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Contribution of Genetic and Clinical Risk Factors to Development of Candidemia in Patients Receiving Home Parenteral Nutrition.

ABSTRACT: BACKGROUND:Patients receiving home parenteral nutrition (HPN) have an increased risk for central line-associated bloodstream infections (CLABSIs), including candidemia. Recently, 7 single-nucleotide polymorphisms (SNPs) in TLR1, CD58, LCE4A-Clorf68, and TAGAP have been associated with the development of candidemia. Identification of host-genetic as well as clinical risk factors may help to identify patients who have an increased susceptibility to such infections. The aim of this study was to investigate the relevance of the reported SNPs in patients receiving HPN, and to explore clinical risk factors associated with candidemia. METHODS:We analyzed blood samples of adult patients who started HPN between 1976 and 2017 at our referral center for intestinal failure. Primary outcome was the association between TLR1, CD58, LCE4A-Clorf68, or TAGAP SNPs and candidemia. Secondary outcomes included the relation between severity of infection and these SNPs, and clinical risk factors for candidemia. RESULTS:Of 341 included patients, 42 (12%) experienced a candidemia (range 1-6). None of the 7 SNPs were associated with candidemia or the severity of infection. The rate of non-Candida-related CLABSIs was significantly associated with candidemia (rate ratio, 1.29; 95% CI, 1.14-1.46; P < 0.001). CONCLUSIONS:None of 7 known SNPs in TLR1, CD58, LCE4A-Clorf68, or TAGAP were associated with candidemia or severity of infection in patients receiving HPN. The rate of non-Candida-related CLABSIs was significantly associated with the development of candidemia. The latter supports the key role of aseptic catheter handling with respect to Candida susceptibility in patients receiving HPN.

SUBMITTER: Wouters Y

PROVIDER: S-EPMC7065185 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Contribution of Genetic and Clinical Risk Factors to Development of Candidemia in Patients Receiving Home Parenteral Nutrition.

Wouters Yannick Y Roelofs Hennie M J HMJ Netea Mihai G MG Te Morsche René H M RHM Wanten Geert J A GJA

JPEN. Journal of parenteral and enteral nutrition 20190510 2

<h4>Background</h4>Patients receiving home parenteral nutrition (HPN) have an increased risk for central line-associated bloodstream infections (CLABSIs), including candidemia. Recently, 7 single-nucleotide polymorphisms (SNPs) in TLR1, CD58, LCE4A-Clorf68, and TAGAP have been associated with the development of candidemia. Identification of host-genetic as well as clinical risk factors may help to identify patients who have an increased susceptibility to such infections. The aim of this study wa ...[more]

PMID: 31074043

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Project description:Manganese, an essential metal for normal growth and development, is neurotoxic on excessive exposure. Standard trace element-supplemented neonatal parenteral nutrition (PN) has a high manganese content and bypasses normal gastrointestinal absorptive control mechanisms, which places infants at risk of manganese neurotoxicity. Magnetic resonance (MR) relaxometry demonstrating short T1 relaxation time (T1R) in the basal ganglia reflects excessive brain manganese accumulation.This study tested the hypothesis that infants with greater parenteral manganese exposure have higher brain manganese accumulation, as measured by MR imaging, than do infants with lower parenteral manganese exposure.Infants exposed to parenteral manganese were enrolled in a prospective cohort study. Infants classified as having high manganese exposure received >75% of their nutrition in the preceding 4 wk as PN. All others were classified as having low exposure. Daily parenteral and enteral manganese intakes were calculated. Whole-blood manganese was measured by high-resolution inductively coupled plasma mass spectrometry. Brain MR relaxometry was interpreted by a masked reviewer. Linear regression models, adjusted for gestational age (GA) at birth, estimated the association of relaxometry indexes with total and parenteral manganese exposures.Seventy-three infants were enrolled. High-quality MR images were available for 58 infants, 39 with high and 19 with low manganese exposure. Four infants with a high exposure had blood manganese concentrations >30 ?g/L. After controlling for GA, higher parenteral and total manganese intakes were associated with a lower T1R (P = 0.01) in the globus pallidus and putamen but were not associated with whole-blood manganese (range: 3.6-56.6 ?g/L). Elevated conjugated bilirubin magnified the association between parenteral manganese and decreasing T1R.A short T1R for GA identifies infants at risk of increased brain manganese deposition associated with PN solutions commonly used to nourish critically ill infants. These trials were registered at clinicaltrials.gov as NCT00392977 and NCT00392730.

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Contribution of Genetic and Clinical Risk Factors to Development of Candidemia in Patients Receiving Home Parenteral Nutrition.

Publications

Contribution of Genetic and Clinical Risk Factors to Development of Candidemia in Patients Receiving Home Parenteral Nutrition.

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