Comparative Analysis of Prevalence, Risk Factors, and Molecular Epidemiology of Antibiotic-Associated Diarrhea Due to Clostridium difficile, Clostridium perfringens, and Staphylococcus aureus

ABSTRACTWe prospectively studied the comparative epidemiology and risk factors for Clostridium difficile, Clostridium perfringens, and Staphylococcus aureusantibiotic-associated diarrhea (AAD). Four thousand six hundred fifty-nine inpatient fecal specimens (11 months) were tested for C. difficilecytotoxin, C. perfringensenterotoxin, and S. aureusby Vero cell assay, enzyme-linked immunosorbent assay, and growth on fresh blood agar, respectively. Two distinct age-, sex-, and location-matched control patient groups were used for multivariate logistic regression risk factor analyses: symptomatic patients who were AAD pathogen negative and asymptomatic patients with histories of recent antimicrobial therapy. All AAD pathogen isolates were DNA fingerprinted. In AAD cases, the prevalences of C. difficilecytotoxin, C. perfringensenterotoxin, and S. aureuswere 12.7%, 3.3%, and 0.2%, respectively (15.8% overall). Age of >70 years was a common risk factor. Other risk factors for infective AAD and C. difficileAAD included length of hospital stay and use of feeding tubes (length of stay odds ratios [OR], 1.017 and 1.012; feeding tube OR, 1.864 and 2.808). Female gender and use of antacids were significantly associated with increased risk of C. perfringensAAD (OR, 2.08 and 2.789, respectively), but unlike what was found for C. difficileAAD, specific antibiotic classes were not associated with increased risk. A limited number of genotypes caused the majority of C. difficileand C. perfringensAAD cases. Similar to what was found for C. difficileAAD, there was epidemiological evidence of C. perfringensAAD case clustering and reinfection due to different strains. C. difficileAAD was approximately 4 and 60 times more common than C. perfringensAAD and S. aureusAAD, respectively. Risk factors for these AAD pathogens differed, highlighting the need to define specific control measures. There is evidence of nosocomial transmission in cases of C. perfringensAAD.