(1 → 3)-β-D-Glucan-guided antifungal therapy in adults with sepsis: the CandiSep randomized clinical trial.

Patrick Meybohm, Daniel Thomas-Rüddel, Michael Bauer, Oliver A Cornely, Peter Schlattmann, Oliver Kurzai, Ixchel Castellanos, Christian Putensen, Raphael Weiss, Dirk Schädler, Ulf Günther, Onnen Moerer, Ulrich Jaschinski, Daniel Richter, Frank Bloos, Matthias Gründling, Matthias Drüner, Andreas Weyland, Norbert Weiler, Gunther Hempel, Johann Motsch, Dominik Jarczak, Sven-Olaf Kuhn, Geraldine de Heer, Klaus Kogelmann, Philipp Simon, Stefan Kluge, Jürgen Held

Journal: Intensive care medicine 2022;48(7):865-875

PMID: 35708758

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Abstract

PURPOSE

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).

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

Address: Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany. [email protected].; Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Am Klinikum 1, 07747, Jena, Germany. [email protected].; Mikrobiologisches Institut-Klinische Mikrobiologie Immunologie und Hygiene, Universitätsklinikum Erlangen Und Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Erlangen, Germany.; Department of Intensive Care Medicine, University Hospital Hamburg-Eppendorf, Hamburg, Germany.; Department of Anesthesiology and Intensive Care Medicine, University of Leipzig Medical Centre, Leipzig, Germany.; Department of Anesthesiology and Surgical Intensive Care Medicine, University Hospital Augsburg, Augsburg, Germany.; Department of Anesthesiology and Intensive Care Medicine, Hospital Emden, Emden, Germany.; Department of Anesthesiology and Intensive Care Medicine, University Hospital Greifswald, Greifswald, Germany.; Department of Anesthesiology, University Hospital Heidelberg, Heidelberg, Germany.; Department of Anesthesiology and Intensive Care Medicine, University Medical Center Kiel, Kiel, Germany.; Research Center Neurosensory Science, Carl von Ossietzky Universität Oldenburg, Oldenburg, Germany.; Department of Anesthesiology, Intensive Care, Emergency and Pain Medicine, University Hospital Wuerzburg, Würzburg, Germany.; Department of Anesthesiology, University Medical Center, Georg-August-University, Göttingen, Germany.; University Clinic of Anaesthesiology, Intensive Care, Emergency Medicine and Pain Therapy, Klinikum Oldenburg, Oldenburg, Germany.; Department of Anesthesiology, Surgical Intensive Care Medicine and Pain Therapy, University Hospital Münster, Munster, Germany.; Division of Intensive Care Medicine, Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany.; Department of Anesthesiology, University Hospital, Erlangen, Germany.; Institute for Hygiene and Microbiology, Julius Maximilians University Würzburg, Würzburg, Germany.; National Reference Center for Invasive Fungal Infections NRZMyk, Leibniz Institute for Natural Product Research and Infection Biology-Hans-Knoell-Insitute, Jena, Germany.; Institute of Medical Statistics, Computer Sciences and Data Science, Jena University Hospital, Jena, Germany.; Department I of Internal Medicine, Excellence Center for Medical Mycology (ECMM), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.; Chair Translational Research, Faculty of Medicine and University Hospital Cologne, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.; Faculty of Medicine and University Hospital Cologne, Clinical Trials Centre Cologne (ZKS Köln), University of Cologne, Cologne, Germany.; German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany.; Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany.; Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Am Klinikum 1, 07747, Jena, Germany.

DOI: 10.1007/s00134-022-06733-x

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https://dx.doi.org/10.1007/s00134-022-06733-x

MeSH Terms: Adult, Antifungal Agents, Candidiasis, Invasive, Glucans, Humans, Sensitivity and Specificity, Sepsis, beta-Glucans