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

Sponsor

Centre Hospitalier de Valenciennes (Other)

Overall Status

Recruiting

CT.gov ID

NCT03897582

Collaborator

Centre Hospitalier de Lens (Other), Centre Hospitalier de Bethune (Other), University Hospital, Lille (Other), General Hospital of Douai (Other), Centre hospitalier de Boulogne (Other)

Enrollment

Location

51.2

Anticipated Duration (Months)

1.3

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Beta-lactam Continuous Renal Replacement Therapy Pneumonia Antibiotic

Detailed Description

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.

Study Design

Study Type:

Observational

Anticipated Enrollment :

65 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Beta-Lactams Dosing In Pneumonia in ICU in Patients Treated by Continuous Renal Replacement Therapy

Actual Study Start Date :

Feb 22, 2019

Anticipated Primary Completion Date :

May 31, 2023

Anticipated Study Completion Date :

May 31, 2023

Outcome Measures

Primary Outcome Measures

Percentage of beta-lactams concentrations above plasma therapeutic levels [Day 3 after start of antibiotic and continuous veino-veinous hemodialysis]
We aimed to obtain concentrations over 5 MIC (Minimum inhibitory concentration) for at least 80% of patients.

Secondary Outcome Measures

Distribution of steady state beta-lactam concentrations and their variability [Day 3 after start of antibiotic and continuous veino-veinous hemodialysis]
Description of beta-lactam concentration
Incidence of neurotoxicity [Day 7 after start of antibiotic and continuous veino-veinous hemodialysis]
Percentage of neurotoxicity
Trends in beta-lactam concentrations between 2 days [At Day 1 and Day 2]
Comparaison between 24 hours and 48 hours samples
Clinical response observed when beta-lactam concentrations achieved 5 MIC [At Day 28 and day 90]
Survival at Day 28 and Day 90

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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