(868) Early Meropenem Clearance of Critically Ill Patients in a Pediatric Intensive Care Unit

Introduction: Meropenem (MEM), a β-lactam antibiotic, is primarily renally cleared. Empiric dosing is often based on creatinine clearance (CrCL). Our group previously identified MEM clearance (CL) as a key factor in overall time over minimum inhibitory concentration (T>MIC) for critically ill children. The current study aims to analyze clinical factors in early MEM course that can identify PICU patients at risk of high MEM CL and thus inadequate T>MIC. We hypothesize higher CrCL is associated with higher MEM CL.

Methods: This was part of a prospective study of patients admitted to Cincinnati Children’s PICU from 2018-21 and treated with β-lactams. Patients were included if they received ≥3 MEM doses and had ≥1 plasma total MEM concentration collected via opportunistic sampling within 24hrs of MEM start; and excluded if on extracorporeal support or started on MEM in surgery. Individual concentration-time profiles and MEM CL for the first 24hrs were generated by Bayesian estimation using measured concentrations and a population pharmacokinetic model (Saito, AAC 2021) in MwPharm++. Clinical data were captured from the medical record. Patients in the highest quartile of MEM CL (“higher group”) and thus at risk of inadequate T>MIC were compared to those in the lower 3 quartiles (“lower group”) via Mann-Whitney or Fisher’s Exact tests.

Results: 36 patients (age 0.4-33 yrs) were included. CL ranged 0.08 to 0.64 L/kg/hr (median 0.22, 3rd quartile 0.36). Median CL was 0.2 L/kg/hr for the lower group (n=27) and 0.48 for the higher group (n=9) (p < 0.01). There was no difference in median CrCL between lower and higher MEM CL groups (129 vs 147 mL/kg/1.73m², p=0.15). Further, there was no difference in age, weight, Day 1 fever or abnormal heart rate, or need for vasopressors. For patients on 20mg/kg (or 1g) q8hr MEM dosing, lower CL patients (n=21) had better median T>MIC 2 µg/mL than higher CL patients (n=9) (100 vs 45%, p< 0.01).

Conclusions: Higher MEM CL was not predicted by easily observed factors like age, weight, abnormal vitals, or CrCL. Small sample size likely impacts these results. CrCL is likely an unreliable marker of renal function in early critical illness. Investigation into other markers of MEM CL or routine MEM concentration measurement may be warranted to ensure adequate dosing and target attainment.