Clostridioides difficile infection (CDI) may be rising in severity in the US over the past decade and its treatment landscape is changing given the recent adoption of fecal microbiota transplantation (FMT)
We built a retrospective observational cohort using a database of a national care-plan containing medical claims of over 50 million individuals between 2008 and 2019. We used International Classification of Disease (ICD) and prescription data to identify patients with CDI. We estimated trends in disease burden and FMT use, and evaluated complications post FMT using a phenome-wide association approach.
We identified 38,396 patients with CDI; the median age was 60 years (IQR 45–74) and 60% were female (n = 23,374). The rate of CDI increased from 33.4 to 69.46 cases per 100,000 person-years between 2008 and 2015, and stabilized from 2015 to 2019 (increase of 4.77 cases per 100,000 person-years per year, 95% CI 3.55–5.98 prior to 2015 vs. 2.01 95% CI − 10.16 to 14.18 after 2015). Of the 7715 patients with recurrent CDI, 407 patients (5%) underwent FMT. Gastrointestinal complications were increased within 1 month post FMT (OR 99.60, p < 0.001). Sepsis was identified in two individuals (0.49% 95% CI 0.05–1.7%) within the first month post FMT. The risk of CDI recurrence significantly decreased post FMT compared with anti-CDI antibiotics in the multivariable model (raw-recurrence rate 9.8% vs 36%, aOR = 0.21, 95% CI 0.12–0.53, p < 0.001).
We show that FMT is strongly associated with a decrease in CDI recurrence compared with the usual care with generally mild complications for up to 2 years.
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Leffler DA, Lamont JT. Clostridium difficile infection. N Engl J Med. 2015;372:1539–48.
Kelly CP, Pothoulakis C, LaMont JT. Clostridium difficile colitis. N Engl J Med. 1994;330:257–62.
Centers for Disease Control and Prevention (CDC). Antibiotic resistance threats in the United States. USA: Centers for Disease Control and Prevention; 2019.
Dubberke ER, Olsen MA. Burden of Clostridium difficile on the healthcare system. Clin Infect Dis. 2012;55:S88–92.
Magill SS, Edwards JR, Bamberg W, et al. Multistate point-prevalence survey of health care–associated infections. N Engl J Med. 2014;370:1198–208.
Agency for Healthcare Research and Quality (AHRQ). Chronic condition indicator (CCI) for ICD-9-CM. Healthcare Cost and Utilization Project (HCUP); 2016.
Hirschhorn LR, Trnka Y, Onderdonk A, et al. Epidemiology of community—acquired Clostridium difficile-associated diarrhea. J Infect Dis. 1994;169:127–33.
Khanna S, Pardi DS, Aronson SL, et al. The epidemiology of community-acquired Clostridium difficile infection: a population-based study. Am J Gastroenterol. 2012;107:89–95.
Naggie S, Miller BA, Zuzak KB, et al. A case-control study of community-associated Clostridium difficile infection: no role for proton pump inhibitors. Am J Med. 2011;124:276.e1-7.
Chitnis AS, Holzbauer SM, Belflower RM, et al. Epidemiology of community-associated Clostridium difficile Infection, 2009 through 2011. JAMA Intern Med. 2013;173:1359–67.
Guh AY, Mu Y, Winston LG, et al. Trends in U.S. burden of Clostridioides difficile infection and outcomes. N Engl J Med. 2020;382:1320–30.
Centers for Disease Control and Prevention (CDC). Antibiotic-resistant germs: new threats. Centers for Disease Control and Prevention (CDC); 2020.
Brenner AV, Wang Z, Kleinerman RA, et al. Previous pulmonary diseases and risk of lung cancer in Gansu Province, China. Int J Epidemiol. 2001;30:118–24.
McFarland LV, Surawicz CM, Rubin M, et al. Recurrent Clostridium difficile disease: epidemiology and clinical characteristics. Infect Control Hosp Epidemiol. 1999;20:43–50.
Fekety R, McFarland LV, Surawicz CM, et al. Recurrent Clostridium difficile diarrhea: characteristics of and risk factors for patients enrolled in a prospective, randomized, double-blinded trial. Clin Infect Dis. 1997;24:324–33.
Bakken JS, Borody T, Brandt LJ, et al. Treating Clostridium difficile infection with fecal microbiota transplantation. Clin Gastroenterol Hepatol. 2011;9:1044–9.
Borody TJ, Khoruts A. Fecal microbiota transplantation and emerging applications. Nat Rev Gastroenterol Hepatol. 2012;9:88–96.
Brandt LJ, Aroniadis OC, Mellow M, et al. Long-term follow-up of colonoscopic fecal microbiota transplant for recurrent Clostridium difficile infection. Am J Gastroenterol. 2012;107:1079–87.
Hamilton MJ, Weingarden AR, Sadowsky MJ, et al. Standardized frozen preparation for transplantation of fecal microbiota for recurrent Clostridium difficile infection. Am J Gastroenterol. 2012;107:761–7.
Mellow MH, Kanatzar A. Colonoscopic fecal bacteriotherapy in the treatment of recurrent Clostridium difficile infection-results and follow-up. J Okla State Med Assoc. 2011;104:89–91.
DeFilipp Z, Bloom PP, Soto MT, et al. Drug-resistant E. coli bacteremia transmitted by fecal microbiota transplant. N Engl J Med. 2019;381:2043–50.
Wu P, Gifford A, Meng X, et al. Mapping ICD-10 and ICD-10-CM codes to phecodes: workflow development and initial evaluation. JMIR Med Inform. 2019;7: e14325.
Silverman MS, Davis I, Pillai DR. Success of self-administered home fecal transplantation for chronic Clostridium difficile infection. Clin Gastroenterol Hepatol. 2010;8:471–3.
Nowak A, Hedenstierna M, Ursing J, et al. Efficacy of routine fecal microbiota transplantation for treatment of recurrent Clostridium difficile infection: a retrospective cohort study. Int J Microbiol. 2019;2019:7395127.
Tvede M, Tinggaard M, Helms M. Rectal bacteriotherapy for recurrent Clostridium difficile-associated diarrhoea: results from a case series of 55 patients in Denmark 2000–2012. Clin Microbiol Infect. 2015;21:48–53.
Jorup-Rönström C, Håkanson A, Sandell S, et al. Fecal transplant against relapsing Clostridium difficile-associated diarrhea in 32 patients. Scand J Gastroenterol. 2012;47:548–52.
Lee CH, Belanger JE, Kassam Z, et al. The outcome and long-term follow-up of 94 patients with recurrent and refractory Clostridium difficile infection using single to multiple fecal microbiota transplantation via retention enema. Eur J Clin Microbiol Infect Dis. 2014;33:1425–8.
Zainah H, Hassan M, Shiekh-Sroujieh L, et al. Intestinal microbiota transplantation, a simple and effective treatment for severe and refractory Clostridium difficile infection. Dig Dis Sci. 2015;60:181–5.
Trubiano JA, Gardiner B, Kwong JC, et al. Faecal microbiota transplantation for severe Clostridium difficile infection in the intensive care unit. Eur J Gastroenterol Hepatol. 2013;25:255–7.
Marcella C, Cui B, Kelly CR, et al. Systematic review: the global incidence of faecal microbiota transplantation-related adverse events from 2000 to 2020. Aliment Pharmacol Ther. 2021;53:33–42.
This study was funded by the T15LM007092 Grant (JH), Biomedical Informatics and Data Science Research Training Program (PIs: Dr. Alexa T. McCray and Dr. Nils Gehlenborg) and by an NIH/BD2K award K01 ES026835 (MF). The funding source of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.
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Dr. Fox reports personal fees from Aetna, outside of the submitted work, otherwise we declare that we have no conflicts of interest.
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El Halabi, J., Palmer, N., Fox, K. et al. Fecal microbiota transplantation and Clostridioides difficile infection among privately insured patients in the United States. J Gastroenterol (2021). https://doi.org/10.1007/s00535-021-01822-y
- Clostridioides difficile
- Fecal microbiota transplantation
- Biomedical informatics