Journal Article

Plasma concentrations might lead to overestimation of target site activity of piperacillin in patients with sepsis

M. A. Zeitlinger, B. M. Erovic, R. Sauermann, A. Georgopoulos, M. Müller and C. Joukhadar

in Journal of Antimicrobial Chemotherapy

Published on behalf of British Society for Antimicrobial Chemotherapy

Volume 56, issue 4, pages 703-708
Published in print October 2005 | ISSN: 0305-7453
Published online August 2005 | e-ISSN: 1460-2091 | DOI: http://dx.doi.org/10.1093/jac/dki284
Plasma concentrations might lead to overestimation of target site activity of piperacillin in patients with sepsis

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  • Medical Oncology
  • Critical Care

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Objectives: Pharmacokinetic (PK)/pharmacodynamic (PD) models have become increasingly important in optimizing antimicrobial therapy. This approach is highly recommended by regulatory authorities intending to force the evaluation of antimicrobial action at the site of infection.

Methods: Clinical isolates of Pseudomonas aeruginosa and Staphylococcus aureus with MICs of 4, 8 and 16 mg/L for piperacillin were used in an in vivo PK/in vitro PD model. Bacteria were exposed in vitro to the concentration-versus-time profiles of piperacillin in plasma and subcutaneous adipose tissue measured in vivo in septic patients. Samples were withdrawn at defined intervals and the numbers of bacteria per mL were counted and plotted against time.

Results: Piperacillin levels determined in plasma were able to effectively inhibit bacterial growth of all bacterial strains used in the present study (MIC ranged from 4–16 mg/L). In contrast, concentration-versus-time profiles of subcutaneous adipose tissue were effective in killing isolates with MICs of 4 and 8 mg/L only, while bacterial growth of S. aureus and P. aeruginosa with MICs of 16 mg/L was not inhibited.

Conclusions: Bacteria with MICs < 16 mg/L were effectively inhibited in subcutaneous adipose tissue in patients with sepsis. The prediction of microbiological outcome based on concentrations of piperacillin in plasma resulted in a marked overestimation of antimicrobial activity at the site of infection.

Keywords: pharmacokinetics; pharmacodynamics; PK/PD; β-lactams; in vitro

Journal Article.  3520 words.  Illustrated.

Subjects: Medical Oncology ; Critical Care

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