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Published in: Critical Care 1/2020

01-12-2020 | Metronidazole | Research

Risk factors and intestinal microbiota: Clostridioides difficile infection in patients receiving enteral nutrition at Intensive Care Units

Authors: Daosheng Wang, Danfeng Dong, Chen Wang, Yingchao Cui, Cen Jiang, Qi Ni, Tongxuan Su, Guanzheng Wang, Enqiang Mao, Yibing Peng

Published in: Critical Care | Issue 1/2020

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Abstract

Background

Clostridioides difficile infection (CDI) is a leading cause of nosocomial diarrhea. Patients receiving enteral nutrition (EN) in the intensive care unit (ICU) are potentially at high risk of CDI. In the present study, we assessed the risk factors and intestinal microbiome of patients to better understand the occurrence and development of CDI.

Methods

Patients were screened for C. difficile every week after starting EN, and their clinical records were collected for risk factor identification. Fecal samples were analyzed using 16S rRNA sequencing to evaluate the intestinal microbiota.

Results

Overall incidence of CDI was 10.7% (18/168 patients). History of cerebral infarction was significantly associated with CDI occurrence (OR, 9.759; 95% CI, 2.140–44.498), and treatment with metronidazole was identified to be protective (OR, 0.287; 95% CI, 0.091–0.902). Patients with EN had lower bacterial richness and diversity, accompanied by a remarkable decrease in the abundance of Bacteroides, Prevotella_9, Ruminococcaceae, and Lachnospiraceae. Of these patients, acquisition of C. difficile resulted in a transient increase in microbial diversity, along with consistent alterations in the proportion of some bacterial taxa, especially Ruminococcaceae and Lachnospiraceae. Upon initiation of EN, patients who were positive for C. difficile later showed an enhanced load of Bacteroides, which was negatively correlated with the abundance of C. difficile when CDI developed.

Conclusion

ICU patients receiving EN have a high prevalence of CDI and a fragile intestinal microbial environment. History of cerebral infarction and prior treatment with metronidazole are considered as vital risk and protective factors, respectively. We propose that the emergence of CDI could cause a protective alteration of the intestinal microbiota. Additionally, Bacteroides loads seem to be closely related to the occurrence and development of CDI.
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Literature
2.
go back to reference Lim SC, Knight DR, Riley TV. Clostridium difficile and One Health. Clin Microbiol Infect. 2020;26(7):857–863. Lim SC, Knight DR, Riley TV. Clostridium difficile and One Health. Clin Microbiol Infect. 2020;26(7):857–863.
3.
go back to reference Kuy S, et al. Increasing incidence of and increased mortality associated with Clostridium difficile-associated megacolon. JAMA Surg. 2016;151(1):85–6.PubMedCrossRef Kuy S, et al. Increasing incidence of and increased mortality associated with Clostridium difficile-associated megacolon. JAMA Surg. 2016;151(1):85–6.PubMedCrossRef
4.
go back to reference Samarkos M, Mastrogianni E, Kampouropoulou O. The role of gut microbiota in Clostridium difficile infection. Eur J Intern Med. 2018;50:28–32.PubMedCrossRef Samarkos M, Mastrogianni E, Kampouropoulou O. The role of gut microbiota in Clostridium difficile infection. Eur J Intern Med. 2018;50:28–32.PubMedCrossRef
5.
go back to reference Dubberke ER, et al. Clostridium difficile--associated disease in a setting of endemicity: identification of novel risk factors. Clin Infect Dis. 2007;45(12):1543–9.PubMedCrossRef Dubberke ER, et al. Clostridium difficile--associated disease in a setting of endemicity: identification of novel risk factors. Clin Infect Dis. 2007;45(12):1543–9.PubMedCrossRef
6.
go back to reference Bliss DZ, et al. Acquisition of Clostridium difficile and Clostridium difficile-associated diarrhea in hospitalized patients receiving tube feeding. Ann Intern Med. 1998;129(12):1012–9.PubMedCrossRef Bliss DZ, et al. Acquisition of Clostridium difficile and Clostridium difficile-associated diarrhea in hospitalized patients receiving tube feeding. Ann Intern Med. 1998;129(12):1012–9.PubMedCrossRef
7.
go back to reference Balsells E, et al. Global burden of infections: a systematic review and meta-analysis. J Glob Health. 2019;9(1):010407.PubMedCrossRef Balsells E, et al. Global burden of infections: a systematic review and meta-analysis. J Glob Health. 2019;9(1):010407.PubMedCrossRef
8.
go back to reference Barletta JF, Sclar DA. Proton pump inhibitors increase the risk for hospital-acquired Clostridium difficile infection in critically ill patients. Crit Care. 2014;18(6):714.PubMedPubMedCentralCrossRef Barletta JF, Sclar DA. Proton pump inhibitors increase the risk for hospital-acquired Clostridium difficile infection in critically ill patients. Crit Care. 2014;18(6):714.PubMedPubMedCentralCrossRef
9.
go back to reference O'Keefe SJ. Tube feeding, the microbiota, and Clostridium difficile infection. World J Gastroenterol. 2010;16(2):139–42. O'Keefe SJ. Tube feeding, the microbiota, and Clostridium difficile infection. World J Gastroenterol. 2010;16(2):139–42.
10.
go back to reference Cui, Y., et al., Risk factors for Clostridioides difficile infection and colonization among patients admitted to an intensive care unit in Shanghai, China, BMC Infect Dis, 2019. 19(1): p. 961. Cui, Y., et al., Risk factors for Clostridioides difficile infection and colonization among patients admitted to an intensive care unit in Shanghai, China, BMC Infect Dis, 2019. 19(1): p. 961.
11.
13.
go back to reference DDebast SB, Bauer MP, Kuijper EJ. European Society of Clinical Microbiology and Infectious Diseases: update of the treatment guidance document for Clostridium difficile infection. Clin Microbiol Infect. 2014;20(Suppl 2):1–26. DDebast SB, Bauer MP, Kuijper EJ. European Society of Clinical Microbiology and Infectious Diseases: update of the treatment guidance document for Clostridium difficile infection. Clin Microbiol Infect. 2014;20(Suppl 2):1–26.
16.
go back to reference Lucado J, Gould C, Elixhauser A. Clostridium difficile infections (CDI) in hospital stays, 2009: statistical brief# 124; 2006. Lucado J, Gould C, Elixhauser A. Clostridium difficile infections (CDI) in hospital stays, 2009: statistical brief# 124; 2006.
17.
go back to reference Manthey CF, et al. Initial therapy affects duration of diarrhoea in critically ill patients with Clostridioides difficile infection (CDI). Crit Care. 2019;23(1):399. Manthey CF, et al. Initial therapy affects duration of diarrhoea in critically ill patients with Clostridioides difficile infection (CDI). Crit Care. 2019;23(1):399.
18.
go back to reference Wang W, et al. The characteristics analysis of intestinal microecology on cerebral infarction patients and its correlation with apolipoprotein E. Medicine (Baltimore). 2018;97(41):e12805.CrossRef Wang W, et al. The characteristics analysis of intestinal microecology on cerebral infarction patients and its correlation with apolipoprotein E. Medicine (Baltimore). 2018;97(41):e12805.CrossRef
19.
go back to reference Guh AY, et al. Risk factors for community-associated Clostridium difficile infection in adults: a case-control study. Open Forum Infect Dis. 2017;4(4):ofx171.PubMedPubMedCentralCrossRef Guh AY, et al. Risk factors for community-associated Clostridium difficile infection in adults: a case-control study. Open Forum Infect Dis. 2017;4(4):ofx171.PubMedPubMedCentralCrossRef
20.
go back to reference Teasley DG, et al. Prospective randomised trial of metronidazole versus vancomycin for Clostridium-difficile-associated diarrhoea and colitis. Lancet (London). 1983;2(8358):1043–6.CrossRef Teasley DG, et al. Prospective randomised trial of metronidazole versus vancomycin for Clostridium-difficile-associated diarrhoea and colitis. Lancet (London). 1983;2(8358):1043–6.CrossRef
21.
go back to reference Whelan K, Schneider SM. Mechanisms, prevention, and management of diarrhea in enteral nutrition. Curr Opin Gastroenterol. 2011;27(2):152–9.PubMedCrossRef Whelan K, Schneider SM. Mechanisms, prevention, and management of diarrhea in enteral nutrition. Curr Opin Gastroenterol. 2011;27(2):152–9.PubMedCrossRef
22.
go back to reference Bäckhed F, et al. Host-bacterial mutualism in the human intestine. Science (New York). 2005;307(5717):1915–20.CrossRef Bäckhed F, et al. Host-bacterial mutualism in the human intestine. Science (New York). 2005;307(5717):1915–20.CrossRef
24.
go back to reference Atarashi K, et al. Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota. Nature. 2013;500(7461):232–6.CrossRefPubMed Atarashi K, et al. Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota. Nature. 2013;500(7461):232–6.CrossRefPubMed
25.
go back to reference Lee YJ, et al. Protective factors in the intestinal microbiome against Clostridium difficile infection in recipients of allogeneic hematopoietic stem cell transplantation. J Infect Dis. 2017;215(7):1117–23.PubMedPubMedCentralCrossRef Lee YJ, et al. Protective factors in the intestinal microbiome against Clostridium difficile infection in recipients of allogeneic hematopoietic stem cell transplantation. J Infect Dis. 2017;215(7):1117–23.PubMedPubMedCentralCrossRef
26.
go back to reference Freedberg DE, et al. Pathogen colonization of the gastrointestinal microbiome at intensive care unit admission and risk for subsequent death or infection. Intensive Care Med. 2018;44(8):1203–11.PubMedPubMedCentralCrossRef Freedberg DE, et al. Pathogen colonization of the gastrointestinal microbiome at intensive care unit admission and risk for subsequent death or infection. Intensive Care Med. 2018;44(8):1203–11.PubMedPubMedCentralCrossRef
27.
go back to reference Zhang L, et al. Insight into alteration of gut microbiota in Clostridium difficile infection and asymptomatic C. difficile colonization. Anaerobe. 2015;34:1–7.PubMedCrossRef Zhang L, et al. Insight into alteration of gut microbiota in Clostridium difficile infection and asymptomatic C. difficile colonization. Anaerobe. 2015;34:1–7.PubMedCrossRef
28.
go back to reference Schubert AM, et al. Microbiome data distinguish patients with Clostridium difficile infection and non-C. difficile-associated diarrhea from healthy controls. mBio. 2014;5(3):e01021–14.PubMedPubMedCentralCrossRef Schubert AM, et al. Microbiome data distinguish patients with Clostridium difficile infection and non-C. difficile-associated diarrhea from healthy controls. mBio. 2014;5(3):e01021–14.PubMedPubMedCentralCrossRef
29.
go back to reference Gu S, et al. Identification of key taxa that favor intestinal colonization of Clostridium difficile in an adult Chinese population. Microbes Infect. 2016;18(1):30–8.PubMedCrossRef Gu S, et al. Identification of key taxa that favor intestinal colonization of Clostridium difficile in an adult Chinese population. Microbes Infect. 2016;18(1):30–8.PubMedCrossRef
30.
go back to reference Antharam VC, et al. Intestinal dysbiosis and depletion of butyrogenic bacteria in Clostridium difficile infection and nosocomial diarrhea. J Clin Microbiol. 2013;51(9):2884–92.PubMedPubMedCentralCrossRef Antharam VC, et al. Intestinal dysbiosis and depletion of butyrogenic bacteria in Clostridium difficile infection and nosocomial diarrhea. J Clin Microbiol. 2013;51(9):2884–92.PubMedPubMedCentralCrossRef
31.
go back to reference Crobach MJT, et al. Understanding Clostridium difficile Colonization. Clin Microbiol Rev. 2018;31(2):e00021–17. Crobach MJT, et al. Understanding Clostridium difficile Colonization. Clin Microbiol Rev. 2018;31(2):e00021–17.
32.
go back to reference Morrison DJ, Preston T. Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism. Gut Microbes. 2016;7(3):189–200.PubMedPubMedCentralCrossRef Morrison DJ, Preston T. Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism. Gut Microbes. 2016;7(3):189–200.PubMedPubMedCentralCrossRef
33.
go back to reference Buffie CG, et al. Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile. Nature. 2015;517(7533):205–8.CrossRefPubMed Buffie CG, et al. Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile. Nature. 2015;517(7533):205–8.CrossRefPubMed
34.
go back to reference Vincent C, et al. Bloom and bust: intestinal microbiota dynamics in response to hospital exposures and Clostridium difficile colonization or infection. Microbiome. 2016;4:12.PubMedPubMedCentralCrossRef Vincent C, et al. Bloom and bust: intestinal microbiota dynamics in response to hospital exposures and Clostridium difficile colonization or infection. Microbiome. 2016;4:12.PubMedPubMedCentralCrossRef
36.
go back to reference Sangster W, et al. Bacterial and Fungal Microbiota Changes Distinguish C. difficile Infection from Other Forms of Diarrhea: Results of a Prospective Inpatient Study. Front Microbiol. 2016;7:789. Sangster W, et al. Bacterial and Fungal Microbiota Changes Distinguish C. difficile Infection from Other Forms of Diarrhea: Results of a Prospective Inpatient Study. Front Microbiol. 2016;7:789.
37.
go back to reference Deng H, et al. Bacteroides fragilis prevents Clostridium difficile infection in a mouse model by restoring gut barrier and microbiome regulation. Front Microbiol. 2018;9:2976.PubMedPubMedCentralCrossRef Deng H, et al. Bacteroides fragilis prevents Clostridium difficile infection in a mouse model by restoring gut barrier and microbiome regulation. Front Microbiol. 2018;9:2976.PubMedPubMedCentralCrossRef
38.
go back to reference Mullish BH, et al. Microbial bile salt hydrolases mediate the efficacy of faecal microbiota transplant in the treatment of recurrent infection. Gut. 2019;68(10):1791–800.PubMedCrossRef Mullish BH, et al. Microbial bile salt hydrolases mediate the efficacy of faecal microbiota transplant in the treatment of recurrent infection. Gut. 2019;68(10):1791–800.PubMedCrossRef
39.
go back to reference Ferreyra JA, et al. Gut microbiota-produced succinate promotes C. difficile infection after antibiotic treatment or motility disturbance. Cell Host Microbe. 2014;16(6):770–7.PubMedPubMedCentralCrossRef Ferreyra JA, et al. Gut microbiota-produced succinate promotes C. difficile infection after antibiotic treatment or motility disturbance. Cell Host Microbe. 2014;16(6):770–7.PubMedPubMedCentralCrossRef
Metadata
Title
Risk factors and intestinal microbiota: Clostridioides difficile infection in patients receiving enteral nutrition at Intensive Care Units
Authors
Daosheng Wang
Danfeng Dong
Chen Wang
Yingchao Cui
Cen Jiang
Qi Ni
Tongxuan Su
Guanzheng Wang
Enqiang Mao
Yibing Peng
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2020
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-020-03119-7

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