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Comorbid CDI Leads to Worse Outcomes in Patients With COVID-19


Investigators say their data show the importance of vaccination and antibiotic stewardship programs.

Clostridioides difficile infection (CDI) increases the risk of in-hospital mortality and complications among patients with COVID-19, according to a new report.

The authors of the study, published in Infectious Disease Reports, wrote that health care providers need to be aware of the risks associated with concurrent COVID-19 and CDI because COVID-19 has entered an endemic phase and CDI rates increased after the start of the pandemic. They noted that there are several theories about why CDI rates increased during the pandemic.

“The increased use of antibiotics during the COVID-19 pandemic, particularly for treating bacterial co-infections and as a prophylactic measure, may have contributed to the higher incidence of CDI and the emergence of more resistant strains of Clostridioides difficile,” they wrote.

The exact nature of the correlation between COVID-19 and CDI remains unclear, but the authors said the association is strong enough to warrant action.

“A reduction in the current overuse of antibiotics could potentially control antibiotic resistance and side effects, including CDI, during the COVID-19 pandemic,” they said.

To better understand the interplay between CDI and COVID-19, the investigators decided to see how CDI affected outcomes in patients with COVID-19. They used data from the 2020 National Inpatient Sample, which includes more than 1.6 million patients who were hospitalized with COVID-19. Of those, 10,710 (0.6%) also had a diagnosis of CDI.

When they compared the outcomes of patients with COVID-19 with and without concurrent CDI, they found that patients with CDI had higher rates of in-hospital mortality (23% vs 13.4%), in-hospital complications (2.7% vs 0.8%), and septic shock (21.0% vs 7.2%). Furthermore, patients with concurrent CDI stayed in the hospital nearly twice as long (15.1 vs 8 days), and their hospitalization costs were double those of patients without CDI.

One likely reason for the poorer outcomes in the concurrent CDI cohort, the authors said, was the higher prevalence of chronic medical conditions among that group. For instance, patients in the CDI group were more likely to have hypertension, coronary artery disease, and congestive heart failure. Many patients in the CDI/COVID group also had diabetes, which they said increases a patient’s risk of morbidity and mortality.

In addition, the authors found a positive association between CDI and COVID-19 and chronic liver disease (CLD). They noted that CLD is associated with changes in the gut microbiome and bile acid synthesis, both of which increase the risk of CDI.

“Keeping the above mechanisms in mind, multiple studies have shown that CDI and COVID-19 are individually associated with higher morbidity and mortality in patients with CLD,” they wrote.

Turning toward solutions, the investigators began by urging better antibiotic stewardship. They said many patients with COVID-19 are given antibiotics even though they are ineffective against viruses like SARS-CoV-2 and that providers sometimes use antibiotics to treat bacterial co-infections or to prevent secondary infections.

“However, the inappropriate use of antibiotics can lead to increased resistance, CDI, allergic reactions, and increased health care costs,” they warned.

The investigators said health care providers should also redouble their efforts to recommend vaccinations against COVID-19, especially in patients who are immunocompromised. They also emphasized that patients with COVID-19 who develop diarrhea should be tested for CDI to ensure prompt diagnosis and treatment and that providers should aggressively use physical and occupational therapy to reduce long hospital stays and help patients return to their normal activities sooner.


Awan RU, Gangu K, Nguyen A, et al. COVID-19 and Clostridioides difficile coinfection outcomes among hospitalized patients in the United States: an insight from National Inpatient Database. Infect Dis Rep. 2023;15(3):279-291. doi:10.3390/idr15030028

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