Pharmacokinetics of an extended 4-hour infusion of piperacillin-tazobactam in critically ill patients undergoing continuous renal replacement therapy.

Abstract

STUDY 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).

DESIGN:

Prospective, observational, pharmacokinetic study.

SETTING:

Intensive care unit of a tertiary care hospital in Montréal, Canada.

PATIENTS:

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.

INTERVENTION:

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.

MEASUREMENTS AND MAIN 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: Don-Kelena Awissi, Annie Beauchamp, Elisabeth Hébert, Viviane Lavigne, Danya Lucia Munoz, Geneviève Lebrun, Michel Savoie, Mylène Fagnan, Julie Amyot, Nicolas Tétreault, Robert Robitaille, France Varin, Christian Lavallée, Vincent Pichette, Martine Leblanc
• Journal: Pharmacotherapy (Pharmacotherapy) Vol. 35 Issue 6 Pg. 600-7 (Jun 2015) ISSN: 1875-9114 [Electronic] United States
• PMID: 26095008 (Publication Type: Journal Article, Observational Study)
• Copyright: © 2015 Pharmacotherapy Publications, Inc.

Chemical References

• Anti-Bacterial Agents
• Piperacillin, Tazobactam Drug Combination
• Penicillanic Acid
• Piperacillin

Topics

• Aged
• Anti-Bacterial Agents (pharmacokinetics)
• Critical Illness
• Female
• Hemodiafiltration
• Humans
• Infusions, Intravenous
• Male
• Microbial Sensitivity Tests
• Middle Aged
• Penicillanic Acid (analogs & derivatives, pharmacokinetics)
• Piperacillin (pharmacokinetics)
• Piperacillin, Tazobactam Drug Combination
• Prospective Studies
• Pseudomonas Infections (prevention & control)
• Pseudomonas aeruginosa (drug effects)
• Tertiary Care Centers