Citations

IMPORTANCE: Meropenem dosing is typically guided by creatinine-based estimated glomerular filtration rate (eGFR), but creatinine is a suboptimal GFR marker in the critically ill. OBJECTIVES: This study aimed to develop and qualify a population pharmacokinetic model for meropenem in critically ill adults and to determine which eGFR equation based on creatinine, cystatin C, or both biomarkers best improves model performance. DESIGN, SETTING, AND PARTICIPANTS: This single-center study evaluated adults hospitalized in an ICU who received IV meropenem from 2018 to 2022. Patients were excluded if they had acute kidney injury, were on kidney replacement therapy, or were treated with extracorporeal membrane oxygenation. Two cohorts were used for population pharmacokinetic modeling: a richly sampled development cohort (n = 19) and an opportunistically sampled qualification cohort (n = 32). MAIN OUTCOMES AND MEASURES: A nonlinear mixed-effects model was developed using parametric methods to estimate meropenem serum concentrations. RESULTS: The best-fit structural model in the richly sampled development cohort was a two-compartment model with first-order elimination. The final model included time-dependent weight normalized to a 70-kg adult as a covariate for volume of distribution (Vd) and time-dependent eGFR for clearance. Among the eGFR equations evaluated, eGFR based on creatinine and cystatin C expressed in mL/min best-predicted meropenem clearance. The mean (se) Vd in the final model was 18.2 (3.5) liters and clearance was 11.5 (1.3) L/hr. Using the development cohort as the Bayesian prior, the opportunistically sampled cohort demonstrated good accuracy and low bias. CONCLUSIONS AND RELEVANCE: Contemporary eGFR equations that use both creatinine and cystatin C improved meropenem population pharmacokinetic model performance compared with creatinine-only or cystatin C-only eGFR equations in adult critically ill patients.

Abstract Introduction The pivotal study of the extravascular implantable cardioverter‐defibrillator (EV ICD) recently demonstrated primary efficacy and safety endpoints comparable to previous ICD systems. Patient experience with this novel device has not been reported. The current study examined the standardized patient‐reported outcome (PRO) metrics of quality of life (QOL) and patient acceptance of the device. Methods The EV ICD Pivotal Study was a prospective, single‐arm, nonrandomized, global, premarket approval trial. Patients completed the 12‐Item Short Form Survey (SF‐12) QOL surveys at baseline and at 6 months following implant. Additionally, patients completed the Florida Patient Acceptance Survey (FPAS) QOL survey at 6 months. Results From baseline to 6 months, patients within the EV ICD Pivotal Study ( n = 247) reported statistically significant SF‐12 improvements in physical QOL (45.4 ± 9.4 vs. 46.8 ± 9.1 respectively, p = .020) and no changes in mental QOL (49.3 ± 10.4 vs. 50.5 ± 9.7, p = .061). No differences were noted by sex, atrial fibrillation, or the experience of ICD shock. EV ICD patients reported better total FPAS patient acceptance of their ICD than TV‐ICD or S‐ICD patients using historical norms comparisons (80.4 ± 15.7 vs. 70.2 ± 17.8, p < .0001 for S‐ICD and 73.0 ± 17.4, p = .004 for TV‐ICD). Conclusion The initial PROs for EV ICD patients indicated that patients had improvements in physical QOL from baseline to 6‐month follow‐up and markedly better overall acceptance of their ICD compared to a previous study with S‐ICD and TV‐ICD data. These initial results suggest that the EV ICD is evaluated positively by patients.