Primary Prevention of Clostridium difficile-Associated Diarrhea: Current Controversies and Future Tools

  • Zachary A. RubinEmail author
  • Elise M. Martin
  • Paul Allyn
Healthcare Associated Infections (G Bearman and D Morgan, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Healthcare Associated Infections


Purpose of Review

Clostridium difficile infection (CDI) is a major cause of morbidity and mortality in hospitalized patients and rates in most places have not decreased significantly despite broad efforts by both hospitals and public health entities. This review aims to provide readers with a better understanding of the limitations of current prevention strategies. We also review potential future tools that may be available for the primary prevention of CDI in the next decade.

Recent Findings

Research over the last decade has expanded our appreciation of the role of asymptomatic shedding in the healthcare setting and in the community. This review demonstrates that poor quality data underlies even well-established guidance from national authorities on basic topics such as contact precautions, avoidance of alcohol-based hand hygiene products, CDI testing, supplemental cleaning modalities, and the use of bleach solutions. Additionally, we review research on novel preventative interventions such as identification of asymptomatic carriers, supplemental environmental cleaning technologies, vaccines, and the manipulation of the intestinal microbiome. While there is preliminary data that supports further research in all of these areas, the research is not yet robust enough on which to base local or national policy recommendations, though late-phase human clinical trials of CDI vaccine trials are ongoing.


Over the last decade, researchers have begun to reassess the traditional infection prevention model for CDI. Data suggesting a greater role for asymptomatic shedders has increased our understanding of current vertical prevention techniques and is forcing researchers to look more at new processes and technologies to decrease disease incidence.


Clostridium difficile Review Prevention 


Compliance with Ethical Standards

Conflict of Interest

Zachary Rubin and Elise Martin are receiving research funding from Pfizer for an ongoing clinical trial on a CDI vaccine. Paul Allyn owns stock in Pfizer.

Human and Animal Rights and Informed Consent

This article cites one study with human subjects performed by Zachary Rubin, which previously was reviewed and approved by the local IRB. All other studies cited with human or animal subjects were not performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Lessa FC, Mu Y, Bamberg WM, Beldavs ZG, Dumyati GK, Dunn JR, et al. Burden of Clostridium difficile infection in the United States. New Engl J Med. 2015;372:825–34.CrossRefPubMedGoogle Scholar
  2. 2.
    Zilberg MD, Shorr AF, Koleff MH. Increase in adult Clostridium difficile-related hospitalizations and case fatality rate, United States, 2000-2005. Emerg Infect Dis. 2008;14:929–31.CrossRefGoogle Scholar
  3. 3.
    Reveles KR, Lee GC, Boyd NK, Frei CR. The rise in Clostridium difficile infection incidence among hospitalized adults in the United States: 2001-2010. Am J Infect Dis. 2014;42:1028–32.Google Scholar
  4. 4.
    See I, Mu Y, Cohen J, Beldavs ZG, Winston LG, Dumyati G, et al. NAP1 strain type predicts outcomes from Clostridium difficile infection. Clin Infectious Dis. 2014;58:1394–400.CrossRefGoogle Scholar
  5. 5.
    Scardina T, Labuszewski L, Pacheco SM, Adams W, Schreckenberger P, Johnson S. Clostridium difficile infection (CDI) severity and outcome among patients infected with the Nap1/B1/027 strain in non-epidemic setting. Infect Control Hosp Epidemiol. 2015;36:280–6.CrossRefPubMedGoogle Scholar
  6. 6.
    Bauer KA, Johnston JEW, Wenzler E, Goff DA, Cook CH, Balada-Llasat JM, et al. Impact of the NAP-1 strain on disease severity, mortality and recurrence of healthcare-associated Clostridium difficile infection. Anaerobe. 2017;48:1–6.CrossRefPubMedGoogle Scholar
  7. 7.
    CDC. Antimicrobial resistance threats.
  8. 8.
    •• 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. This article provides the most up to date guidance from public health. Google Scholar
  9. 9.
    Dubberke ER, Carling P, Carrico R, Donskey CJ, Loo VG, McDonald LC, et al. Strategies to prevent Clostridium difficile infections in acute care hospitals: 2014 update. Infect Control Hosp Epidemiol. 2014;35:S48–65.CrossRefPubMedGoogle Scholar
  10. 10.
    Cohen SH, Gerding DN, Johnson S, et al. Clinical practice guidelines: guidelines for Clostridium difficile infection in adults: 2010 update by the Society of Healthcare Epidemiology of America (SHEA) and in the Infectious Diseases Society of America. Infect Control Hosp Epidemiol. 2010;31:431–55.Google Scholar
  11. 11.
    McFarland LV, Mulligan ME, Kwok RYY, Stamm WE. Nosocomial acquisition of Clostridium difficile infection. N Engl J Med. 1989;320:204–10.CrossRefPubMedGoogle Scholar
  12. 12.
    Curry SR, Muto CA, Schlackman JL, Pasculle AW, Shutt KA, Marsh JW, et al. Use of multilocus variable number of tandem repeats analysis genotyping to determine the role of asymptomatic carriers in Clostridium difficile transmission. Clin Infect Dis. 2013;57:1094–102.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    •• Donskey CJ, Kundrapa S, Despande A. Colonization versus carriage of Clostridium difficile. Infect Dis Clin N Am. 2015;29:13–28. Well researched review of the evidence surrounding asymptomatic carriage of CD. CrossRefGoogle Scholar
  14. 14.
    Sethi AK, Al-Nassir WN, Nerandzic MM, et al. Persistence of skin contamination and environmental shedding of Clostridium difficile during and after treatment of C. difficile infection. Infect Control Hosp Epidem. 2010;32:21–7.CrossRefGoogle Scholar
  15. 15.
    Riggs MM, Sethi AK, Zabarsky TF, Eckstein EC, Jump RLP, Donskey CJ. Asymptomatic carriers are a potential source for transmission of epidemic and nonepidemic Clostridium difficile strains among long-term care facility residents. Clin Infect Dis. 2007;45:992–8.CrossRefPubMedGoogle Scholar
  16. 16.
    Jinno S, Kundrapu S, Guerrero DM, Jury LA, Nerandzic MM, Donskey CJ. Potential for transmission of Clostridium difficile by asymptomatic acute care patients and long-term care facility residents with prior C. difficile infection. Infect Contr Hosp Epidemiol. 2012;33:638–9.CrossRefGoogle Scholar
  17. 17.
    • Fuyura-Kanamori L, Riley TV, Paterson DL, et al. Comparison of Clostridium difficile ribotypes circulating in Australian hospitals and communities. J Clin Microbiol. 2017;55:216–25. Provocative study looking at the interaction between the community and the hospital CDI suggesting that the community maybe the source of significant hospital-onset CDI. CrossRefGoogle Scholar
  18. 18.
    • Eyre DW, Cule ML, Wilson DJ, Griffiths D, Vaughan A, O'Connor L, et al. Diverse sources of C. difficile infection identified on whole genome sequencing. New England J Med. 2013;369:1195–205. Despite some methodologic concerns, this is the largest study demonstrating the likely large contribution of asymptomatic CD carriers to endemic CDI incidence. CrossRefGoogle Scholar
  19. 19.
    Walker AS, Eyre DW, Wyllie DH, Dingle KE, Harding RM, O'Connor L, et al. Characterization of Clostridium difficile hospital ward-based transmission using extensive epidemiologic data and molecular typing. PLoS Med. 2012;9:e1001172.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Noren T, Akerlund T, Back E, Sjoberg L, Persson I, Alriksson I, et al. Molecular epidemiology of hospital-associated and community-acquired Clostridium difficile infection in a Swedish county. J Clin Microbiol. 2004;42:3635–43.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Fisher A, Dembry LLM. Norovirus and Clostridium difficile: squelching the wildfire. Curr Opinion in Infect Dis. 2017;30:440–7.CrossRefGoogle Scholar
  22. 22.
    McMullen KM, Zack J, Coopersmith CM, et al. Use of hypochlorite solution to decrease rates of Clostridium difficile-associated diarrhea. Infect Control Hosp Epidemiol. 2007;28(2007):205–7.CrossRefPubMedGoogle Scholar
  23. 23.
    Hacek DM, Ogle AM, Fisher A, Robicsek A, Peterson LR. Significant impact of terminal room cleaning with bleach on reducing nosocomial Clostridium difficile. Am J Infect Control. 2010;38:350–3.CrossRefPubMedGoogle Scholar
  24. 24.
    Maghdoori S, Moghadas SM. Assessing the effect of patient screening and isolation on curtailing Clostridium difficile infection in hospital settings. BMC Infect Dis. 2017;17:384.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Lanzas C, Dubberke ER, Lu Z, Reske KA, Grohn YT. Epidemiologic model for Clostridium difficile transmission in healthcare settings. Infect Control Hosp Epidemiol. 2011;32:553–61.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    • Longtin Y, Paquet-Bolduc B, Gilca R, Garenc C, Fortin E, Longtin J, 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;176:796–804. Study demonstrating that CDI incidence decreases with aggressive screening and isolation of CD carriers in addition to symptomatic cases. CrossRefPubMedGoogle Scholar
  27. 27.
    WHO guidelines on hand hygiene in health care: first global patient safety challenge clean care is safer care. Geneva: World Health Organization; 2009.Google Scholar
  28. 28.
    Oughton MT, Loo VG, Dendukuri N, Fenn S, Libman MD. Hand hygiene with soap and water is superior to alcohol rub and antiseptic wipes for removal of Clostridium difficile. Infect Control Hosp Epidemiol. 2009;30(10):939–44.CrossRefPubMedGoogle Scholar
  29. 29.
    Jabbar U, Leischner J, Kasper D, Gerber R, Sambol SP, Parada JP, et al. Effectiveness of alcohol-based hand rubs for removal of Clostridium difficile spores from hands. Infect Control Hosp Epidemiol. 2010;31(6):565–70.CrossRefPubMedGoogle Scholar
  30. 30.
    Kundrapu S, Sunkesula V, Jury I, Deshpande A, Donskey CJ. A randomized trial of soap and water hand wash versus alcohol hand rub for removal of Clostridium difficile spores from hands of patients. Infect Control Hosp Epidemiol. 2014;35(2):204–6.CrossRefPubMedGoogle Scholar
  31. 31.
    Knight N, Strait T, Anthony N, Lovell R, Norton HJ, Sautter R, et al. Clostridium difficile colitis: a retrospective study of incidence and severity before and after institution of an alcohol-based hand rub policy. Am J Infect Control. 2010;38(7):523–8.CrossRefPubMedGoogle Scholar
  32. 32.
    Isaacson D, Haller B, Leslie H, Roemer M, Winston L. Novel handwashes are superior to soap and water in removal of Clostridium difficile spores from the hands. Am J Infect Control. 2015;43(5):530–2.CrossRefPubMedGoogle Scholar
  33. 33.
    Nerandzic MM, Sankar TC, Setlow P, et al. A cumulative spore killing approach: synergistic sporicidal activity of dilute peracetic acid and ethanol at low pH against Clostridium difficile and Bacillus subtilis spores. Open Forum Infect Dis. 2016;3(1):ofv206.CrossRefPubMedGoogle Scholar
  34. 34.
    Zellmer C, Blakney R, Van Hoof S, et al. Impact of sink location on hand hygiene compliance for Clostridium difficile infection. Am J Infect Control. 2015;43(4):387–9.CrossRefPubMedGoogle Scholar
  35. 35.
    Kim KH, Fekety R, Batts DH, Brown D, Cudmore M, Silva J, et al. Isolation of Clostridium difficile from the environment and contacts of patients with antibiotic-associated colitis. J Infect Dis. 1981;143(1):42–50.CrossRefPubMedGoogle Scholar
  36. 36.
    Barbut F. How to eradicate Clostridium difficile from the environment. J Hosp Infect. 2015;89(4):287–95.CrossRefPubMedGoogle Scholar
  37. 37.
    Kaatz GW, Gitlin SD, Schaberg DR, et al. Acquisition of Clostridium difficile from the hospital environment. Am J Epidemiol. 1988;127(6):1289–94.CrossRefPubMedGoogle Scholar
  38. 38.
    Mayfield JL, Leet T, Miller J, Mundy LM. Environmental control to reduce transmission of Clostridium difficile. Clin Infect Dis. 2000;31(4):995–1000.CrossRefPubMedGoogle Scholar
  39. 39.
    Delclos GL, Gimeno D, Arif AA, Burau KD, Carson A, Lusk C, et al. Occupational risk factors and asthma among health care professionals. Am J Respir Crit Care Med. 2007;175(7):667–75.CrossRefPubMedGoogle Scholar
  40. 40.
    Sastre J, Madero MF, Fernández-Nieto M, Sastre B, del Pozo V, Potro MGD, et al. Airway response to chlorine inhalation (bleach) among cleaning workers with and without bronchial hyperresponsiveness. Am J Ind Med. 2011;54(4):293–9.CrossRefPubMedGoogle Scholar
  41. 41.
    • Marra AR, Schweizer ML, Edmond MB. No-touch disinfection methods to decrease multidrug-resistant organism infections: a systematic review and meta-analysis. Infect Control Hosp Epidemiol. 2018;39(1):20–31. A thoughtful review of newer no-touch disinfection prevention modalities. CrossRefPubMedGoogle Scholar
  42. 42.
    • Anderson DJ, Chen LF, Weber DJ, Moehring RW, Lewis SS, Triplett PF, et al. Enhanced terminal room disinfection and acquisition and infection caused by multidrug resistant organisms and Clostridium difficile (the Benefits of Enhanced Terminal Room Disinfection study): a cluster-randomised, multicentre, crossover study. Lancet. 2017;389:805–14. Interesting, though largely negative, trial of bleach and UV light compared to standard of care. Results may have been hampered by failure to eradicate CD spores shed by asymptomatic patients in addition to reasons cited in paper and accompanying editorial. CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Napolitano NA, Mahapatra T, Tang W. The effectiveness of UV-C radiation for facility-wide environmental disinfection to reduce healthcare-acquired infections. Am J Infect Control. 2015;43:1342–6.CrossRefPubMedGoogle Scholar
  44. 44.
    Pegues DA, Han J, Gilmar C, McDonnell B, Gaynes S. Impact of ultraviolet germicidal irradiation for no-touch terminal room disinfection on Clostridium difficile infection incidence among hematology-oncology patients. Infect Control Hosp Epidemiol. 2017;38:39–44.CrossRefPubMedGoogle Scholar
  45. 45.
    Levin J, Riley LS, Parrish C, English D, Ahn S. The effect of portable pulsed xenon ultraviolet light after terminal cleaning on hospital-associated Clostridium difficile infection in a community hospital. Am J Infect Control. 2013;41:746–8.CrossRefPubMedGoogle Scholar
  46. 46.
    Haas JP, Menz J, Dusza S, Montecalvo MA. Implementation and impact of ultraviolet environmental disinfection in acute care setting. Am J Infect Control. 2014;42:586–90.CrossRefPubMedGoogle Scholar
  47. 47.
    Miller R, Simmons S, Dale C, Stachowiak J, Stibich M. Utilization and impact of a pulsed-xenon ultraviolet room disinfection system and multidisciplinary care team on Clostridium difficile in a long-term acute care facility. Am J Infect Control. 2015;43:1350–3.CrossRefPubMedGoogle Scholar
  48. 48.
    Vianna PG, Dale CR Jr, Simmons S, Stibich M, Licitra CM. Impact of pulsed xenon ultraviolet light on hospital-acquired infection rates in a community hospital. Am J Infect Control. 2016;44:299–303.CrossRefPubMedGoogle Scholar
  49. 49.
    Nagaraja A, Visintainer P, Haas JP, Menz J, Wormser GP, Montecalvo MA. Clostridium difficile infections before and during use of ultraviolet disinfection. Am J Infect Control. 2015;43:940–5.CrossRefPubMedGoogle Scholar
  50. 50.
    Passaretti CL, Otter JA, Reich NG, Myers J, Shepard J, Ross T, et al. An evaluation of environmental decontamination with hydrogen peroxide vapor for reducing the risk of patient acquisition of multidrug-resistant organisms. Clin Infect Dis. 2013;56(1):27–35.CrossRefPubMedGoogle Scholar
  51. 51.
    Boyce JM, Havill NL, Otter JA, McDonald LC, Adams NMT, Cooper T, et al. Impact of hydrogen peroxide vapor room decontamination on Clostridium difficile environmental contamination and transmission in a healthcare setting. Infect Control Hosp Epidemiol. 2008;29:723–9.CrossRefPubMedGoogle Scholar
  52. 52.
    Horn K, Otter JA. Hydrogen peroxide vapor room disinfection and hand hygiene improvements reduce Clostridium difficile infection, methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and extended-spectrum β-lactamase. Am J Infect Control. 2015;43:1354–6.CrossRefPubMedGoogle Scholar
  53. 53.
    Manian FA, Griesnauer S, Bryant A. Implementation of hospital-wide enhanced terminal cleaning of targeted patient rooms and its impact on endemic Clostridium difficile infection rates. Am J Infect Control. 2013;41:537–41.CrossRefPubMedGoogle Scholar
  54. 54.
    McCord J, Prewitt M, Dyakova E, Mookerjee S, Otter JA. Reduction in Clostridium difficile infection associated with the introduction of hydrogen peroxide vapour automated room disinfection. J Hosp Infect. 2016;94:185–7.CrossRefPubMedGoogle Scholar
  55. 55.
    Gateau C, Couturier J, Coia J, Barbut F. How to: diagnose infection caused by Clostridium difficile. Clin Microbiol Infect. 2018; in press.Google Scholar
  56. 56.
    Crobach MJT, Planche T, Eckert C, Barbut F, Terveer EM, Dekkers OM, et al. European Society of Clinical Microbiology and Infectious Diseases: update of the diagnostic guidance document for Clostridium difficile infection. Clin Microbiol Infect. 2016;22(Suppl 4):S63–81.CrossRefPubMedGoogle Scholar
  57. 57.
    Cohen SH, Gerding DN, Johnson S, Kelly CP, Loo VG, McDonald L, et al. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and in the Infectious Diseases Society of America (IDSA). Infect Control Hosp Epidemiol. 2010;31(5):431–55.CrossRefPubMedGoogle Scholar
  58. 58.
    Planche T, Wilcox MH. Diagnostic pitfalls in Clostridium difficile infection. Infect Dis Clin N Am. 2015;29(1):63–82.CrossRefGoogle Scholar
  59. 59.
    Planche TD, Davies KA, Coen PG, Finney JM, Monahan IM, Morris KA, et al. Differences in outcome according to Clostridium difficile testing method: a prospective multicentre diagnostic validation study of C. difficile infection. Lancet Infect Dis. 2013;13(11):936–45.CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Bartlett JG. Clostridium difficile infection. Infect Dis Clin N Am. 2017;31(3):489–95.CrossRefGoogle Scholar
  61. 61.
    Humphries RM, Uslan DZ, Rubin Z. Performance of Clostridium difficile toxin enzyme immunoassay and nucleic acid amplification tests stratified by patient disease severity. J Clin Microbiol. 2013;51(3):869–73.CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Carman RJ, Wickham KN, Chen L, Lawrence AM, Boone JH, Wilkins TD, et al. Glutamate dehydrogenase is highly conserved among Clostridium difficile ribotypes. J Clin Microbiol. 2012;50(4):1425–6.CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Bagdasarian N, Rao K, Malani PN. Diagnosis and treatment of Clostridium difficile in adults. JAMA. 2015;313(4):398–408.CrossRefPubMedGoogle Scholar
  64. 64.
    • Polage CR, Gyorke CE, Kennedy MA, Leslie JL, Chin DL, Wang S, et al. Overdiagnosis of Clostridium difficile infection in the molecular test era. JAMA Intern Med. 2015;175(11):1792. Important study used as justification to move away from nucleic acid testing for CDI. CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Rees WD, Steiner TS. Adaptive immune response to Clostridium difficile infection: a perspective for prevention and therapy. Eur J Immunol. 2018;00:1–9.Google Scholar
  66. 66.
    Wilcox MH, Gerding DN, Poxton IR, Kelly C, Nathan R, Birch T, et al. Bezlotoxumab for prevention of recurrent Clostridium difficile infection. N Engl J Med. 2017;376:305–17.CrossRefPubMedGoogle Scholar
  67. 67.
    De Bruyne G, Saleh J, Workman D, et al. Defining the optimal formulation and schedule of a candidate toxoid vaccine against Clostridium difficile infection: a randomized phase 2 trial. Vaccine. 2016;34:2170–8.CrossRefGoogle Scholar
  68. 68.
    Pfizer. Pfizer announces positive top-line results from phase 2 study of investigational clostridium difficile vaccine for the prevention of C. difficile infection. 2017. Accessed 16 Feb 2017.
  69. 69.
    Kyne L, Warny M, Qamar A, Kelly CP. Asymptomatic carriage of Clostridium difficile and serum levels of IgG antibody against toxin A. N Engl J Med. 2000;342:390–7.CrossRefPubMedGoogle Scholar
  70. 70.
    Zhang K, Zhao S, Wang Y, Zhu X, Shen H, Chen Y, et al. The non-toxigenic Clostridium difficile strain CD37 protects mice against infection with a B1/NAP1/027 type of C. difficile strain. Anaerobe. 2015;36:49–52.CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Nagaro KJ, Philllips ST, Cheknis AK, et al. Nontoxigenic Clostridium difficile protects hamsters against challenge with historic and epidemic strains of toxigenic B1/NAP1/027 C. difficile. Animicrob Agents Chemother. 2013;57:5266–70.CrossRefGoogle Scholar
  72. 72.
    Merrigan MM, Sambol SP, Johnson S, Gerding DN. New approach to the management of Clostridium difficile infection: colonization with non-toxigenic C. difficile during daily ampicillin or ceftriaxone administration. Int J Antimicrob Agents. 2009;33(suppl 1):s46–50.CrossRefPubMedGoogle Scholar
  73. 73.
    Villano SA, Seiberling M, Tatarowicz W, Monnot-Chase E, Gerding DN. Evaluation of an oral suspension of VP20621, spores of a nontoxigenic Clostridium difficile strain M3, in healthy subjects. Animicrob Agents Chemother. 2012;56:5224–9.CrossRefGoogle Scholar
  74. 74.
    Goldenberg JZ, Yap C, Lytvyn L, Lo CKF, Beardsley J, Mertz D, et al. Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children. Cochrane Database Systemat Rev. 2017;12:CD006095.Google Scholar
  75. 75.
    Evans CT, Johnson S. Prevention of Clostridium difficile infection with probiotics. Clin Infect Dis. 2015;60(suppl_2):S122–8.CrossRefPubMedGoogle Scholar
  76. 76.
    Khanna S, Pardi DS, Kelly CR, Kraft CS, Dhere T, Henn MR, et al. A novel microbiome therapeutic increases gut microbial diversity and prevents recurrent Clostridium difficile infection. J Infect Dis. 2016;214:173–81.CrossRefPubMedGoogle Scholar
  77. 77.
    Ott SJ, Waetzig GH, Rehman A, Moltzau-Anderson J, Bharti R, Grasis JA, et al. Efficacy of sterile fecal filtrate transfer for treating patients with Clostridium difficile infection. Gastroenterology. 2017;152:799–811.e7.CrossRefPubMedGoogle Scholar
  78. 78.
    Nale JY, Spencer J, Hargreaves KR, Buckley AM, Trzepiński P, Douce GR, et al. Bacteriophage combinations significantly reduce Clostridium difficile growth in vitro and proliferation in vivo. Antimicrob Agents Chemother. 2016;60:968–81.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Zachary A. Rubin
    • 1
    • 2
    Email author
  • Elise M. Martin
    • 1
    • 2
    • 3
  • Paul Allyn
    • 1
  1. 1.Division of Infectious DiseasesDavid Geffen School of Medicine at UCLALos AngelesUSA
  2. 2.UCLA Clinical Epidemiology & Infection PreventionLos AngelesUSA
  3. 3.UCLA Antibiotic Stewardship ProgramLos AngelesUSA

Personalised recommendations