PII-112 - EARLY MEROPENEM PHARMACOKINETICS AND TARGET ATTAINMENT IN CHILDREN WITH SEVERE VS NON-SEVERE SEPSIS

K. Paice¹, S. Tang Girdwood², K. Pavia², T. Mizuno², J. Kaplan²; ¹Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA, ²Cincinnati Children's Hospital Medical Center.

Background: Early severe sepsis is suspected to alter the pharmacokinetic (PK) parameters of antibiotics. Meropenem is a β-lactam used to treat critically ill children at risk of antibiotic-resistant infections. We hypothesized that children with severe sepsis would have lower time that meropenem concentrations remain above target minimum inhibitory concentration (T>MIC) in the first 24 h of therapy compared to those with non-severe sepsis due to higher volume of distribution (Vd).

Methods: This is a single-center prospective study of patients admitted to a pediatric ICU and treated with meropenem. Patients were included if they newly started meropenem, received ≥3 doses, and had ≥1 opportunistic plasma samples obtained within 24 h. Patients were excluded if on extracorporeal support. Sepsis was considered severe if patients were treated with antibiotics for ≥7 days and had ≥1 of the following within 12-24 h of meropenem start: A) positive pressure ventilation above baseline, B) vasopressors, or C) ≥40 mL/kg bolus fluid. Non-severe sepsis patients did not meet criteria A, B or C. Concentration-time profiles of first 24 h of meropenem were created using a population PK model (Saito, AAC, 2021), measured concentrations, and Bayesian estimation with MwPharm++. A target of 4 µg/mL (4x MIC of 1 µg/mL) was used to assess T>MIC. Comparisons between groups were made via Student’s T or Mann-Whitney tests.

Results: 15 severe and 7 non-severe sepsis patients were included. All were dosed 20 mg/kg (or 1 g) q8h, except 2 severe sepsis patients dosed 40 mg/kg q8h. The severe sepsis group was younger, had lower weight, and had more fluid overload at 24 h (Table 1). There were no differences in weight-adjusted Vd or T>MIC. There were no differences in creatinine clearance (CrCL) or allometrically scaled meropenem CL.

Conclusion: There were no differences in key meropenem PK parameters or target attainment in early severe versus non-severe sepsis in this cohort, despite difference in fluid overload. CrCL and meropenem CL were also not different between groups. Lack of detectable differences may reflect small sample size and large variability of PK parameters. Further investigation is needed to study a larger cohort and identify specific severe sepsis features that most significantly alter PK and identify patients who might benefit most from model-informed precision dosing.