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Author(s): Stefan Hagel [sup.1] [sup.2], Friedhelm Bach [sup.3], Thorsten Brenner [sup.4] [sup.5], Hendrik Bracht [sup.6], Alexander Brinkmann [sup.7], Thorsten Annecke [sup.8] [sup.9], Andreas Hohn [sup.8] [sup.10], Markus Weigand [sup.5], Guido [...], Purpose Insufficient antimicrobial exposure is associated with worse outcomes in sepsis. We evaluated whether therapeutic drug monitoring (TDM)-guided antibiotic therapy improves outcomes. Methods Randomized, multicenter, controlled trial from January 2017 to December 2019. Adult patients (n = 254) with sepsis or septic shock were randomly assigned 1:1 to receive continuous infusion of piperacillin/tazobactam with dosing guided by daily TDM of piperacillin or continuous infusion with a fixed dose (13.5 g/24 h if eGFR [greater than or equal to] 20 mL/min). Target plasma concentration was four times the minimal inhibitory concentration (range ± 20%) of the underlying pathogen, respectively, of Pseudomonas aeruginosa in empiric situation. Primary outcome was the mean of daily total Sequential Organ Failure Assessment (SOFA) score up to day 10. Results Among 249 evaluable patients (66.3 ± 13.7 years; female, 30.9%), there was no significant difference in mean SOFA score between patients with TDM (7.9 points; 95% CI 7.1-8.7) and without TDM (8.2 points; 95% CI 7.5-9.0) (p = 0.39). Patients with TDM-guided therapy showed a lower 28-day mortality (21.6% vs. 25.8%, RR 0.8, 95% CI 0.5-1.3, p = 0.44) and a higher rate of clinical (OR 1.9; 95% CI 0.5-6.2, p = 0.30) and microbiological cure (OR 2.4; 95% CI 0.7-7.4, p = 0.12), but these differences did not reach statistical significance. Attainment of target concentration was more common in patients with TDM (37.3% vs. 14.6%, OR 4.5, CI 95%, 2.9-6.9, p < 0.001). Conclusion TDM-guided therapy showed no beneficial effect in patients with sepsis and continuous infusion of piperacillin/tazobactam with regard to the mean SOFA score. Larger studies with strategies to ensure optimization of antimicrobial exposure are needed to definitively answer the question.

Background: Major trauma, as well as traumatic hemorrhagic shock go along with early damage to the endothelial glycocalyx (EG). Shed glycocalyx constituents can activate the innate immune system and aggravate secondary injury. Subsequently, we investigated the relationship between glycocalyx shedding and the occurrence of coagulopathy, multiple organ failure (MOF) and outcome in our cohort after severe trauma. Methods: We included multiple trauma patients, as defined by Injury Severity Score (ISS). Polytraumatized patients must have arrived in our level 1 trauma center within 60 min after trauma. Retrospectively, patients were assigned to predefined clinical conditions, based on injury severity (ISS ≥ 16 points), multiple organ failure (MOF score ≥ 6 points), need for massive transfusion (≥10 RBC units/first 24 h), coagulopathy (prothrombin time < 70% at 0 h) and survival (90-day survival). Syndecan-1 (Sdc-1) and hyaluronan (HA) plasma concentrations were evaluated immediately (0 h), 6 h and 12 h after trauma. Results: 49 patients (mean ISS 35.7 ± 12.1 SD, mean age 45.78 ± 15.6 SD) were included in this study. A total of 37 patients (75.5%) survived, while 12 patients died within the observation period of 90 days after trauma (24.5%). A total of 77% of all patients suffered multiple organ failure (MOF score ≥ 6, n = 30). Initial prothrombin time at 0 h was <70% in 31 patients. Plasma concentrations of circulating both glycocalyx constituents showed a significant increase over the first 12 h after trauma (p = 0.001; p = 0.008). Patients with multiple organ failure showed significantly increased hyaluronan concentrations at all three time points (p = 0.007/0.006/<0.001), and the syndecan-1 levels were significantly elevated 12 h after trauma in the MOF group (p = 0.01). Patients with coagulopathy on admission exhibited significantly higher hyaluronan levels at 12 h (p = 0.042). Non-survivors showed significantly increased syndecan-1 levels at 12 h after trauma (p = 0.024). Conclusions: Glycocalyx shedding occurs immediately after major trauma. Coagulopathy is associated with significantly increased plasma hyaluronan. Further, significant changes in plasma concentrations within the first 12 h help to identify subgroups at risk for developing MOF and death. [ABSTRACT FROM AUTHOR]

Summary: Stevens‐Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are rare, predominantly drug‐induced, acute life‐threatening diseases of skin and mucosae. SJS and TEN are nowadays considered as variants of one disease entity with varying degrees of severity called epidermal necrolysis (EN). EN is associated with high morbidity and mortality and constitutes a major disease burden for affected patients. The guideline "Diagnosis and treatment of epidermal necrolysis (Stevens‐Johnson syndrome and toxic epidermal necrolysis)" was developed under systematic consideration of existing scientific literature and in a formal consensus process according to regulations issued by the Association of Scientific Medical Societies in Germany (AWMF) to establish an evidence‐based framework to support clinical decision‐making. The interdisciplinary guideline commission consisted of representatives from various specialist societies and of patient representatives. The guideline is aimed at specialists in the fields of dermatology, ophthalmology, plastic surgery, intensive care, and pediatrics in hospitals and offices, as well as other medical specialties involved in the diagnosis and treatment of EN. The guideline is also aimed at patients, their relatives, insurance funds, and policymakers. The second part is concerned with the topics of supportive therapy in the acute phase of EN and outpatient follow‐up treatment. [ABSTRACT FROM AUTHOR]

Copyright of Journal der Deutschen Dermatologischen Gesellschaft is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal der Deutschen Dermatologischen Gesellschaft is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)