Experience with Implementing a Beta-lactam Therapeutic Drug Monitoring Service in a Burn Intensive Care Unit: A Retrospective Chart Review

Abstract

Thermal injuries alter pharmacokinetics, complicating the prediction of standard antibiotic dose effectiveness. Therapeutic drug monitoring has been proposed to prevent subtherapeutic dosing of antibiotic therapy, but remains scarcely studied in the burn patient population. A retrospective chart review of burn patients receiving beta-lactam therapeutic drug monitoring from 2016 to 2019 was conducted. Adult patients with thermal injury receiving cefepime, piperacillin/tazobactam, or meropenem for ≥48 hours were included. Between February 2016 and July 2017, we utilized selective therapeutic drug monitoring based on clinical judgement to guide treatment. From October 2018 until July 2019, therapeutic drug monitoring was expanded to all burn patients on beta-lactams. The primary endpoint was achievement of therapeutic concentration, and the secondary endpoints were clinical cure, culture clearance, new resistance, length of stay and mortality. The selective (control) group included 19 patients and the universal (study) group reviewed 23 patients. In both groups, skin and lungs were the most common primary infection sources, with Pseudomonas aeruginosa as the most common species. In the universal cohort, patients were older with higher risk factors, but more frequently achieved the target drug concentration, required less days to start therapeutic drug monitoring (p<0.0001), and had more frequent measurements and beta-lactam dose adjustments. Positive clinical outcome was reported in 77%, and microbial eradication in 82% of all patients. All clinical outcomes were similar between the groups. The implementation of beta-lactam therapeutic drug monitoring protocol shortened the time, increased the probability of appropriate target attainment, and individualized beta-lactam therapy in burn patients.

Which Are the Best Regimens of Broad-Spectrum Beta-Lactam Antibiotics in Burn Patients? A Systematic Review of Evidence from Pharmacology Studies

“…Moreover, they estimated that different regimens (1 g every 8 h, 2 g every 12 h or 2 g every 8 h, administered over 30 min) were sufficient to achieve a target of 60% T > MIC with MIC values ≤ 8 mL/L. In addition, Alshaer et al [22] recently performed a before/after study investigating the implementation of TDM in a burn unit. They administered 6 g of cefepime (mean values not specified at patient level) in 42 infectious episodes and found an overall PTA ranging from 60% to 100%, according to different targets.…”

“…Four papers [14,15,22,41] reported monocentric experiences of the implementation of TDM in guiding antibiotic treatment in burn patients, including piperacillin or piperacilintazobactam. Patel et al [41] reported using TDM in a sample of 50 burn patients, which included 6 patients treated with 4.5 g piperacillin-tazobactam every 6 h. Given an MIC of 2 mg/L, they reported attaining a 100% fT > 4 × MIC target in 2/6 patients (34%).…”

“…They used a regimen of 4.5 g every 8 h, over 30 min or 2 h, and included infections caused by different bacterial species, including P. aeruginosa. Finally, Alshaer et al [22] showed that the use of TDM was associated with an increased PTA, but they did not give detailed information about the drug regimens associated with target attainment.…”

“…Meropenem was also examined in 4 studies focusing on the effect of TDM use in burn patients [14,15,22,41]. The randomized controlled trial by Fournier et al [14] aimed at determining the impact of TDM in a sample of 38 burn patients and also included some patients treated with meropenem.…”

“…The PTA increased under treatment guided by TDM. Machado et al [15] and Alshaer et al [22] performed two before/after studies on the implementation of TDM that included patients on meropenem, but they did not provide information regarding which drug regimens were better associated with target attainment. Patel et al [41] reported on using TDM in 50 burn patients.…”