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

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

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.

Study Overview

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

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 65

Contacts and Locations

• Study Contact: Name: Fabien Lambiotte, MD; Phone Number: 40258 + 33 3 27 14 33 33; Email: lambiotte-f@ch-valenciennes.fr
• Study Contact Backup: Name: Justine Lemtiri, Pharm D; Phone Number: 49732 + 33 3 27 14 33 33; Email: lemtiri-j@ch-valenciennes.fr

Study Locations

• France
  • Nord
    • Valenciennes, Nord, France, 59300
      • Recruiting
      • Centre Hospitalier de Valenciennes
      • Contact: Elodie Matusik; Phone Number: + 33 6 37 94 22 60; Email: elodie.matusik@gmail.com
      • Contact: Hanane Fodil; Phone Number: + 33 3 27 14 06 65; Email: fodil-h@ch-valenciennes.fr
      • Sub-Investigator: Guillaume Brunin, MD
      • Sub-Investigator: Nicolas Van Grunderbeeck, MD
      • Sub-Investigator: Christophe VINSONNEAU, MD
      • Sub-Investigator: Geneviève BARJON, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Adults with pneumonia in ICU treated with intraveinous beta-lactams and CVVHD

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Centre Hospitalier de Valenciennes
• Collaborators: University Hospital, Lille; Centre Hospitalier de Bethune; Centre Hospitalier de Lens; General Hospital of Douai; Centre hospitalier de Boulogne
• Investigators: Study Chair: Fabien Lambiotte, MD, Centre Hospitalier de Valenciennes

Publications and helpful links

Helpful Links

• SFAR, SFPT, Recommandations de Pratiques Professionnelles, Optimisation du traitement par bêta-lactamines chez le patient de soins critiques 2018.

Study record dates

Study Major Dates

• Study Start (Actual): February 22, 2019
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): May 31, 2026

Study Registration Dates

• First Submitted: March 7, 2019
• First Submitted That Met QC Criteria: March 29, 2019
• First Posted (Actual): April 1, 2019

Study Record Updates

• Last Update Posted (Estimated): February 2, 2024
• Last Update Submitted That Met QC Criteria: February 1, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: meropenem; Therapeutic Drug Monitoring; citrate; amoxicillin; piperacillin-tazobactam; TDM; imipenem; ceftazidime; amoxicillin-clavulanic acid; cefotaxime; cefepime; multifiltrate; CVVHD; extended and continuous infusion
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Pneumonia
• Other Study ID Numbers: 2018-05

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No