Beta-Lactams Dosing In Pneumonia in ICU in Patients Treated by Continuous Renal Replacement Therapy: the BLIPIC Study

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 \< 36°C with no other explanation ; leukopenia \< 4 G/L ou leukocytosis \> 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) ou 6 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) ou 1g (\> 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