authors.forename: France
authors.initials: F
authors.lastname: Varin
authors.affiliation: Department of Infectious Diseases and Medical Microbioloy, Hôpital Maisonneuve-Rosemont, Montreal, Quebec, Canada.
authors.forename: Christian
authors.initials: C
authors.lastname: Lavallée
authors.affiliation: Department of Nephrology, Hôpital Maisonneuve-Rosemont, Montreal, Quebec, Canada.
authors.forename: Vincent
authors.initials: V
authors.lastname: Pichette
authors.affiliation: Department of Nephrology, Hôpital Maisonneuve-Rosemont, Montreal, Quebec, Canada.|Intensive Care Unit, Hôpital Maisonneuve-Rosemont, Montreal, Quebec, Canada.
authors.forename: Martine
authors.initials: M
authors.lastname: Leblanc
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D016638:Critical Illness; D005260:Female; D017583:Hemodiafiltration; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D010397:Penicillanic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D010878:Piperacillin / Q000493:pharmacokinetics; D000077725:Piperacillin, Tazobactam Drug Combination; D011446:Prospective Studies; D011552:Pseudomonas Infections / Q000517:prevention & control; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D062606:Tertiary Care Centers
chemical_list: D000900:Anti-Bacterial Agents; D000077725:Piperacillin, Tazobactam Drug Combination; D010397:Penicillanic Acid; D010878:Piperacillin
keywords: continuous renal replacement therapy; critical care; hemodiafiltration; pharmacokinetics; piperacillin-tazobactam; prolonged infusion