Mohammad Alshaer, PharmD, PhD
University of Florida
Gainesville, Florida
Disclosure information not submitted.
Kelly Maguigan, PharmD
Clinical Pharmacy Specialist
UF Health Shands Childrens Hospital, United States
Disclosure information not submitted.
Melissa Murray, PharmD
Clinical Pharmacy Specialist
UF Health, United States
Disclosure information not submitted.
Veena Venugopalan, PharmD
Clinical Associate Professor
UF and UF Health, United States
Disclosure information not submitted.
Jennifer Ashton, BCCCP, BCPS, PharmD
Clinical Pharmacy Specialist
UF Health Shands Childrens Hospital, United States
Disclosure information not submitted.
Bethany Shoulders, BCCCP, BS, PharmD
Clinical Assistant Professor
University of Florida Health
Gainesville, Florida
Disclosure information not submitted.
Kathryn DeSear, PharmD
Clinical Pharmacy Specialist
UF Health, United States
Disclosure information not submitted.
Barbara Santevecchi, PharmD
Clinical Pharmacy Specialist
UF Health, United States
Disclosure information not submitted.
Kartik Cherabuddi, MD
Associate Professor
UF Health Shands Hospital, United States
Disclosure information not submitted.
Title: Beta-Lactams Exposure in ICU Patients and Associated Outcomes: A Prospective Observational Study
Introduction: Critically ill patients show variability in beta-lactams (BL) exposure throughout their hospital course. Previous BL pharmacokinetic studies were mostly retrospective or had small sample size. There is a need for larger clinical exposure-response BL studies in this population.
Methods: This is an ongoing prospective observation study including adult patients admitted to the intensive care unit (ICU) from June 2021 to December 2022 at UF Health Shands Hospital, Gainesville, FL. Patients who received BL for the treatment of infection and had BL concentration measured were included. Patient demographics, infection sources, minimum inhibitory concentrations (MICs), BL regimens and concentrations, clinical outcomes, and 30-day mortality data were collected. The standard practice is to collect BL peak and trough samples. Total BL drug concentration was measured using validated LC-MS-MS assays at UF and unbound fraction was calculated. The time the free BL concentration was above the MIC (fTMIC), 4 times the MIC (fT4xMIC), and free trough:MIC (fCmin/MIC) were calculated for every patient.
Results: This interim analysis included 37 patients with 43 episodes of infections. Mean (SD) age was 55 years (15), 51% were males and mean hospital stay was 39 days. 33% of patients had pneumonia and 20% had bacteremia. The median (IQR) MIC was 2 mg/L (1-4) and Pseudomonas aeruginosa was the most common pathogen isolated (n=10). Eight patients died within 30 days of completing BL therapy. The BLs received (n) were cefepime (30), meropenem (3), piperacillin (3), ampicillin (2), cefazolin (2), amoxicillin (1), imipenem (1), and oxacillin (1), with a median (IQR) duration of 9 days (6-31). The median (IQR) time from starting to measuring BL concentration was 5 days (2-6). The median calculated fTMIC was 100% (88% achieved 100%), fT4xMIC 100% (44% achieved 100%), and fCmin/MIC 3.7. Patients who achieved 100% fTMIC were more likely to have clinical cure (OR 11.2, p=0.019). For 30-day mortality, both increase in fT4xMIC and achieving 100% fT4xMIC were associated with lower mortality (OR 0.97, p=0.01 and 0.13, p=0.034, respectively).
Conclusions: Optimization of BL concentrations may affect clinical cure and mortality and remains a focus for the ICU population. Further analysis will be conducted as more patients are included.