Related Experiment Video

Updated: Mar 27, 2026

Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses
11:17

Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses

Published on: August 30, 2018

13.5K

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

Tongtong Li1, Xianglong Chen1, Jinhui Xu1

  • 1Department of Pharmacy, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, Jiangsu, People's Republic of China.

Drug Design, Development and Therapy
|March 25, 2026
PubMed
Abstract

Insights

A pharmacist-led stewardship model improved meropenem levels in neurosurgical patients with hospital-acquired pneumonia (HAP). This enhanced drug stability and reduced degradation, leading to better eradication of susceptible Gram-negative bacteria.

Area of Science:

  • Pharmacology
  • Infectious Diseases
  • Neurosurgery

Background:

  • Hospital-acquired pneumonia (HAP) poses a significant risk in neurosurgical patients.
  • Meropenem is a critical antibiotic for treating HAP, but its efficacy can be limited by suboptimal drug exposure.
  • Pharmacist-driven stewardship models are emerging strategies to optimize antibiotic therapy.

Purpose of the Study:

  • To assess the impact of a pharmacist-driven closed-loop stewardship model on meropenem stability and therapeutic efficacy.
  • To evaluate meropenem trough concentrations (Cmin) and open-ring metabolite (ORM) levels in serum and cerebrospinal fluid (CSF).
  • To determine the effect of the stewardship model on clinical outcomes in neurosurgical patients with HAP.

Main Methods:

  • An interrupted time series study comparing retrospective (control) and prospective (intervention) cohorts of neurosurgical patients with HAP treated with meropenem.
  • Intervention included optimized drug preparation, administration, specimen processing, therapeutic drug monitoring, and dynamic dose adjustments.
  • Analysis of steady-state trough concentrations (Cmin), ORM levels in serum and CSF, and clinical outcomes.

Main Results:

  • The intervention group showed significantly higher median Cmin [3.75 mg/L vs 0.78 mg/L] and a lower subtherapeutic exposure rate (35.48% vs 70.59%).
  • Lower ratios of ORM/Cmin in serum and CSF indicated mitigated meropenem degradation in the intervention group.
  • While overall clinical response and bacterial eradication rates did not differ significantly, eradication of Gram-negative bacteria with minimum inhibitory concentration (MIC) ≤8 mg/L improved (84.4% vs 69.1%).

Conclusions:

  • A pharmacist-driven closed-loop stewardship model effectively enhanced meropenem target concentration attainment.
  • The model reduced drug loss via degradation and metabolism, optimizing meropenem exposure.
  • This optimized exposure profile correlated with improved eradication rates for susceptible Gram-negative bacteria.
Keywords:
acute brain injuryclosed-loop management of precision medicationconcentrationhospital-acquired pneumoniameropenemopen-ring metabolite

More Related Videos

Antibiotic Efficacy Testing in an Ex vivo Model of Pseudomonas aeruginosa and Staphylococcus aureus Biofilms in the Cystic Fibrosis Lung09:26

Antibiotic Efficacy Testing in an Ex vivo Model of Pseudomonas aeruginosa and Staphylococcus aureus Biofilms in the Cystic Fibrosis Lung

Published on: January 22, 2021

7.9K

Related Concept Videos

Clinical Significance of Antibiotic Resistance01:25

Clinical Significance of Antibiotic Resistance

Methicillin-resistant Staphylococcus aureus (MRSA) presents a critical public health threat, arising from its capacity to resist β-lactam antibiotics due to acquisition of the mecA gene within the staphylococcal cassette chromosome mec (SCCmec). This gene encodes penicillin-binding protein 2a (PBP2a), which impairs binding efficacy of methicillin and other β-lactams. MRSA has evolved into distinct clonal lineages impacting humans and animals alike, reinforcing its significance within...
26
Impact of Pharmacokinetic–Pharmacodynamic Models: Regulatory Decisions01:15

Impact of Pharmacokinetic–Pharmacodynamic Models: Regulatory Decisions

PK–PD modeling has significantly influenced FDA regulatory decisions, particularly drug approval, dosage optimization, and labeling. These models integrate pharmacokinetics (PK) and pharmacodynamics (PD) to predict drug behavior and effects, aiding in optimizing dosing regimens and enhancing the probability of clinical trial success.One notable example is Nesiritide (Natrecor®), a recombinant human brain natriuretic peptide for treating acute decompensated congestive heart failure...
71
Pharmaceutical Alternatives: Stability-Related Therapeutic Nonequivalence01:22

Pharmaceutical Alternatives: Stability-Related Therapeutic Nonequivalence

Generic intravenous (IV) drugs are considered bioequivalent to their branded counterparts due to their 100% bioavailability upon administration. However, variations in stability among different drug products can significantly influence their therapeutic performance, even if they are pharmaceutically equivalent.Cefuroxime, a prophylactic antimicrobial, is often used as a single-dose IV injection for patients undergoing coronary artery bypass grafting surgery. A 3 g dose typically provides...
240
Mechanism of Antibiotic Resistance in MRSA01:25

Mechanism of Antibiotic Resistance in MRSA

Antibiotic resistance in bacteria arises when microorganisms evolve the ability to withstand drugs designed to kill them or inhibit their growth, rendering once-effective treatments useless. This phenomenon, driven by genetic change and selection under antibiotic exposure, poses a profound threat to modern medicine. Mechanisms include drug-inactivating enzymes (e.g., β-lactamases), efflux pumps that eject antibiotics, mutations altering antibiotic targets, decreased drug uptake, and...
69
Pharmacokinetic–Pharmacodynamic Relationship: Influence of Elimination Half-Life on Effect Duration01:23

Pharmacokinetic–Pharmacodynamic Relationship: Influence of Elimination Half-Life on Effect Duration

Drug elimination from the body primarily occurs through metabolic and excretion pathways. Hepatic metabolism transforms lipophilic drugs into hydrophilic forms for excretion, typically via enzymatic processes classified as phase I (modification) and phase II (conjugation). Renal excretion eliminates drugs and metabolites through filtration and secretion in the kidneys. Impairment in liver or kidney function can hinder these processes, delaying drug clearance and extending the drug’s...
90
Pharmaceutical Poisoning: Treatment Strategies01:26

Pharmaceutical Poisoning: Treatment Strategies

Treatment strategies for poisoning are a critical aspect of emergency medicine, focusing on preventing the absorption of toxins and enhancing their elimination. When a poisoning incident occurs, the first response is to halt exposure and decontaminate the patient, particularly through gastrointestinal (GI) methods if the poison was ingested.Gastrointestinal Decontamination Techniques:Activated charcoal is the cornerstone of GI decontamination. It works through adsorption, binding the toxin to...
150