1. bookVolume 59 (2021): Issue 3 (September 2021)
Journal Details
First Published
30 Mar 2015
Publication timeframe
4 times per year
access type Open Access

Clostridioides difficile infection: a comprehensive review for primary providers

Published Online: 26 Aug 2021
Page range: 262 - 269
Received: 01 Feb 2021
Journal Details
First Published
30 Mar 2015
Publication timeframe
4 times per year

Clostridioides difficile infection (CDI) is an issue of great concern due to its rising incidence, recurrence, morbidity and impact on healthcare spending. Treatment guidelines have changed in the last few years, and new therapies are being considered. This is a practical review for the primary care practitioner of the latest guidelines for CDI diagnosis, treatment, and emerging therapies.


1. BARTLETT JG. Narrative review: the new epidemic of Clostridium difficile-associated enteric disease. Ann Intern Med. 2006;145(10):75864. Search in Google Scholar

2. LAWSON PA., CITRON DM., TYRRELL KL., FINEGOLD SM. Reclassification of Clostridium difficile as Clostridioides difficile (Hall and O’Toole 1935) Prévot 1938. Anaerobe. 2016;40:959. Search in Google Scholar

3. LESSA FC., WINSTON LG., MCDONALD LC. Emerging Infections Program CdST. Burden of Clostridium difficile infection in the United States. N Engl J Med. 2015;372(24):23692370. Search in Google Scholar

4. MILLER M., GRAVEL D., MULVEY M., TAYLOR G., BOYD D., SIMOR A., et al. Health care-associated Clostridium difficile infection in Canada: patient age and infecting strain type are highly predictive of severe outcome and mortality. Clin Infect Dis. 2010;50(2):194201. Search in Google Scholar

5. GUH AY., MU Y., WINSTON LG., JOHNSTON H., OLSON D., FARLEY MM., et al. Trends in U.S. Burden of Clostridioides difficile Infection and Outcomes. N Engl J Med. 2020;382(14):13201330. Search in Google Scholar

6. MCDONALD LC., GERDING DN., JOHNSON S., BAKKEN JS., CARROLL KC., COFFIN SE., et al. Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) Clin Inf Diseases. 2018;66(7):e1e48. Search in Google Scholar

7. THOMAS C., STEVENSON M., RILEY TV. Antibiotics and hospital-acquired Clostridium difficile-associated diarrhoea: a systematic review. J Antimicrob Chemother. 2003;51(6):133950. Search in Google Scholar

8. WISTROM J., NORRBY SR., MYHRE EB., ERIKSSON S., GRANSTROM G., LAGERGREN., et al. Frequency of antibiotic-associated diarrhoea in 2462 antibiotic-treated hospitalized patients: a prospective study. J Antimicrob Chemother. 2001;47(1):4350. Search in Google Scholar

9. LOO VG., BOURGAUALT AM., POIRIER L., LAMOTHE F., MICHAUD S., TURGEON N., et al. Host and pathogen factors for Clostridium difficile infection and colonization. N Engl J Med. 2011;365(18):1693703. Search in Google Scholar

10. BLISS DZ., JOHNSON S., SAVIK K., CLABOTS CR., WILLARD K., GERDING DN., et al. Acquisition of Clostridium difficile and Clostridium difficile-associated diarrhea in hospitalized patients receiving tube feedings. Ann Intern Med. 1998;129(12):10129. Search in Google Scholar

11. SINGH H., NUGENT Z., YU BN., LIX LM., TARGOWNIK LE., BERNSTEIN CN., et al. Higher Incidence of Clostridium difficile Infection Among Individuals With Inflammatory Bowel Disease. Gastroenterology. 2017;153(2):430438. Search in Google Scholar

12. REIGADAS E., ALCALA L., GOMEZ J., MARIN M., MARTIN A., ONORI R., et al. Breakthrough Clostridium difficile Infection in Cirrhotic Patients Receiving Rifaximin. Clin Infect Dis. 2018;66(7):10861091. Search in Google Scholar

13. HU MY., KATCHAR K., KYNE L., MAROO S., TUMMALA S., DREISBACH V., et al. Prospective derivation and validation of a clinical prediction rule for recurrent Clostridium difficile infection. Gastroenterology. 2009;136(4):120614. Search in Google Scholar

14. D’AGOSTINO RB SR., COLLINS SH., PENCINA KM., KEAN Y., GORBACH S. Risk estimation for recurrent Clostridium difficile infection based on clinical factors. Clin Infect Dis. 2014;58(10);138693. Search in Google Scholar

15. KYNE L., WARNY M., QAMAR A., KELLY CP. Association between antibody response to toxin A and protection against recurrent Clostridium difficile diarrhoea. Lancet. 2001;357(9251):18993. Search in Google Scholar

16. GUPTA SB., MEHTA V., DUBBERKE ER., ZHAO X., DORR MB., GURIS D., et al. Antibodies to Toxin B Are Protective Against Clostridium difficile Infection Recurrence. Clin Infec Dis. 2016;63(6):730734. Search in Google Scholar

17. ABOU CHAKRA CN., MCGEER A., LABBE AC., SIMOR AE., GOLD WL., MULLER MP., et al. Factors Associated With Complications of Clostridium difficile Infection in a Multicenter Prospective Cohort. Clin Infect Dis. 2015;61(12):17818. Search in Google Scholar

18. ABRAHAM FM., TALAN DA., KRISHNADASAN A., CITRON DM., PAULICK AL., ANDERSON LJ., et al. Clostridium difficile Infection Among US Emergency Department With Diarrhea and No Vomiting. Ann Emerg Med. 2017;70(1):1927. Search in Google Scholar

19. SURAWICZ CM., BRANDT LJ., BINION DG., ANANTHAKRISHNAN AN., CURRY SR., GILLIGAN PH., et al. Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. Am J Gastroenterol. 2013;108(4):47898. Search in Google Scholar

20. BAUER MP., KUIJPER EJ., VAN DISSEL JT. European Society of Clinical Microbiology and Infectious Diseases (ESCMID): treatment guidance document for Clostridium difficile infection (CDI). Clin Microbiol Infect. 2009;15(12):106779. Search in Google Scholar

21. DEBAST 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 Supple 2:126. Search in Google Scholar

22. ABUJAMEL T., CADNUM JL., JURY LA., SUNKESULA VC., KUNDRAPU S., JUMP RL., et al. Defining the vulnerable period of re-establishment of Clostridium-difficile colonization after treatment of C. difficile infection with oral vancomycin or metronidazole. PLoS One. 2013;8(10):e76269. Search in Google Scholar

23. DOLL M., MARRA AR., APISARNTHANARAK A., AL-MAANI AS., ABBAS S., ROSENTHAL VD. Prevention of Clostridioides difficile in hospitals: A position paper of the International Society for Infectious Diseases. Int J Infect Dis. 2021;102;188195. Search in Google Scholar

24. FORRESTER JD., BANAEI N., BUCHNER P., SPAIN DA., STAUDENMAYER KL. Environmental Sampling for Clostridium Difficile on Alcohol-Based Hand Rub Dispensers in an Academic Medical Center. Surg Infect. 2014;15(5):5814. Search in Google Scholar

25. MULLISH BH., MARCHESI JR., THURSZ MR., WILLIAMS HR. Microbiome manipulation with faecal microbiome transplantation as a therapeutic strategy in Clostridium difficile infection. QJM. 2015;108(5):3559. Search in Google Scholar

26. CHO JM., PARDI DS., KHANNA S. Update on Treatment of Clostridioides difficile Infection. Mayo Clin Proc. 2020;95(4):758769. Search in Google Scholar

27. KWAK S., CHOI J., HINK T., RESKE KA., BLOUNT K., JONES C., et al. Impact of investigational microbiota therapeutic RBX2660 on the gut microbiome and resistome revealed by a placebo-controlled clinical trial. Microbiome. 2020;8(1):125. Search in Google Scholar

28. GERDING DN., MEYER T., LEE C., COHEN SH., MURTHY UK., POIRIER A., et al. Administration of spores of nontoxigenic Clostridium difficile strain M2 for prevention of recurrent C. difficile infection: a randomized clinical trial. JAMA. 2015;313(17):171927. Search in Google Scholar

29. ALONSO CD., MAHONEY MV. Bezlotoxumab for the prevention of Clostridium difficile infection: a review of current and safety profile. Infect Drug Resist. 2018;12:19. Search in Google Scholar

30. WILCOX MH., GERDING DN., POXTON IR., KELLY C., NATHAN R., BIRCH T., et al. Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection. N Engl J Med. 2017;376(4):305317. Search in Google Scholar

31. GERDING DN., KELLY CP., RAHAV G., LEE C., DUBBERKE ER., KUMAR PN., et al. Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection in Patients at Increased Risk for Recurrence. Clin Infect Dis. 2018;67(5):649656. Search in Google Scholar

32. VICKERS RJ., TILLOTSON GS., NATHAN R., HAZAN S., PULLMAN J., LUCASTI C., et al. Efficacy and safety of ridinilazole compared with vancomycin for the treatment of Clostridium difficile infection: a phase 2, randomised, double-blind, active-controlled, non-inferiority study. Lancet Infect Dis. 2017;17(7):735744. Search in Google Scholar

33. GANETSKY A., HAN JH., HUGHES ME., BABUSHOK DV., FREY NV. GILL SI., et al. Oral Vancomycin Prophylaxis Is Highly Effective in Preventing Clostridium difficile Infection in Allogeneic Hematopoietic Cell Transplant Recipients. Clin Infect Dis. 2019;68(12):20032009. Search in Google Scholar

34. SENOH M., IWAKI M., YAMAMOTO A., KATO H. FUKUDA T. SHIBAYAMA K. Development of vaccine for Clostridium difficile infection using membrane fraction of nontoxigenic Clostridium difficile. Microb Pathog. 2018;123:4246. Search in Google Scholar

35. ZHANG C., JIN K., XIAO Y., CHENG Y., HUANG Z., WANG S., et al. Potent monoclonal antibodies against Clostridium difficile toxin A elicited by DNA immunization. Hum Vaccin Immunother. 2013;9(10):215764. Search in Google Scholar

36. HOPKINS RJ., WILSON RB. Treatment of recurrent Clostridium diffiicle colitis: a narrative review. Gastroenterol Rep. 2018;6(1):2128. Search in Google Scholar

37. OOIJEVAAR RE., VAN VEURDEN YH., TERVEER EM., GOORHUIS A., BAUER MP., KELLER JJ., et al. Update on treatment algorithms for Clostridium difficile infection. Clin Micribiol Infect. 2018;24(5):452462. Search in Google Scholar

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