Skip to main content Accessibility help

Cost-Effectiveness of Competing Treatment Strategies for Clostridium difficile Infection: A Systematic Review

  • Phuc Le (a1), Van T. Nghiem (a2), Patricia Dolan Mullen (a3) and Abhishek Deshpande (a1) (a4)



Clostridium difficile infection (CDI) presents a substantial economic burden and is associated with significant morbidity. While multiple treatment strategies have been evaluated, a cost-effective management strategy remains unclear.


We conducted a systematic review to assess cost-effectiveness analyses of CDI treatment and to summarize key issues for clinicians and policy makers to consider.


We searched PubMed and 5 other databases from inception to August 2016. These searches were not limited by study design or language of publication. Two reviewers independently screened the literature, abstracted data, and assessed methodological quality using the Drummond and Jefferson checklist. We extracted data on study characteristics, type of CDI, treatment characteristics, and model structure and inputs.


We included 14 studies, and 13 of these were from high-income countries. More than 90% of these studies were deemed moderate-to-high or high quality. Overall, 6 studies used a decision-tree model and 7 studies used a Markov model. Cost of therapy, time horizon, treatment cure rates, and recurrence rates were common influential factors in the study results. For initial CDI, fidaxomicin was a more cost-effective therapy than metronidazole or vancomycin in 2 of 3 studies. For severe initial CDI, 2 of 3 studies found fidaxomicin to be the most cost-effective therapy. For recurrent CDI, fidaxomicin was cost-effective in 3 of 5 studies, while fecal microbiota transplantation (FMT) by colonoscopy was consistently cost-effective in 4 of 4 studies.


The cost-effectiveness of fidaxomicin compared with other pharmacologic therapies was not definitive for either initial or recurrent CDI. Despite its high cost, FMT by colonoscopy may be a cost-effective therapy for recurrent CDI. A consensus on model design and assumptions are necessary for future comparison of CDI treatment.

Infect Control Hosp Epidemiol 2018;39:412–424


Corresponding author

Address correspondence to Abhishek Deshpande MD, PhD, Center for Value-based Care Research, Medicine Institute, Cleveland Clinic, 9500 Euclid Ave, G10, Cleveland, OH 44195 (


Hide All
1. Loo, VG, Poirier, L, Miller, MA, et al. A predominantly clonal multi-institutional outbreak of Clostridium difficile-associated diarrhea with high morbidity and mortality. N Engl J Med 2005;353:24422449.
2. Lessa, FC, Winston, LG, McDonald, LC, Emerging Infections Program C. difficile Surveillance Team. Burden of Clostridium difficile infection in the United States. N Engl J Med 2015;372:23692370.
3. Cohen, SH, Gerding, DN, Johnson, S, 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;31:431455.
4. O’Connor, JR, Johnson, S, Gerding, DN. Clostridium difficile infection caused by the epidemic BI/NAP1/027 strain. Gastroenterology 2009;136:19131924.
5. McFarland, LV. Alternative treatments for Clostridium difficile disease: what really works? J Med Microbiol 2005;54:101111.
6. Eyre, DW, Walker, AS, Wyllie, D, et al. Predictors of first recurrence of Clostridium difficile infection: implications for initial management. Clin Infect Dis 2012;55(Suppl 2):S77S87.
7. Kelly, CP. Can we identify patients at high risk of recurrent Clostridium difficile infection? Clin Microbiol Infect 2012;18(Suppl 6):2127.
8. Desai, K, Gupta, SB, Dubberke, ER, Prabhu, VS, Browne, C, Mast, TC. Epidemiological and economic burden of Clostridium difficile in the United States: estimates from a modeling approach. BMC Infect Dis 2016;16:303.
9. Debast, SB, Bauer, MP, Kuijper, EJ, European Society of Clinical Microbiology and Infectious Diseases. 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):126.
10. Bakken, JS, Borody, T, Brandt, LJ, et al. Treating Clostridium difficile infection with fecal microbiota transplantation. Clin Gastroenterol Hepatol 2011;9:10441049.
11. Surawicz, CM, Brandt, LJ, Binion, DG, et al. Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. Am J Gastroenterol 2013;108:478498; quiz 499.
12. Bartsch, SM, Umscheid, CA, Fishman, N, Lee, BY. Is fidaxomicin worth the cost? An economic analysis. Clin Infect Dis 2013;57:555561.
13. Konijeti, GG, Sauk, J, Shrime, MG, Gupta, M, Ananthakrishnan, AN. Cost-effectiveness of competing strategies for management of recurrent Clostridium difficile infection: a decision analysis. Clin Infect Dis 2014;58:15071514.
14. Lapointe-Shaw, L, Tran, KL, Coyte, PC, et al. Cost-effectiveness analysis of six strategies to treat recurrent Clostridium difficile infection. PLoS One 2016;11:e0149521.
15. Varier, RU, Biltaji, E, Smith, KJ, et al. Cost-effectiveness analysis of treatment strategies for initial Clostridium difficile infection. Clin Microbiol Infect 2014;20:13431351.
16. Varier, RU, Biltaji, E, Smith, KJ, et al. Cost-effectiveness analysis of fecal microbiota transplantation for recurrent Clostridium difficile infection. Infect Control Hosp Epidemiol 2015;36:438444.
17. Watt, M, McCrea, C, Johal, S, Posnett, J, Nazir, J. A cost-effectiveness and budget impact analysis of first-line fidaxomicin for patients with Clostridium difficile infection (CDI) in Germany. Infection 2016;44:599606.
18. Mergenhagen, KA, Wojciechowski, AL, Paladino, JA. A review of the economics of treating Clostridium difficile infection. Pharmacoeconomics 2014;32:639650.
19. Moher, D, Liberati, A, Tetzlaff, J, Altman, DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med 2009;151:264269.
20. Shea, BJ, Grimshaw, JM, Wells, GA, et al. Development of AMSTAR: a measurement tool to assess the methodological quality of systematic reviews. BMC Med Res Methodol 2007;7:10.
21. Drummond, MF, Jefferson, TO. Guidelines for authors and peer reviewers of economic submissions to the BMJ. The BMJ Economic Evaluation Working Party. BMJ 1996;313:275283.
22. Husereau, D, Drummond, M, Petrou, S, et al. Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement. Value Health 2013;16:e1e5.
23. Consumer price indices. Organisation for Economic Co-operation and Development (OECD) website. Accessed August 25, 2016.
24. Rubio-Terres, C, Cobo Reinoso, J, Grau Cerrato, S, et al. Economic assessment of fidaxomicin for the treatment of Clostridium difficile infection (CDI) in special populations (patients with cancer, concomitant antibiotic treatment or renal impairment) in Spain. Eur J Clin Microbiol Infect Dis 2015;34:22132223.
25. Nathwani, D, Cornely, OA, Van Engen, AK, Odufowora-Sita, O, Retsa, P, Odeyemi, IA. Cost-effectiveness analysis of fidaxomicin versus vancomycin in Clostridium difficile infection. J Antimicrob Chemother 2014;69:29012912.
26. Merlo, G, Graves, N, Brain, D, Connelly, L. Economic evaluation of fecal microbiota transplantation for the treatment of recurrent Clostridium difficile infection in Australia. J Gastroenterol Hepatol 2016;31:19271932.
27. Stranges, PM, Hutton, DW, Collins, CD. Cost-effectiveness analysis evaluating fidaxomicin versus oral vancomycin for the treatment of Clostridium difficile infection in the United States. Value Health 2013;16:297304.
28. Markovic, V, Kostic, M, Ilickovic, I, Jankovic, SM. Cost-effectiveness comparison of fidaxomicin and vancomycin for treatment of Clostridium difficile infection: a Markov model based on data from a South West Balkan country in socioeconomic transition. Value in Health Regional Issues 2014;4C:8794.
29. Wagner, M, Lavoie, L, Goetghebeur, M. Clinical and economic consequences of vancomycin and fidaxomicin for the treatment of Clostridium difficile infection in Canada. Can J Infect Dis Med Microbiol 2014;25:8794.
30. Perras, C, Tsakonas, E, Ndegwa, S, Conly, J, Valiquette, L, Farrah, K. Vancomycin or metronidazole for treatment of Clostridium difficile infection: clinical and economic analyses. Ottawa: Canadian Agency for Drugs and Technologies in Health; 2011 (Technology report; no. 136).
31. Gidengil, CA, Caloyeras, JP, Hanson, M, Hillestad, R, Mattke, S. Comparative effectiveness of fidaxomicin for treatment of Clostridium difficile infection. Am J Pharmacy Benefit 2014;6:161170.
32. Cornely, OA, Crook, DW, Esposito, R, et al. Fidaxomicin versus vancomycin for infection with Clostridium difficile in Europe, Canada, and the USA: a double-blind, non-inferiority, randomised controlled trial. Lancet Infect Dis 2012;12:281289.
33. Louie, TJ, Miller, MA, Mullane, KM, et al. Fidaxomicin versus vancomycin for Clostridium difficile infection. N Engl J Med 2011;364:422431.
34. Lee, CH, Steiner, T, Petrof, EO, et al. Frozen vs fresh fecal microbiota transplantation and clinical resolution of diarrhea in patients with recurrent Clostridium difficile infection: a randomized clinical trial. JAMA 2016;315:142149.
35. van Nood, E, Vrieze, A, Nieuwdorp, M, et al. Duodenal infusion of donor feces for recurrent Clostridium difficile . N Engl J Med 2013;368:407415.
36. Li, YT, Cai, HF, Wang, ZH, Xu, J, Fang, JY. Systematic review with meta-analysis: long-term outcomes of faecal microbiota transplantation for Clostridium difficile infection. Aliment Pharmacol Ther 2016;43:445457.
37. Kassam, Z, Hundal, R, Marshall, JK, Lee, CH. Fecal transplant via retention enema for refractory or recurrent Clostridium difficile infection. Arch Intern Med 2012;172:191193.
38. Kassam, Z, Lee, CH, Yuan, Y, Hunt, RH. Fecal microbiota transplantation for Clostridium difficile infection: systematic review and meta-analysis. Am J Gastroenterol 2013;108:500508.
39. Hebbard, AIT, Slavin, MA, Reed, C, et al. Risks factors and outcomes of Clostridium difficile infection in patients with cancer: a matched case-control study. Support Care Cancer 2017;25:19231930.
40. Abrahamian, FM, Talan, DA, Krishnadasan, A, et al. Clostridium difficile infection among US emergency department patients with diarrhea and no vomiting. Ann Emerg Med 2017;70:1927.
41. Bagdasarian, N, Rao, K, Malani, PN. Diagnosis and treatment of Clostridium difficile in adults: a systematic review. JAMA 2015;313:398408.
42. Ananthakrishnan, AN, McGinley, EL, Binion, DG. Excess hospitalisation burden associated with Clostridium difficile in patients with inflammatory bowel disease. Gut 2008;57:205210.
43. McDonald, EG, Milligan, J, Frenette, C, Lee, TC. Continuous proton pump inhibitor therapy and the associated risk of recurrent Clostridium difficile infection. JAMA Intern Med 2015;175:784791.
44. Bell, CM, Urbach, DR, Ray, JG, et al. Bias in published cost-effectiveness studies: systematic review. BMJ 2006;332:699703.
45. Garey, KW, Aitken, SL, Gschwind, L, et al. Development and validation of a Clostridium difficile health-related quality-of-life questionnaire. J Clin Gastroenterol 2016;50:631637.
Type Description Title
Supplementary materials

Le et al. supplementary material
Le et al. supplementary material 1

 Word (42 KB)
42 KB


Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed