Epidemic Clostridium difficile- Associated Diarrhea: Role of Second- and Third-Generation Cephalosporins

OBJECTIVE: To better define the role of multiple risk factors for cytotoxic Clostridium difficile-associated diarrhea. DESIGN: Case-control study. SETTING: A Veterans Affairs Medical Center. PATIENTS: Thirty-three case patients with C difficile-associated diarrhea. Two control groups were used: one group consisted of 32 patients from the same ward as the case patients, and one group consisted of 34 patients with nosocomial diarrhea and negative C difficile toxin assays. INTERVENTION: None. RESULTS: Multivariate analyses revealed that exposure to second- or third-generation cephalosporins was the most important independent risk factor, even after controlling for other antimicrobial use (odds ratio OR = 8.3, 95% confidence interval CI95 = 1.4 to 48.9 compared to ward controls; OR = 9.6, CI95 = 2.1 to 44.1 compared with diarrhea controls). Persons exposed to two or more antimicrobials simultaneously were at substantially elevated risk (OR = 18.7, CI95 = 4.1 to 85.8 compared with ward controls; OR = 21.5, CI95 = 3.2 to 141.9 compared with diarrhea controls). CONCLUSION: Physicians should consider carefully the appropriateness of second- and third-generation cephalosporin use and combination antimicrobial therapy, especially during nosocomial C difficile-associated diarrhea outbreaks (Infect Control Hosp Epidemiol 1994;15:88-94).