Vitamin D Deficiency Linked With CDI Recurrence, Study Finds

People with vitamin D deficiency (VDD) who become infected with Clostridioides difficile may face a higher risk of recurrence, according to a new report.

The study, published in the journal Cureus, suggests that vitamin D supplementation in initial cases of C diff infection (CDI) could be one method by which to reduce the risk of recurrence.

CDI is a persistent problem in health care facilities, accounting for 15% of all health care–associated infections in the United States, said the study authors. Although initial cases of the disease can often be successfully treated with antibiotics, patients who experience a recurrence often must use other approaches to overcome their infections, such as fecal microbiota transplants. Even with successful treatment of a recurrence, many patients will continue to have further recurrences.

The authors said CDI has previously been linked with nutritional deficiencies, including VDD. However, they said there has been limited investigation into the question of how VDD affects the morbidity and mortality of hospitalized patients with CDI.

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The investigators pulled data from the National Inpatient Survey of US hospitalizations, focusing on 2016 through 2019. They found 73,745 patients who were admitted to the hospital with CDI during those years. Of those, 1756 patients also had VDD. The authors then compared those 2 groups to identify trends in terms of outcomes and other disease characteristics.

They found that patients with VDD had a higher rate of recurrence after CDI than did patients without the deficiency (17.4% vs 14.7%; P < .05). Patients with VDD also tended to stay about a half-day longer in the hospital (10.38 days vs 9.83 days; P = .039). Conversely, those who did not have VDD had a higher mortality rate (6.1% vs 3.1%; P < .05), higher ileus rates (3.6% vs 2.6%; P = .024), and more expensive hospital stays ($102,527.90 vs $93,935.85).

The study authors said several reasons have been proposed for the apparent link between VDD and higher rates of recurrence.

“Firstly, vitamin D increases the expression of several antimicrobial peptides in the intestinal epithelium, such as cathelicidins (LL-37) and β-defensin, which serve critical roles in maintaining gut microbiome integrity,” they said.

In addition, they said vitamin D appears to promote the structural integrity of the intestinal lining. Vitamin D also seems to help protect the gut microbiome, they said.

“In fact, vitamin D supplementation in deficient patients significantly improved gut microbiota diversity,” they wrote.

It’s unclear why patients without VDD had higher mortality rates, the investigators said, noting that their study contradicts previous reports. They noted that some reports have suggested that patients with very high and very low levels of vitamin D had the highest mortality rates (a U-shaped correlation). In such studies, they said, it could be that the sickest patients (those at highest risk of mortality in the first place) might be receiving vitamin D supplementation, “providing a fictitious inverse correlation between VDD and mortality.”

They said studies like theirs are likely to be increasingly important as hospitals and public health workers continue to fight recurrent CDI, but they said more data will be needed to better understand exactly how to leverage their insights.

“Further investigation is needed to evaluate the impact of varying degrees of VDD on the chances of developing recurrent CDI,” they said. “In addition, future research may evaluate the impact of vitamin D supplementation even in nondeficient patients in improving CDI outcomes.”

Reference

Khrais A, Mathew AG, Kahlam A, Le A, Mittal A, Verma S. Investigating the correlation between clostridioides difficile infection and vitamin D deficiency. Cureus. Published online June 5, 2023. doi:10.7759/cureus.39970