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Indian Journal of Gastroenterology
Published in: Indian Journal of Gastroenterology 1/2017

01-01-2017 | Review Article

Clostridium difficile infection: Updates in management

Authors: Raseen Tariq, Sahil Khanna

Published in: Indian Journal of Gastroenterology | Issue 1/2017

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Abstract

Clostridium difficile was first identified in 1978 as a diarrhea-causing bacterium in humans. In the last three decades, C. difficile infection (CDI) has reached an epidemic state, both in health care and community settings worldwide. There has been substantial progress in the field of CDI, including identification of novel risk factors, presence of CDI in individuals not considered at risk previously, and treatment options including new drugs, monoclonal antibodies, and fecal microbiota transplantation. This review discusses epidemiology, novel and traditional risk factors, and updates in management for CDI.
Literature
1.
Bartlett JG, Chang TW, Gurwith M, Gorbach SL, Onderdonk AB. Antibiotic-associated pseudomembranous colitis due to toxin-producing clostridia. N Engl J Med. 1978;298:531–4.CrossRefPubMed
2.
Miller BA, Chen LF, Sexton DJ, Anderson DJ. Comparison of the burdens of hospital-onset, healthcare facility-associated Clostridium difficile infection and of healthcare-associated infection due to methicillin-resistant Staphylococcus aureus in community hospitals. Infect Control Hosp Epidemiol. 2011;32:387–90.CrossRefPubMed
3.
Khanna S, Baddour LM, Huskins WC, et al. The epidemiology of Clostridium difficile infection in children: a population-based study. Clin Infect Dis. 2013;56:1401–6.CrossRefPubMedPubMedCentral
4.
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.CrossRefPubMed
5.
6.
Zilberberg MD, Shorr AF, Kollef MH. Increase in adult Clostridium difficile-related hospitalizations and case-fatality rate, United States, 2000-2005. Emerg Infect Dis. 2008;14:929–31.CrossRefPubMedPubMedCentral
7.
Steiner CBM, Weiss A. HCUP projections: Clostridium difficile hospitalizations 2001 to 2013. HCUP projections report #2014-01. Rockville: Agency for Healthcare Research and Quality; 2014.
8.
McDonald LC, Owings M, Jernigan DB. Clostridium difficile infection in patients discharged from US short-stay hospitals, 1996-2003. Emerg Infect Dis. 2006;12:409–15.CrossRefPubMedPubMedCentral
9.
Khanna S, Pardi DS. Community-acquired Clostridium difficile infection: an emerging entity. Clin Infect Dis. 2012;55:1741–2.CrossRefPubMed
10.
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.CrossRefPubMed
11.
Allard R, Dascal A, Camara B, Létourneau J, Valiquette L. Community-acquired Clostridium difficile-associated diarrhea, Montréal, 2005-2006: frequency estimates and their validity. Infect Control Hosp Epidemiol. 2011;32:1032–4.CrossRefPubMed
12.
Bhattacharya MK, Niyogi SK, Rasaily R, et al. Clinical manifestation of Clostridium difficile enteritis in Calcutta. J Assoc Physicians India. 1991;39:683–4.PubMed
13.
Gupta U, Yadav RN. Clostridium difficile in hospital patients. Indian J Med Res. 1985;82:398–401.PubMed
14.
Niyogi SK, Bhattacharya SK, Dutta P, et al. Prevalence of Clostridium difficile in hospitalised patients with acute diarrhoea in Calcutta. J Diarrhoeal Dis Res. 1991;9:16–9.
15.
Kaneria MV, Paul S. Incidence of Clostridium difficile associated diarrhoea in a tertiary care hospital. J Assoc Physicians India. 2012;60:26–8.PubMed
16.
Linsky A, Gupta K, Lawler EV, Fonda JR, Hermos JA. Proton pump inhibitors and risk for recurrent Clostridium difficile infection. Arch Intern Med. 2010;170:772–8.CrossRefPubMed
17.
Khanna S, Pardi DS. IBD: poor outcomes after Clostridium difficile infection in IBD. Nat Rev Gastroenterol Hepatol. 2012;9:307–8.CrossRefPubMed
18.
Khanna S, Pardi DS. The growing incidence and severity of Clostridium difficile infection in inpatient and outpatient settings. Expert Rev Gastroenterol Hepatol. 2010;4:409–16.CrossRefPubMed
19.
Otten AM, Reid-Smith RJ, Fazil A, Weese JS. Disease transmission model for community-associated Clostridium difficile infection. Epidemiol Infect. 2010;138:907–14.CrossRefPubMed
20.
21.
Poxton IR, McCoubrey J, Blair G. The pathogenicity of Clostridium difficile. Clin Microbiol Infect. 2001;7:421–7.CrossRefPubMed
22.
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;31:431–55.CrossRefPubMed
23.
Surawicz CM, Brandt LJ, Binion DG, et al. Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. Am J Gastroenterol. 2013;108:478–98. quiz 499CrossRefPubMed
24.
Carroll KC. Tests for the diagnosis of Clostridium difficile infection: the next generation. Anaerobe. 2011;17:170–4.CrossRefPubMed
25.
Reddymasu S, Sheth A, Banks DE. Is fecal leukocyte test a good predictor of Clostridium difficile associated diarrhea? Ann Clin Microbiol Antimicrob. 2006;5:9.CrossRefPubMedPubMedCentral
26.
Khanna S, Pardi DS, Rosenblatt JE, Patel R, Kammer PP, Baddour LM. An evaluation of repeat stool testing for Clostridium difficile infection by polymerase chain reaction. J Clin Gastroenterol. 2012;46:846–9.CrossRefPubMed
27.
Shivashankar R, Khanna S, Kammer PP, et al. Clinical factors associated with development of severe-complicated Clostridium difficile infection. Clin Gastroenterol Hepatol. 2013;11:1466–71.CrossRefPubMed
28.
Orenstein R, Aronhalt KC, McManus JE Jr, Fedraw LA. A targeted strategy to wipe out Clostridium difficile. Infect Control Hosp Epidemiol. 2011;32:1137–9.
29.
Kelly CP, LaMont JT. Clostridium difficile—more difficult than ever. N Engl J Med. 2008;359:1932–40.CrossRefPubMed
30.
Dubberke ER, Gerding DN, Classen D, et al. Strategies to prevent Clostridium difficile infections in acute care hospitals. Infect Control Hosp Epidemiol. 2008;29 Suppl 1:S81–92.
31.
Zar FA, Bakkanagari SR, Moorthi KM, Davis MB. A comparison of vancomycin and metronidazole for the treatment of Clostridium difficile-associated diarrhea, stratified by disease severity. Clin Infect Dis. 2007;45:302–7.CrossRefPubMed
32.
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;59:345–54.CrossRefPubMed
33.
Musher DM, Aslam S, Logan N, et al. Relatively poor outcome after treatment of Clostridium difficile colitis with metronidazole. Clin Infect Dis. 2005;40:1586–90.CrossRefPubMed
34.
Pépin J, Valiquette L, Alary ME, et al. Clostridium difficile-associated diarrhea in a region of Quebec from 1991 to 2003: a changing pattern of disease severity. CMAJ. 2004;171:466–72.CrossRefPubMedPubMedCentral
35.
Gerber M, Ackermann G. OPT-80, a macrocyclic antimicrobial agent for the treatment of Clostridium difficile infections: a review. Expert Opin Investig Drugs. 2008;17:547–53.CrossRefPubMed
36.
Finegold SM, Molitoris D, Vaisanen ML, Song Y, Liu C, Bolaños M. In vitro activities of OPT-80 and comparator drugs against intestinal bacteria. Antimicrob Agents Chemother. 2004;48:4898–902.CrossRefPubMedPubMedCentral
37.
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;12:281–9.CrossRefPubMed
38.
Louie TJ, Miller MA, Mullane KM, et al. Fidaxomicin versus vancomycin for Clostridium difficile infection. N Engl J Med. 2011;364:422–31.CrossRefPubMed
39.
Cornely OA, Nathwani D, Ivanescu C, Odufowora-Sita O, Retsa P, Odeyemi IA. Clinical efficacy of fidaxomicin compared with vancomycin and metronidazole in Clostridium difficile infections: a meta-analysis and indirect treatment comparison. J Antimicrob Chemother. 2014;69:2892–900.CrossRefPubMed
40.
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;53:440–7.CrossRefPubMedPubMedCentral
41.
Lancaster JW, Matthews SJ. Fidaxomicin: the newest addition to the armamentarium against Clostridium difficile infections. Clin Ther. 2012;34:1–13.CrossRefPubMed
42.
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;69:2901–12.CrossRefPubMedPubMedCentral
43.
44.
Garey KW, Ghantoji SS, Shah DN, et al. A randomized, double-blind, placebo-controlled pilot study to assess the ability of rifaximin to prevent recurrent diarrhoea in patients with Clostridium difficile infection. J Antimicrob Chemother. 2011;66:2850–5.CrossRefPubMed
45.
Mattila E, Arkkila P, Mattila PS, Tarkka E, Tissari P, Anttila VJ. Rifaximin in the treatment of recurrent Clostridium difficile infection. Aliment Pharmacol Ther. 2013;37:122–8.CrossRefPubMed
46.
White CA Jr. Nitazoxanide: a new broad spectrum antiparasitic agent. Expert Rev Anti-Infect Ther. 2004;2:43–9.
47.
Musher DM, Logan N, Bressler AM, Johnson DP, Rossignol JF. Nitazoxanide versus vancomycin in Clostridium difficile infection: a randomized, double-blind study. Clin Infect Dis. 2009;48:e41–6.CrossRefPubMed
48.
Locher HH, Caspers P, Bruyère T, et al. Investigations of the mode of action and resistance development of cadazolid, a new antibiotic for treatment of Clostridium difficile infections. Antimicrob Agents Chemother. 2014;58:901–8.CrossRefPubMedPubMedCentral
49.
Baldoni D, Gutierrez M, Timmer W, Dingemanse J. Cadazolid, a novel antibiotic with potent activity against Clostridium difficile: safety, tolerability and pharmacokinetics in healthy subjects following single and multiple oral doses. J Antimicrob Chemother. 2014;69:706–14.CrossRefPubMed
50.
Louie T, Nord CE, Talbot GH, et al. Multicenter, double-blind, randomized, phase 2 study evaluating the novel antibiotic cadazolid in patients with Clostridium difficile infection. Antimicrob Agents Chemother. 2015;59:6266–73.CrossRefPubMedPubMedCentral
51.
Mascio CT, Chesnel L, Thorne G, Silverman JA. Surotomycin demonstrates low in vitro frequency of resistance and rapid bactericidal activity in Clostridium Difficile, Enterococcus faecalis, and Enterococcus faecium. Antimicrob Agents Chemother. 2014;58:3976–82.CrossRefPubMedPubMedCentral
52.
Knight-Connoni V, Mascio C, Chesnel L, Silverman J. Discovery and development of surotomycin for the treatment of Clostridium difficile. J Ind Microbiol Biotechnol. 2016;43:195–204.CrossRefPubMed
53.
Lee CH, Patino H, Stevens C, et al. Surotomycin versus vancomycin for Clostridium difficile infection: phase 2, randomized, controlled, double-blind, non-inferiority, multicentre trial. J Antimicrob Chemother. 2016;71:2964–71.CrossRefPubMed
54.
Vickers RJ. Ridinilazole for Clostridium difficile infections: safety and efficacy compared with vancomycin from the CoDIFy phase 2 trial. European Society of Clinical Microbiology and Infectious Diseases (ECCMID) 2016, 2016
55.
Chang J, et al.Ridinilazole preserves major components of the intestinal microbiota during treatment of clostridium difficile infection. American Society for Microbiology (ASM) Microbe 2016, 2016
56.
Allen SJ, Wareham K, Wang D, et al. Lactobacilli and Bifidobacteria in the prevention of antibiotic-associated diarrhoea and Clostridium difficile diarrhoea in older inpatients (PLACIDE): a randomised, double-blind, placebo-controlled, multicentre trial. Lancet. 2013;382:1249–57.CrossRefPubMed
57.
Hempel S, Newberry SJ, Maher AR, et al. Probiotics for the prevention and treatment of antibiotic-associated diarrhea: a systematic review and meta-analysis. JAMA. 2012;307:1959–69.CrossRefPubMed
58.
59.
Pillai A, Nelson R. Probiotics for treatment of Clostridium difficile-associated colitis in adults. Cochrane Database Syst Rev. 2008;CD004611
60.
Johnston BC, Ma SS, Goldenberg JZ, et al. Probiotics for the prevention of Clostridium difficile-associated diarrhea: a systematic review and meta-analysis. Ann Intern Med. 2012;157:878–88.CrossRefPubMed
61.
McFarland LV. Meta-analysis of probiotics for the prevention of antibiotic associated diarrhea and the treatment of Clostridium difficile disease. Am J Gastroenterol. 2006;101:812–22.CrossRefPubMed
62.
Kreutzer EW, Milligan FD. Treatment of antibiotic-associated pseudomembranous colitis with cholestyramine resin. Johns Hopkins Med J. 1978;143:67–72.PubMed
63.
Kassam Z, Lee CH, Yuan Y, Hunt RH. Fecal microbiota transplantation for Clostridium difficile infection: systematic review and meta-analysis. Am J Gastroenterol. 2013;108:500–8.CrossRefPubMed
64.
Hu MY, Katchar K, Kyne L, et al. Prospective derivation and validation of a clinical prediction rule for recurrent Clostridium difficile infection. Gastroenterology. 2009;136:1206–14.CrossRefPubMed
65.
van Nood E, Vrieze A, Nieuwdorp M, et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013;368:407–15.CrossRefPubMed
66.
Drekonja D, Reich J, Gezahegn S, et al. Fecal microbiota transplantation for Clostridium difficile infection: a systematic review. Ann Intern Med. 2015;162:630–8.CrossRefPubMed
67.
Kelly CR, Ihunnah C, Fischer M, et al. Fecal microbiota transplant for treatment of Clostridium difficile infection in immunocompromised patients. Am J Gastroenterol. 2014;109:1065–71.CrossRefPubMed
68.
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.CrossRefPubMed
69.
Tariq R, Smyrk T, Pardi DS, Tremaine WJ, Khanna S. New-onset microscopic colitis in an ulcerative colitis patient after fecal microbiota transplantation. Am J Gastroenterol. 2016;111:751–2.CrossRefPubMed
70.
De Leon LM, Watson JB, Kelly CR. Transient flare of ulcerative colitis after fecal microbiota transplantation for recurrent Clostridium difficile infection. Clin Gastroenterol Hepatol. 2013;11:1036–8.CrossRefPubMed
71.
Quera R, Espinoza R, Estay C, Rivera D. Bacteremia as an adverse event of fecal microbiota transplantation in a patient with Crohn’s disease and recurrent Clostridium difficile infection. J Crohns Colitis. 2014;8:252–3.CrossRefPubMed
72.
73.
Paramsothy S, Borody TJ, Lin E, et al. Donor recruitment for fecal microbiota transplantation. Inflamm Bowel Dis. 2015;21:1600–6.CrossRefPubMed
74.
Youngster I, Russell GH, Pindar C, Ziv-Baran T, Sauk J, Hohmann EL. Oral, capsulized, frozen fecal microbiota transplantation for relapsing Clostridium difficile infection. JAMA. 2014;312:1772–8.CrossRefPubMed
75.
Gerding DN, Meyer T, Lee C, et al. Administration of spores of nontoxigenic Clostridium difficile strain M3 for prevention of recurrent C. difficile infection: a randomized clinical trial. JAMA. 2015;313:1719–27.CrossRefPubMed
76.
Orenstein R, Dubberke E, Hardi R, et al. Safety and durability of RBX2660 (microbiota suspension) for recurrent Clostridium difficile infection: results of the PUNCH CD study. Clin Infect Dis. 2016;62:596–602.CrossRefPubMed
77.
Khanna S, Pardi DS, Kelly CR, et al. A novel microbiome therapeutic increases gut microbial diversity and prevents recurrent Clostridium difficile infection. J Infect Dis. 2016;214:173–81.CrossRefPubMed
78.
Aboudola S, Kotloff KL, Kyne L, et al. Clostridium difficile vaccine and serum immunoglobulin G antibody response to toxin A. Infect Immun. 2003;71:1608–10.CrossRefPubMedPubMedCentral
79.
Lowy I, Molrine DC, Leav BA, et al. Treatment with monoclonal antibodies against Clostridium difficile toxins. N Engl J Med. 2010;362:197–205.CrossRefPubMed
80.
Wilcox M. Bezlotoxumab alone and with actoxumab for prevention of recurrent Clostridium difficile infection in patients on standard of care antibiotics: integrated results of 2 phase 3 studies (MODIFY I and MODIFY II). Open Forum Infectious Diseases, 2015. 2 Suppl 1: 67
81.
Kelly CP, et al. The monoclonal antibody, bezlotoxumab targeting C. difficile toxin B shows efficacy in preventing recurrent C. difficile infection (CDI) in patients at high risk of recurrence or of CDI-related adverse outcomes. Gastroenterology, 2016;150:4 Suppl. 1: p. S122
Metadata
Title
Clostridium difficile infection: Updates in management
Authors
Raseen Tariq
Sahil Khanna
Publication date
01-01-2017
Publisher
Springer India
Published in
Indian Journal of Gastroenterology / Issue 1/2017
Print ISSN: 0254-8860
Electronic ISSN: 0975-0711
DOI
https://doi.org/10.1007/s12664-016-0719-z

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