Original Article

Outcomes of Clostridioides difficile in Patients with Vitamin D Deficiency: A Propensity-Matched National Inpatient Sample Analysis

Authors: Vijay Gayam, MD, FACP, Amrendra Kumar Mandal, MD, Chobufo Muchi Ditah, MD, Jasdeep Sidhu, MD, Venu Madhav Konala, MD, Sreedhar Adapa, MD, Srikanth Naramala, MD, Pavani Garlapati, MD


Objectives: We aimed to determine in-hospital outcomes, length of hospital stay, and resource utilization in a contemporary cohort of Clostridioides difficile infection (CDI) and vitamin D deficiency (VDD).

Methods: The National Inpatient Sample database for 2016 and 2017 was used for data analysis using International Classification of Diseases, Tenth Revision, Clinical Modification/Procedure Coding System (ICD-10-CM/PCS) codes to identify the patients with the principal diagnosis of CDI and VDD. We assessed the all-cause in-hospital mortality, morbidity, length of hospital stay (LOS), and total costs between propensity-matched groups of CDI without VDD versus CDI with VDD.

Results: We identified 202,234 patients with CDI, 4515 of whom were patients with VDD and 197,719 of whom were without VDD. After propensity matching, there was no difference in the in-hospital mortality between the two groups (odds ratio [OR] 1.5, 95% confidence interval [CI] 0.58–4.3; P = 0.90). CDI with VDD has a higher odds of sepsis (OR 1.6, 95% CI 1.3–1.9; P = 0.0), and peritonitis (OR 1.6, 95% CI 1.4–3.8; P = 0.01). Mean LOS (5.9 ± 1.8 vs 5.4 ± 2, P < 0.01) and mean total charges ($11,500 vs $9971, P < 0.04) were higher in CDI with VDD. The factors affecting the LOS were acute coronary syndrome (P = 0.04), mechanical ventilation (P = 0.03), obesity (P = 0.004), acute kidney injury (P = 0.04), and sepsis (P = 0.05).

Conclusions: In this large cohort in a propensity-matched analysis, VDD does not increase the in-hospital mortality in CDI. VDD increases the odds of complications with a higher LOS and resource utilization. These findings may be clinically relevant to guide clinicians to routinely monitor vitamin D status and supplement in patients at risk of CDI.
Posted in: Infectious Disease30

This content is limited to qualifying members.

Existing members, please login first.

If you have an existing account please login now to access this article or view your purchase options.

Purchase only this article ($15)

Create a free account, then purchase this article to download or access it online for 24 hours.

Purchase an SMJ online subscription ($75)

Create a free account, then purchase a subscription to get complete access to all articles for a full year.

Purchase a membership plan (fees vary)

Premium members can access all articles plus recieve many more benefits. View all membership plans and benefit packages.


1. Ananthakrishnan AN. Clostridium difficile infection: epidemiology, risk factors and management. Nat Rev Gastroenterol Hepatol 2011;8:17–26. 2. Zilberberg MD, Shorr AF, Kollef MH. Increase in adult Clostridium difficile-related hospitalizations and case-fatality rate, United States, 2000-2005. Emerg Infect Dis 2008;14:929–31. 3. Lessa FC, Mu Y, Bamberg WM, et al. Burden of Clostridium difficile infection in the United States. N Engl J Med 2015;372:825–834. 4. Centers for Disease Control and Prevention. Vital signs: preventing Clostridium difficile infections. MMWR Morb Mortal Wkly Rep 2012;61:157–162. 5. Dubberke ER, Wertheimer AI. Review of current literature on the economic burden of Clostridium difficile infection. Infect Control Hosp Epidemiol 2009;30:57–66. 6. Wenisch J, Schmid D, Tucek G, et al. A prospective cohort study on hospital mortality due to Clostridium difficile infection. Infection 2012;40:479–484. 7. Bikle DD. Vitamin D and the immune system: role in protection against bacterial infection. Curr Opin Nephrol Hypertens 2008;17:348–352. 8. Hing TC, Ho S, Shih DQ, et al. The antimicrobial peptide cathelicidin modulates Clostridium difficile-associated colitis and toxin A-mediated enteritis in mice. Gut 2013;62:1295–1305. 9. Adams JS, Ren S, Liu PT, et al. Vitamin d-directed rheostatic regulation of monocyte antibacterial responses. J Immunol 2009;182:4289–4295. 10. Ananthakrishnan AN, Cagan A, Gainer VS, et al. Higher plasma vitamin D is associated with reduced risk of Clostridium difficile infection in patients with inflammatory bowel diseases. Aliment Pharmacol Ther 2014;39:1136–1142. 11. Abdelfatah M, Nayfe R, Moftakhar B, et al. Low vitamin D level and impact on severity and recurrence of Clostridium difficile infections. J Investig Med 2015;63:17–21. 12. van der Wilden GM, Fagenholz PJ, Velmahos GC, et al. Vitamin D status and severity of Clostridium difficile infections: a prospective cohort study in hospitalized adults. JPEN J Parenter Enteral Nutr 2015;39:465–470. 13. Furuya-Kanamori L, Wangdi K, Yakob L, et al. 25-hydroxyvitamin D concentrations and clostridium difficile infection: a meta-analysis. JPEN J Parenter Enteral Nutr 2017;41:890–895. 14. Agency for Healthcare Research and Quality, Healthcare Cost and Utilization Project. Healthcare Cost and Utilization Project. https://www. hcup-us.ahrq.gov. Accessed September 13, 2020. 15. Khera R, Angraal S, Couch T, et al. Adherence to methodological standards in research using the National Inpatient Sample. JAMA 2017;318:2011–2018. 16. D’Agostino RB Jr. Propensity scores in cardiovascular research. Circulation 2007;115:23403. 17. Austin PC. An introduction to propensity score methods for reducing the effects of confounding in observational studies. Multivariate Behav Res 2011;46:399–424. 18. Giustina A, Adler RA, Binkley N, et al. Controversies in vitamin D: summary statement from an international conference. J Clin Endocrinol Metab 2019;104:234–240. 19. Wong KK, Lee R, Watkins RR, et al. Prolonged Clostridium difficile infection may be associated with vitamin D deficiency. BMC Infect Dis 2016;40:682–687. 20. Youssef D, Bailey B, El Abbassi A, et al. Healthcare costs of Staphylococcus aureus and Clostridium difficile infections in veterans: role of vitamin D deficiency. Epidemiol Infect 2010;138:1322–1327.