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.
Pharmacokinetic parameters can be significantly altered for both extracorporeal life support (ECLS) and continuous renal replacement therapy (CRRT). This case report describes the pharmacokinetics of continuousinfusion meropenem in a patient on ECLS with concurrent CRRT. A 2.8-kg, 10-day-old, full-term neonate born via spontaneous vaginal delivery presented with hypothermia, lethargy, and a ~500-g weight loss from birth. She progressed to respiratory failure on hospital day 2 (HD 2) and developed sepsis, disseminated intravascular coagulation, and liver failure as a result of disseminated adenoviral infection. By HD 6, acute kidney injury was evident, with progressive fluid overload >1500 mL (+) for the admission. On HD 6 venoarterial ECLS was instituted for lung protection and fluid removal. On HD 7 she was initiated on CRRT. On HD 12, a blood culture returned positive and subsequently grew Pseudomonas aeruginosa with a minimum inhibitory concentration (MIC) for meropenem of 0.25 mg/L. She was started on vancomycin, meropenem, and amikacin. A meropenem bolus of 40 mg/kg was given, followed by a continuous infusion of 10 mg/kg/hr (240 mg/kg/day). On HD 15 (ECLS day 9) a meropenem serum concentration of 21 mcg/mL was obtained, corresponding to a clearance of 7.9 mL/kg/min. Repeat cultures from HDs 13 to 15 (ECLS days 7-9) were sterile. This meropenem regimen was successful in providing a target attainment of 100% for serum concentrations above the MIC for ≥40% of the dosing interval and was associated with a sterilization of blood in this complex patient on concurrent ECLS and CRRT circuits.
Neither guidelines nor best practices for the treatment of external ventricular drain (EVD) and ventriculoperitoneal shunt infections exist. An antimicrobial regimen with a broad spectrum of activity and adequate cerebrospinal fluid (CSF) penetration is vital in the management of both EVD and ventriculoperitoneal infections. In this case report, we describe the pharmacokinetics of continuous-infusion meropenem for a 2-year-old girl with Serratia marcescens ventriculitis. A right frontal EVD was placed for the management of a posterior fossa mass with hydrocephalus and intraventricular hemorrhage. On hospital day 6, CSF specimens were cultured, which identified a pan-sensitive Serratia marcescens with an initial cefotaxime minimum inhibitory concentration of 1 μg/ml or less. The patient was treated with cefotaxime monotherapy from hospital days 6 to 17, during which her CSF cultures and Gram's stain remained positive. On hospital day 26, Serratia marcescens was noted to be resistant to cefotaxime (minimum inhibitory concentration > 16 μg/ml), and the antimicrobial regimen was ultimately changed to meropenem and amikacin. Meropenem was dosed at 40 mg/kg/dose intravenously every 6 hours, infused over 30 minutes, during which, simultaneous serum and CSF meropenem levels were measured. Meropenem serum and CSF levels were measured at 2 and 4 hours from the end of the infusion with the intent to perform a pharmacokinetic/pharmacodynamic analysis. The resulting serum meropenem levels were 12 μg/ml at 2 hours and "undetectable" at 4 hours, with CSF levels of 1 and 0.5 μg/ml at 2 and 4 hours, respectively. On hospital day 27, the meropenem regimen was changed to a continuous infusion of 200 mg/kg/day, with repeat serum and CSF meropenem levels measured on hospital day 33. The serum and CSF levels were noted to be 13 and 0.5 μg/ml, respectively. The serum level of 13 μg/ml corresponds to an estimated meropenem clearance from the serum of 10.2 ml/kg/minute. Repeat meropenem levels from the serum and CSF on hospital day 37 were 15 and 0.5 μg/ml, respectively. After instituting the continuous-infusion meropenem regimen, only three positive CSF Gram's stains were noted, with the CSF cultures remaining negative. The continuous-infusion dosing regimen allowed for 100% probability of target attainment in the serum and CSF and a successful clinical outcome.
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