title: β-Lactam pharmacokinetics during extracorporeal membrane oxygenation therapy: A case-control study.
abstract: Most adult patients receiving extracorporeal membrane oxygenation (ECMO) require antibiotic therapy, however the pharmacokinetics of β-lactams have not been well studied in these conditions. In this study, data from all patients receiving ECMO support and meropenem (MEM) or piperacillin/tazobactam (TZP) were reviewed. Drug concentrations were measured 2h after the start of a 30-min infusion and just before the subsequent dose. Therapeutic drug monitoring (TDM) results in ECMO patients were matched with those in non-ECMO patients for (i) drug regimen, (ii) renal function, (iii) total body weight, (iv) severity of organ dysfunction and (v) age. Drug concentrations were considered adequate if they remained 4-8× the clinical MIC breakpoint for Pseudomonas aeruginosa for 50% (TZP) or 40% (MEM) of the dosing interval. A total of 41 TDM results (27 MEM; 14 TZP) were obtained in 26 ECMO patients, with 41 matched controls. There were no significant differences in serum concentrations or pharmacokinetic parameters between ECMO and non-ECMO patients, including Vd [0.38 (0.27-0.68) vs. 0.46 (0.33-0.79)L/kg; P=0.37], half-life [2.6 (1.8-4.4) vs. 2.9 (1.7-3.7)h; P=0.96] and clearance [132 (66-200) vs. 141 (93-197)mL/min; P=0.52]. The proportion of insufficient (13/41 vs. 12/41), adequate (15/41 vs. 19/41) and excessive (13/41 vs. 10/41) drug concentrations was similar in ECMO and non-ECMO patients. Achievement of target concentrations of these β-lactams was poor in ECMO and non-ECMO patients. The influence of ECMO on MEM and TZP pharmacokinetics does not appear to be significant.
authors.affiliation: Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles, Route de Lennik 808, 1070 Brussels, Belgium.
authors.forename: Katia
authors.initials: K
authors.lastname: Donadello
authors.affiliation: Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles, Route de Lennik 808, 1070 Brussels, Belgium.
authors.forename: Elio
authors.initials: E
authors.lastname: Antonucci
authors.affiliation: Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles, Route de Lennik 808, 1070 Brussels, Belgium.
authors.forename: Stefano
authors.initials: S
authors.lastname: Cristallini
authors.affiliation: Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, QLD, Australia; Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Roberts
authors.affiliation: Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles, Route de Lennik 808, 1070 Brussels, Belgium.
authors.forename: Marjorie
authors.initials: M
authors.lastname: Beumier
authors.affiliation: Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles, Route de Lennik 808, 1070 Brussels, Belgium.
authors.forename: Sabino
authors.initials: S
authors.lastname: Scolletta
authors.affiliation: Department of Infectious Diseases, Erasme Hospital, Université Libre de Bruxelles, Route de Lennik 808, 1070 Brussels, Belgium.
authors.forename: Frédérique
authors.initials: F
authors.lastname: Jacobs
authors.affiliation: Department of Thoracic Surgery, Erasme Hospital, Université Libre de Bruxelles, Route de Lennik 808, 1070 Brussels, Belgium.
authors.forename: Benoit
authors.initials: B
authors.lastname: Rondelet
authors.affiliation: Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles, Route de Lennik 808, 1070 Brussels, Belgium.
authors.forename: Daniel
authors.initials: D
authors.lastname: de Backer
authors.affiliation: Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles, Route de Lennik 808, 1070 Brussels, Belgium.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Vincent
authors.affiliation: Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles, Route de Lennik 808, 1070 Brussels, Belgium. Electronic address: ftaccone@ulb.ac.be.
authors.forename: Fabio Silvio
authors.initials: FS
authors.lastname: Taccone
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016022:Case-Control Studies; D015199:Extracorporeal Membrane Oxygenation; D005260:Female; D006801:Humans; D008297:Male; D000077731:Meropenem; D008875:Middle Aged; D010397:Penicillanic Acid / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000627:therapeutic use; D010878:Piperacillin / Q000493:pharmacokinetics / Q000627:therapeutic use; D000077725:Piperacillin, Tazobactam Drug Combination; D011552:Pseudomonas Infections / Q000188:drug therapy; D018805:Sepsis / Q000188:drug therapy* / Q000382:microbiology; D044967:Serum / Q000737:chemistry; D013845:Thienamycins / Q000493:pharmacokinetics / Q000627:therapeutic use; D016896:Treatment Outcome; D047090:beta-Lactams / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D013845:Thienamycins; D047090:beta-Lactams; D000077725:Piperacillin, Tazobactam Drug Combination; D010397:Penicillanic Acid; D000077731:Meropenem; D010878:Piperacillin
keywords: Antibiotic; ECMO; Extracorporeal membrane oxygenation; ICU; Pharmacokinetics; Sepsis