By Stan Deresinski, MD, FACP, FIDSA

Clinical Professor of Medicine, Stanford University

Dr. Deresinski reports no financial relationships relevant to this field of study.

SYNOPSIS: Approximately one-tenth of asymptomatic patients with Clostridioides difficile colonization went on to develop disease. A wide range of antibiotic exposures represent a significant risk.

SOURCES: Poirier D, Gervais P, Fuchs M, et al. Predictors of Clostridioides difficile infection among asymptomatic, colonized patients: A retrospective cohort study. Clin Infect Dis 2020;70:2103-2210.

Webb BJ, Subramanian A, Lopansri B, et al. Antibiotic exposure and risk for hospital-associated Clostridioides difficile infection. Antimicrob Agents Chemother 2020;64(4). pii: e02169-19.

A retrospective examination by Webb et al of patients with Clostridioides difficile infection (CDI) in InterMountain Healthcare Hospitals from 2006 to 2012 identified multiple risk factors by multivariate analysis. These factors included prior exposure to each of a wide range (approximately 20) of antibiotics. The antibiotics posing the greatest risk were cephalosporins (beyond first-generation), carbapenems, fluoroquinolones, and clindamycin. The odds ratios for daptomycin and doxycycline were < 1.0, suggesting a possibly protective effect. Perhaps the most interesting result in the study was the finding that antibiotics received in the 60 days prior to hospital admission (often during a prior hospitalization) posed a greater risk than antibiotics administered during the index hospitalization, with the risk increasing by 12.8% for every day of prior antibiotic exposure.

The recognition of asymptomatic colonization of new hospital admissions by Clostridioides difficile has raised important questions regarding the risk of disease development. Beginning in November 2013, the Quebec Heart and Lung Institute began screening all admissions for evidence of asymptomatic colonization with Clostridioides difficile by detection of the tcdB gene by polymerase chain reaction (PCR), with isolation of all who had a positive test. By January 2017, they identified colonization in 960 (5%) of 19,112 admissions. Sixty-three percent received at least one dose of a systemically administered antibiotic, with a median duration of receipt of seven days.

Of the 513 colonized individuals who met criteria for inclusion in their study, 39 (7.6%) developed hospital-onset CDI at a median of four days after admission, although in one-fifth the diagnosis was based on new diarrhea and a positive admission test without repeat testing. The attributable mortality was 15%. Another 17 patients were deemed to have developed CDI after discharge, bringing the total proportion of colonized individuals who developed disease to 56 (10.9%).

Exposures to β-lactam/β-lactamase inhibitors (BL/BLI), second-generation cephalosporins, and carbapenems, as well as exposures to multiple antibiotic classes, were associated with an increased risk of CDI. Additional risk factors were cirrhosis, use of opioids, and increased length of stay. Of note is that the use of proton pump inhibitors was not found to be a risk factor, nor was the administration of antibiotics aimed to prevent the development of CDI, although the number of patients in this group was small.

COMMENTARY

All studies of risk factors for CDI have several limitations, beginning with the variable means of diagnosis. That is true regarding the two papers reviewed here. In the study by Poirier and colleagues, the range of intervals from admission testing to onset of CDI was apparently 1-27 days, meaning that some cases with “hospital-onset” disease likely were incubating the illness at the time of hospital entry. Poirier et al also do not provide information regarding antibiotic exposure prior to hospitalization.

In fact, antibiotic exposure in the 60 days prior to the hospitalization under examination was identified as an important risk factor in unscreened admissions by Webb and colleagues. As many others have, Poirier et al identified exposure to BL/BLI, cephalosporins, and carbapenems as risk factors, while Webb’s group found that almost any antibiotic (with the exceptions of daptomycin and doxycycline) potentially was implicated. The lesson is that a focus on reducing the use of individual antibiotics is an inadequate approach, and that all unnecessary antibiotic use must be targeted. In patients admitted to hospitals where screening for colonization is performed, special antibiotic stewardship attention could be directed at those whose tests are positive.