There has been increasing interest in incorporating β‐lactam precision dosing into routine clinical care, but robust population pharmacokinetic models in critically ill children are needed for these purposes. The objective of this study was to demonstrate the feasibility of an opportunistic sampling approach that utilizes scavenged residual blood for future pharmacokinetic studies of cefepime, meropenem, and piperacillin. We aimed to show that opportunistic samples would cover the full concentration‐versus‐time profiles and to evaluate stability of the antibiotics in whole blood and plasma to optimize future use of the opportunistic sampling approach. A prospective observational study was conducted in a single‐center pediatric intensive care unit, where pediatric patients administered at least 1 dose of cefepime, meropenem, or piperacillin/tazobactam and who had residual blood scavenged from samples obtained for routine clinical care were enrolled. A total of 138 samples from 22 pediatric patients were collected in a 2‐week period. For all 3 antibiotics, the samples collected covered the entire dosing intervals and were not clustered around specific times. There was high variability in the free concentrations and in the percentage of drug bound to protein. There was less than 15% degradation for meropenem or piperacillin when stored in whole blood or plasma at 4°C after 6 days. Cefepime degraded by more than 15% after 3 days. The opportunistic sampling approach is a powerful and feasible method to obtain sufficient samples to study the variability of drug concentrations and protein binding for future pharmacokinetic studies in the pediatric critical care population.
BackgroundLimited data exists regarding antivirals and extracorporeal membrane oxygenation (ECMO). We present a case of pharmacokinetics (PK) of ganciclovir in an immunocompromised patient with respiratory failure requiring veno-venous ECMO support without continuous renal replacement therapy (CRRT). A 6-year old with a stage IV rhabdoid tumor s/p autologous bone marrow transplant rescue after chemotherapy 80 days prior to illness, developed acute respiratory failure. Patient was started on cefepime, vancomycin, trimethoprim/sulfamethoxazole, ganciclovir and micafungin. On Day (D) 7 of ICU stay, ECMO initiated due to concerns for air leak syndrome. Bronchoalveolar lavage on D8 resulted positive for Pneumocystis and CMV by PCR. Prior to ECMO initiation, CMV levels were <500 IU/mL. After the initiation of ECMO, patient had up-trending CMV PCR that peaked at 139,000 IU/mL with concerns for antiviral resistance or ganciclovir underdosing (5 mg/kg/dose) on ECMO.MethodsPeak and random plasma levels to calculate AUC24 were drawn after concerns for under dosing on ICU D16/ECMO D9. Ganciclovir concentrations were determined by HPLC in the Special Chemistry Department at Cincinnati Children’s Hospital Medical Center. After dose adjustments on ICU D17/ECMO D10, repeat peak/random levels were obtained on ICU D19 after steady state was achieved.ResultsGanciclovir dosing of 5 mg/kg every 12 hours was subtherapeutic, both clinically and based upon PK analysis. 0.5 and 5 hours post-infusion levels were 5.47 and 0.76 μg/mL respectively with a calculated AUC24 to be 26 mg hour/L. After increasing the dose to 10 mg/kg every 12 hours, repeat levels at 1 and 5 hours were 4.53 and 1.48 μg/mL, respectively, achieving the AUC24 goal of 50 mg hour/L.ConclusionThis is the first case report of ganciclovir PK in either pediatric or adult ECMO populations. Standard recommended dosing of 5 mg/kg every 12 hours provided a low, subtherapeutic AUC24 with increased CMV viral load. With dose increase to 10 mg/kg, targeted AUC24 of 50 for ganciclovir was achieved; clinically, CMV viral loads decreased and remained suppressed. Higher doses of ganciclovir may be required in ECMO patients, especially without concurrent CRRT, although further pharmacokinetic/pharmacodynamic studies are needed in these critically ill patients.Disclosures All authors: No reported disclosures.
What is known and objective Ganciclovir is a first‐line antiviral agent to treat cytomegalovirus disease in immunocomprimised patients. Ganciclovir pharmacokinetics in ECMO is unknown. Case description A 6‐year‐old with a stage IV extra‐renal rhabdoid tumor with respiratory failure leading to extracorporeal membrane oxygenation had increasing serum CMV DNAemia while on ganciclovir. What is new and conclusion This is the first case report of ganciclovir pharmacokinetics in either paediatric or adult ECMO populations. Recommended dosing provided a low, subtherapeutic AUC24 with an associated increase CMV viral load. Higher doses of ganciclovir may be required in ECMO patients, especially without concurrent CRRT.
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