title: Alveolar and serum concentrations of imipenem in two lung transplant recipients supported with extracorporeal membrane oxygenation.
abstract: Venovenous extracorporeal membrane oxygenation (ECMO) is increasingly used in patients with respiratory failure who fail conventional treatment. Postoperative pneumonia is the most common infection after lung transplantation (40%). Imipenem is frequently used for empirical treatment of nosocomial pneumonia in the intensive care unit. Nevertheless, few data are available on the impact of ECMO on pharmacokinetics, and no data on imipenem dosing during ECMO. Currently, no guidelines exist for antibiotic dosing during ECMO support. We report the cases of 2 patients supported with venovenous ECMO for refractory acute respiratory distress syndrome following single lung transplantation for pulmonary fibrosis, treated empirically with 1 g of imipenem intravenously every 6 h. Enterobacter cloacae was isolated from the respiratory sample of Patient 1 and Klebsiella pneumoniae was isolated from the respiratory sample of Patient 2. Minimum inhibitory concentrations of the 2 isolated strains were 0.125 and 0.25 mg/L, respectively. Both patients were still alive on day 28. This is the first report, to our knowledge, of imipenem concentrations in lung transplantation patients supported with ECMO. This study confirms high variability in imipenem trough concentrations in patients on ECMO and with preserved renal function. An elevated dosing regimen (4 g/24 h) is more likely to optimize drug exposure, and therapeutic drug monitoring is recommended, where available. Population pharmacokinetic studies are indicated to develop evidence-based dosing guidelines for ECMO patients.
authors.affiliation: Département d'Anesthésie-Réanimation, AP-HP, Hôpital Bichat, Paris, France; Sorbonne Paris Cité, Univiversité Paris Diderot, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Welsch
authors.forename: P
authors.initials: P
authors.lastname: Augustin
authors.forename: J
authors.initials: J
authors.lastname: Allyn
authors.forename: L
authors.initials: L
authors.lastname: Massias
authors.forename: P
authors.initials: P
authors.lastname: Montravers
authors.forename: N
authors.initials: N
authors.lastname: Allou
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003404:Creatinine / Q000097:blood; D003428:Cross Infection; D015199:Extracorporeal Membrane Oxygenation; D006801:Humans; D015378:Imipenem / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016040:Lung Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D012128:Respiratory Distress Syndrome / Q000628:therapy*; D012131:Respiratory Insufficiency / Q000628:therapy*; D066027:Transplant Recipients
chemical_list: D000900:Anti-Bacterial Agents; D015378:Imipenem; D003404:Creatinine
keywords: extracorporeal membrane oxygenation; imipenem pharmacokinetics; lung transplantation