title: Single nucleotide polymorphisms of the tcdC gene and presence of the binary toxin gene predict recurrent episodes of Clostridium difficile infection.
abstract: OBJECTIVE
  To identify Clostridium difficile genotypes, which are associated with recurrent C difficile infection (RCDI).
  
  
  BACKGROUND
  Reliable bacterial genetic factors predicting RCDI are currently lacking.
  
  
  METHODS
  Inpatients and outpatients 18 years or older treated at our institution for C difficile infection (CDI) of any severity were consecutively enrolled. CDI was defined as symptoms of colitis with a positive PCR stool test. Each bacterial isolate was studied for virulence factors: tcdC mutations, including single nucleotide polymorphisms (SNPs) via PCR, the presence of genes for toxins A, B and binary toxin using restriction fragment length polymorphism, and identification of ribotype by PCR. χ tests, t tests, and logistic and linear regression were used to determine which virulence factors predicted RCDI and the need for hospital admission, with corrections made for multiple statistical comparisons.
  
  
  RESULTS
  Seventy-three patients (male: 52%; mean age: 66 ± 15 years) were studied. Binary toxin gene (P = 0.03) was associated with at least 1 episode of RCDI, as was the presence of SNPs C184T (P = 0.006) and A117T (P = 0.003). The presence of the binary toxin gene with either of these tcdC SNPs increased RCDI by 80% (P = 0.0002) but did not predict the need for hospital admission. None of the other virulence factors, including ribotype 027, were predictive of RCDI.
  
  
  CONCLUSIONS
  The presence of the binary toxin gene and tcdC SNPs C184T and A117T strongly predict RCDI. The presence of both tcdC SNPs and the binary toxin gene significantly increased the risk of RCDI, which might warrant longer antibiotic courses to eradicate the infection.
authors.affiliation: Departments of *Surgery †Public Health Sciences and Statistics, The Pennsylvania State University College of Medicine, Hershey, PA.
authors.forename: David B
authors.initials: DB
authors.lastname: Stewart
authors.forename: Arthur S
authors.initials: AS
authors.lastname: Berg
authors.forename: John P
authors.initials: JP
authors.lastname: Hegarty
mesh_terms: D000368:Aged; D001426:Bacterial Proteins / Q000235:genetics*; D001427:Bacterial Toxins / Q000235:genetics*; D016360:Clostridioides difficile / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity*; D003015:Clostridium Infections / Q000235:genetics / Q000382:microbiology*; D004768:Enterotoxins / Q000235:genetics; D005243:Feces / Q000382:microbiology; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D012008:Recurrence; D012097:Repressor Proteins / Q000235:genetics*; D021521:Ribotyping; D037521:Virulence Factors / Q000235:genetics*
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D004768:Enterotoxins; D005819:Genetic Markers; D012097:Repressor Proteins; C105615:TcdC protein, Clostridium difficile; D037521:Virulence Factors