Originally published by our sister publication Pharmacy Practice News
By Gina Shaw
Experts offered guidance about identifying patients who may benefit from beta-lactam therapeutic drug monitoring (TDM) during the 2023 Making a Difference in Infectious Disease (MAD-ID) conference, held in Orlando, Fla.
Monitoring plasma levels during beta-lactam treatment improves pharmacokinetic and pharmacodynamic (PK/PD) target attainment in critical care. However, recent randomized clinical trials suggest that the practice does not lead to improved outcomes in terms of length of stay or mortality benefits. Despite these findings, it is thought that a TDM-guided approach to prescribing beta-lactams may be beneficial in specific subgroups of critically ill patients (Antibiotics [Basel] 2023;12[3]:568).
“There are several factors producing PK/PD variability that would make a patient a candidate for beta-lactam TDM,” said Veena Venugopalan, PharmD, BCIDP, a clinical associate professor in the Department of Pharmacotherapy and Translational Research at the University of Florida’s College of Pharmacy, in Gainesville. “These can be categorized as patient factors, pathogen factors and external/equipment factors.”
Patient factors, she said, pertain to critically ill patients who are significantly obese or underweight, those who have impaired renal clearance such as trauma patients, burn patients, and patients with cystic fibrosis. Pathogen factors include bacteria with a high minimum inhibitory concentration (MIC) as the cause of infection or bacteria with MICs close to their breakpoints. Examples of “other” or external factors that could justify the use of beta-lactam TDM, Dr. Venugopalan said, include the use of extracorporeal membrane oxygenation or renal replacement therapy.
“There is a special subset of patients where a number of these factors add up into a perfect storm,” said Kate DeSear, PharmD, BCIDP, a clinical infectious disease pharmacist at UF Health Shands Hospital, in Gainesville. “You might have a burn patient who is morbidly obese and has had amputations because of DIC [disseminated intravascular coagulation], and you are dosing based on the package insert plus a ‘thumb in the wind’ method. We need a better way.”
In a study published in the American Journal of Health-System Pharmacy in 2022, Dr. Venugopalan, Dr. DeSear, and colleagues reported on their beta-lactam TDM monitoring program, which was first introduced in 2015. Analyzing the first beta-lactam-TDM encounter for 1,438 patients, the team found that monitoring was most frequently performed for cefepime (61%; n=882), piperacillin (15%; n=218) and meropenem (11%; n=151) for a median of three days from beta-lactam initiation. Among patients with available MIC values and trough concentrations, the (PK/PD) target of 100% fT>MIC was achieved in 308 patients (88%). Beta-lactam TDM resulted in a dosage adjustment in 25% (n=361) of patients (2022;79[18]:1586-1591).
The UF Health system has embedded a scoring tool into its Epic electronic health record that puts the risk for beta-lactam PK/PD derangement at the forefront of the clinician’s decision making as they are screening patients, alongside sepsis scores and antimicrobial stewardship alerts.
Beta-lactam TDM is initiated early in targeted patients for dose optimization in critical illness, Dr. Venugopalan said. “During the course of treatment, we also check levels in patients who have definitive therapies and an elevated MIC,” she said. “In the late phase of treatment, infectious diseases providers will often seek a consult prior to discharge to optimize dosing.”
For those seeking to pilot beta-lactam TDM, Dr. DeSear made several recommendations.
“Find a patient with undeniably altered kinetics—someone who is hypermetabolic, possibly a burn patient, who is clearing vancomycin like crazy,” she said. “Try to rule out cefepime neurotoxicity. Send two concentrations to a reference lab, perform first-order kinetics on two samples and adjust for protein binding. Once you have done this over and over in a few hand-picked patients, you will be convinced you need to be doing it more routinely.”
Dr. DeSear reported grants from Merck and Shionogi, and has served on the advisory committee/board for Shionogi, Spero Therapeutics and Melinta Therapeutics. Dr. Venugopalan reported compensation for contributing data to a drug registry with Merck, and Melinta Therapeutics.
