Optimal dosing of piperacillin-tazobactam for the treatment of Pseudomonas aeruginosa infections: prolonged or continuous infusion?
OBJECTIVE
To compare conventional intermittent dosing regimens of piperacillin-tazobactam with prolonged and continuous infusions to determine the optimal dosing scheme against a local Pseudomonas aeruginosa population.


METHODS
Pharmacodynamic Monte Carlo simulation model.


METHODS
Microbiologic data from 470 consecutive non duplicate P. aeruginosa isolates collected from a single institution over 6 months in 2006.


METHODS
Five thousand simulated surgical patients and patients with neutropenia.


RESULTS
We simulated serum concentration-time profiles at steady state for several piperacillin-tazobactam dosing regimens, including intermittent, prolonged, and continuous infusions. The probability of achieving 50% free time above the MIC against 470 P. aeruginosa isolates was calculated. The cumulative fractions of response for the intermittent-infusion regimens were 74.7% (3.375 g every 6 hrs), 79.9% (4.5 g every 6 hrs), and 85.6% (3.375 g every 4 hrs). For prolonged infusion regimens, the cumulative fractions of response were 83.3% (3.375 g every 8 hrs, 4-hr infusion), 87.1% (4.5 g every 8 hrs, 4-hr infusion), and 89.6% (4.5 g every 6 hrs, 3-hr infusion). For continuous-infusion regimens, the cumulative fractions of response were 82.3% (10.125 g), 86.5% (13.5 g), 89.2% (18 g), 90.0% (20.25 g), and 90.6% (22.5 g).


CONCLUSIONS
Both prolonged- and continuous-infusion strategies improved the pharmacodynamics of piperacillin-tazobactam over those of traditional 30-minute intermittent-infusion regimens. Prolonged- and continuous infusion regimens that contained the same daily doses of piperacillin had similar likelihoods of bactericidal exposure. Thus, the selection of dosing strategy depends on the availability of intravenous access versus the convenience of once-daily administration.
Kim
Aryun
A
Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut 06102, USA.
Sutherland
Christina A
CA
Kuti
Joseph L
JL
Nicolau
David P
DP
D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D003198:Computer Simulation; D004334:Drug Administration Schedule; D024881:Drug Resistance, Bacterial; D006761:Hospitals; D006801:Humans; D007262:Infusions, Intravenous; D008826:Microbial Sensitivity Tests; D009010:Monte Carlo Method; D010397:Penicillanic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000627:therapeutic use; D010878:Piperacillin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D000077725:Piperacillin, Tazobactam Drug Combination; D011552:Pseudomonas Infections / Q000188:drug therapy*; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D013997:Time Factors
D000900:Anti-Bacterial Agents; D000077725:Piperacillin, Tazobactam Drug Combination; D010397:Penicillanic Acid; D010878:Piperacillin