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Steady-state plasma and intrapulmonary concentrations of piperacillin/tazobactam 4 g/0.5 g administered to critically ill patients with severe nosocomial pneumonia.

AbstractOBJECTIVE:
To determine the steady-state plasma and epithelial lining fluid (ELF) concentrations of piperacillin/tazobactam (P/T) administered to critically ill patients with severe bacterial pneumonia.
DESIGN:
Prospective, open-label study.
SETTING:
An intensive care unit and research ward in a university hospital.
PATIENTS:
Ten adult patients with severe nosocomial bacterial pneumonia on mechanical ventilation.
INTERVENTIONS:
All subjects received a 30-min intravenous infusion of P/T 4 g/0.5 g every 8 h. The steady-state plasma and ELF concentrations of P/T were determined by high-performance liquid chromatography.
MEASUREMENTS AND MAIN RESULTS:
The mean+/-SD steady-state plasma trough, peak, and intermediate concentrations were 8.5+/-4.6 microg/ml, 55.9+/-21.6 microg/ml, and 24.0+/-13.8 microg/ml for piperacillin, and 2.1+/-1.0 microg/ml, 4.8+/-2.1 microg/ml, and 2.4+/-1.2 microg/ml for tazobactam, respectively. The mean+/-SD steady-state intermediate ELF concentrations were 13.6+/-9.4 microg/ml for piperacillin and 2.1+/-1.1 microg/ml for tazobactam, respectively, showing a mean percentage penetration of piperacillin and tazobactam into ELF of 56.8% and 91.3 %, respectively, with a P/T ratio of 6.5:1.
CONCLUSION:
Our results show that during the treatment of severe nosocomial pneumonia, a regimen of P/T 4 g/0.5 g every 8 h might provide insufficient concentrations into lung tissue to exceed the MIC of many causative pathogens. This suggests that higher doses of P/T should be administered in order to maximize the antibiotic concentration at the site of infection, or that a second antimicrobial agent should be used in association.
AuthorsEmmanuel Boselli, Dominique Breilh, Maxime Cannesson, Fabien Xuereb, Thomas Rimmelé, Dominique Chassard, Marie-Claude Saux, Bernard Allaouchiche
JournalIntensive care medicine (Intensive Care Med) Vol. 30 Issue 5 Pg. 976-9 (May 2004) ISSN: 0342-4642 [Print] United States
PMID15057512 (Publication Type: Journal Article)
Chemical References
  • piperacillin, tazobactam drug combination
  • Penicillanic Acid
  • Piperacillin
Topics
  • Cross Infection (blood, drug therapy)
  • Epithelial Cells (metabolism)
  • Female
  • Humans
  • Intensive Care Units
  • Lung (metabolism)
  • Male
  • Middle Aged
  • Penicillanic Acid (analogs & derivatives, blood, therapeutic use)
  • Piperacillin (blood, therapeutic use)
  • Pneumonia, Bacterial (blood, drug therapy, etiology)
  • Prospective Studies
  • Respiration, Artificial (adverse effects)

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