Epidemiology Of Fungal Infection And β-defensin 1 Gene Polymorphisms In Sepsis

Part 1 Epidemiology of invasive fungal infection in severe sepsisObjective:Invasive fungal infection (IFI) is increasingly common in critical illness with severe sepsis and may be associated with extra mortality and resourse consumption. The aim of this study was to determine the rate and characteristics of IFI in severe sepsis within Chinese intensive care units (ICUs), as well as to investigate the impact of IFI on the outcomes of critically ill surgical patients with severe sepsis by means of matched cohort analysis.Methods:Records for all admissions to 10 university hospital surgical intensive care units (ICUs) from December 2004 to November 2005 were reviewed. Patients who met criteria for severe sepsis were included. IFI was identified using established criteria based on microbiologic or histological evidence. A matched cohort study was conducted to analyze the relationship between IFI and outcomes of severe sepsis.Results:A total of 318 patients with severe sepsis were enrolled during the study period, of whom 90 (28.3%) were identified as having IFI. A total of 100 strains of fungi (58% Candida albicans) were isolated from these patients. Independent risk factors for IFI in patients with severe sepsis included mechanical ventilation (>3 days), Acute Physiology and Chronic Health Evaluation score, coexisting infection with both Gram-positive and Gram-negative bacteria, and urethral catheterization (>3 days). Compared with the control cohort, IFI was associated with increased hospital mortality (P＜0.001), high hospital costs (P=0.038), and prolonged stay in the ICU (P<0.001) and hospital (P =0.020).Conclusion:IFI is frequent in patients with severe sepsis in surgical ICUs and is associated with excess risk for hospital mortality, longer ICU and hospital stays, and greater consumption of medical resources. Part 2 Association study betweenβ-defensin 1 gene polymorphisms and fungal infection in severe sepsisObjective:To investigate whether single nucleotide polymorphisms (SNPs) and haplotypes within the promoter ofβ-defensin 1 (DEFB1) gene are associated with the incidence of fungal infection in patients suffering from severe sepsis by case-control association analysis.Method:In the present case-control study,211 patients with severe sepsis were enrolled. Sepsis was diagnosed according to the American College of Chest Physician/Society of Critical Care Medicine Consensus Conference Communittee criteria and severity of sepsis was assessed using the Sepsis-related Organ Failure Assessment Score. Based on the detection of fungal infection during the ICU stay, the 211 patients were divided into the fungal infection group (groupⅠ) or the control group (group C). Genotypes of-1816A/G,-390A/T,-52A/G,-44C/G and-20A/G within DEFB1 gene were assayed in all 211 patients by means of direct sequencing, Allele-specific PCR amplifications or high-throughput site-specific TaqMan assay. Haplotype was estimated using StatSNPs program. The association between the genomic variations (allele, genotype and haplotype) and fungal infection were analyzed using x2-test or Fisher's exact test. Odds ratios in the case-control study were calculated to evaluate allele's risk for the predisposition to fungal infection in severe sepsis.Results:GroupⅠenrolled 80 patients,43 of which were male, with a mean age of 60.81±18.30. GroupⅠenrolled 131 patients,80 of which were male, with a mean age of 60.42±17.03. The two groups had similar gender composition and mean age (all, p>0.05) Assayed SNPs of both groups were in Hardy-Weinberg equilibrium. The distributions of allelic frequencies and genotype frequencies between groupⅠand group C showed no significant difference (all, p>0.05). Four common haplotypes AAACG, ATGCA, GTGGG and ATACG were estimated in the studied cohort. The distributions of haplotype frequencies in the defined groups showed no significant difference (all, p>0.05).Conclusion:The genomic variations within DEFB1 gene were not associated with fungal infections in severe sepsis. These findings suggest that DEFB1 gene polymorphism may not serve as an important genetic marker for predisposition to fungal infection in severe sepsis.