Polymorphisms in tumor necrosis factor-α increase susceptibility to intra-abdominal Candida infection in high-risk surgical ICU patients*

Wójtowicz, Agnieszka and Tissot, Frederic and Lamoth, Frederic and Orasch, Christina and Eggimann, Philippe and Siegemund, Martin and Zimmerli, Stephan and Flueckiger, Ursula Maria and Bille, Jacques and Calandra, Thierry and Marchetti, Oscar and Bochud, Pierre-Yves and Fungal Infection Network of Switzerland, . (2014) Polymorphisms in tumor necrosis factor-α increase susceptibility to intra-abdominal Candida infection in high-risk surgical ICU patients*. Critical Care Medicine, 42 (4). pp. 304-308.

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Official URL: http://edoc.unibas.ch/54291/

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To evaluate the influence of genetic polymorphisms on the susceptibility to Candida colonization and intra-abdominal candidiasis, a blood culture-negative life-threatening infection in high-risk surgical ICU patients.; Prospective observational cohort study.; Surgical ICUs from two University hospitals of the Fungal Infection Network of Switzerland.; Eighty-nine patients at high risk for intra-abdominal candidiasis (68 with recurrent gastrointestinal perforation and 21 with acute necrotizing pancreatitis).; Eighteen single-nucleotide polymorphisms in 16 genes previously associated with development of fungal infections were analyzed from patient's DNA by using an Illumina Veracode genotyping platform. Candida colonization was defined by recovery of Candida species from at least one nonsterile site by twice weekly monitoring of cultures from oropharynx, stools, urine, skin, and/or respiratory tract. A corrected colonization index greater than or equal to 0.4 defined "heavy" colonization. Intra-abdominal candidiasis was defined by the presence of clinical symptoms and signs of peritonitis or intra-abdominal abscess and isolation of Candida species either in pure or mixed culture from intraoperatively collected abdominal samples. Single-nucleotide polymorphisms in three innate immune genes were associated with development of a Candida corrected colonization index greater than or equal to 0.4 (Toll-like receptor rs4986790, hazard ratio = 3.39; 95% CI, 1.45-7.93; p = 0.005) or occurrence of intra-abdominal candidiasis (tumor necrosis factor-α rs1800629, hazard ratio = 4.31; 95% CI, 1.85-10.1; p= 0.0007; β-defensin 1 rs1800972, hazard ratio = 3.21; 95% CI, 1.36-7.59; p = 0.008).; We report a strong association between the promoter rs1800629 single-nucleotide polymorphism in tumor necrosis factor-α and an increased susceptibility to intra-abdominal candidiasis in a homogenous prospective cohort of high-risk surgical ICU patients. This finding highlights the relevance of the tumor necrosis factor-α functional polymorphism in immune response to fungal pathogens. Immunogenetic profiling in patients at clinical high risk followed by targeted antifungal interventions may improve the prevention or preemptive management of this life-threatening infection.
Faculties and Departments:03 Faculty of Medicine > Bereich Querschnittsfächer (Klinik) > Anästhesiologie > Anästhesiologie (Steiner)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Querschnittsfächer (Klinik) > Anästhesiologie > Anästhesiologie (Steiner)
UniBasel Contributors:Siegemund, Martin
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Lippincott, Williams & Wilkins
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:09 Oct 2017 06:36
Deposited On:09 Oct 2017 06:36

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