MSACL 2026 Abstract

Clinical Implementation of a Stable Isotope Dilution Lc-MS/MS Method for Beta-Lactam Quantification: Experience From a Large Academic Medical Center

Ibrahim Choucair, William Feeney, Katie B. Olney
University of Kentucky College of Medicine, Lexington, KY

Ibrahim Choucair, PhD (Presenter) University of Kentucky College of Medicine

Presenter Bio: I am an Assistant Professor and Director of the Special Chemistry and Toxicology Laboratory in the Department of Pathology and Laboratory Medicine at the University of Kentucky. I also serve as Associate Core Director of the Biofluids Biomarker Core at the University of Kentucky Alzheimer’s Disease Research Center and as Associate Medical Director of the Kentucky State Public Health Laboratory, where I lead Newborn Screening activities.

I received my Bachelor of Science in Clinical Laboratory Science and his master’s degree in Bioanalytical Toxicology from the American University of Science and Technology in Beirut, Lebanon. I later earned my PhD in Clinical Bioanalytical Chemistry through the joint program between Cleveland State University and the Cleveland Clinic and then completed a Clinical Chemistry fellowship at Yale School of Medicine.

My research is centered on two primary objectives: (1) advancing clinical laboratory testing through the development of innovative tools and methodologies, and (2) exploring the relationships between proteins or small molecules and disease pathogenesis to reduce the impact of conditions such as liver disease, cardiovascular disease, diabetes, and Alzheimer’s disease.

Through my work, I strive to deepen our understanding of the mechanisms underlying these disorders, identify novel therapeutic targets, and develop cutting-edge diagnostic tools and treatment approaches. To achieve these goals, I leverage advanced technologies such as mass spectrometry, as well as bioinformatics tools including R and Python, to analyze complex datasets and uncover actionable insights.

I am committed to bridging the gap between basic research and clinical practice, with the ultimate aim of translating scientific discoveries into meaningful improvements in patient care. My passion for this translational approach drives my dedication to advancing the fields of clinical chemistry and toxicology and contributing to better health outcomes.

Relevant Financial Disclosures (within past 24 months, reported on Jun 17, 2026) No relevant financial relationship(s) to disclose.

INTRODUCTION:
The global rise in antimicrobial resistance and the growing adoption of precision medicine have renewed interest in therapeutic drug monitoring (TDM) for beta-lactam antibiotics. Once considered straightforward due to wide therapeutic indices, beta-lactams are now recognized as drugs whose pharmacokinetic variability, especially in critically ill, renally impaired, or pediatric patients, can lead to both therapeutic failure and toxicity when unmonitored. Recent evidence demonstrated that optimizing time above the minimum inhibitory concentration (fT>MIC) through individualized dosing improves clinical outcomes and reduces antimicrobial resistance. Despite increasing interest, implementation of beta-lactam TDM across healthcare systems remains limited. Barriers include lack of standardized assays, uncertainty about appropriate sample timing, limited clinician familiarity with pharmacokinetic and pharmacodynamic principles, and suboptimal communication channels between the clinical laboratory and prescribers. Additionally, while many hospital laboratories possess the analytical capability to perform beta-lactam assays, uncertainties remain regarding turnaround time requirements and the operational feasibility of low-volume, high-complexity testing on daily bases.

OBJECTIVE:
To develop, validate, and clinically implement a stable isotope dilution LC-MS/MS assay for beta-lactam antibiotics, and to evaluate its impact on identifying non-therapeutic drug exposures and guiding individualized dosing in hospitalized patients.

METHODS:
We developed and fully validated a stable isotope dilution LC-MS/MS assay for the quantification of three bet-lactam antibiotics: cefepime, meropenem, and piperacillin. The validated assay was implemented clinically to support TDM for all hospitalized patients receiving these agents. For each patient, at least two plasma concentrations (peak and trough) were measured. Pharmacokinetic modeling was performed by the pharmacy team using patient specific parameters to guide dose adjustments. Data was collected over a 12-month period from March 2025 till February 2026.

RESULTS:
A total of 252 patients underwent beta-lactam TDM during the study period, including 131 receiving cefepime, 49 meropenem, and 71 piperacillin. Overall, 60 to 70% of patients demonstrated non-therapeutic exposures requiring dose adjustment, cefepime and meropenem were most frequently associated with supratherapeutic concentrations (52% and 49%, respectively), while piperacillin exposures were commonly within the therapeutic range (41%) or subtherapeutic (38%).

CONCLUSION:
Implementation of beta-lactam TDM using a robust LC-MS/MS platform is feasible in a clinical laboratory setting and identifies a high prevalence of suboptimal drug exposure. TDM enables individualized dosing strategies that have the potential to improve clinical outcomes, reduce toxicity and support antimicrobial stewardship efforts. These findings support the integration of beta-lactam TDM into routine clinical practice as a key component of precision medicine.