Optimal piperacillin/tazobactam dosing against Pseudomonas aeruginosa: prolonged or continuous infusion?

Abstract number: 1733_869

Kim A., Sutherland C., Kuti J., Nicolau D.

Objectives: As a result of increasing resistance among Pseudomonas aeruginosa (PSA), alternative dosing strategies to optimise piperacillin/tazobactam (TZP) pharmacodynamics, such as prolonged (PI) and continuous infusion (CI), have been advocated; however, comparative data to aid in deciding which to use are sparse. Monte Carlo simulation was utilised to compare the bactericidal cumulative fraction of response (CFR) between PI and CI regimens against a local population of PSA.

Methods: TZP pharmacokinetics were extrapolated from a published population pharmacokinetic study in surgical and neutropenic patients. A 2-compartment model was used to calculate steady-state concentration time profiles for the piperacillin component of the following TZP dosages: 4.5 g q6h (30 minute infusion), 3.375 g q8h (4 h PI), 4.5 g q8h (4 h PI), 4.5 g q6h (3 h PI), 10.125 g CI, 13.5 g CI, 18 g CI, 20.25 g CI, and 22.5 g CI. A 5,000 Monte Carlo simulation with covariance matrix was conducted. Pharmacodynamic targets were 50% free time above the MIC (T>MIC) for the 30 minute infusion and PI regimens, and 100% free T>MIC for CI regimens. MICs for 416 consecutive nonduplicate PSA collected from our institution over a 6 month period during 2006 were tested via E-test.

Results: 92.3% of PSA were TZP susceptible; the MIC50 and MIC90 were 8 and 32 mg/mL, respectively. CFR was 79.6 (4.5 g q6h, 30 minute infusion), 83.1 (3.375 g q8h, 4 h PI), 86.9 (4.5 g q8h, 4 h PI), 89.6 (4.5 g q6h, 3 h PI), 82.0 (10.125 g CI), 86.3 (13.5 g CI), 89.2 (18 g CI), 90.0 (20.25 g CI), and 90.6 (22.5 g CI).

Conclusion: Both PI and CI dosing strategies improve the pharmacodynamics of TZP over that of standard infusion regimens; moreover, PI and CI regimens that contain the same daily piperacillin dose will have similar likelihood of bactericidal exposure. Thus, the choice of administration strategy depends on the convenience of once daily dosing versus line access availability. Finally, dosing regimens that contained greater than 18 g TZP daily did not appear to provide any meaningful additional exposure for this PSA population.

Session Details

Date: 31/03/2007
Time: 00:00-00:00
Session name: European Society of Clinical Microbiology and Infectious Diseases
Location: ICC, Munich, Germany
Presentation type:
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