title: Pharmacokinetics of continuous-infusion meropenem in a pediatric patient receiving extracorporeal life support.
abstract: Meropenem, a broad-spectrum carbapenem, is commonly used for empirical and definitive therapy in the pediatric intensive care unit (ICU). Pharmacokinetic data to guide dosing in children, however, are limited to healthy volunteers or patients who are not in the ICU. Adult data demonstrate that pharmacokinetic parameters such as the volume of distribution and clearance can be significantly altered in individuals receiving extracorporeal membrane oxygenation (ECMO). Alterations in the volume of distribution and clearance of antimicrobials in patients with sepsis and septic shock have also been documented, and these patients have demonstrated lower than expected antimicrobial serum concentrations based on standard dosing regimens. Therefore, an understanding of the pharmacokinetic changes in critically ill children receiving ECMO is crucial to determining the most appropriate dose and dosing interval selection for any antimicrobial therapy. In this case report, we describe the pharmacokinetics of a continuous infusion of meropenem in a pediatric cardiac ICU patient who was receiving concurrent extracorporeal life support. The patient was an 8-month-old male infant who underwent a Glenn procedure and pulmonary artery reconstruction. Postoperatively, he required ECMO with a total run of 21 days. On day 11 of ECMO, a bronchoalveolar lavage was performed, and blood cultures from days 11 and 12 of ECMO grew Pseudomonas aeruginosa, with a meropenem minimum inhibitory concentration (MIC) of 0.5 μg/ml. On ECMO day 13, meropenem was initiated with a loading dose of 40 mg/kg and infused over 30 minutes, followed by a continuous infusion of 200 mg/kg/day. A meropenem serum concentration measured 8 hours after the start of the infusion was 46 μg/ml. Repeat levels were measured on days 3 and 9 of meropenem therapy and were 39 and 42 μg/ml, respectively. Repeat blood and respiratory cultures remained negative. This meropenem regimen (40-mg/kg bolus followed by a continuous infusion of 200 mg/kg/day) was successful in providing a target attainment of 100% for serum and lung concentrations above the MIC for at least 40% of the dosing interval and was associated with a successful clinical outcome.
authors.affiliation: St. Christopher's Hospital for Children, Philadelphia, Pennsylvania; Drexel University College of Medicine, Philadelphia, Pennsylvania; Alfred I. duPont Hospital for Children, Wilmington, Delaware.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Cies
authors.forename: Wayne S
authors.initials: WS
authors.lastname: Moore
authors.forename: Mindy J
authors.initials: MJ
authors.lastname: Dickerman
authors.forename: Christine
authors.initials: C
authors.lastname: Small
authors.forename: Dominick
authors.initials: D
authors.lastname: Carella
authors.forename: Arun
authors.initials: A
authors.lastname: Chopra
authors.forename: Jason
authors.initials: J
authors.lastname: Parker
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood*; D015199:Extracorporeal Membrane Oxygenation / Q000379:methods*; D006801:Humans; D007223:Infant; D007262:Infusions, Intravenous; D008021:Life Support Systems; D008297:Male; D000077731:Meropenem; D011552:Pseudomonas Infections / Q000097:blood / Q000188:drug therapy; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000302:isolation & purification; D013845:Thienamycins / Q000008:administration & dosage / Q000097:blood*
chemical_list: D000900:Anti-Bacterial Agents; D013845:Thienamycins; D000077731:Meropenem
keywords: ECMO; Meropenem; carbapenem; pediatric; pharmacodynamics; pharmacokinetic