Strategies to prevent adverse outcomes following Clostridioides difficile infection in the elderly

References

• Lessa FC, Mu Y, Bamberg WM, et al. Burden of Clostridium difficile infection in the United States. N Engl J Med. 2015;372(9):825–859.
   PubMed Web of Science ®Google Scholar
• Olsen MA, Young-Xu Y, Stwalley D, et al. The burden of Clostridium difficile infection: estimates of the incidence of CDI from U.S. Administrative databases. BMC Infect Dis. 2016;16:177.
   PubMed Web of Science ®Google Scholar
• Olsen MA, Stwalley D, Demont C, et al. Increasing age has limited impact on risk of Clostridium difficile infection in an elderly population. Open Forum Infect Dis. 2018;5(7):ofy160.
   PubMed Web of Science ®Google Scholar
• Centers for Disease Control and Prevention. Antibiotic resistance threats in the United States; 2013 [cited 2019 May 16]. Available from: https://www.cdc.gov/drugresistance/threat-report-2013/pdf/ar-threats-2013-508.pdf
   Google Scholar
• Dubberke ER, Olsen MA. Burden of Clostridium difficile on the healthcare system. Clin Infect Dis. 2012;55(2):88–92.
   PubMedGoogle Scholar
• Asempa TE, Nicolau DP. Clostridium difficile infection in the elderly: an update on management. Clin Interv Aging. 2017;12:1799–1809.
   PubMed Web of Science ®Google Scholar
• Centers for Disease Control and Prevention. 2017 Annual report for the emerging infections program for Clostridioides difficile infection; 2017 [cited 2019 Oct 11]. Available from: https://www.cdc.gov/hai/eip/pdf/cdiff/2017-CDI-Report-H.pdf
   Google Scholar
• Olsen MA, Stwalley D, Demont C, et al. Clostridium difficile infection increases acute and chronic morbidity and mortality. Infect Control Hosp Epidemiol. 2019;40(1):65–71.
   PubMed Web of Science ®Google Scholar
• Khanna S, Pardi DS. Clostridium difficile infection: management strategies for a difficult disease. Therap Adv Gastroenterol. 2014;7(2):72–86.
   PubMed Web of Science ®Google Scholar
• Bartlett JG, Moon N, Chang TW, et al. Role of Clostridium difficile in antibiotic-associated pseudomembranous colitis. Gastroenterology. 1978;75(5):778–782.
   PubMed Web of Science ®Google Scholar
• Kwon JH, Olsen MA, Dubberke ER. The morbidity, mortality, and costs associated with Clostridium difficile infection. Infect Dis Clin North Am. 2015;29(1):123–134.
   PubMed Web of Science ®Google Scholar
• Pépin J, Valiquette L, Cossette B. Mortality attributable to nosocomial Clostridium difficile-associated disease during an epidemic caused by a hypervirulent strain in Quebec. CMAJ. 2005;173(9):1037–1042.
   PubMed Web of Science ®Google Scholar
• Lucado J, Gould C, Elixhauser A. Clostridium Difficile Infections (CDI) in hospital stays, 2009. Healthcare Costs and Utilization Project (HCUP) statistical brief #124; 2012. Agency for Heathcare Research and Quality, Rockville, MD, USA.
   Google Scholar
• Shorr AF, Zilberberg MD, Wang L, et al. Mortality and costs in Clostridium difficile infection among the elderly in the United States. Infect Control Hosp Epidemiol. 2016;37(11):1331–1336.
   PubMed Web of Science ®Google Scholar
• McDonald LC, Killgore GE, Thompson A, et al. An epidemic, toxin gene–variant strain of Clostridium difficile. N Engl J Med. 2005;353(23):2433–2441.
   PubMed Web of Science ®Google Scholar
• Rao K, Micic D, Natarajan M, et al. Clostridium difficile ribotype 027: relationship to age, detectability of toxins A or B in stool with rapid testing, severe infection, and mortality. Clin Infect Dis. 2015;61(2):233–241.
   PubMed Web of Science ®Google Scholar
• Loo VG, Bourgault A-M, Poirier L, et al. Host and pathogen factors for Clostridium difficile infection and colonization. N Engl J Med. 2011;365(18):1693–1703.
   PubMed Web of Science ®Google Scholar
• Miller M, Gravel D, Mulvey M, 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):194–201.
   PubMed Web of Science ®Google Scholar
• Walker AS, Eyre DW, Wyllie DH, et al. Relationship between bacterial strain type, host biomarkers, and mortality in Clostridium difficile infection. Clin Infect Dis. 2013;56(11):1589–1600.
   PubMed Web of Science ®Google Scholar
• See I, Mu Y, Cohen J, et al. NAP1 strain type predicts outcomes from Clostridium difficile infection. Clin Infect Dis. 2014;58(10):1394–1400.
   PubMed Web of Science ®Google Scholar
• Guh AY, Mu Y, Baggs J, et al. Trends in incidence of long-term-care facility onset Clostridium difficile infections in 10 US geographic locations during 2011-2015. Am J Infect Control. 2018;46(7):840–842.
   PubMed Web of Science ®Google Scholar
• Centers for Disease Control and Prevention. 2015 Annual report for the emerging infections program for Clostridium difficile infection; 2015 [cited 2019 Jul 8]. Available from: https://www.cdc.gov/hai/eip/pdf/cdiff/2015-CDI-Report.pdf
   Google Scholar
• Samarkos M, Mastrogianni E, Olga K. The role of gut microbiota in Clostridium difficile infection. Eur J Intern Med. 2018;50:28–32.
   PubMed Web of Science ®Google Scholar
• McDonald LC, Gerding DN, Johnson S, 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 Infect Dis. 2018;66(7):e1–e48.
   PubMed Web of Science ®Google Scholar
• Crobach MJT, Vernon JJ, Loo VG, et al. Understanding Clostridium difficile colonization. Clin Microbiol Rev. 2018;31(2):e00021–e17.
   PubMed Web of Science ®Google Scholar
• Furuya-Kanamori L, Marquess J, Yakob L, et al. Asymptomatic Clostridium difficile colonization: epidemiology and clinical implications. BMC Infect Dis. 2015;15(1):516.
   PubMedGoogle Scholar
• Rea MC, O’Sullivan O, Shanahan F, et al. Clostridium difficile carriage in elderly subjects and associated changes in the intestinal microbiota. J Clin Microbiol. 2012;50(3):867–875.
   PubMed Web of Science ®Google Scholar
• Zacharioudakis IM, Zervou FN, Pliakos EE, et al. Colonization with toxinogenic C. difficile upon hospital admission, and risk of infection: a systematic review and meta-analysis. Am J Gastroenterol. 2015;110(3):381–390.
   PubMed Web of Science ®Google Scholar
• Giel JL, Sorg JA, Sonenshein AL, et al. Metabolism of bile salts in mice influences spore germination in Clostridium difficile. PLoS One. 2010;5(1):e8740.
   PubMed Web of Science ®Google Scholar
• Sorg JA, Sonenshein AL. Inhibiting the initiation of Clostridium difficile spore germination using analogs of chenodeoxycholic acid, a bile acid. J Bacteriol. 2010;192(19):4983–4990.
   PubMed Web of Science ®Google Scholar
• Sorg JA, Sonenshein AL. Chenodeoxycholate is an inhibitor of Clostridium difficile spore germination. J Bacteriol. 2009;191(3):1115–1117.
   PubMed Web of Science ®Google Scholar
• Hashimoto S, Igimi H, Uchida K, et al. Effects of β-lactam antibiotics on intestinal microflora and bile acid metabolism in rats. Lipids. 1996;31(6):601–609.
   PubMed Web of Science ®Google Scholar
• Theriot CM, Koenigsknecht MJ, Carlson PE, et al. Antibiotic-induced shifts in the mouse gut microbiome and metabolome increase susceptibility to Clostridium difficile infection. Nat Commun. 2014;5:3114.
   PubMed Web of Science ®Google Scholar
• Kho ZY, Lal SK. The human gut microbiome – A potential controller of wellness and disease. Front Microbiol. 2018;9:1835.
   PubMed Web of Science ®Google Scholar
• Lyras D, O’Connor JR, Howarth PM, et al. Toxin B is essential for virulence of Clostridium difficile. Nature. 2009;458(7242):1176.
   PubMed Web of Science ®Google Scholar
• Kuehne SA, Cartman ST, Heap JT, et al. The role of toxin A and toxin B in Clostridium difficile infection. Nature. 2010;467(7):711–714.
   PubMedGoogle Scholar
• Di Bella S, Ascenzi P, Siarakas S, et al. Clostridium difficile toxins a and b: insights into pathogenic properties and extraintestinal effects. Toxins (Basel). 2016;8(5):E134.
   PubMed Web of Science ®Google Scholar
• Gupta SB, Mehta V, Dubberke ER, et al. Antibodies to toxin B are protective against Clostridium difficile infection recurrence. Clin Infect Dis. 2016;63(6):730–734.
   PubMed Web of Science ®Google Scholar
• Kelly CP, Poxton IR, Shen J, et al. Effect of endogenous Clostridioides difficile toxin antibodies on recurrence of C. difficile infection. Clin Infect Dis. 2019 October;ciz809.
   PubMed Web of Science ®Google Scholar
• Wilcox MH, Gerding DN, Poxton IR, et al. Bezlotoxumab for prevention of recurrent Clostridium difficile infection. N Engl J Med. 2017;376(4):305–317.
   PubMed Web of Science ®Google Scholar
• Jernberg C, Lofmark S, Edlund C, et al. Long-term impacts of antibiotic exposure on the human intestinal microbiota. Microbiology. 2010;156(11):3216–3223.
   PubMedGoogle Scholar
• Czepiel J, Dróżdż M, Pituch H, et al. Clostridium difficile infection: review. Eur J Clin Microbiol Infect Dis. 2019;38:1211–1221.
   PubMed Web of Science ®Google Scholar
• Stevens V, Dumyati G, Fine LS, et al. Cumulative antibiotic exposures over time and the risk of Clostridium difficile infection. Clin Infect Dis. 2011;53(1):42–48.
   PubMed Web of Science ®Google Scholar
• Palmore TN, Sohn S, Malak SF, et al. Risk factors for acquisition of Clostridium difficile-associated diarrhea among outpatients at a cancer hospital. Infect Control Hosp Epidemiol. 2005;26(8):680–684.
   PubMed Web of Science ®Google Scholar
• Dubberke ER, Reske KA, Yan Y, et al. Clostridium difficile–associated disease in a setting of endemicity: identification of novel risk factors. Clin Infect Dis. 2007;45(12):1543–1549.
   PubMed Web of Science ®Google Scholar
• Nagpal R, Mainali R, Ahmadi S, et al. Gut microbiome and aging: physiological and mechanistic insights. Nutr Heal Aging. 2018;4(4):267–285.
   PubMedGoogle Scholar
• O’Toole PW, Jeffery IB. Microbiome–health interactions in older people. Cell Mol Life Sci. 2018;75(1):119–128.
   PubMed Web of Science ®Google Scholar
• Valdes AM, Walter J, Segal E, et al. Role of the gut microbiota in nutrition and health. BMJ. 2018;361:36–44.
   Google Scholar
• Suez J, Zmora N, Zilberman-Schapira G, et al. Post-antibiotic gut mucosal microbiome reconstitution is impaired by probiotics and improved by autologous FMT. Cell. 2018;174(6):1406–1423.e16.
   PubMed Web of Science ®Google Scholar
• Kim S, Jazwinski SM. The gut microbiota and healthy aging: a mini-review. Gerontology. 2018;64(6):513–520.
   PubMed Web of Science ®Google Scholar
• Shin JH, High KP, Warren CA. Older is not wiser, immunologically speaking: effect of aging on host response to Clostridium difficile infections. J Gerontol A Biol Sci Med Sci. 2016;71(7):916–922.
   PubMed Web of Science ®Google Scholar
• Frasca D, Landin AM, Lechner SC, et al. Aging down-regulates the transcription factor E2A, activation-induced cytidine deaminase, and Ig class switch in human B cells. J Immunol. 2008;180(8):5283–5290.
   PubMed Web of Science ®Google Scholar
• Jump RLP, Crnich CJ, Lona M, et al. Infectious diseases in older adults of long-term care facilities: update on approach to diagnosis and management. J Am Geriatr Soc. 2018;66(4):789–803.
   PubMed Web of Science ®Google Scholar
• Kyne L, Warny M, Qamar A, et al. Asymptomatic carriage of Clostridium difficile and serum levels of IgG antibody against toxin A. N Engl J Med. 2000;342(6):390–397.
   PubMed Web of Science ®Google Scholar
• Kyne L, Warny M, Qamar A, et al. Association between antibody response to toxin A and protection against recurrent Clostridium difficile diarrhoea. Lancet. 2001;357(9251):189–193.
   PubMed Web of Science ®Google Scholar
• Louie TJ, Miller MA, Crook DW, et al. Effect of Age on treatment outcomes in Clostridium difficile infection. J Am Geriatr Soc. 2013;61(2):222–230.
   PubMed Web of Science ®Google Scholar
• Donskey CJ. Clostridium difficile in older adults. Infect Dis Clin North Am. 2017;31(4):743–756.
   PubMed Web of Science ®Google Scholar
• Khanna S, Pardi DS, Aronson SL, et al. The epidemiology of community-acquired Clostridium difficile infection: a population-based study. Am J Gastroenterol. 2012;2011(1):89–95.
   Google Scholar
• Abou Chakra NC, Pepin J, Sirard S, et al. Risk factors for recurrence, complications and mortality in Clostridium difficile infection: a systematic review. PLoS One. 2014;9(6):e98400.
   PubMed Web of Science ®Google Scholar
• Abou Chakra NC, Mcgeer A, Labbé A-C, et al. Factors associated with complications of Clostridium difficile infection in a multicenter prospective cohort. Clin Infect Dis. 2015;61(12):1781–1788.
   PubMed Web of Science ®Google Scholar
• Khanafer N, Barbut F, Eckert C, et al. Factors predictive of severe Clostridium difficile infection depend on the definition used. Anaerobe. 2016;37:43–48.
   PubMed Web of Science ®Google Scholar
• Shivashankar R, Khanna S, Kammer PP, et al. Clinical factors associated with development of severe-complicated Clostridium difficile infection. Clin Gastroenterol Hepatol. 2013;11(11):1466–1471.
   PubMed Web of Science ®Google Scholar
• Rao K, Micic D, Chenoweth E, et al. Decreased functional status as a risk factor for severe Clostridium difficile infection among hospitalized older adults. J Am Geriatr Soc. 2013;61(10):1738–1742.
   PubMed Web of Science ®Google Scholar
• Goorhuis A. Editorial commentary: clostridium difficile ribotype 027: an intrinsically virulent strain, but clinical virulence remains to be determined at the bedside. Clin Infect Dis. 2015;61(2):242–243.
   PubMed Web of Science ®Google Scholar
• Stevens VW, Khader K, Nelson RE, 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.
   PubMed Web of Science ®Google Scholar
• Pechal A, Lin K, Allen S, et al. National age group trends in Clostridium difficile infection incidence and health outcomes in United States community hospitals. BMC Infect Dis. 2016;16(1):682.
   PubMedGoogle Scholar
• Campbell R, Dean B, Nathanson B, et al. 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.
   PubMedGoogle Scholar
• Elixhauser A, Steiner C, Gould C. Readmissions following hospitalizations with Clostridium difficile infections, 2009. Healthcare Cost and Utilization Project (HCUP) statistical brief #145; 2012. Agency for Heathcare Research and Quality, Rockville, MD, USA.
   Google Scholar
• Dubberke ER, Butler AM, Reske KA, et al. Attributable outcomes of endemic Clostridium difficile-associated disease in nonsurgical patients. Emerg Infect Dis. 2008;14(7):1031–1038.
   PubMed Web of Science ®Google Scholar
• Reveles KR, Dotson KM, Gonzales-Luna A, et al. Clostridioides (formerly Clostridium) difficile infection during hospitalization increases the likelihood of nonhome patient discharge. Clin Infect Dis. 2019;68(11):1887–1893.
   PubMed Web of Science ®Google Scholar
• Sheitoyan-Pesant C, Abou Chakra CN, Pépin J, et al. Clinical and healthcare burden of multiple recurrences of Clostridium difficile infection. Clin Infect Dis. 2016;62(5):574–580.
   PubMed Web of Science ®Google Scholar
• Chilton CH, Pickering DS, Freeman J. Narrative review microbiologic factors affecting Clostridium difficile recurrence. Clin Microbiol Infect. 2018;24:476.
   PubMed Web of Science ®Google Scholar
• McFarland LV, Elmer GW, Surawicz CM. Breaking the cycle: treatment strategies for 163 cases of recurrent Clostridium difficile disease. Am J Gastroenterol. 2002;97(7):1769–1775.
   PubMed Web of Science ®Google Scholar
• Kelly CP. Can we identify patients at high risk of recurrent Clostridium difficile infection? Clin Microbiol Infect. 2012;18:21–27.
   PubMed Web of Science ®Google Scholar
• Deshpande A, Pasupuleti V, Thota P, et al. Risk factors for recurrent Clostridium difficile infection: a systematic review and meta-analysis. Infect Control Hosp Epidemiol. 2015;36(4):454–460.
   Web of Science ®Google Scholar
• Zilberberg MD, Reske K, Olsen M, et al. Risk factors for recurrent Clostridium difficile infection (CDI) hospitalization among hospitalized patients with an initial CDI episode: a retrospective cohort study. BMC Infect Dis. 2014;14:306.
   PubMed Web of Science ®Google Scholar
• Zilberberg MD, Reske K, Olsen M, et al. Development and validation of a recurrent Clostridium difficile risk-prediction model. J Hosp Med. 2014;9(7):418–423.
   PubMed Web of Science ®Google Scholar
• 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(8):631–637.
   PubMed Web of Science ®Google Scholar
• Olsen MA, Yan Y, Reske KA, et al. Impact of Clostridium difficile recurrence on hospital readmissions. Am J Infect Control. 2015;43(4):318–322.
   PubMed Web of Science ®Google Scholar
• Kuntz JL, Baker JM, Kipnis P, et al. Utilization of health services among adults with recurrent Clostridium difficile infection: a 12-year population-based study. Infect Control Hosp Epidemiol. 2017;38(1):45–52.
   PubMed Web of Science ®Google Scholar
• Pépin J, Routhier S, Gagnon S, et al. Management and outcomes of a first recurrence of Clostridium difficile-associated disease in Quebec, Canada. Clin Infect Dis. 2006;42(6):758–764.
   PubMed Web of Science ®Google Scholar
• Olsen MA, Yan Y, Reske KA, et al. Recurrent Clostridium difficile infection is associated with increased mortality. Clin Microbiol Infect. 2015;21(2):164–170.
   PubMed Web of Science ®Google Scholar
• Kochanek KD, Murphy SL, Xu J, et al. Deaths: final data for 2017. National vital statistics reports; 2019 [cited 2019 Oct 16]. Available from: https://www.cdc.gov/nchs/data/nvsr/nvsr68/nvsr68_09-508.pdf
   Google Scholar
• Baur D, Primrose Gladstone B, Burkert F, et al. Effect of antibiotic stewardship on the incidence of infection and colonisation with antibiotic-resistant bacteria and Clostridium difficile infection: a systematic review and meta-analysis. Lancet Infect Dis. 2017;17:990–1001.
   PubMed Web of Science ®Google Scholar
• Feazel LM, Malhotra A, Perencevich EN, et al. Effect of antibiotic stewardship programmes on Clostridium difficile incidence: a systematic review and meta-analysis. J Antimicrob Chemother. 2014;69:1748–1754.
   PubMed Web of Science ®Google Scholar
• Davey P, Marwick CA, Scott CL, et al. Interventions to improve antibiotic prescribing practices for hospital inpatients. Cochrane Database Syst Rev. 2017;2(CD003543):1–368.
   Google Scholar
• Centers for Disease Control and Prevention. Core elements of hospital antibiotic stewardship programs; 2015 [cited 2019 July 15]. Available from: https://www.cdc.gov/antibiotic-use/healthcare/implementation/core-elements.html
   Google Scholar
• Fleming A, Bradley C, Cullinan S, et al. Antibiotic prescribing in long-term care facilities: a meta-synthesis of qualitative research. Drugs Aging. 2015;32(4):295–303.
   PubMed Web of Science ®Google Scholar
• Dingle KE, Didelot X, Quan TP, et al. Effects of control interventions on Clostridium difficile infection in England: an observational study. Lancet Infect Dis. 2017;17(4):411–421.
   PubMed Web of Science ®Google Scholar
• Kazakova SV, Baggs J, McDonald LC, et al. Association between antibiotic use and hospital-onset Clostridioides difficile. 2020 Jan 1;70(1):11-18
   Google Scholar
• Schwartz DN, Abiad H, DeMarais PL, et al. An educational intervention to improve antimicrobial use in a hospital-based long-term care facility. J Am Geriatr Soc. 2007;55(8):1236–1242.
   PubMed Web of Science ®Google Scholar
• Jump RL, Olds DM, Seifi N, et al. Effective antimicrobial stewardship in a long-term care facility through an infectious disease consultation service: keeping a LID on antibiotic use HHS public access. Antimicrob Agents Chemother. 2011;33(12):1185–1192.
   Google Scholar
• Dubberke ER, Olsen MA, Stwalley D, et al. Identification of medicare recipients at highest risk for Clostridium difficile infection in the US by population attributable risk analysis. PLoS One. 2016;11(2):1–14.
   Web of Science ®Google Scholar
• Cortes-Penfield NW, Trautner BW, Jump R. Urinary tract infection and asymptomatic bacteriuria in older adults. Infect Dis Clin North Am. 2017;31(4):673–688.
   PubMed Web of Science ®Google Scholar
• Polgreen PM, Chen YY, Cavanaugh JE, et al. An outbreak of severe Clostridium difficile –associated disease possibly related to inappropriate antimicrobial therapy for community-acquired pneumonia. Infect Control Hosp Epidemiol. 2007;28(2):212–214.
   PubMed Web of Science ®Google Scholar
• Durham DP, Olsen MA, Dubberke ER, et al. Quantifying transmission of Clostridium difficile within and outside healthcare settings. Emerg Infect Dis. 2016;22(4):608–616.
   PubMed Web of Science ®Google Scholar
• Barker AK, Cowley ES, McKinley L, et al. An in-room observation study of hand hygiene and contact precaution compliance for Clostridioides difficile patients. Am J Infect Control. 2019;47(10):1273–1276.
   PubMed Web of Science ®Google Scholar
• Kwon JH, Burnham C-AD, Reske KA, et al. Assessment of healthcare worker protocol deviations and self-contamination during personal protective equipment donning and doffing. Infect Control Hosp Epidemiol. 2017;38(9):1077–1083.
   PubMed Web of Science ®Google Scholar
• Longtin Y, Paquet-Bolduc B, Gilca R, et al. Effect of detecting and isolating Clostridium difficile carriers at hospital admission on the incidence of C difficile infections: a quasi-experimental controlled study. JAMA Intern Med. 2016;176(6):796–804.
   PubMed Web of Science ®Google Scholar
• Paquet-Bolduc B, Gervais P, Roussy JF, et al. Detection and isolation of Clostridium difficile asymptomatic carriers during Clostridium difficile infection outbreaks: an exploratory study. Clin Infect Dis. 2018;67(11):1784–1787.
   PubMed Web of Science ®Google Scholar
• Kong LY, Eyre DW, Corbeil J, et al. Clostridium difficile : investigating transmission patterns between infected and colonized patients using whole genome sequencing. Clin Infect Dis. 2019;68(2):204–209.
   PubMed Web of Science ®Google Scholar
• Mullane KM, Miller MA, Weiss K, et al. Efficacy of fidaxomicin versus vancomycin as therapy for Clostridium difficile infection in individuals taking concomitant antibiotics for other concurrent infections. Clin Infect Dis. 2011;53(5):440–447.
   PubMed Web of Science ®Google Scholar
• Musher DM, Aslam S, Logan N, et al. Relatively poor outcome after treatment of Clostridium difficile colitis with metronidazole. Clin Infect Dis. 2005;40(11):1586–1590.
   PubMed Web of Science ®Google Scholar
• Pépin J, Alary M-E, Valiquette L, et al. Increasing risk of relapse after treatment of Clostridium difficile colitis in Quebec, Canada. Clin Infect Dis. 2005;40(11):1591–1597.
   PubMed Web of Science ®Google Scholar
• Al‐Nassir WN, Sethi AK, Nerandzic MM, et al. Comparison of clinical and microbiological response to treatment of Clostridium difficile –associated disease with metronidazole and vancomycin. Clin Infect Dis. 2008;47(1):56–62.
   PubMed Web of Science ®Google Scholar
• Zar FA, Bakkanagari SR, Moorthi KMLST, et al. A comparison of vancomycin and metronidazole for the treatment of Clostridium difficile-associated diarrhea, stratified by disease severity. Clin Infect Dis. 2007;45(3):302–307.
   PubMed Web of Science ®Google Scholar
• 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(5):431–455.
   PubMed Web of Science ®Google Scholar
• Johnson S, Louie TJ, Gerding DN, et al. Vancomycin, metronidazole, or tolevamer for Clostridium difficile infection: results from two multinational, randomized, controlled trials. Clin Infect Dis. 2014;59(3):345–354.
   PubMed Web of Science ®Google Scholar
• Stevens VW, Nelson RE, Schwab-Daugherty EM, et al. Comparative effectiveness of vancomycin and metronidazole for the prevention of recurrence and death in patients with Clostridium difficile infection. JAMA Intern Med. 2017;177(4):546–553.
   PubMed Web of Science ®Google Scholar
• Louie TJ, Miller MA, Mullane KM, et al. Fidaxomicin versus vancomycin for Clostridium difficile infection. N Engl J Med. 2011;364:422–453.
   PubMed Web of Science ®Google Scholar
• 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;12:281–289.
   PubMed Web of Science ®Google Scholar
• Isaac S, Scher JU, Djukovic A, et al. Short-and long-term effects of oral vancomycin on the human intestinal microbiota. J Antimicrob Chemother. 2017;72:128–136.
   PubMed Web of Science ®Google Scholar
• Bolton RP, Culshaw MA. Faecal metronidazole concentrations during oral and intravenous therapy for antibiotic associated colitis due to Clostridium difficile. Gut. 1986;27(10):1169–1172.
   PubMed Web of Science ®Google Scholar
• Rokas KEE, Johnson JW, Beardsley JR, et al. The addition of intravenous metronidazole to oral vancomycin is associated with improved mortality in critically Ill patients with Clostridium difficile infection. Clin Infect Dis. 2015;61(6):934–941.
   PubMed Web of Science ®Google Scholar
• Fekety R, Silva J, Kauffman C, et al. Treatment of antibiotic-associated Clostridium difficile colitis with oral vancomycin: comparison of two dosage regimens. Am J Med. 1989;86(1 C):15–19.
   PubMed Web of Science ®Google Scholar
• Lamontagne F, Labbé A-C, Haeck O, et al. Impact of emergency colectomy on survival of patients with fulminant Clostridium difficile colitis during an epidemic caused by a hypervirulent strain. Ann Surg. 2007;245:267–272.
   PubMed Web of Science ®Google Scholar
• Neal MD, Alverdy JC, Hall DE, et al. Diverting loop ileostomy and colonic lavage. Ann Surg. 2011;254(3):423–429.
   PubMed Web of Science ®Google Scholar
• Ferrada P, Callcut R, Zielinski MD, et al. Loop ileostomy versus total colectomy as surgical treatment for Clostridium difficile–associated disease. J Trauma Acute Care Surg. 2017;83(1):36–40.
   PubMed Web of Science ®Google Scholar
• Sirbu BD, Soriano MM, Manzo C, et al. Vancomycin taper and pulse regimen with careful follow-up for patients with recurrent Clostridium difficile infection. Clin Infect Dis. 2017;65(8):1396–1399.
   PubMed Web of Science ®Google Scholar
• O’Connor JR, Galang MA, Sambol SP, et al. Rifampin and rifaximin resistance in clinical isolates of Clostridium difficile. Antimicrob Agents Chemother. 2008;52(8):2813–2817.
   PubMed Web of Science ®Google Scholar
• Soriano MM, Danziger LH, Gerding DN, et al. Novel fidaxomicin treatment regimens for patients with multiple Clostridium difficile infection recurrences that are refractory to standard therapies. Open Forum Infect Dis. 2014;1(2):ofu069.
   PubMedGoogle Scholar
• Kelly BJ, Tebas P. Clinical practice and infrastructure review of fecal microbiota transplantation for Clostridium difficile infection. Chest. 2018;153(1):266–277.
   PubMed Web of Science ®Google Scholar
• van Nood E, Vrieze A, Nieuwdorp M, et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013;5:407–422.
   Google Scholar
• Kelly CR, Khoruts A, Staley C, et al. Effect of fecal microbiota transplantation on recurrence in multiply recurrent Clostridium difficile infection: a randomized trial. Ann Intern Med. 2016;165(9):609–616.
   PubMed Web of Science ®Google Scholar
• Dubberke ER, Lee CH, Orenstein R, et al. Results from a randomized, placebo-controlled clinical trial of a RBX2660 - a microbiota-based drug for the prevention of recurrent Clostridium difficile infection. Clin Infect Dis. 2018;67(8):1198–1204.
   PubMed Web of Science ®Google Scholar
• Hota SS, Sales V, Tomlinson G, et al. Oral vancomycin followed by fecal transplantation versus tapering oral vancomycin treatment for recurrent Clostridium difficile infection: an open-label, randomized controlled trial. Clin Infect Dis. 2017;64(3):265–271.
   PubMed Web of Science ®Google Scholar
• U.S. Food & Drug Administration. Important safety alert regarding use of fecal microbiota for transplantation and risk of serious adverse reactions due to transmission of multi-drug resistant organisms. [cited 2019 Sept 29]. Available from: https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/important-safety-alert-regarding-use-fecal-microbiota-transplantation-and-risk-serious-adverse
   Google Scholar
• Gerding DN, Kelly CP, Rahav G, et al. Bezlotoxumab for prevention of recurrent Clostridium difficile infection in patients at increased risk for recurrence. Clin Infect Dis. 2018;67(5):649–656.
   PubMed Web of Science ®Google Scholar
• Johnson S, Gerding DN. Bezlotoxumab. Clin Infect Dis. 2019;68(4):699–704.
   PubMed Web of Science ®Google Scholar