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Superbug (Clostridium difficile) Infections strongly associated with low vitamin D - many studies

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Low Vitamin D Level and Impact on Severity and Recurrence of Clostridium difficile Infections - Dec 2014

J Investig Med. 2014 Dec 4.
Abdelfatah M1, Nayfe R, Moftakhar B, Nijim A, El Zoghbi M, Donskey J, Kandil H, Watkins RR.
1From the *Department of Medicine, Akron General Medical Center, Akron; †Department Gastroenterology and Hepatology, University Hospitals Case Medical Center, Cleveland; ‡Division of Infectious Diseases, Department of Medicine, Case Western Reserve University; §Geriatric Research, Education, and Clinical Center, Cleveland Veterans Affairs Medical Center, Cleveland; ∥Division of Gastroenterology and Hepatology, East Carolina University, Greenville; ¶Division of Infectious Diseases, Akron General Medical Center, Akron; and #Department of Medicine, Northeast Ohio Medical University, Rootstown, OH.

VitaminDWiki Summary

271 patients

    Vitamin D level < 10 ng10-20 ng 20-30 ng > 30 ng
Severe complicated CDI 18%18%14%4%

Clostridium difficile infection (CDI) has recently markedly increased, incurring greater health care-associated costs and hospitalizations especially in vitamin D deficient patients. Accordingly, the aim of this study was to evaluate the relationship between low vitamin D levels and the severity and recurrence of CDI.

A retrospective case-control study evaluated patients hospitalized between 2007 and 2013 with CDI and a positive C. difficile toxin assay.
Severe complicated CD was defined based on (1) laboratory or radiological criteria correlated clinically and (2) sepsis requiring intensive care unit admission. Recurrent CDI (RCDI) was defined as a new episode of diarrhea occurring within 90 days of resolution of the initial episode for at least 10 days after discontinuing therapy and confirmed by positive stool C. difficile toxin assay or polymerase chain reaction. Patients were divided into 4 groups based on vitamin D level (ng/mL): severely deficient (<10), insufficient (10-19.9), predeficient (20-29.9), and control group (≥30).

Two hundred seventy-one patients were diagnosed with CDI, of which 48 had RCDI distributed as 5 (12.5%), 15 (16.1%), 10 (15.6%), and 13 (17.5%) patients in each of the aforementioned groups, respectively (P= 0.55). Severe complicated CDI was identified in 7 (17.5%), 17 (18.2%), 9 (14%), and 3 (4%) patients, respectively (P = 0.04). Thirty-day mortality was 1 of 40, 1 of 93, 2 of 64, and 2 of 74 patients, respectively (P = 0.43).

Normal vitamin D level has a protective effect against severe CDI, and low vitamin D is associated with greater severity of CDI but not with an increased risk of RCDI or 30-day mortality.

Clostridium difficile associated with low vitamin D, 6 days vs 4 days of diarrhea and almost 2X more sepsis - Jan 2015

Prolonged Clostridium difficile Infection May Be Associated With Vitamin D Deficiency.
JPEN J Parenter Enteral Nutr. 2015 Jan 26. pii: 0148607114568121. [Epub ahead of print]
Wong KK1, Lee R2, Watkins RR3, Haller N4.

Background: Clostridium difficile infection (CDI) is one of the leading causes of hospital-acquired infections, creating a financial burden for the U.S. healthcare system. Reports suggest that vitamin D-deficient CDI patients incur higher healthcare-associated expenses and longer lengths of stay compared to nondeficient counterparts. The objective here was to evaluate the relationship between vitamin D level and CDI recurrence.

Materials and Methods: A retrospective chart review was conducted for 112 patients with vitamin D level drawn within 3 months of CDI diagnosis.
Recurrence, severity of disease, 30-day mortality, and course of CDI were assessed.

Results: The vitamin D-deficient group included 56 patients, and the normal group included 56 patients.
The mean age of vitamin D-deficient and -sufficient groups was 68 ± 15.7 and 71 ± 14.4 years, respectively.
The mean 25(OH) D level in the deficient group was 11.7 ± 4.6 ng/mL, and it was 36.2 ± 16.2 ng/mL in the normal group.
A longer course of diarrhea was apparent in the vitamin D-deficient group compared to the normal group: 6.1 days (95% confidence interval [CI], 4.9-7.2) vs 4.2 days (95% CI, 3.5-4.9; P = .01). Sepsis rate was 24% in vitamin D-deficient group and 13% in normal group (P = .03).
There were no differences in CDI recurrence, length of stay, severity of illness, and mortality with respect to vitamin D status.

Conclusion: There may be an association between course of diarrhea and increased rate of sepsis in vitamin D-deficient CDI patients.

CD 5X more likely if low vitamin D - Jan 2017

Association between prehospital vitamin D status and hospital-acquired Clostridium difficile infections
JPEN J Parenter Enteral Nutr. 2015 Jan;39(1):47-55. doi: 10.1177/0148607113511991
Sadeq A Quraishi 1 , Augusto A Litonjua 2 , Takuhiro Moromizato 3 , Fiona K Gibbons 4 , Carlos A Camargo Jr 5 , Edward Giovannucci 6 , Kenneth B Christopher 7

Objective: To investigate whether preadmission 25-hydroxyvitamin D (25(OH)D) levels are associated with the risk of hospital-acquired Clostridium difficile infection (HACDI).

Materials and methods: Our retrospective cohort study focused on 568 adult patients from 2 Boston teaching hospitals between August 1993 and November 2006. All patients had 25(OH)D levels measured before hospitalization and were at risk for HACDI (defined as the presence of C difficile toxin A or B in stool samples obtained >48 hours after hospitalization). We performed multivariable regression analyses to test the association of prehospital 25(OH)D levels with HACDI while adjusting for clinically relevant covariates.

Results: In these 568 patients, mean (SD) 25(OH)D level was 19 (12) ng/mL, and 11% of patients met criteria for incident HACDI. Following adjustment for age, sex, race (nonwhite vs white), patient type (medical vs surgical), and Deyo-Charlson index, patients with 25(OH)D levels <10 ng/mL had higher odds of HACDI (odds ratio OR, 2.90; 95% confidence interval CI, 1.01-8.34) compared with patients with 25(OH)D levels ≥30 ng/mL. When patients with HACDI were analyzed relative to a larger patient cohort without HACDI (n = 5047), those with 25(OH)D levels

  • <10 ng/mL (OR, 4.96; 95% CI, 1.84-13.38) and
  • 10-19.9 ng/mL (OR, 3.36; 95% CI, 1.28-8.85)

had higher adjusted odds of HACDI compared with patients with 25(OH)D levels ≥30 ng/mL.

Conclusions: In our cohort of adult patients, vitamin D status before hospital admission was inversely associated with the risk of developing HACDI. These data support the need for randomized, controlled trials to test the role of vitamin D supplementation to prevent HACDI.
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CD 4X more likely if low vitamin D - Dec 2014

Vitamin D deficiency is associated with community-acquired clostridium difficile infection: a case-control study.
BMC Infect Dis. 2014 Dec 4;14:661. doi: 10.1186/s12879-014-0661-6.
Sahay T, Ananthakrishnan AN1.

Clostridium difficile infection (CDI) is increasingly recognized as an important community acquired pathogen causing disease (CA-CDI). Vitamin D [25(OH)D] has immune modulatory effects and plays an important role in intestinal immunity. The role of vitamin D in CA-CDI has not been examined previously.

This was a single referral center case-control study. Cases comprised of all patients with CA-CDI who had a serum 25(OH)D measured within 12 months prior to infection. Controls were drawn from patients who had 25(OH)D checked and matched based on age, gender, race and health status. Serum 25(OH)D was stratified as < 15 ng/mL, 15-30 ng/mL or > 30 ng/mL. Regression models adjusting for potential confounders were used to define independent association between vitamin D and CA-CDI.

We identified 58 matched case-control pairs (66% women; 85% Caucasian). The mean age was 62 years. The mean serum 25(OH)D level was significantly lower in CA-CDI cases compared to controls (28.5 ng/mL vs. 33.8 ng/mL, p = 0.046). Cases had higher rate of antibiotic exposure and more comorbidity.
Serum 25(OH)D < 15 ng/mL was associated with an increased risk of CA-CDI on univariate (Odds ratio (OR) 5.10, 95% confidence interval (CI) 1.51 - 17.24) and multivariate analysis (OR 3.84, 95% CI 1.10 - 13.42). Vitamin D levels between 15-30 ng/mL did not modify disease risk.

Low serum 25(OH)D < 15 ng/mL was associated with increased risk of CA-CDI. This suggests vitamin D may have a role in determining susceptibility to CA-CDI.

PMID: 25471926  Download the PDF from VitaminDWiki

Elderly were 4.7 time less likely to resolve CDAD if low vitamin D - Jan 2015 (died?)

Low vitamin D level is an independent predictor of poor outcomes in Clostridium difficile-associated diarrhea.
Therap Adv Gastroenterol. 2014 Jan;7(1):14-9. doi: 10.1177/1756283X13502838.
Wang WJ1, Gray S2, Sison C3, Arramraju S2, John BK2, Hussain SA4, Kim SH4, Mehta P4, Rubin M4.

The incidence, recurrence, and all-cause mortality rate for Clostridium difficile-associated diarrhea (CDAD) has increased markedly over the past 10 years despite treatment. Low vitamin D levels are known to impair immune responses to infection and are associated with increased mortality. We compared the role of patient comorbidity measured by the Charlson Comorbidity Index (CCI) with vitamin D levels to ascertain whether vitamin D levels were an independent variable affecting the outcome of CDAD or a marker of overall comorbidity.
A prospective cohort study studied 62 patients hospitalized between 2008 and 2009 with manifestations of CDAD and a positive C. difficile toxin assay. All patients received standard antibiotics (metronidazole and/or vancomycin). Their status at 30-day follow up was classified as resolved or recurred/expired. Patients' CCI was calculated using their medical history. Logistic regression analysis of variables including 25-hydroxyvitamin D, CCI, age, gender, white blood cell count (WBC), albumin and residence type were performed.
There were 62 patients (43.6% men, 56.4% women) with CDAD; mean age was 75 ± 17 years. At 30-day follow up, 28 (45.2%) expired, 10 (16.1%) had persistent or recurrent diarrhea and 24 (38.7%) resolved. Nonresolution was seen in 38 (61.3%). There was no significant association between 30-day resolution status and CCI, gender, WBC, albumin level or residence type. Two variables were found to be independent predictors of resolution of CDAD: normal vitamin D levels (p = 0.028) and age <70 years (p = 0.024).
Subjects with low vitamin D were 4.75 times more likely to fail to resolve CDAD than subjects with normal Vitamin D.
In this study, vitamin D level and age are independent predictors of CDAD resolution in hospitalized patients. Low vitamin D levels and age >70 years old are associated with increased likelihood of recurrence. Low vitamin D levels are not a marker of comorbidity or advanced age
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Clostridium difficile 60% more likely if low vitamin D - meta-analysis Dec 2015

25-Hydroxyvitamin D Concentrations and Clostridium difficile Infection: A Meta-Analysis.
JPEN J Parenter Enteral Nutr. 2015 Dec 23. pii: 0148607115623457. [Epub ahead of print]
Furuya-Kanamori L1, Wangdi K2, Yakob L3, McKenzie SJ4, Doi SA2, Clark J5, Paterson DL6, Riley TV7, Clements AC2.

Well-known risk factors for Clostridium difficile infection (CDI) are exposure to antibiotics and gastric acid suppressants. Recent studies have provided some evidence of an association between hypovitaminosis D and the risk of CDI. Therefore, this meta-analysis aimed to pool all the existing evidence to investigate the association between 25-hydroxyvitamin D (25[OH]D) and CDI.

A systematic search was conducted in 3 databases (PubMed, Embase, and Web of Sciences) for epidemiological studies that examined the association between mean 25(OH)D concentrations and CDI as well as between 25(OH)D status and CDI severity or recurrence. 25(OH)D status was defined as "lower" or "higher" at a threshold concentration of <20 or ≥20 ng/mL, respectively. Pooled effect sizes were computed using the inverse variance heterogeneity model of meta-analysis.

Eight publications (n = 4479 patients) were included in the meta-analysis. The mean concentration of 25(OH)D in patients with CDI was 3.54 ng/mL (95% confidence interval [CI], 0.39-6.89 ng/mL) lower than in patients without CDI. Patients with lower 25(OH)D status had a higher odds (odds ratio [OR], 1.61; 95% CI, 1.02-2.53) of developing severe CDI compared with those with a higher 25(OH)D status. No significant association was found between 25(OH)D status and CDI recurrence.

The results of this meta-analysis suggest that lower mean concentrations of 25(OH)D were associated with CDI.
A lower 25(OH)D status increased the odds of severe CDI but not of CDI recurrence.

Fecal transplants greatly reduce Clostridium difficile - RCT June 2018

Fecal Microbiota Transplantation for Primary Clostridium difficile Infection NEJM

Recurrent Clostridioides difficile Infection in a RCT (Microbiome Therapeutic SER-109) - Oct 2022

JAMA doi:10.1001/jama.2022.16476 FREE PDF Reduced risk by 2.5X
Is 2.5X much less than risk reduction by Vitamin D?

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Created by admin. Last Modification: Wednesday March 29, 2023 21:20:02 GMT-0000 by admin. (Version 34)

Attached files

ID Name Comment Uploaded Size Downloads
18684 CD 2015.jpg admin 21 Oct, 2022 14.27 Kb 363
18683 Clostridium difficile 2015.pdf admin 21 Oct, 2022 306.96 Kb 235
9935 Fecal CD.jpg admin 07 Jun, 2018 51.61 Kb 1159
7597 Clostridium difficile-associated diarrhea.pdf admin 29 Dec, 2016 1,011.34 Kb 1058
5440 CD Dec 2014.pdf admin 09 May, 2015 186.20 Kb 1545