beta-lactams dosing in pneumonia in icu in patients treated by continuous renal replacement therapy: the blipic study

Conditions: Beta-lactam; Continuous Renal Replacement Therapy; Pneumonia; Antibiotic

Summary: pneumonia are the most frequent infections in icu. little is known about beta-lactam doses necessary for this infection for patients treated with continuous veino-veinous hemodialysis. the pharmacokinetic variability expose to over and underdosage leading to toxicity or therapeutic failure. the aim of this study is to define if beta-lactams doses used in pneumonia for patients with acute kidney injury treated with our hemodialysis conditions lead to beta-lactam therapeutic plasma levels.

pneumonia are the most frequent infections in icu. little is known about beta-lactam doses necessary for this infection for patients treated with continuous veino-veinous hemodialysis. the pharmacokinetic variability expose to over and underdosage leading to toxicity or therapeutic failure. the aim of this study is to define if beta-lactams doses used in pneumonia for patients with acute kidney injury treated with our hemodialysis conditions lead to beta-lactam therapeutic plasma levels. this prospective observational multicenter study will include all patients with pneumonia treated by beta-lactam and continuous veino-veinous hemodialysis in 5 icu. blood sampling will be done at assumed pharmacokinetic steady state. protocol sample concentrations of beta-lactams immediately prior to re-dosing, after 24 hours of association of intraveinous beta-lactam and continuous veino-veinous hemodialysis. another sample will be done after 48 hours. the icu measured bacterial mics routinely when the pathogen will be determined. surveyed icus will adopt sfm-eucast breakpoints for the targeted (or suspected) bacteria to determine pharmacokinetic/pharmacodynamic targets when a mesured mic (minimum inhibitory concentration) is not available. local hospital antibiogram data can also be used to describe likely pathogen susceptibility. target attainment is defined as 100% ft\> 5 mic. due to the long delay to receive therapeutic drug monitoring results, doses could not be ajusted. factors which could cause concentrations variations will be registered. when neurotoxicity is suspected, a sample will be realized to know beta-lactam concentration and the adverse event will be notified.

Eligibility criteria:
inclusion criteria: * aged ≥ 18 years * receiving intraveinous beta-lactam : amoxicillin, amoxicillin-clavulanic acid, piperacillin-tazobactam, cefotaxime, ceftazidime, cefepime, meropenem, imipenem * with aki defined as any of the following, and treated with multifiltrate ci-ca cvvhd 1000® kit with a dialysis dose of 25 ml/kg/h : * increase in creatininemia ≥ 0.3 mg/dl (≥ 26.5 µmol/l) within 48 hours * increase in creatininemia ≥ 1.5 times baseline, which is known or presumed to have occurred within the prior 7 days * urine volume \< 0.5 ml/kg/h for 6 hours * hospitalized in icu * presence of a catheter to facilitate sample collection * with pneumonia defined as any of the following : * chest x-ray pneumonia : opacities, new or progressive infiltrates * and at least one of the following : hyperthermia \> 38°c or hypothermia \ 12g/l * and at least one of the following : new onset purulent sputum or change in sputum character, new onset or worsening cough or dyspnea or tachypnea, rales or bronchial breathing, lower oxygen saturation/hypoxemia or increase of oxygen needs or respiratory assistance * treated within 24 hours by citrate hemodialysis and beta-lactam respecting dose and administration conditions of the study : * amoxicillin : loading dose followed immediately by 2g by extended infusion for 4 hours every 8 hours * amoxicillin-clavulanic acid : 2g every 8 hours by intermittent bolus * piperacillin-tazobactam: loading dose followed immediately by 4g/0.5g by continuous infusion every 8 hours (\ 80 kg) * cefotaxime: loading dose followed immediately by 2g by continuous infusion every 8 hours ceftazidime : loading dose followed immediately by 2g by continuous infusion every 8 hours * cefepime: loading dose followed immediately by 2g by continuous infusion every 8 hours * meropenem : loading dose followed immediately by 2g (\> 60 kg) ou 1,33g (\< 60 kg) by extended infusion for 4 hours every 8 hours * imipenem : loading dose followed immediately by 750 mg (\ 80 kg) by extended infusion for 4 hours every 6 hours in case of extrem weight, dose will be on investigator's discretion but administration conditions have be to respected. * no objection has been obtained from the patient or their legally authorised representative exclusion criteria: * aged \< 18 years * ecmo * cystic fibrosis * burn victim * pregnant woman * any rapidly-progressing disease or immediately life-threatening illness * objection from the patients or their legally authorised representative * no social security scheme * interruption of antibiotic before samples * patient in prison

Keywords: amoxicillin amoxicillin-clavulanic acid piperacillin-tazobactam cefotaxime ceftazidime cefepime meropenem imipenem multifiltrate citrate cvvhd extended and continuous infusion tdm therapeutic drug monitoring