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To investigate whether (1 → 3)-β-d-Glucan (BDG)-guidance shortens time to antifungal therapy and thereby reduces mortality of sepsis patients with high risk of invasive Candida infection (ICI).Multicenter, randomized, controlled trial carried out between September 2016 and September 2019 in 18 intensive care units enrolling adult sepsis patients at high risk for ICI. Patients in the control group received targeted antifungal therapy driven by culture results. In addition to targeted therapy, patients in the BDG group received antifungals if at least one of two consecutive BDG samples taken during the first two study days was ≥ 80 pg/mL. Empirical antifungal therapy was discouraged in both groups. The primary endpoint was 28-day-mortality.339 patients were enrolled. ICI was diagnosed in 48 patients (14.2%) within the first 96 h after enrollment. In the BDG-group, 48.8% (84/172) patients received antifungals during the first 96 h after enrollment and 6% (10/167) patients in the control group. Death until day 28 occurred in 58 of 172 patients (33.7%) in the BDG group and 51 of 167 patients (30.5%) in the control group (relative risk 1.10; 95% confidence interval, 0.80-1.51; p = 0.53). Median time to antifungal therapy was 1.1 [interquartile range (IQR) 1.0-2.2] days in the BDG group and 4.4 (IQR 2.0-9.1, p 0.01) days in the control group.Serum BDG guided antifungal treatment did not improve 28-day mortality among sepsis patients with risk factors for but unexpected low rate of IC. This study cannot comment on the potential benefit of BDG-guidance in a more selected at-risk population.

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 ≥ 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.

In this article, the affiliation details for Dominic Witzke were incorrectly given as 'Department of Infectious Diseases, Evangelisches Klinikum Bethel, Bielefeld, Germany', but should have read instead 'Department of Anaesthesiology, Intensive Care, Protestant Hospital of the Bethel Foundation, University Hospital of Bielefeld, Campus Bielefeld-Bethel, University of Bielefeld, Germany'. Additionally, the correct full name of Markus Weigand is Markus Alexander Weigand. Finally, the wrong Supplementary file 1 was originally published with this article; it has now been replaced with the correct file containing the missing eFigure1. The authors apologize for these mistakes. The original article has been corrected.

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SPIRIT 2013 Checklist: recommended items to address in a clinical trial protocol and related documents*. (DOC 122 kb)

Metastatic liver resection following cytoreductive chemotherapy is an accepted treatment for oligometastatic tumor diseases. Although pulmonary complications are frequently reported in patients undergoing liver surgery including liver transplantation, life-threatening acute respiratory failures in the absence of aspiration, embolism, transfusion-related acute lung injury (TRALI), pulmonary infection, or an obvious source of systemic sepsis are rare. We performed an extensive clinical review of a patient undergoing metastatic liver resection who had a clinical course compatible to an acute respiratory distress syndrome (ARDS) without an obvious cause except for the surgical procedure and multiple preoperative chemotherapies. We hypothesize that either the surgical procedure mediated by cytokines and tumor necrosis factor or possible toxic effects of oxygen applied during general anesthesia were associated with life-threatening respiratory failure in the patient. Discrete and subclinical inflammated alveoli (probably due to multiple preoperative chemotherapies with substances at potential risk for interstitial pneumonitis as well as chest radiation) might therefore be considered as risk factors.