β-Lactam pharmacokinetics during extracorporeal membrane oxygenation therapy: A case-control study

Donadello, Katia;Antonucci, Elio;Cristallini, Stefano;Roberts, Jason A.;Taccone, Fabio Silvio;et.al.
(2015) International Journal of Antimicrobial Agents — Vol. 45, n° 3, p. 278-282 (2015)

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  • Donadello, Katia
    Author
  • Antonucci, Elio
    Author
  • Cristallini, Stefano
    Author
  • Roberts, Jason A.
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  • Taccone, Fabio Silvio
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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 2 h 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. © 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.
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Donadello, K., Antonucci, E., Cristallini, S., Roberts, J. A., Beumier, M., Scolletta, S., Jacobs, F., Rondelet, B., De Backer, D., Vincent, J.-L., & Taccone, F. S. (2015). β-Lactam pharmacokinetics during extracorporeal membrane oxygenation therapy: A case-control study. International Journal of Antimicrobial Agents, 45(3), 278-282. https://doi.org/10.1016/j.ijantimicag.2014.11.005 (Original work published 2015)