A Pharmacist-Driven Closed-Loop Stewardship Model of Meropenem: Impact on Stability and Efficacy in Neurosurgery Patients

Purpose: To evaluate the impact of a pharmacist-driven closed-loop stewardship model on meropenem stability and therapeutic efficacy in neurosurgical patients with hospital-acquired pneumonia (HAP). Patients and Methods: An interrupted time series study enrolled neurosurgical patients treated with meropenem for HAP. The patients from October 2019 to December 2021 were retrospectively collected as the control group, whereas the patients were prospectively enrolled from January 2022 to March 2025 as the intervention group. The intervention featured optimized drug preparation, prioritized administration, rapid specimen processing, real-time therapeutic drug monitoring and dynamic dose adjustments. Steady-state trough concentrations (C min ) and open-ring metabolite (ORM) levels in serum and cerebrospinal fluid (CSF), and clinical outcomes were analyzed. Results: A total of 227 patients was included (control group: n = 102; intervention group: n = 125). The intervention group demonstrated a significantly higher median C min 3.75 (1.45, 8.64) mg/L vs 0.78 (0.25, 2.74) mg/L, P < 0.001 and lower subtherapeutic exposure rate (35.48% vs 70.59%, P < 0.0001) compared to control group. The ratio of ORM/C min in serum 0.83 (0.62, 1.24) vs 1.97 (1.42, 2.65), P < 0.0001 and CSF 1.21 (0.84, 1.90) vs 2.05 (1.27, 2.81), P < 0.05 were also lower in the intervention group, indicating mitigated degradation. There were no significant differences in clinical response rates (72.5% vs 61.3%, P = 0.157) or bacterial eradication rates (68.1% vs 59.4%, P = 0.160). However, the bacterial eradication rates improved for Gram-negative isolates with Minimum inhibitory concentration (MIC) ≤ 8 mg/L in the intervention group than the control group (84.4% vs 69.1%, P < 0.05). Conclusion: The closed-loop stewardship model effectively improved meropenem target concentration attainment by systematically reducing drug loss through degradation and metabolism. This optimized exposure profile correlated with improved eradication rates of Gram-negative sensitive bacteria. Keywords: meropenem, closed-loop management of precision medication, concentration, open-ring metabolite, hospital-acquired pneumonia, acute brain injury