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Association of Immune Cell Subtypes and Phenotype With Subsequent Invasive Candidiasis in Patients With Abdominal Sepsis

Arens, Christoph; Kramm, Timo; Decker, Sebastian; Spannenberger, Jens; Brenner, Thorsten; Richter, Daniel Christoph; Weigand, Markus Alexander; Uhle, Florian; Lichtenstern, Christoph

doi: 10.1097/SHK.0000000000001251
Clinical Science Aspects

Background: In nonneutropenic intensive care unit (ICU) patients, current risk stratification scores lack specificity to reliably predict the risk of a prospective invasive candidiasis (IC). We aimed to explore possible associations of distinct immunological markers with different degrees of Candida affection in patients with abdominal sepsis.

Methods: The presented explorative, noninterventional diagnosis study recruited patients admitted to the surgical ICU at Heidelberg University Hospital with abdominal sepsis. Over 5 days, we determined white blood cell count, 1,3-β-D-glucan, and HLA-DR expression; the amount of Th1, Th17, regulatory T, T helper, and cytotoxic T cells; Dectin-1 and TLR2-expression; the amount of T, B, and NK cells; the ex vivo secretion of IL-8 upon stimulation with LPS, flagellin, and zymosan; and the distribution of distinct T-cell cytokines in a daily manner. On day 21, patients’ Candida infection status was stratified in no colonization or IC, colonization or IC.

Results: A total of 26 patients were included. On day 21, five patients showed no colonization or IC, in 13 patients a colonization was detected, and eight patients were diagnosed with IC. On study inclusion, the stratification groups showed comparable values in standard laboratory parameters and morbidity scores. Decreased B and NK cell counts, as well as reduced IL-8 secretion after ex vivo stimulation with LPS or flagellin seemed to be associated with a higher risk of subsequent Candida colonization. Even lower values could distinguish the therapy-relevant difference between prospective IC from colonization alone.

Conclusions: We were able to show distinct immune system impairments in early abdominal sepsis by specific immune-based measurements. A possible association of these impairments with a subsequent Candida affection is shown.

Department of Anaesthesiology, Heidelberg University Hospital, Heidelberg, Germany

Address reprint requests to Christoph Lichtenstern, MD, Department of Anaesthesiology, Heidelberg University Hospital, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany. E-mail:

Received 24 May, 2018

Revised 19 June, 2018

Accepted 8 August, 2018

The study protocol (trial code: S-444/2014) was approved by the local ethics committee of the Medical Faculty of the Ruprecht-Karls-University Heidelberg, Germany. After patient identification, the consent by a relative with a health care proxy or a medical consultant was obtained. Informed consent of the patient was obtained at the earliest possible time point after extubation.

Authors’ contributions: CA, MAW, FU, and CL were responsible for study design and conduct, data and sample acquisition, statistical analysis, and interpretation as well as for writing the manuscript. TK, SD, and JS acquired samples and data, assisted in the statistical analysis and interpretation, approved, and helped to draft the manuscript. TB and DCR supported the study conduct as well as data acquisition, discussed the data, and participated in data interpretation as well as manuscript preparation. All authors read and approved the final version of the manuscript.

The investigator-initiated study was supported by an ASPIRE grant of the PFIZER Corporation (New York City, USA). The funding body did not have a bearing on the design of the study, collection, analysis, and interpretation of data or in writing the manuscript.

The authors report no conflicts of interest.

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