Pharmacokinetic of Doripenem and Piperacillin/Tazobactam in More Than 120 kg Critically Ill Patients

Overweight patients are susceptible to develop acute complications when they are admitted in an Intensive Care Unit (ICU). Severe infection can be associated with cardiovascular failure ('shock") and is associated with 35-50% mortality. One of the key issue to cure infection is to administer antibiotics. However, under dosing antibiotic is one of the main reason that explain treatment failure. There are very few data concerning particularities of antibiotic dosing in critically ill, overweight, patients. The aim of the present study is to describe the pharmacokinetic of two main antibiotics (doripenem and piperacillin/Tazobactam) in both overweight and non overweight critically ill patients presenting a septic shock. The investigators hypothesis is that usual dose for those antibiotic may be accurate in non overweight patients but is not in overweight patients.

N=52 patients divided in 4*13 patients (13 per antibiotic and per group, overweight or non overweight). Overweight is defined by a weight over 120kg. Antibiotic chosen by the intensivist in charge of the case. Doripenem 1g/8h with a 4h IV infusion whatever the patient's weight. Piperacillin/Tazobactam 4g IV (1h) and then 16g/24h IV continuously whatever the patient's weight. Piperacillin/Tazobactam plasma dosage: after the first dose and then every 12h. Doripenem plasma dosage: after the first dose and then twice a day, at peak and residual value. Usual plasma and urine samples for urea, creatinine, electrolytes, platelets and bilirubin each 24h. Microbiology: bacterial identification and MIC measurement with E-test

This arm is composed of 26 no overweight patients, Antibiotic (Doripenem or Piperacillin/Tazobactam) is chosen by the intensivist in charge of the case: in 13 no overweight patients, Pipéracilline/tazobactam will be administered in 4g IV (1h) and then 16g/24h IV continuously. Piperacillin/Tazobactam plasma dosage: after the first dose and then every 12h. in 13 patients no overweight: doripénème will be administered in 1g/8h with a 4h IV infusion. Doripenem plasma dosage: after the first dose and then twice a day, at peak and residual value.

This arm is composed of 26 overweight patients, Antibiotic (Doripenem or Piperacillin/Tazobactam) is chosen by the intensivist in charge of the case: in 13 overweight patients, Pipéracilline/tazobactam will be administered in 4g IV (1h) and then 16g/24h IV continuously. Piperacillin/Tazobactam plasma dosage: after the first dose and then every 12h. in 13 patients overweight: doripénème will be administered in 1g/8h with a 4h IV infusion. Doripenem plasma dosage: after the first dose and then twice a day, at peak and residual value.

Inclusion Criteria: General: Patients in severe sepsis or septic shock defined by Bone criteria (proved or very suspected infection with organ impairment and/or need of vasopressive agent to keep a mean arterial pressure more than 65mmHg) Patient requiring a treatment by study's antibiotics Informed consent signed Patient must be affiliated or beneficiary of a social medical insurance Participation of patient to the trial must be noted in the medical file Specific to overweight patients: Weight > 120kg Specific to no overweight patients: Weight less than or equal to 120kg Exclusion Criteria: Pregnant women Under age patient minor Patient protected by law Known allergy to study's antibiotics