Antibiotic, Beta-lactam, Continuous Renal Replacement Therapy, Pneumonia
Conditions
Keywords
amoxicillin, amoxicillin-clavulanic acid, piperacillin-tazobactam, cefotaxime, ceftazidime, cefepime, meropenem, imipenem, multifiltrate, citrate, CVVHD, extended and continuous infusion, TDM, Therapeutic Drug Monitoring
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.
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.
Interventions
None listed
Sponsors
Centre Hospitalier de Lens
Centre Hospitalier de Bethune
University Hospital, Lille
General Hospital of Douai
Centre hospitalier de Boulogne
Centre Hospitalier de Valenciennes
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
France
Contacts
Primary ContactFabien Lambiotte, MD
Backup ContactJustine Lemtiri, Pharm D
Outcome results
None listed