Update of treatment algorithms for Clostridium difficile infection

Clinical Microbiology and Infection

Volumn 24, Issue 5, 2018, Pages 452-462

  Ooijevaar, R E ^a   van Beurden, Y H ^a   Terveer, E M ^c   Goorhuis, A ^b   Bauer, M P ^c   Keller, J J ^c,d   Mulder, C J J ^a   Kuijper, E J ^c,e  

^a VU UNIVERSITY MEDICAL CENTER   (Netherlands)

^b ACADEMIC MEDICAL CENTER   (Netherlands)

^c LEIDEN UNIVERSITY MEDICAL CENTER   (Netherlands)

^d MEDICAL CENTER HAAGLANDEN   (Netherlands)

^e European Study Group of C difficile (ESGCD)   (United Kingdom)

Author keywords

Algorithm; Antibiotics; CDI; Clostridium difficile infection; Faecal microbiota; Review; Treatment

Indexed keywords

ANTIBIOTIC AGENT; BEZLOTOXUMAB; CADAZOLID; FIDAXOMICIN; LFF 571; METRONIDAZOLE; MONOCLONAL ANTIBODY; RIDINILAZOLE; RIFAXIMIN; SUROTOMYCIN; VANCOMYCIN; ANTIINFECTIVE AGENT;

ANTIBIOTIC THERAPY; BACTERIAL STRAIN; CLOSTRIDIUM DIFFICILE INFECTION; FECAL MICROBIOTA TRANSPLANTATION; HIGH RISK POPULATION; HUMAN; INTESTINE FLORA; MICROCAPSULE; PRIORITY JOURNAL; RELAPSE; REVIEW; ALGORITHM; CLINICAL TRIAL (TOPIC); CLOSTRIDIUM INFECTION; DISEASE MANAGEMENT; DRUG DEVELOPMENT; DRUG EFFECT; MICROBIOLOGY; PEPTOCLOSTRIDIUM DIFFICILE; PHYSIOLOGY; PRACTICE GUIDELINE;

ALGORITHMS; ANTI-BACTERIAL AGENTS; CLINICAL TRIALS AS TOPIC; CLOSTRIDIUM DIFFICILE; CLOSTRIDIUM INFECTIONS; DISEASE MANAGEMENT; DRUG DISCOVERY; FECAL MICROBIOTA TRANSPLANTATION; HUMANS; PRACTICE GUIDELINES AS TOPIC;

EID: 85044651737     PISSN: 1198743X     EISSN: 14690691     Source Type: Journal    
DOI: 10.1016/j.cmi.2017.12.022     Document Type: Review

References (91)

1. Magill, S.S., Edwards, J.R., Bamberg, W., Beldavs, Z.G., Dumyati, G., Kainer, M.A., et al. Multistate point-prevalence survey of health care–associated infections. N Engl J Med 370 (2014), 1198–1208.
2. Smits, W.K., Lyras, D., Borden Lacy, D., Wilcox, M.H., Kuijper, E.J., Clostridium difficile infection. Nat Rev Dis Primers, 2, 2016, 16021.
3. Deshpande, A., Pasupuleti, V., Thota, P., Pant, C., Rolston, D.D., Hernandez, A.V., et al. Risk factors for recurrent Clostridium difficile infection: a systematic review and meta-analysis. Infect Control Hosp Epidemiol 36 (2015), 452–460.
4. Shields, K., Araujo-Castillo, R.V., Theethira, T.G., Alonso, C.D., Kelly, C.P., Recurrent Clostridium difficile infection: from colonization to cure. Anaerobe 34 (2015), 59–73.
5. Debast, S.B., Bauer, M.P., Kuijper, E.J., European Society of Clinical Microbiology and Infectious Diseases (ESCMID). European Society of Clinical Microbiology and Infectious Diseases: update of the treatment guidance document for Clostridium difficile infection. Clin Microbiol Infect 20:Suppl. 2 (2014), 1–26.
6. Cohen, S.H., Gerding, D.N., Johnson, S., Kelly, C.P., Loo, V.G., McDonald, L.C., 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 31 (2010), 431–455.
7. Surawicz, C.M., Brandt, L.J., Binion, D.G., Ananthakrishnan, A.N., Curry, S.R., Gilligan, P.H., et al. Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. Am J Gastroenterol 108 (2013), 478–498.
8. Pechine, S., Janoir, C., Collignon, A., Emerging monoclonal antibodies against Clostridium difficile infection. Expert Opin Biol Ther 17 (2017), 415–427.
9. Slayton, E.T., Hay, A.S., Babcock, C.K., Long, T.E., New antibiotics in clinical trials for Clostridium difficile. Expert Rev Anti Infect Ther, 2016, 1–12.
10. Johnson, S., Louie, T.J., Gerding, D.N., Cornely, O.A., Chasan-Taber, S., Fitts, D., et al. Vancomycin, metronidazole, or tolevamer for Clostridium difficile infection: results from two multinational, randomized, controlled trials. Clin Infect Dis 59 (2014), 345–354.
11. Nelson, R.L., Suda, K.J., Evans, C.T., Antibiotic treatment for Clostridium difficile–associated diarrhoea in adults. Cochrane Database Syst Rev, 3, 2017, CD004610.
12. Bolton, R.P., Culshaw, M.A., Faecal metronidazole concentrations during oral and intravenous therapy for antibiotic associated colitis due to Clostridium difficile. Gut 27 (1986), 1169–1172.
13. Goldenberg, S.D., Brown, S., Edwards, L., Gnanarajah, D., Howard, P., Jenkins, D., et al. The impact of the introduction of fidaxomicin on the management of Clostridium difficile infection in seven NHS secondary care hospitals in England: a series of local service evaluations. Eur J Clin Microbiol Infect Dis 35 (2016), 251–259.
14. Guery, B., Menichetti, F., Anttila, V.J., Adomakoh, N., Aguado, J.M., Bisnauthsing, K., et al. Extended-pulsed fidaxomicin versus vancomycin for Clostridium difficile infection in patients 60 years and older (EXTEND): a randomised, controlled, open-label, phase 3b/4 trial. Lancet Infect Dis, 2017.
15. Markham, A., Bezlotoxumab: first global approval. Drugs 76 (2016), 1793–1798.
16. Orth, P., Xiao, L., Hernandez, L.D., Reichert, P., Sheth, P.R., Beaumont, M., et al. Mechanism of action and epitopes of Clostridium difficile toxin B–neutralizing antibody bezlotoxumab revealed by X-ray crystallography. J Biol Chem 289 (2014), 18008–18021.
17. Wilcox, M.H., Gerding, D.N., Poxton, I.R., Kelly, C., Nathan, R., Birch, T., et al. Bezlotoxumab for prevention of recurrent Clostridium difficile infection. N Engl J Med 376 (2017), 305–317.
18. Chapin, R.W., Lee, T., McCoy, C., Alonso, C.D., Mahoney, M.V., Bezlotoxumab: could this be the answer for Clostridium difficile recurrence?. Ann Pharmacother 51 (2017), 804–810.
19. Babcock, G.J., Broering, T.J., Hernandez, H.J., Mandell, R.B., Donahue, K., Boatright, N., et al. Human monoclonal antibodies directed against toxins A and B prevent Clostridium difficile–induced mortality in hamsters. Infect Immun 74 (2006), 6339–6347.
20. Taylor, C.P., Tummala, S., Molrine, D., Davidson, L., Farrell, R.J., Lembo, A., et al. Open-label, dose escalation phase I study in healthy volunteers to evaluate the safety and pharmacokinetics of a human monoclonal antibody to Clostridium difficile toxin A. Vaccine 26 (2008), 3404–3409.
21. Lowy, I., Molrine, D.C., Leav, B.A., Blair, B.M., Baxter, R., Gerding, D.N., et al. Treatment with monoclonal antibodies against Clostridium difficile toxins. N Engl J Med 362 (2010), 197–205.
22. Boix, V., Fedorak, R.N., Mullane, K.M., Pesant, Y., Stoutenburgh, U., Jin, M., et al. Primary outcomes from a phase 3, randomized, double-blind, active-controlled trial of surotomycin in subjects with Clostridium difficile infection. Open Forum Infect Dis, 4, 2017 ofw275.
23. Daley, P., Louie, T., Lutz, J.E., Khanna, S., Stoutenburgh, U., Jin, M., et al. Surotomycin versus vancomycin in adults with Clostridium difficile infection: primary clinical outcomes from the second pivotal, randomized, double-blind, phase 3 trial. J Antimicrob Chemother 72 (2017), 3462–3470.
24. Yin, N., Li, J., He, Y., Herradura, P., Pearson, A., Mesleh, M.F., et al. Structure–activity relationship studies of a series of semisynthetic lipopeptides leading to the discovery of surotomycin, a novel cyclic lipopeptide being developed for the treatment of Clostridium difficile–associated diarrhea. J Med Chem 58 (2015), 5137–5142.
25. Alam, M.Z., Wu, X., Mascio, C., Chesnel, L., Hurdle, J.G., Mode of action and bactericidal properties of surotomycin against growing and nongrowing Clostridium difficile. Antimicrob Agents Chemother 59 (2015), 5165–5170.
26. Mascio, C.T., Chesnel, L., Thorne, G., Silverman, J.A., Surotomycin demonstrates low in vitro frequency of resistance and rapid bactericidal activity in Clostridium difficile, Enterococcus faecalis, and Enterococcus faecium. Antimicrob Agents Chemother 58 (2014), 3976–3982.
27. Chandorkar, G., Zhan, Q., Donovan, J., Rege, S., Patino, H., Pharmacokinetics of surotomycin from phase 1 single and multiple ascending dose studies in healthy volunteers. BMC Pharmacol Toxicol, 18, 2017, 24.
28. Citron, D.M., Tyrrell, K.L., Dale, S.E., Chesnel, L., Goldstein, E.J., Impact of surotomycin on the gut microbiota of healthy volunteers in a phase 1 clinical trial. Antimicrob Agents Chemother 60 (2016), 2069–2074.
29. Lee, C.H., Patino, H., Stevens, C., Rege, S., Chesnel, L., Louie, T., et al. Surotomycin versus vancomycin for Clostridium difficile infection: phase 2, randomized, controlled, double-blind, non-inferiority, multicentre trial. J Antimicrob Chemother 71 (2016), 2964–2971.
30. Descombe, J.J., Dubourg, D., Picard, M., Palazzini, E., Pharmacokinetic study of rifaximin after oral administration in healthy volunteers. Int J Clin Pharmacol Res 14 (1994), 51–56.
31. Huang, D.B., DuPont, H.L., Rifaximin—a novel antimicrobial for enteric infections. J Infect 50 (2005), 97–106.
32. Hartmann, G., Honikel, K.O., Knusel, F., Nuesch, J., The specific inhibition of the DNA-directed RNA synthesis by rifamycin. Biochim Biophys Acta 145 (1967), 843–844.
33. Hecht, D.W., Galang, M.A., Sambol, S.P., Osmolski, J.R., Johnson, S., Gerding, D.N., In vitro activities of 15 antimicrobial agents against 110 toxigenic Clostridium difficile clinical isolates collected from 1983 to 2004. Antimicrob Agents Chemother 51 (2007), 2716–2719.
34. O'Connor, J.R., Galang, M.A., Sambol, S.P., Hecht, D.W., Vedantam, G., Gerding, D.N., et al. Rifampin and rifaximin resistance in clinical isolates of Clostridium difficile. Antimicrob Agents Chemother 52 (2008), 2813–2817.
35. Ponziani, F.R., Scaldaferri, F., Petito, V., Paroni Sterbini, F., Pecere, S., Lopetuso, L.R., et al. The role of antibiotics in gut microbiota modulation: the eubiotic effects of rifaximin. Dig Dis 34 (2016), 269–278.
36. Soldi, S., Vasileiadis, S., Uggeri, F., Campanale, M., Morelli, L., Fogli, M.V., et al. Modulation of the gut microbiota composition by rifaximin in non-constipated irritable bowel syndrome patients: a molecular approach. Clin Exp Gastroenterol 8 (2015), 309–325.
37. Garey, K.W., Ghantoji, S.S., Shah, D.N., Habib, M., Arora, V., Jiang, Z.D., 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 66 (2011), 2850–2855.
38. Locher, H.H., Caspers, P., Bruyere, T., Schroeder, S., Pfaff, P., Knezevic, A., 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 58 (2014), 901–908.
39. 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 69 (2014), 706–714.
40. Chilton, C.H., Crowther, G.S., Baines, S.D., Todhunter, S.L., Freeman, J., Locher, H.H., et al. In vitro activity of cadazolid against clinically relevant Clostridium difficile isolates and in an in vitro gut model of C. difficile infection. J Antimicrob Chemother 69 (2014), 697–705.
41. Louie, T., Nord, C.E., Talbot, G.H., Wilcox, M., Gerding, D.N., Buitrago, M., et al. Multicenter, double-blind, randomized, phase 2 study evaluating the novel antibiotic cadazolid in patients with Clostridium difficile infection. Antimicrob Agents Chemother 59 (2015), 6266–6273.
42. Citron, D.M., Tyrrell, K.L., Merriam, C.V., Goldstein, E.J., Comparative in vitro activities of LFF571 against Clostridium difficile and 630 other intestinal strains of aerobic and anaerobic bacteria. Antimicrob Agents Chemother 56 (2012), 2493–2503.
43. Debast, S.B., Bauer, M.P., Sanders, I.M., Wilcox, M.H., Kuijper, E.J., Group, E.S., Antimicrobial activity of LFF571 and three treatment agents against Clostridium difficile isolates collected for a pan-European survey in 2008: clinical and therapeutic implications. J Antimicrob Chemother 68 (2013), 1305–1311.
44. Bhansali, S.G., Mullane, K., Ting, L.S., Leeds, J.A., Dabovic, K., Praestgaard, J., et al. Pharmacokinetics of LFF571 and vancomycin in patients with moderate Clostridium difficile infections. Antimicrob Agents Chemother 59 (2015), 1441–1445.
45. Ting, L.S., Praestgaard, J., Grunenberg, N., Yang, J.C., Leeds, J.A., Pertel, P., A first-in-human, randomized, double-blind, placebo-controlled, single- and multiple-ascending oral dose study to assess the safety and tolerability of LFF571 in healthy volunteers. Antimicrob Agents Chemother 56 (2012), 5946–5951.
46. Mullane, K., Lee, C., Bressler, A., Buitrago, M., Weiss, K., Dabovic, K., et al. Multicenter, randomized clinical trial to compare the safety and efficacy of LFF571 and vancomycin for Clostridium difficile infections. Antimicrob Agents Chemother 59 (2015), 1435–1440.
47. Corbett, D., Wise, A., Birchall, S., Warn, P., Baines, S.D., Crowther, G., et al. In vitro susceptibility of Clostridium difficile to SMT19969 and comparators, as well as the killing kinetics and post-antibiotic effects of SMT19969 and comparators against C. difficile. J Antimicrob Chemother 70 (2015), 1751–1756.
48. Basseres, E., Endres, B.T., Khaleduzzaman, M., Miraftabi, F., Alam, M.J., Vickers, R.J., et al. Impact on toxin production and cell morphology in Clostridium difficile by ridinilazole (SMT19969), a novel treatment for C. difficile infection. J Antimicrob Chemother 71 (2016), 1245–1251.
49. Vickers, R., Robinson, N., Best, E., Echols, R., Tillotson, G., Wilcox, M., A randomised phase 1 study to investigate safety, pharmacokinetics and impact on gut microbiota following single and multiple oral doses in healthy male subjects of SMT19969, a novel agent for Clostridium difficile infections. BMC Infect Dis, 15, 2015, 91.
50. Vickers, R.J., Tillotson, G.S., Nathan, R., Hazan, S., Pullman, J., Lucasti, C., et al. Efficacy and safety of ridinilazole compared with vancomycin for the treatment of Clostridium difficile infection: a phase 2, randomised, double-blind, active-controlled, non-inferiority study. Lancet Infect Dis 17 (2017), 735–744.
51. Olson, M.W., Ruzin, A., Feyfant, E., Rush, T.S. 3rd, O'Connell, J., Bradford, P.A., Functional, biophysical, and structural bases for antibacterial activity of tigecycline. Antimicrob Agents Chemother 50 (2006), 2156–2166.
52. Babinchak, T., Ellis-Grosse, E., Dartois, N., Rose, G.M., Loh, E. Tigecycline 301 Study G, Tigecycline 306 Study Group. The efficacy and safety of tigecycline for the treatment of complicated intra-abdominal infections: analysis of pooled clinical trial data. Clin Infect Dis 41:Suppl. 5 (2005), S354–S367.
53. Gergely Szabo, B., Kadar, B., Szidonia Lenart, K., Dezsenyi, B., Kunovszki, P., Fried, K., et al. Use of intravenous tigecycline in patients with severe Clostridium difficile infection: a retrospective observational cohort study. Clin Microbiol Infect 22 (2016), 990–995.
54. Manea, E., Sojo-Dorado, J., Jipa, R.E., Benea, S.N., Rodríguez-Baño, J., Hristea, A., The role of tigecycline in the management of Clostridium difficile infection: a retrospective cohort study. Clin Microbiol Infect 24 (2018), 180–184.
55. Thomas, A., Khan, F., Uddin, N., Wallace, M.R., Tigecycline for severe Clostridium difficile infection. Int J Infect Dis 26 (2014), 171–172.
56. Citron, D.M., Warren, Y.A., Tyrrell, K.L., Merriam, V., Goldstein, E.J., Comparative in vitro activity of REP3123 against Clostridium difficile and other anaerobic intestinal bacteria. J Antimicrob Chemother 63 (2009), 972–976.
57. Nayak, S.U., Griffiss, J.M., Blumer, J., O'Riordan, M.A., Gray, W., McKenzie, R., et al. Safety, tolerability, systemic exposure, and metabolism of CRS3123, a methionyl-tRNA synthetase inhibitor developed for treatment of Clostridium difficile, in a phase 1 study. Antimicrob Agents Chemother, 61, 2017.
58. Chang, J.Y., Antonopoulos, D.A., Kalra, A., Tonelli, A., Khalife, W.T., Schmidt, T.M., et al. Decreased diversity of the fecal microbiome in recurrent Clostridium difficile–associated diarrhea. J Infect Dis 197 (2008), 435–438.
59. Seekatz, A.M., Rao, K., Santhosh, K., Young, V.B., Dynamics of the fecal microbiome in patients with recurrent and nonrecurrent Clostridium difficile infection. Genome Med, 8, 2016, 47.
60. Buffie, C.G., Bucci, V., Stein, R.R., McKenney, P.T., Ling, L., Gobourne, A., et al. Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile. Nature 517 (2015), 205–208.
61. Ott, S.J., Waetzig, G.H., Rehman, A., Moltzau-Anderson, J., Bharti, R., Grasis, J.A., et al. Efficacy of sterile fecal filtrate transfer for treating patients with Clostridium difficile infection. Gastroenterology, 152, 2017 799–811.e7.
62. Allegretti, J.R., Kassam, Z., Osman, M., Budree, S., Fischer, M., Kelly, C.R., The 5D framework: a clinical primer for fecal microbiota transplantation to treat Clostridium difficile infection. Gastrointest Endosc 87 (2018), 18–29.
63. Gough, E., Shaikh, H., Manges, A.R., Systematic review of intestinal microbiota transplantation (fecal bacteriotherapy) for recurrent Clostridium difficile infection. Clin Infect Dis 53 (2011), 994–1002.
64. van Nood, E., Vrieze, A., Nieuwdorp, M., Fuentes, S., Zoetendal, E.G., de Vos, W.M., et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med 368 (2013), 407–415.
65. Cammarota, G., Masucci, L., Ianiro, G., Bibbo, S., Dinoi, G., Costamagna, G., et al. Randomised clinical trial: faecal microbiota transplantation by colonoscopy vs. vancomycin for the treatment of recurrent Clostridium difficile infection. Aliment Pharmacol Ther 41 (2015), 835–843.
66. Hota, S.S., Sales, V., Tomlinson, G., Salpeter, M.J., McGeer, A., Coburn, B., 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 64 (2017), 265–271.
67. Kao, D., Roach, B., Silva, M., Beck, P., Rioux, K., Kaplan, G.G., et al. Effect of oral capsule- vs colonoscopy-delivered fecal microbiota transplantation on recurrent Clostridium difficile infection: a randomized clinical trial. JAMA 318 (2017), 1985–1993.
68. Kelly, C.R., Khoruts, A., Staley, C., Sadowsky, M.J., Abd, M., Alani, M., et al. Effect of fecal microbiota transplantation on recurrence in multiply recurrent Clostridium difficile infection: a randomized trial. Ann Intern Med 165 (2016), 609–616.
69. Orenstein, R., Dubberke, E., Hardi, R., Ray, A., Mullane, K., Pardi, D.S., et al. Safety and durability of RBX2660 (microbiota suspension) for recurrent Clostridium difficile infection: results of the PUNCH CD study. Clin Infect Dis 62 (2016), 596–602.
70. Youngster, I., Mahabamunuge, J., Systrom, H.K., Sauk, J., Khalili, H., Levin, J., et al. Oral, frozen fecal microbiota transplant (FMT) capsules for recurrent Clostridium difficile infection. BMC Med, 14, 2016, 134.
71. Moayyedi, P., Yuan, Y., Baharith, H., Ford, A.C., Faecal microbiota transplantation for Clostridium difficile–associated diarrhoea: a systematic review of randomised controlled trials. Med J Aust 207 (2017), 166–172.
72. Baxter, M., Colville, A., Adverse events in faecal microbiota transplant: a review of the literature. J Hosp Infect 92 (2016), 117–127.
73. van Beurden, Y.H., de Groot, P.F., van Nood, E., Keller, J.J., Goorhuis, A., Complications, effectiveness, and long term follow-up of fecal microbiota transfer by nasoduodenal tube for treatment of recurrent Clostridium difficile infection. United Eur Gastroenterol J 5 (2017), 868–879.
74. Terveer, E.M., van Beurden, Y.H., Goorhuis, A., Seegers, J., Bauer, M.P., van Nood, E., et al. How to: establish and run a stool bank. Clin Microbiol Infect 23 (2017), 924–930.
75. Khanna, S., Pardi, D.S., Kelly, C.R., Kraft, C.S., Dhere, T., Henn, M.R., et al. A novel microbiome therapeutic increases gut microbial diversity and prevents recurrent Clostridium difficile infection. J Infect Dis 214 (2016), 173–181.
76. Crobach, M.J., Planche, T., Eckert, C., Barbut, F., Terveer, E.M., Dekkers, O.M., et al. European Society of Clinical Microbiology and Infectious Diseases: update of the diagnostic guidance document for Clostridium difficile infection. Clin Microbiol Infect 22:Suppl. 4 (2016), S63–S81.
77. Villano, S.A., Seiberling, M., Tatarowicz, W., Monnot-Chase, E., Gerding, D.N., Evaluation of an oral suspension of VP20621, spores of nontoxigenic Clostridium difficile strain M3, in healthy subjects. Antimicrob Agents Chemother 56 (2012), 5224–5229.
78. Gerding, D.N., Meyer, T., Lee, C., Cohen, S.H., Murthy, U.K., Poirier, A., et al. Administration of spores of nontoxigenic Clostridium difficile strain M3 for prevention of recurrent C. difficile infection: a randomized clinical trial. JAMA 313 (2015), 1719–1727.
79. Kaleko, M., Bristol, J.A., Hubert, S., Parsley, T., Widmer, G., Tzipori, S., et al. Development of SYN-004, an oral beta-lactamase treatment to protect the gut microbiome from antibiotic-mediated damage and prevent Clostridium difficile infection. Anaerobe 41 (2016), 58–67.
80. Johanesen, P.A., Mackin, K.E., Hutton, M.L., Awad, M.M., Larcombe, S., Amy, J.M., et al. Disruption of the gut microbiome: Clostridium difficile infection and the threat of antibiotic resistance. Genes (Basel) 6 (2015), 1347–1360.
81. Roberts, T., Kokai-Kun, J.F., Coughlin, O., Lopez, B.V., Whalen, H., Bristol, J.A., et al. Tolerability and pharmacokinetics of SYN-004, an orally administered beta-lactamase for the prevention of Clostridium difficile–associated disease and antibiotic-associated diarrhea, in two phase 1 studies. Clin Drug Investig 36 (2016), 725–734.
82. Kokai-Kun, J.F., Roberts, T., Coughlin, O., Sicard, E., Rufiange, M., Fedorak, R., et al. The oral β-lactamase SYN-004 (ribaxamase) degrades ceftriaxone excreted into the intestine in phase 2a clinical studies. Antimicrob Agents Chemother, 61, 2017 e02197–16.
83. Cornely, O.A., Nathwani, D., Ivanescu, C., Odufowora-Sita, O., Retsa, P., Odeyemi, I.A., Clinical efficacy of fidaxomicin compared with vancomycin and metronidazole in Clostridium difficile infections: a meta-analysis and indirect treatment comparison. J Antimicrob Chemother 69 (2014), 2892–2900.
84. Kelly, S.G., Yarrington, M., Zembower, T.R., Sutton, S.H., Silkaitis, C., Postelnick, M., et al. Inappropriate Clostridium difficile testing and consequent overtreatment and inaccurate publicly reported metrics. Infect Control Hosp Epidemiol 37 (2016), 1395–1400.
85. Polage, C.R., Gyorke, C.E., Kennedy, M.A., Leslie, J.L., Chin, D.L., Wang, S., et al. Overdiagnosis of Clostridium difficile infection in the molecular test era. JAMA Intern Med 175 (2015), 1792–1801.
86. Mergenhagen, Kari A., Wojciechowski, Amy L., Paladino, Joseph A., A review of the economics of treating Clostridium difficile infection. Pharmacoeconomics 32 (2014), 639–650.
87. Zar, F.A., Bakkanagari, S.R., Moorthi, K.M., Davis, M.B., A comparison of vancomycin and metronidazole for the treatment of Clostridium difficile–associated diarrhea, stratified by disease severity. Clin Infect Dis 45 (2007), 302–307.
88. Quraishi, M.N., Widlak, M., Bhala, N., Moore, D., Price, M., Sharma, N., et al. Systematic review with meta-analysis: the efficacy of faecal microbiota transplantation for the treatment of recurrent and refractory Clostridium difficile infection. Aliment Pharmacol Ther 46 (2017), 479–493.
89. de Gunzburg, J., Ducher, A., Modess, C., Wegner, D., Oswald, S., Dressman, J., 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 55 (2015), 10–16.
90. van Beurden, Y.H., Nieuwdorp, M., van de Berg, P.J.E.J., Mulder, C.J.J., Goorhuis, A., ’Current challenges in the treatment of severe Clostridium difficile infection: early treatment potential of fecal microbiota transplantation’. Therapeutic Adv Gastroenterol 10 (2017), 373–381.
91. Stevens, V.W., Nelson, R.E., Schwab-Daugherty, E.M., Khader, K., Jones, M.M., Brown, K.A., et al. Comparative effectiveness of vancomycin and metronidazole for the prevention of recurrence and death in patients with Clostridium difficile infection. JAMA Intern Med 177 (2017), 546–553.