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Is Greater BSA Use for Sepsis, Bacteremia Affecting HO-CDIs?

Clostridium difficile infections (CDIs), which were responsible for over 500,000 infections and 44,000 deaths in 2014, represent a substantial burden to patients and our health care systems.1 The rate of CDI is higher among hospitalized patients in part because of the higher rate of extrinsic risk factors in this population, such as broad-spectrum antibiotic (BSA) use.2,3 BSAs are commonly used in the health care setting for empiric treatment of suspected bacteremia and sepsis. Guidelines for the treatment of sepsis have led to increased use of BSAs and, therefore, higher rates of hospital-onset CDI (HO-CDI).4

Increasing rates and severity of CDIs in the community and hospital settings have also been attributed to the emergence of a hypervirulent strain, B1/NAP1/027.5,6 The NAP1 strain demonstrates a higher rate of toxin production that has led to outbreaks and epidemics exhibiting a high incidence of severe and fatal complications.2,7,8 In the face of epidemiologic changes in CDIs, increased incidence of NAP1 strains, and overwhelming use of BSAs for sepsis, an examination of BSA use in this patient population is essential in developing strategies to mitigate these risks.

CDI and Broad-Spectrum Antibiotic Use 

Risk of CDI remains highest after the use of fluoroquinolones, clindamycin, and the broader spectrum beta-lactams.9 A cohort study by Brown and colleagues analyzed the charts of 34,000 patients admitted to an acute care hospital for more than 2 days, and the results revealed that antibiotic use was the strongest predictor of CDI incidence.10 Every 10% increase in antibiotic use was associated with an increase in CDI incidence of 2.1 per 10,000 patient days. To assess the risk of CDIs in patients admitted for sepsis, it is important to distinguish between overall antibiotic use and those commonly used to treat sepsis. In patients without antibiotic allergies, common regimens include vancomycin, beta-lactam/beta-lactamase combinations, third- and fourth-generation cephalosporins, and fluoroquinolones.

In many scenarios, vancomycin is the preferred empiric agent for the treatment of sepsis due to its broad activity against gram-positive organisms, including methicillin-resistant Staphylococcus aureus. Vancomycin is not often associated with development of CDI; however, a retrospective cohort study of 382 patients with HO-CDIs revealed that use of intravenous (IV) vancomycin for more than 7 days’ was independently associated with the development of HO-CDI (odds ratio [OR] 1.9).11 This was in contrast to metronidazole, which was shown to decrease the risk of HO-CDI (OR, 0.5). Several other studies’ results demonstrate similar associations between vancomycin and CDI.12,13 Hecht and colleagues describe a case of CDI after 29 days of IV vancomycin for the treatment of osteomyelitis.12 These findings may be due to the fact that IV vancomycin disrupts the gastrointestinal (GI) flora, yet does not achieve the levels needed to prevent CDIs.14 Vancomycin is infrequently associated with development of CDI, but the risk appears to be highest after prolonged therapy.