Pharmacokinetics of Continuous Infusion Meropenem With Concurrent Extracorporeal Life Support and Continuous Renal Replacement Therapy: A Case Report.

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 continuous-infusion 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.

Therapeutic drug monitoring of continuous-infusion acylovir for disseminated herpes simplex virus infection in a neonate receiving concurrent extracorporeal life support and continuous renal replacement therapy.

Disseminated herpes simplex virus (HSV) infection in neonates represents a devastating entity that yields high mortality. Acyclovir is the primary antiviral agent used to treat life-threatening HSV infections in neonates; however, even though the agent has reduced morbidity overall from these infections, mortality with disseminated disease remains high. Currently, to our knowledge, no data exist regarding therapeutic drug monitoring of acyclovir in the setting of extracorporeal life support (ECLS) or continuous renal replacement therapy (CRRT) coupled with ECLS. We describe the case of a 14-day-old female with disseminated HSV-1 infection that progressed to fulminant hepatic and renal failure, necessitating the use of ECLS for hemodynamic support and CRRT as a treatment modality for hepatic and renal failure. The standard dosage of acyclovir 20 mg/kg/dose intravenously every 8 hours had been initiated, but after conversion to ECLS and CRRT, the patient's dosage was increased to 30 mg/kg/dose every 8 hours. After a repeat viral load remained unchanged from the initial viral load at 1 × 10(8)  copies/ml, the patient was transitioned from intermittent dosing to a continuous infusion of acyclovir added to the dialysate solution for CRRT at a concentration of 5.5 mg/L. To provide an optimal outcome, dosing was designed to maintain acyclovir plasma concentrations of at least 3 mg/L in order to maintain an acyclovir concentration of at least 1 mg/L in the cerebrospinal fluid. The patient's acyclovir serum concentrations measured at 24 and 72 hours after starting continuous-infusion acyclovir via the dialysate were 8.8 and 5.3 mg/L, respectively, allowing for a continuous serum concentration above 3 mg/L. Unfortunately, before a repeat viral load could be obtained to assess the efficacy of the continuous infusion acyclovir, the patient experienced an intracerebral hemorrhage as a complication related to ECLS after which technological support was withdrawn. This is the first report to describe the pharmacokinetics of continuous-infusion acyclovir in a neonate receiving ECLS with concurrent CRRT. These data suggest that adding acyclovir to the dialysate fluid during CRRT is effective in achieving therapeutic drug concentrations despite the complications of adding ECLS and CRRT circuits to a small patient.

Pharmacokinetics of continuous-infusion meropenem in a pediatric patient receiving extracorporeal life support.

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.