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


METHODS
Prospective, open-label study.


METHODS
An intensive care unit and research ward in a university hospital.


METHODS
Ten adult patients with severe nosocomial bacterial pneumonia on mechanical ventilation.


METHODS
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.


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.


CONCLUSIONS
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.
Boselli
Emmanuel
E
Department of Anesthesiology and Intensive Care, Hôtel-Dieu, 1 Place de l'Hôpital, 69288 Lyon Cedex 02, France. emmanuel.boselli@chu-lyon.fr
Breilh
Dominique
D
Cannesson
Maxime
M
Xuereb
Fabien
F
Rimmelé
Thomas
T
Chassard
Dominique
D
Saux
Marie-Claude
MC
Allaouchiche
Bernard
B
D003428:Cross Infection / Q000097:blood / Q000188:drug therapy*; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D006801:Humans; D007362:Intensive Care Units; D008168:Lung / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010397:Penicillanic Acid / Q000031:analogs & derivatives / Q000097:blood / Q000627:therapeutic use*; D010878:Piperacillin / Q000097:blood / Q000627:therapeutic use*; D000077725:Piperacillin, Tazobactam Drug Combination; D018410:Pneumonia, Bacterial / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D011446:Prospective Studies; D012121:Respiration, Artificial / Q000009:adverse effects*
D000077725:Piperacillin, Tazobactam Drug Combination; D010397:Penicillanic Acid; D010878:Piperacillin