A Large Outbreak ofClostridium difficile–Associated Disease with an Unexpected Proportion of Deaths and Colectomies at a Teaching Hospital Following Increased Fluoroquinolone Use

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Abstract
Background and Objective: Fluoroquinolones have not been frequently implicated as a cause ofClostridium difficileoutbreaks. NosocomialC. difficileinfections increased from 2.7 to 6.8 cases per 1,000 discharges (P< .001). During the first 2 years of the outbreak, there were 253 nosocomialC. difficileinfections; of these, 26 resulted in colectomy and 18 resulted in death. We conducted an investigation of a largeC. difficileoutbreak in our hospital to identify risk factors and characterize the outbreak.Methods: A retrospective case-control study of case-patients withC. difficileinfection from January 2000 through April 2001 and control-patients matched by date of hospital admission, type of medical service, and length of stay; an analysis of inpatient antibiotic use; and antibiotic susceptibility testing and molecular subtyping of isolates were performed.Results: On logistic regression analysis, clindamycin (odds ratio [OR], 4.8; 95% confidence interval [CI95], 1.9-12.0), ceftriaxone (OR, 5.4; CI95, 1.8-15.8), and levofloxacin (OR, 2.0; CI95, 1.2-3.3) were independently associated with infection. The etiologic fractions for these three agents were 10.0%, 6.7%, and 30.8%, respectively. Fluoroquinolone use increased before the onset of the outbreak (P< .001); 59% of case-patients and 41% of control-patients had received this antibiotic class. The outbreak was polyclonal, although 52% of isolates belonged to two highly related molecular subtypes.Conclusions: Exposure to levofloxacin was an independent risk factor forC. difficile-associateddiarrhea and appeared to contribute substantially to the outbreak. Restricted use of levofloxacin and the other implicated antibiotics may be required to control the outbreak.

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