ABSTRACT: Previous studies have shown that failure to produce serum antibodies to C. difficile (CD) toxin A is associated with more severe and recurrent C. difficile-associated diarrhea (CDAD); and that presence of AA genotype in the interleukin (IL)-8 gene promoter -251 position is associated with increased susceptibility to CDAD. This study examined the relationship between serum immunoglobulin G antibodies to CD toxin A and the presence of IL-8 AA genotype in hospitalized patients with CDAD.
At enrollment, blood for host IL-8 genotype, serum for CD anti-toxin A antibody, and stool for IL-8 by enzyme-linked immunosorbent assay were obtained in CDAD patients and in CD-toxin-negative asymptomatic controls.
Nine of 24 (37.5%) CDAD and 3 of 20 (15%) controls were CD anti-toxin A positive (P = .095). Eleven of 24 (45.8%) CDAD subjects were positive for AA genotype compared with 5 of 20 (25.0%) controls (P = .0019). One of 11 (9.1%) CDAD with AA genotype were positive for anti-toxin A antibodies compared with 8 of 13 (61.5%) non-AA genotype CDAD (P < .0001). Fecal IL-8 concentration for the single antibody-positive CDAD subject with AA genotype was lower than the median level of 822 microg/mL seen in 10 anti-toxin A antibody-negative subjects with CDAD.
This study provided evidence that host susceptibility to C. difficile diarrhea is related both to a defective humoral immune response to CD toxin A and host IL-8 AA genotype.
Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 09/2007; 5(8):964-8. · 5.64 Impact Factor
ABSTRACT: To assess the prevalence of diarrhea at a university-affiliated medical center and the presence of modifiable risk factors.
A point prevalence survey was conducted. All patients hospitalized for more than 24 hours were asked if they were experiencing diarrhea. Stools of patients not previously tested were assessed for Clostridium difficile (CD) toxins A and B. Univariate analysis and multivariate logistic regression analyses were used to identify modifiable variables associated with diarrhea (significance defined as p < 0.05).
Four hundred eighty-five hospitalized patients were interviewed, of whom 60 (12.4%) reported 2 or more loose, unformed stools in the last 24 hours. Six of 81 (7.4%) patients tested positive for CD toxin. Three (50%) of the CD toxin-positive patients had not previously been tested during the current admission. Patients with diarrhea were more likely to have tested CD toxin-positive (OR 10.6; p = 0.01), received antibiotics (OR 1.79; p = 0.04), or been hospitalized for a longer period of time (p = 0.04).
Diarrhea was prevalent in 12.4% of hospitalized patients at a large university hospital at one point in time. Patients with diarrhea were more likely to have CD infection, receive antibiotics, or experience a longer hospitalization. Half of the CD diarrhea cases occurring in the hospital had been previously unidentified. Hospitalized patients should be evaluated for diarrhea on an ongoing basis with appropriate interventions instituted.
Annals of Pharmacotherapy 07/2006; 40(6):1030-4. · 2.13 Impact Factor
ABSTRACT: Mucosal interleukin 8 (IL-8) and neutrophil recruitment are central to the pathogenesis of Clostridium difficile (CD) toxin-induced diarrhea (CDD). We hypothesized that like other inflammatory mucosal infections, susceptibility to CDD would relate to genetically determined variations in the production of IL-8.
Fecal IL-8 production and single nucleotide polymorphism (SNP) frequency in the -251 region of the IL-8 gene were determined in hospitalized patients: 42 with CDD, 42 with CD-negative diarrhea, and 41 without diarrhea. Cases and controls were matched by age, length of hospital stay, comorbidity, and receipt of antibiotics.
An association was found between the IL-8 -251 A/A allele and occurrence of CDD, 39%versus 16% (OR = 3.26, 95% CI 1.09-9.17) and 17% (OR = 5.50, 95% CI 1.22-24.8) for the two control groups. Comparing results by IL-8 genotype for the CDD cases, median and mean fecal IL-8 levels were significantly higher for the -251 A/A genotype (p = 0.03 for median and 0.001 for mean).
These studies indicate a common SNP in the IL-8 gene is associated with increased susceptibility to CDD and with increased fecal IL-8 in diarrheal stools.
The American Journal of Gastroenterology 06/2006; 101(5):1112-6. · 7.28 Impact Factor