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

Fournier, Anne; Eggimann, P; Pantet, O; Pagani, J L; Dupuis Lozeron, Elise; Pannatier, A; Sadeghipour, Farshid; Voirol, Pierre; Que, Y-A

doi:10.1128/AAC.01818-17

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Title		Impact of Real-Time Therapeutic Drug Monitoring on the Prescription of Antibiotics in Burn Patients Requiring Admission to the Intensive Care Unit
Authors		Fournier, Anne Eggimann, P Pantet, O Pagani, J L Dupuis Lozeron, Elise Pannatier, A Sadeghipour, Farshid Voirol, Pierre Que, Y-A show all authors [1 - 9]
Published in		Antimicrobial agents and chemotherapy. 2018, vol. 62, no. 3
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.).
Keywords		Adult — Aged — 80 and over — Anti-Bacterial Agents/therapeutic use — Burns/drug therapy — Drug Monitoring/methods — Female — Humans — Intensive Care Units/statistics & numerical data — Male — Middle Aged — Prospective Studies — Young Adult
Identifiers		DOI: 10.1128/AAC.01818-17 PMID: 29263079
Full text		Article (Published version) (539 Kb) - Free access Other version: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5826126/
Structures		Faculté des sciences / Section des sciences pharmaceutiques Faculté de médecine / Section de médecine clinique / Département de santé et médecine communautaires
Research group		Epidémiologie clinique (115)
Projects		Swiss National Science Foundation: CRAGP3_151512 Swiss National Science Foundation: IZ73Z0_152319 Swiss National Science Foundation: SNF no. CRAGP3- 151512, IZ73Z0-152319, and CR31I3_166124
Citation (ISO format)		FOURNIER, Anne et al. Impact of Real-Time Therapeutic Drug Monitoring on the Prescription of Antibiotics in Burn Patients Requiring Admission to the Intensive Care Unit. In: Antimicrobial Agents and Chemotherapy, 2018, vol. 62, n° 3. doi: 10.1128/AAC.01818-17 https://archive-ouverte.unige.ch/unige:127894