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Expert Review of Gastroenterology & Hepatology Volume 10, 2016 - Issue 2
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Reviews

Novel approaches to treating Clostridium difficile-associated colitis

David PaduaDepartment of Medicine, University of California, Los Angeles, Los Angeles, CA, USA
&
Charalabos PothoulakisDepartment of Medicine, University of California, Los Angeles, Los Angeles, CA, USACorrespondence[email protected]
Pages 193-204 | Received 03 Aug 2015, Accepted 14 Oct 2015, Published online: 07 Dec 2015

References

  • Papers of special note have been highlighted as:
  • • of interest
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•  Excellent review of the Clostridium difficile field.

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•  In depth review of the standard of care treatment.

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  • Pardi DS, Brennan R, Spinnell M, et al. Mo1116 the efficacy and safety of rifaximin vs. vancomycin in the treatment of mild to moderate C. difficile infection: a randomized double-blind active comparator trial. Gastroenterology. 2012;142(5):S599–S599.
  • Hecht DW, Galang MA, Sambol SP, et al. In vitro activities of 15 antimicrobial agents against 110 toxigenic Clostridium difficile clinical isolates collected from 1983 to 2004. Antimicrob Agents Chemother. 2007;51(8):2716–2719.
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  • Musher DM, Logan N, Mehendiratta V, et al. Clostridium difficile colitis that fails conventional metronidazole therapy: response to nitazoxanide. J Antimicrob Chemother. 2007;59(4):705–710.
  • Musher DM, Logan N, Bressler AM, et al. Nitazoxanide versus vancomycin in Clostridium difficile infection: a randomized, double-blind study. Clin Infect Dis. 2009;48(4):e41–6.
  • Koon HW, Ho S, Hing TC, et al. Fidaxomicin inhibits Clostridium difficile toxin A-mediated enteritis in the mouse ileum. Antimicrob Agents Chemother. 2014;58(8):4642–4650.
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  • Louie TJ, Miller MA, Mullane KM, et al. Fidaxomicin versus vancomycin for Clostridium difficile infection. N Engl J Med. 2011;364(5):422–431.

•  Phase 3 clinical trial comparing the efficacy and safety of fidaxomycin in Clostridium difficile infection.

  • Konijeti GG, Sauk J, Shrime MG, et al. Cost-effectiveness of competing strategies for management of recurrent Clostridium difficile infection: a decision analysis. Clin Infect Dis. 2014;58(11):1507–1514.
  • 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(2):87–94.
  • Bartsch SM, Umscheid CA, Fishman N, et al. Is fidaxomicin worth the cost? An economic analysis. Clin Infect Dis. 2013;57(4):555–561.
  • Bagdasarian N, Rao K, Malani PN. Diagnosis and treatment of Clostridium difficile in adults: a systematic review. Jama. 2015;313(4):398–408.
  • Locher HH, Seiler P, Chen X, et al. In vitro and in vivo antibacterial evaluation of cadazolid, a new antibiotic for treatment of Clostridium difficile infections. Antimicrob Agents Chemother. 2014;58(2):892–900.
  • 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(10):6266–6273.
  • Locher HH, Caspers P, Bruyere 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(2):901–908.
  • Mascio CT, Mortin LI, Howland KT, et al. In vitro and in vivo characterization of CB-183,315, a novel lipopeptide antibiotic for treatment of Clostridium difficile. Antimicrob Agents Chemother. 2012;56(10):5023–5030.
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  • de Gunzburg J, Ducher A, Modess C, et al. Targeted adsorption of molecules in the colon with the novel adsorbent-based medicinal product, DAV132: A proof of concept study in healthy subjects. J Clin Pharmacol. 2015;55(1):10–16.
  • Connelly S, Widmer G, Mukherjee J, et al. Tu2054 SYN-004, a clinical stage oral beta-lactamase therapy, protects the intestinal microflora from antibiotic-mediated damage in humanized pigs. Gastroenterology. 2015;148(4):S1195–S1195.
  • Louie TJ, Peppe J, Watt CK, et al. Tolevamer, a novel nonantibiotic polymer, compared with vancomycin in the treatment of mild to moderately severe Clostridium difficile-associated diarrhea. Clin Infect Dis. 2006;43(4):411–420.
  • 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.
  • Evans CT, Johnson S. Prevention of Clostridium difficile infection with probiotics. Clin Infect Dis. 2015;60(Suppl 2):S122–8.
  • Surawicz CM, McFarland LV, Elmer G, et al. Treatment of recurrent Clostridium difficile colitis with vancomycin and Saccharomyces boulardii. Am J Gastroenterol. 1989;84(10):1285–1287.
  • McFarland LV, Surawicz CM, Greenberg RN, et al. A randomized placebo-controlled trial of Saccharomyces boulardii in combination with standard antibiotics for Clostridium difficile disease. JAMA. 1994;271(24):1913–1918.
  • 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(4):812–822.
  • Kelesidis T, Pothoulakis C. Efficacy and safety of the probiotic Saccharomyces boulardii for the prevention and therapy of gastrointestinal disorders. Therap Adv Gastroenterol. 2012;5(2):111–125.
  • Pothoulakis C. Review article: anti-inflammatory mechanisms of action of Saccharomyces boulardii. Aliment Pharmacol Ther. 2009;30(8):826–833.
  • Goldenberg JZ, Ma SS, Saxton JD, et al. Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children. Cochrane Database Syst Rev. 2013;5:CD006095.

•  Meta-analysis of probiotic therapy in C. difficile.

  • Eiseman B, Silen W, Bascom GS, et al. Fecal enema as an adjunct in the treatment of pseudomembranous enterocolitis. Surgery. 1958;44(5):854–859.
  • van Nood E, Vrieze A, Nieuwdorp M, et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013;368(5):407–415.

•  Landmark study on showing FMT efficacy in recurrent C. difficile.

  • Gough E, Shaikh H, Manges AR. Systematic review of intestinal microbiota transplantation (fecal bacteriotherapy) for recurrent Clostridium difficile infection. Clin Infect Dis. 2011;53(10):994–1002.
  • 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(5):761–767.
  • Hamilton MJ, Weingarden AR, Unno T, et al. High-throughput DNA sequence analysis reveals stable engraftment of gut microbiota following transplantation of previously frozen fecal bacteria. Gut Microbes. 2013;4(2):125–135.
  • Shim JK, Johnson S, Samore MH, et al. Primary symptomless colonisation by Clostridium difficile and decreased risk of subsequent diarrhoea. Lancet. 1998;351(9103):633–636.
  • Borriello SP, Barclay FE. Protection of hamsters against Clostridium difficile ileocaecitis by prior colonisation with non-pathogenic strains. J Med Microbiol. 1985;19(3):339–350.
  • Villano SA, Seiberling M, Tatarowicz W, et al. Evaluation of an oral suspension of VP20621, spores of nontoxigenic Clostridium difficile strain M3, in healthy subjects. Antimicrob Agents Chemother. 2012;56(10):5224–5229.
  • 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(17):1719–1727.

•  Phase 2 randomized, double-blind, placebo-controlled trial looking at nontoxigenic C. difficile therapy.

  • Brouwer MS, Roberts AP, Hussain H, et al. Horizontal gene transfer converts non-toxigenic Clostridium difficile strains into toxin producers. Nat Commun. 2013;4:2601.
  • Ghose C, Kelly CP. The prospect for vaccines to prevent Clostridium difficile infection. Infect Dis Clin North Am. 2015;29(1):145–162.
  • Lowy I, Molrine DC, Leav BA, et al. Treatment with monoclonal antibodies against Clostridium difficile toxins. N Engl J Med. 2010;362(3):197–205.

•  Landmark study evaluating monoclonal antibodies in C. difficile patients.

  • Koon HW, Shih DQ, Hing TC, et al. Human monoclonal antibodies against Clostridium difficile toxins A and B inhibit inflammatory and histologic responses to the toxins in human colon and peripheral blood monocytes. Antimicrob Agents Chemother. 2013;57(7):3214–3223.
  • Foglia G, Shah S, Luxemburger C, et al. Clostridium difficile: development of a novel candidate vaccine. Vaccine. 2012;30(29):4307–4309.
  • Cox AD, St Michael F, Aubry A, et al. Investigating the candidacy of a lipoteichoic acid-based glycoconjugate as a vaccine to combat Clostridium difficile infection. Glycoconj J. 2013;30(9):843–855.

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