Kelli Paice, MD
Pediatric Critical Care Fellow
Cincinnati Childrens Hospital Medical Center
Cincinnati, Ohio
Disclosure information not submitted.
Sonya Tang Girdwood, MD, PhD
Assistant Professor
Cincinnati Children's Hospital Medical Center, United States
Disclosure information not submitted.
Tomoyuki Mizuno, PhD
Assistant Professor
Cincinnati Children's Hospital Medical Center, United States
Disclosure information not submitted.
Peter Tang, PhD
Associate Professor
Cincinnati Children's Hospital Medical Center, United States
Disclosure information not submitted.
Calise Curry
Clinical Research Coordinator
Cincinnati Children's Hospital Medical Center, United States
Disclosure information not submitted.
Rhonda Jones
Research Nurse
Cincinnati Children's Hospital Medical Center, United States
Disclosure information not submitted.
Erin Stoneman
Clinical Research Coordinator
Cincinnati Children's Hospital Medical Center, Ohio, United States
Disclosure information not submitted.
Toni Yunger
Clinical Research Coordinator
Cincinnati Children's Hospital Medical Center, United States
Disclosure information not submitted.
Min Dong, PhD
Assistant Professor
Cincinnati Children's Hospital Medical Center, United States
Disclosure information not submitted.
Alexander Vinks, PharmD, PhD, FCP
Professor, Division Director
Cincinnati Children's Hospital Medical Center, United States
Disclosure information not submitted.
Jennifer Kaplan, MD, MS, FCCM
Professor, Attending Physician
Cincinnati Children's Hospital Medical Center, United States
Disclosure information not submitted.
Title: Inadequate Meropenem Target Attainment Early in Pediatric Critical Illness
Introduction/Hypothesis: Meropenem (MEM) is a broad spectrum antibiotic. Its efficacy depends on the fraction of time concentrations remain above minimum inhibitory concentrations (T >MIC). MEM concentrations are not routinely monitored. Guidelines encourage immediate dosing of antibiotics when indicated in critically ill children. The goal of this study is to determine how often children achieve target MEM concentrations early in critical illness.
Methods: A prospective study of patients admitted to the pediatric intensive care unit (PICU) at Cincinnati Children’s from 2018 to 2020 and treated with one of 4 β-lactam antibiotics was completed. For this analysis, patients starting MEM on day one of PICU stay were eligible and included if they had plasma total MEM concentrations measured from opportunistic sampling within 8h of a MEM dose. Concentration-time profiles of the first 24h of MEM dosing were created using a previously published MEM pharmacokinetic model (Saito et al, AAC, 2021) and Bayesian estimation in MWPharm++. For each patient, T >MIC for the first MEM dosing interval was assessed using local intermediate and resistant Enterococcus species MIC cutoffs (2 and 4 µg/mL). The impact of T >MIC target attainment on patient outcome measures was assessed via Student’s t, Fisher’s exact or Mann-Whitney U tests. Association of allometric clearance (CL) (L/h/70kgBW^0.75) and volume of distribution (Vd) (L/70kgBW) with T >MIC was assessed via Pearson correlation coefficient.
Results: Eighteen patients were included (median age 7.5 y, median weight 22.1 kg, 61% male). Five (28%) achieved 100% T >MIC 4 µg/mL and 7 (39%) achieved 100% T >MIC 2 µg/mL. Hospital length of stay, PICU length of stay, and 28-day mortality were not associated with target attainment. Average CL was 0.8 L/h/kg - higher than previously published CL for similar populations. For both MIC targets, T >MIC was significantly correlated with CL (4 µg/mL: r = -0.62, p = 0.006; 2 µg/mL: r = -0.61, p = 0.007), but not with Vd.
Conclusions: Within the first MEM dosing interval, critically ill children do not consistently achieve concentration targets sufficient to treat resistant organisms. This may lead to inadequate early therapeutic effect. During this period, CL appears to be a more significant factor in T >MIC than Vd but further study is needed.