Impact of Real-Time Therapeutic Drug Monitoring on the Prescription of Antibiotics in Burn Patients Requiring Admission to the Intensive Care Unit

Abstract

ABSTRACT As pharmacokinetics after burn trauma are difficult to predict, we conducted a 3-year prospective, monocentric, randomized, controlled trial to determine the extent of under- and overdosing of antibiotics and further evaluate the impact of systematic therapeutic drug monitoring (TDM) with same-day real-time dose adaptation to reach and maintain antibiotic concentrations within the therapeutic range. Forty-five consecutive burn patients treated with antibiotics were prospectively screened. Forty fulfilled the inclusion criteria; after one patient refused to participate and one withdrew consent, 19 were randomly assigned to an intervention group (patients with real-time antibiotic concentration determination and subsequent adaptations) and 19 were randomly assigned to a standard-of-care group (patients with antibiotic administration at the physician's discretion without real-time TDM). Seventy-three infection episodes were analyzed. Before the intervention, only 46/82 (56%) initial trough concentrations fell within the range. There was no difference between groups in the initial trough concentrations (adjusted hazard ratio = 1.39 [95% confidence interval {CI}, 0.81 to 2.39], P = 0.227) or the time to reach the target. However, thanks to real-time dose adjustments, the trough concentrations of the intervention group remained more within the predefined range (57/77 [74.0%] versus 48/85 [56.5%]; adjusted odd ratio [OR] = 2.34 [95% CI, 1.17 to 4.81], P = 0.018), more days were spent within the target range (193 days/297 days on antibiotics [65.0%] versus 171 days/311 days in antibiotics [55.0%]; adjusted OR = 1.64 [95% CI, 1.16 to 2.32], P = 0.005), and fewer results were below the target trough concentrations (25/118 [21.2%] versus 44/126 [34.9%]; adjusted OR = 0.47 [95% CI, 0.26 to 0.87], P = 0.015). No difference in infection outcomes was observed between the study groups. Systematic TDM with same-day real-time dose adaptation was effective in reaching and maintaining therapeutic antibiotic concentrations in infected burn patients, which prevented both over- and underdosing. A larger multicentric study is needed to further evaluate the impact of this strategy on infection outcomes and the emergence of antibiotic resistance during long-term burn treatment. (This study was registered with the ClinicalTrials.gov platform under registration no. NCT01965340 on 27 September 2013.)