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

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.).

SUBMITTER: Fournier A

PROVIDER: S-EPMC5826126 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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

Fournier A A Eggimann P P Pantet O O Pagani J L JL Dupuis-Lozeron E E Pannatier A A Sadeghipour F F Voirol P P Que Y-A YA

Antimicrobial agents and chemotherapy 20180223 3

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 ...[more]

PMID: 29263079

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Project description:Highlights • COVID-19 is an adjunctive risk factor for burn injured patients.• Isolation of suspected cases and development of management procedures are essential preventive measures to reduce viral spread.• We developed an admission protocol to our Burn Unit which proved itself effective in minimizing the contagion between patients and healthcare workers. Background The actual pandemic outbreak is the third time in the last two decades in which a coronavirus results in a major global spread with serious consequences in terms of vastity of affected patients, life losses, health system organization efforts and socio-economic implications. Lacking effective therapies and vaccinations, during viral outbreak the major and most incisive mean for viral spread control is spread prevention, especially for the fragile burn-injured patients we are called to care for in Burn Units. Methods We developed an admission and inpatient management protocol to preserve burn patients from SARS-CoV-2 contagion, in order to avoid additional morbidity and mortality in patients with already compromised health conditions. Data from burn-injured patients admitted to our Unit following this new protocol were retrospectively analyzed in order to verify its effectiveness in prevention of viral spread. Results From the 8th of March to the 8th of June, we admitted 18 patients in the Burn Unit ICU and semi-ICU and 17 patients in the Burn Ward. Two of them resulted positive to COVID-19 nasopharyngeal swab and bronchoalveolar lavage collected immediately on admission, for both the extension of burns and their general clinical conditions implied ICU admission. Moreover, a caregiver of an admitted child resulted positive to the nasopharyngeal swab. No other cases of SARS-CoV-2 positivity have been reported neither between hospitalized patients nor between healthcare workers. Conclusion The evidence of high ICU admission rate and high mortality in patients affected by SARS-CoV-2 combined with the fragile clinical conditions of burn patients required the development of an admission and hospitalization management protocol which proved itself effective in minimizing viral spread among patients and healthcare workers.

Project description:Background:Analgosedation is a cornerstone therapy for mechanically ventilated patients in intensive care units (ICU). To avoid inadequate sedation and its complications, monitoring of analgosedation is of great importance. The aim of this study was to investigate whether monitoring of analgosedative drug concentrations (midazolam and sufentanil) might be beneficial to optimize analgosedation and whether drug serum concentrations correlate with the results of subjective (Richmond Agitation-Sedation Scale [RASS]/Ramsay Sedation Scale) and objective (bispectral (BIS) index) monitoring procedures. Methods:Forty-nine intubated, ventilated, and analgosedated critically ill patients treated in ICU were clinically evaluated concerning the depth of sedation using RASS Score, Ramsay Score, and BIS index twice a day. Serum concentrations of midazolam and sufentanil were determined in blood samples drawn at the same time. Clinical and laboratory data were statistically analyzed for correlations using the Spearman's rank correlation coefficient rho (?). Results:Average age of the population was 57.8?±?16.0 years, 61% of the patients were males. Most frequent causes for ICU treatments were sepsis (22%), pneumonia (22%), or a combination of both (25%). Serum concentrations of midazolam correlated weakly with RASS (??=?-?0.467) and Ramsay Scores (??=?0.476). Serum concentrations of sufentanil correlated weakly with RASS (??=?-?0.312) and Ramsay Scores (??=?0.295). Correlations between BIS index and serum concentrations of midazolam (??=?-?0.252) and sufentanil (??=?-?0.166) were low. Conclusion:Correlations between drug serum concentrations and clinical or neurophysiological monitoring procedures were weak. This might be due to intersubject variability, polypharmacy with drug-drug interactions, and complex metabolism, which can be altered in critically ill patients. Therapeutic drug monitoring is not beneficial to determine depth of sedation in ICU patients.

Dataset Information

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

Publications

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

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