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A study of data in the federal National Inpatient Sample from January 2018 to December 2020 showed that adult hospital deaths from Clostridioides difficile infection (CDI) rose by 23% in the US, from 4.2% pre-pandemic to 5.1% in the COVID pandemic. Risk was particularly associated with concomitant infection with SARS-CoV-2 and vice versa.

CDI is the most common nosocomial diarrhea, and the risk is mediated by antimicrobial stewardship, infection prevention, and control measures, all of which were compromised during COVID. This infection is associated with an estimated excess cost to the US healthcare system of $4.8 billion annually.

The nationwide study, published in Gastro Hep Advances, reported that 1 in 20 patients with CDI died in hospital during the pandemic and concomitant COVID-19 increased this risk by more than fivefold.

“In-hospital mortality from CDI is high; clinicians should evaluate these patients carefully, assess for relevant comorbidities, and be vigilant to intervene early and appropriately,” Christopher Ma, MD, MPH, gastroenterologist and an associate professor in the Cummings School of Medicine at the University of Calgary in Calgary, Alberta, Canada, and colleagues wrote.

“COVID-19 had such a major impact on health systems and the way that healthcare was and now continues to be delivered that we wanted to evaluate whether the pandemic impacted C difficile-related outcomes,” Ma told Medscape Medical News. “CDI has always been an important cause of hospitalization and mortality, but during the pandemic it was unclear whether some of the system-wide changes such as an increased emphasis on proper infection prevention and control measures, would ameliorate the impact of CDI — or whether these effects would be outweighed by other potential stressors to the health system.”

Study Details

During the study period, 300,301 unweighted admissions for CDI, representing an estimated 1,501,505 weighted admissions, were assessed. The mean patient age at discharge was 64.6 years, and 54.2% of patients were women. Most admissions (90.4%) involved significant comorbidity and approximately 3% of admissions for CDI involved patients with comorbid inflammatory bowel disease (IBD).

Pre-pandemic, rates of CDI-associated hospitalization were slowly decreasing at an average monthly percent change of -0.5% compared with slowly increasing rates of IBD- and stroke-related hospitalizations (+0.3% for both control conditions).

During the initial pandemic phase, CDI-associated hospitalizations decreased marginally (incidence rate ratio, 0.94; 95% CI, 0.93-0.96; P < .001) but fell significantly vs hospitalizations for the comparator conditions: stroke (P = .01) and IBD (P = .05) during the initial phase.

Mortality in CDI-associated hospitalizations increased most significantly in patients with concomitant COVID (adjusted odds ratio [aOR], 5.33; 95% CI, 4.39-6.48; P < .001).

In primary COVID patients with concurrent CDI, mortality risk also markedly increased (aOR, 1.48; 95% CI, 1.36-1.61; P < .001).

Ma’s group found these results somewhat surprising. “We observed such a dramatic increase in mortality among patients with COVID-19 and concomitant CDI, but of course, this is associational data, not causation,” he said. “We hypothesized that this result is likely related to which patients get CDI, and whether this represents the really sick inpatient population, who are already vulnerable for negative outcomes.”

As to factors driving the mortality spike, “I think everyone remembers how strained health systems were during this time,” Ma said. “There were tremendous pressures on every level of healthcare staff. That highlights the need for standardized protocols — for example, routine testing of CDI inpatients with diarrhea — to help manage the cognitive loads associated with managing sick inpatients.”

While the increase in mortality was modest, it was significant, said Bruce E. Hirsch, MD, of the Division of Infectious Diseases at Northwell Health’s North Shore University Hospital in Manhassett, New York, who was not involved in the analysis.

The COVID epidemic was a time of changing healthcare practices, he told Medscape Medical News. “Avoidance of testing, limitations of hospitalization, extensive antimicrobial use, and the use of alcohol gels for hand hygiene inadequate to eliminate C diff spores, and the challenges of maintaining a clean and well-stocked hospital environment contributed to poorer clinical outcomes, especially early in the evolving epidemic,” he said. 

Hirsch noted that the authors reviewed possible associations with disease severity including altered gut microbiome and enhanced angiotensin-converting enzyme 2 enterocyte expression. “These may have enhanced the severity of illness in patients with both infections,” he said. “The findings reinforce current protocols on diagnostic testing, patient isolation, environmental cleaning, and antibiotic stewardship — protocols that are difficult to implement when challenged in pandemic conditions.”

This study received no financial support. The authors had no potential financial, professional, or personal conflicts of interest. Hirsch had no relevant competing interests.