Gastroenterol Res
Gastroenterology Research, ISSN 1918-2805 print, 1918-2813 online, Open Access
Article copyright, the authors; Journal compilation copyright, Gastroenterol Res and Elmer Press Inc
Journal website http://www.gastrores.org

Original Article

Volume 10, Number 2, April 2017, pages 116-119


Lack of Association Between the Clinical Outcome of Clostridium difficile Infection and Current Steroids Use

Ahmed Dirweesha, c, Chikezie Alvareza, Muhammad Khana, Bushra Ambreena, Rishitha Yelisettia, Shaikh Fawwad Hamiza, Sana Ziaa, Muhammad Tahira, Vincent A. DeBarib, Donald Christmasa, Sara Wallacha

aDepartment of Internal Medicine, Seton Hall University, Saint Francis Medical Center, Trenton, NJ, USA
bDepartment of Internal Medicine, School of Health and Medical Sciences, Seton Hall University, South Orange, NJ, USA
cCorresponding Author: Ahmed Dirweesh, Department of Internal Medicine, Seton Hall University, Saint Francis Medical Center, Trenton, NJ, USA

Manuscript accepted for publication April 04, 2017
Short title: Clostridium difficile Infection and Steroids
doi: https://doi.org/10.14740/gr822w

Abstract▴Top 

Background: The purpose of this study was to compare the outcome of Clostridium difficile infection (CDI) in patients on systemic steroids for various indications to patients not on steroids in term of disease severity, and associated morbidity and mortality.

Methods: We retrospectively reviewed records of all patients with CDI at our hospital from January 2011 to December 2016. Patients were evaluated for baseline characteristics, comorbidities, medications, disease severity, disease-related length of stay (LOS) from the diagnosis of CDI to discharge, need for surgical intervention, and disease-related mortality. Based on systemic steroids use, patients who were using steroids for different indications constituted the study population, and those with no steroids use were clustered as a control group.

Results: Of the 258 patients included, males were 127 (49%). Severe and severe-complicated CDI developed in 21/63 (33.3%) and 1/63 (1.6%) of patients on steroids (average daily dose of 20 mg), and in 73/195 (37.4%) and 5/195 (2.6%) of patients with no steroids use (P = 0.56 and P = 0.66, respectively). Surgical intervention was not required in the steroids group and 5/195 (2.7%) of patients not on steroids underwent bowel surgeries (P = 0.38). Mean LOS (days) was 11.6 ± 1.5 in the steroids group and 10.4 ± 0.7 in the no-steroids group (P = 0.4). CDI-related mortality occurred in 9/63(14.3%) of patients on steroids, and in 15/195 (7.7%) of patients not on steroids (P = 0.12; odds ratio (OR): 2; 95% confidence interval (CI): 0.8 - 4.8).

Conclusion: There was no significant difference in the severity of CDI, need for surgical interventions, disease-related LOS and mortality in systemic steroids users compared to patients not on steroids.

Keywords: Clostridium difficile; Steroids

Introduction▴Top 

Clostridium difficile (C. difficile) is a toxin-producing, spore-forming, gram-positive anaerobic bacillus that causes a spectrum of manifestations ranging from asymptomatic carriage to fulminant disease [1, 2].

In 2011, an estimated 453,000 cases of C. difficile occurred in the United States, and 29,300 patients died [3]. The incidence was higher in women, whites, and in individuals who were 65 years old or older than in those less than 65 years old [4].

Clostridium difficile infection (CDI) is defined as the acute onset of diarrhea with documented toxigenic C. difficile or its toxin and no other documented cause for diarrhea [5]. The diagnosis of CDI is established through a positive laboratory stool test for C. difficile toxins or C. difficile toxin gene. Real-time PCR tests detect one or more genes specific to toxigenic strains and are highly sensitive and specific [6-10].

Mild to moderate disease is defined as either diarrhea as the only symptom, or diarrhea without additional symptoms and signs meeting the definition of severe or complicated CDI. Severe disease is associated with hypoalbuminemia (serum albumin < 3 g/dL) and either a white blood cell (WBC) count ≥ 15,000 cells/mm3 or abdominal tenderness without criteria of complicated disease. Severe complicated disease requires presence of at least one of the following: fever ≥ 38.5 °C, ileus, or significant abdominal distention, WBC ≥ 35,000 cells/mm3 or < 2,000 cells/mm3, serum lactate levels > 2.2 mmol/L, admission to intensive care unit, hypotension with or without required use of vasopressors, changes in mental status, or any evidence of end organ failure [10].

Patients with mild-to-moderate CDI should be treated with metronidazole 500 mg orally three times per day for 10 days unless they are intolerant or allergic to metronidazole or during pregnancy or breastfeeding. Patients with severe disease should be treated with vancomycin 125 mg four times daily for 10 days, and oral vancomycin (125 mg four times per day) plus intravenous metronidazole (500 mg three times a day) is the treatment of choice in patients with severe and complicated disease [10].

Glucocorticoids have inhibitory effects on a broad range of immune responses. Steroids are also among the most potent anti-inflammatory and immunosuppressive agents and can be used to reduce inflammation [11-13]. Currently, studies also focus on other therapeutic measures such as vaccination, toxin binding immunoglobulins, alternative antibiotics and altering gut flora with probiotics and fecal microbiota transplantation (FMT) [14-18].

In this study, we examined the association between the ongoing use of systemic steroids and the clinical outcome of CDI in a single-center retrospective cohort.

Materials and Methods▴Top 

Setting

This study was conducted at an urban teaching acute care healthcare facility in northeastern USA. The study was approved by the Institutional Review Board (IRB) of the facility.

Study design and subjects

We retrospectively reviewed records of all patients with a documented diagnosis of CDI at our hospital from January 1, 2011 to December 31, 2016. Electronic charts of 355 patients admitted to our center with presumptive CDI were identified. Of these, 258 patients were found to have a confirmed diagnosis of CDI based on PCR tests for toxigenic C. difficile in stool samples.

Patients were evaluated to determine age, gender, race, medications including systemic steroids use, comorbidities, disease severity, disease-related length of stay (LOS), need for surgical interventions, and disease-related mortality. Based on the documented systemic use of steroids, patients who were using steroids for different indications (57 patients for chronic obstructive pulmonary disease/asthma, three patients for rheumatologic diseases, two patients for replacement therapy and one post-transplant patient) constituted the study population, while those not on steroids were clustered as a control group. Both groups received CDI treatment based on current national guidelines and there were no management differences within the same severity class between the two groups.

The severity of CDI was determined by the CDI severity scoring system based on the guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections from the American College of Gastroenterology [10].

Statistical analysis

Interval data were tested for fit-to-normality by the D’Agostino-Pearson omnibus normality test. Data which did not distribute normally were subjected to the appropriate non-parametric methods; otherwise parametric methods for group-wise comparisons were used. Normally distributed interval data were expressed as mean ± standard deviation (SD), and non-normally distributed interval data were presented as median and interquartile range (IQR). Univariate categorical data were evaluated for significance by using the Chi-squared test or Fisher’s exact test as appropriate.

Because of the retrospective nature of the study, the odds ratio (OR) and 95% confidence interval (95% CI) were used as the measure of effect size. All inferences regarding statistical significance were based on a P-value < 0.05 on a two-sided basis. Analyses were performed using Prism® software (GraphPad Corp., San Diego, CA) or SPSS® version 22.0 (IBM Corp., Armonk, NY).

Results▴Top 

Demographic and baseline characteristics

Of the 258 patients included, we identified 63 cases in the steroids group, and 195 cases of CDI cases in the non-steroids group. Baseline patients’ characteristics are illustrated in Table 1.

Table 1.
Click to view
Table 1. Baseline Characteristics of Patients With CDI
 

Outcomes

The study did not show a statistical difference in the severity pattern of CDI between the two groups. Only five patients in the non-steroids group underwent surgery and no one in the steroids group needed operative management (P = 0.38; OR: 0.27; 95% CI: 0.01 - 5.0). CDI-related mortality was encountered in nine patients in the steroids group and 15 patients in the non-steroids group. Mortality differences were not statistically significant between the two groups (P = 0.12; OR: 2; 95% CI: 0.8 - 4.8). Table 2 summarizes the different outcomes in these two groups.

Table 2.
Click to view
Table 2. Outcome of CDI Among the Study Groups
 
Discussion▴Top 

The results of this retrospective cohort study show that the severity of CDI is not affected by ongoing steroids use. Although, corticosteroids have remained the mainstay of therapy for acute flare-ups of inflammatory bowel disease [3], there is still no potential role of steroids in the treatment of C. difficile-associated diarrhea (CDAD). As a preventive measure, Wojciechowski et al examined the impact of corticosteroid use on the incidence of CDAD in patients receiving antibiotic treatment for respiratory infections. The use of corticosteroids was associated with a decreased incidence of CDAD (OR: 0.12; 95% CI: 0.006 - 0.95) [19].

Timely surgical consultation is essential in patients with refractory or fulminant colitis and subtotal colectomy with end ileostomy remains the standard operation for fulminant CDI [20]. As there was no statistical difference in the severity of CDI among study population, differences in the surgical interventions rates were similarly not statistically significant.

The study also revealed that steroids use did not affect the LOS in patients with CDI. Campbell et al reported renal impairment, advanced age, and cancer were associated with significantly longer LOS among hospital-onset CDI patients [21, 22]. Stevens et al studied the excess LOS attributable to CDI in acute care hospitalizations, and found that, CDI significantly contributes to the overall LOS. The greatest impact on LOS occurred among patients with severe CDI. The excess LOS for mild-to-moderate CDI was 0.75 days (95% CI: 0.59 - 0.89), and for severe CDI, it was 4.11 days (95% CI: 3.90 - 4.32) [23]. Intensive care unit (ICU) patients with CDI in particular have a greater adverse outcome. Patients with C. difficile in the ICU experienced higher mortality and longer LOS within the hospital [24]. ICU patients also experienced 3.4 times the odds of mortality (95% CI: 1.8 - 6.2) [24]. In comparison, a multicenter retrospective cohort study found CDI acquired in the ICU is associated with an increase in length of ICU and hospital stay but not with any difference in ICU or hospital mortality [25].

In our study, there was no difference in mortality rates among patients with CDI on steroids and patients not on steroids. Bhangus et al examined overall 30-day mortality among patients with CDI [26]. In this study, 30-day mortality was higher among medical patients (46%) and orthopedic patients (37%) compared with general surgical patients (13%, P = 0.006) [26]. Among a Medicare beneficiary cohort of patients, CDI was associated with greater inpatient mortality, 30-day mortality, longer LOS and higher rates of 30-day hospital readmissions [27]. A study of the elderly population (age > 65 years) found a significant excess mortality of 11.5% at 7 days, 26.2% at 30 days, 38.1% at 90 days and 41.4% at 180 days [28].

There were few limitations with this study. Although the study has adequate sample size, it is retrospective nature and being a single center work limits its applicability to patients in other hospitals/facilities.

Conclusions

In this study, since we found no association between the ongoing use of systemic steroids and the clinical outcome for CDI, we suggest that prescribed steroids for chronic diseases can be continued throughout the course of CDI.

Grant Support

None.

Financial Disclosures

None.

Conflicts of Interest

None.


References▴Top 
  1. Kelly CP, LaMont JT. Clostridium difficile - more difficult than ever. N Engl J Med. 2008;359(18):1932-1940.
    doi pubmed
  2. Bagdasarian N, Rao K, Malani PN. Diagnosis and treatment of Clostridium difficile in adults: a systematic review. JAMA. 2015;313(4):398-408.
    doi pubmed
  3. Rezaie A, Kuenzig ME, Benchimol EI, Griffiths AM, Otley AR, Steinhart AH, Kaplan GG, et al. Budesonide for induction of remission in Crohn's disease. Cochrane Database Syst Rev. 2015;6:CD000296.
    doi
  4. Lessa FC, Mu Y, Bamberg WM, Beldavs ZG, Dumyati GK, Dunn JR, Farley MM, et al. Burden of Clostridium difficile infection in the United States. N Engl J Med. 2015;372(9):825-834.
    doi pubmed
  5. Cohen SH, Gerding DN, Johnson S, Kelly CP, Loo VG, McDonald LC, Pepin J, et al. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the society for healthcare epidemiology of America (SHEA) and the infectious diseases society of America (IDSA). Infect Control Hosp Epidemiol. 2010;31(5):431-455.
    doi pubmed
  6. Luo RF, Banaei N. Is repeat PCR needed for diagnosis of Clostridium difficile infection? J Clin Microbiol. 2010;48(10):3738-3741.
    doi pubmed
  7. Belanger SD, Boissinot M, Clairoux N, Picard FJ, Bergeron MG. Rapid detection of Clostridium difficile in feces by real-time PCR. J Clin Microbiol. 2003;41(2):730-734.
    doi pubmed
  8. Longtin Y, Trottier S, Brochu G, Paquet-Bolduc B, Garenc C, Loungnarath V, Beaulieu C, et al. Impact of the type of diagnostic assay on Clostridium difficile infection and complication rates in a mandatory reporting program. Clin Infect Dis. 2013;56(1):67-73.
    doi pubmed
  9. van den Berg RJ, Bruijnesteijn van Coppenraet LS, Gerritsen HJ, Endtz HP, van der Vorm ER, Kuijper EJ. Prospective multicenter evaluation of a new immunoassay and real-time PCR for rapid diagnosis of Clostridium difficile-associated diarrhea in hospitalized patients. J Clin Microbiol. 2005;43(10):5338-5340.
    doi pubmed
  10. Surawicz CM, Brandt LJ, Binion DG, Ananthakrishnan AN, Curry SR, Gilligan PH, McFarland LV, et al. Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. Am J Gastroenterol. 2013;108(4):478-498; quiz 499.
    doi pubmed
  11. Auphan N, DiDonato JA, Rosette C, Helmberg A, Karin M. Immunosuppression by glucocorticoids: inhibition of NF-kappa B activity through induction of I kappa B synthesis. Science. 1995;270(5234):286-290.
    doi pubmed
  12. Rhen T, Cidlowski JA. Antiinflammatory action of glucocorticoids - new mechanisms for old drugs. N Engl J Med. 2005;353(16):1711-1723.
    doi pubmed
  13. Chapman J, Davies M, Wolff B, Dozois E, Tessier D, Harrington J, Larson D. Complicated diverticulitis: is it time to rethink the rules? Ann Surg. 2005;242(4):576-581; discussion 581-573.
  14. Musher DM, Logan N, Mehendiratta V, Melgarejo NA, Garud S, Hamill RJ. Clostridium difficile colitis that fails conventional metronidazole therapy: response to nitazoxanide. J Antimicrob Chemother. 2007;59(4):705-710.
    doi pubmed
  15. Bartlett JG. New drugs for Clostridium difficile infection. Clin Infect Dis. 2006;43(4):428-431.
    doi pubmed
  16. Nelson R. Antibiotic treatment for Clostridium difficile-associated diarrhea in adults. Cochrane Database Syst Rev. 2007;3:CD004610.
    doi
  17. McPherson S, Rees CJ, Ellis R, Soo S, Panter SJ. Intravenous immunoglobulin for the treatment of severe, refractory, and recurrent Clostridium difficile diarrhea. Dis Colon Rectum. 2006;49(5):640-645.
    doi pubmed
  18. Juang P, Skledar SJ, Zgheib NK, Paterson DL, Vergis EN, Shannon WD, Ansani NT, et al. Clinical outcomes of intravenous immune globulin in severe clostridium difficile-associated diarrhea. Am J Infect Control. 2007;35(2):131-137.
    doi pubmed
  19. Wojciechowski AL, Parameswaran GI, Mattappallil A, Mergenhagen KA. Corticosteroid use is associated with a reduced incidence of Clostridium difficile-associated diarrhea: a retrospective cohort study. Anaerobe. 2014;30:27-29.
    doi pubmed
  20. Adams SD, Mercer DW. Fulminant Clostridium difficile colitis. Curr Opin Crit Care. 2007;13(4):450-455.
    doi pubmed
  21. Miller AC, Polgreen LA, Cavanaugh JE, Polgreen PM. Hospital Clostridium difficile Infection Rates and Prediction of Length of Stay in Patients Without C. difficile Infection. Infect Control Hosp Epidemiol. 2016;37(4):404-410.
    doi pubmed
  22. Campbell R, Dean B, Nathanson B, Haidar T, Strauss M, Thomas S. Length of stay and hospital costs among high-risk patients with hospital-origin Clostridium difficile-associated diarrhea. J Med Econ. 2013;16(3):440-448.
    doi pubmed
  23. Stevens VW, Khader K, Nelson RE, Jones M, Rubin MA, Brown KA, Evans ME, et al. Excess Length of Stay Attributable to Clostridium difficile Infection (CDI) in the Acute Care Setting: A Multistate Model. Infect Control Hosp Epidemiol. 2015;36(9):1024-1030.
    doi pubmed
  24. Lofgren ET, Cole SR, Weber DJ, Anderson DJ, Moehring RW. Hospital-acquired Clostridium difficile infections: estimating all-cause mortality and length of stay. Epidemiology. 2014;25(4):570-575.
    doi pubmed
  25. Dodek PM, Norena M, Ayas NT, Romney M, Wong H. Length of stay and mortality due to Clostridium difficile infection acquired in the intensive care unit. J Crit Care. 2013;28(4):335-340.
    doi pubmed
  26. Bhangu S, Bhangu A, Nightingale P, Michael A. Mortality and risk stratification in patients with Clostridium difficile-associated diarrhoea. Colorectal Dis. 2010;12(3):241-246.
    doi pubmed
  27. Drozd EM, Inocencio TJ, Braithwaite S, Jagun D, Shah H, Quon NC, Broderick KC, et al. Mortality, Hospital Costs, Payments, and Readmissions Associated With Clostridium difficile Infection Among Medicare Beneficiaries. Infect Dis Clin Pract (Baltim Md). 2015;23(6):318-323.
    doi pubmed
  28. Karas JA, Bradshaw S, Mahmud W, Enoch DA. Mortality in hospitalized older adults associated with Clostridium difficile infection at a district hospital. Infect Dis Rep. 2010;2(1):e8.
    doi pubmed


This article is distributed under the terms of the Creative Commons Attribution Non-Commercial 4.0 International License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


Gastroenterology Research is published by Elmer Press Inc.

 
Home     |     Log In     |      About     |      Search     |      Current     |      Archives     |      Submit      |     Subscribe


 

     

Aims and Scope

Current Issues

Conflict of Interest

About Publisher

Editorial Board

Archives

Copyright

Company Profile

Editorial Office

Misconduct and Retraction

Permissions

Company Registration

Contact Us

Abstracting and Indexing

ICMJE

Ownership

Instructions to Authors

Access

Declaration of Helsinki

Contact Publisher

Submission Checklist

Reprints

Terms of Use

Company Address

Submit a Manuscript

Open Access Policy

Privacy Policy

Browse Journals

Publishing Fee

Publishing Policy

Disclaimer

Recent Highlights

Peer-Review Process

Publishing Quality

Code of Ethics

Advertising Policy

Manuscript Tracking

Advanced Search

For Librarians

Careers

Publishing Process

Publication Frequency

For Reviewers

Propose a New Journal

       
       

Gastroenterology Research, bimonthly, ISSN 1918-2805 (print), 1918-2813 (online), published by Elmer Press Inc.        
The content of this site is intended for health care professionals.

This is an open-access journal distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License, which permits unrestricted
non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Creative Commons Attribution license (Attribution-NonCommercial 4.0 International CC-BY-NC 4.0)


This journal follows the International Committee of Medical Journal Editors (ICMJE) recommendations for manuscripts submitted to biomedical journals,
the Committee on Publication Ethics (COPE) guidelines, and the Principles of Transparency and Best Practice in Scholarly Publishing.

website: www.gastrores.org   editorial contact: editor@gastrores.org
Address: 9225 Leslie Street, Suite 201, Richmond Hill, Ontario, L4B 3H6, Canada

© Elmer Press Inc. All Rights Reserved.

DECLARATION: THIS JOURNAL SITE OUTLOOK IS DESIGNED BY THE PUBLISHER AND COPYRIGHT PROTECTED. DO NOT COPY!