Current HIV/AIDS Reports

, Volume 10, Issue 3, pp 273–282

Clostridium Difficile Infection in Patients with HIV/AIDS

Co-infections (MA Jacobson, Section Editor)

Abstract

Clostridium difficile infection (CDI) affects significant numbers of hospitalized patients and is an increasing problem in the community. It is also among the most commonly isolated pathogens in HIV patients with diarrheal illness and is ≥2 fold more common in HIV-seropositive individuals. This association is stronger in those with low absolute CD4 T cell counts or meeting clinical criteria for an AIDS diagnosis, and was most pronounced before the wide availability of highly active antiretroviral therapy. The presentation and outcome of CDI in HIV appears similar to the general population. The increased risk can in part be attributed to increased hospitalization and antimicrobial use, but HIV related alterations in fecal microbiota, gut mucosal integrity, and humoral and cell mediated immunity are also likely to play a role. Here we review the evidence for these observations and the relevance of recent advances in the diagnosis and management of CDI for the HIV clinician.

Keywords

HIV HIV/AIDS Co-infections C. difficile infection Clostridium difficile infection (CDI) Immunocompromise 

References

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

  1. 1.
    Bartlett JG, Moon N, Chang TW, et al. Role of Clostridium difficile in antibiotic-associated pseudomembranous colitis. Gastroenterology. 1978;75(5):778–82.PubMedGoogle Scholar
  2. 2.
    George RH, Symonds JM, Dimock F, et al. Identification of Clostridium difficile as a cause of pseudomembranous colitis. Br Med J. 1978;1(6114):695.PubMedCrossRefGoogle Scholar
  3. 3.
    Bauer MP, Notermans DW, van Benthem BH, et al. Clostridium difficile infection in Europe: a hospital-based survey. Lancet. 2011;377(9759):63–73.PubMedCrossRefGoogle Scholar
  4. 4.
    Lucado J, Gould C, Elixhauser A. Clostridium Difficile Infections (CDI) in Hospital Stays, 2009: Statistical Brief #124. 2012 Feb.Google Scholar
  5. 5.
    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(1):89–95.PubMedCrossRefGoogle Scholar
  6. 6.
    • Jones AM, Kuijper EJ, Wilcox MH. Clostridium difficile: a European perspective. J Infect. 2013;66(2):115–28. Recent review article of CDI epidemiology including epidemic strains.Google Scholar
  7. 7.
    Chang JY, Antonopoulos DA, Kalra A, et al. Decreased diversity of the fecal Microbiome in recurrent Clostridium difficile-associated diarrhea. J Infect Dis. 2008;197(3):435–8.PubMedCrossRefGoogle Scholar
  8. 8.
    Collini PJ, Bauer M, Kuijper E, et al. Clostridium difficile infection in HIV-seropositive individuals and transplant recipients. J Infect. 2012;64(2):131–47.PubMedCrossRefGoogle Scholar
  9. 9.
    Dial S, Delaney JA, Barkun AN, et al. Use of gastric acid-suppressive agents and the risk of community-acquired Clostridium difficile-associated disease. JAMA. 2005;294(23):2989–95.PubMedCrossRefGoogle Scholar
  10. 10.
    Fujihashi K, Kiyono H. Mucosal immunosenescence: new developments and vaccines to control infectious diseases. Trends Immunol. 2009;30(7):334–43.PubMedCrossRefGoogle Scholar
  11. 11.
    Hopkins MJ, Macfarlane GT. Changes in predominant bacterial populations in human faeces with age and with Clostridium difficile infection. J Med Microbiol. 2002;51(5):448–54.PubMedGoogle Scholar
  12. 12.
    Shulzhenko N, Morgun A, Hsiao W, et al. Crosstalk between B lymphocytes, microbiota and the intestinal epithelium governs immunity versus metabolism in the gut. Nat Med. 2011;17(12):1585–93.PubMedCrossRefGoogle Scholar
  13. 13.
    • 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):431–55. Infectious Disease Society of America (IDSA) guidelines for CDI diagnosis and management 2010.PubMedCrossRefGoogle Scholar
  14. 14.
    Bauer MP, Kuijper EJ, van Dissel JT. European Society of Clinical Microbiology and Infectious Diseases (ESCMID): treatment guidance document for Clostridium difficile infection (CDI). Clin Microbiol Infect. 2009;15(12):1067–79.PubMedCrossRefGoogle Scholar
  15. 15.
    Kuijper EJ, Coignard B, Tull P. Emergence of Clostridium difficile-associated disease in North America and Europe. Clin Microbiol Infect. 2006;12 Suppl 6:2–18.PubMedCrossRefGoogle Scholar
  16. 16.
    Crobach MJ, Dekkers OM, Wilcox MH, et al. European Society of Clinical Microbiology and Infectious Diseases (ESCMID): data review and recommendations for diagnosing Clostridium difficile-infection (CDI). Clin Microbiol Infect. 2009;15(12):1053–66.PubMedCrossRefGoogle Scholar
  17. 17.
    Robotham J, Wilcox M. Updated Guidance on the Diagnosis and Reporting of Clostridium Difficile. 2012; Available from: http://www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/@dh/@en/documents/digitalasset/dh_133016.pdf.
  18. 18.
    Bartlett JG. Treatment of antibiotic-associated pseudomembranous colitis. Rev Infect Dis. 1984;6 Suppl 1:S235–41.PubMedCrossRefGoogle Scholar
  19. 19.
    Bauer MP, Hensgens MP, Miller MA, et al. Renal failure and leukocytosis are predictors of a complicated course of Clostridium difficile infection if measured on day of diagnosis. Clin Infect Dis. 2012;55 Suppl 2:S149–53.PubMedCrossRefGoogle Scholar
  20. 20.
    Nelson RL, Kelsey P, Leeman H, et al. Antibiotic treatment for Clostridium difficile-associated diarrhea in adults. Cochrane Database Syst Rev. 2011;9:CD004610.PubMedGoogle Scholar
  21. 21.
    Neal MD, Alverdy JC, Hall DE, et al. Diverting loop ileostomy and colonic lavage: an alternative to total abdominal colectomy for the treatment of severe, complicated Clostridium difficile associated disease. Ann Surg. 2011;254(3):423–7. discussion 7–9.PubMedCrossRefGoogle Scholar
  22. 22.
    Johnson S. Recurrent Clostridium difficile infection: a review of risk factors, treatments, and outcomes. J Infect. 2009;58(6):403–10.PubMedCrossRefGoogle Scholar
  23. 23.
    •• Louie TJ, Miller MA, Mullane KM, et al. Fidaxomicin versus vancomycin for Clostridium difficile infection. N Engl J Med. 2011;364(5):422–31. Randomized controlled trial demonstrating efficacy of new drug Fidaxomycin for first episode and recurrent CDI.PubMedCrossRefGoogle Scholar
  24. 24.
    Cornely OA, Miller MA, Louie TJ, et al. Treatment of first recurrence of Clostridium difficile infection: fidaxomicin versus vancomycin. Clin Infect Dis. 2012;55 Suppl 2:S154–61.PubMedCrossRefGoogle Scholar
  25. 25.
    Louie TJ, Cannon K, Byrne B, et al. Fidaxomicin preserves the intestinal microbiome during and after treatment of Clostridium difficile infection (CDI) and reduces both toxin reexpression and recurrence of CDI. Clin Infect Dis. 2012;55 Suppl 2:S132–42.PubMedCrossRefGoogle Scholar
  26. 26.
    Goldstein EJ, Citron DM, Sears P, et al. Comparative susceptibilities to fidaxomicin (OPT-80) of isolates collected at baseline, recurrence, and failure from patients in two phase III trials of fidaxomicin against Clostridium difficile infection. Antimicrob Agents Chemother. 2011;55(11):5194–9.PubMedCrossRefGoogle Scholar
  27. 27.
    Pillai A, Nelson R. Probiotics for treatment of Clostridium difficile-associated colitis in adults. Cochrane Database Syst Rev. 2008;1:CD004611.PubMedGoogle Scholar
  28. 28.
    Pozzoni P, Riva A, Bellatorre AG, et al. Saccharomyces boulardii for the prevention of antibiotic-associated diarrhea in adult hospitalized patients: a single-center, randomized, double-blind, placebo-controlled trial. Am J Gastroenterol. 2012;107(6):922–31.PubMedCrossRefGoogle Scholar
  29. 29.
    Guo B, Harstall C, Louie T, et al. Systematic review: faecal transplantation for the treatment of Clostridium difficile-associated disease. Aliment Pharmacol Ther. 2012;35(8):865–75.PubMedCrossRefGoogle Scholar
  30. 30.
    •• 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):407–15. First randomized controlled trial of fecal microbiota transplantation demonstrating its efficacy for treating recurrent CDI.PubMedCrossRefGoogle Scholar
  31. 31.
    Postigo R, Kim JH. Colonoscopic versus nasogastric fecal transplantation for the treatment of Clostridium difficile infection: a review and pooled analysis. Infection. 2012;40(6):643–8.PubMedCrossRefGoogle Scholar
  32. 32.
    Hota S. Oral vancomycin followed by fecal transplant versus tapering oral vancomycin. clincaltrials.gov; 2010 [18 December 2012]; Available from: http://clinicaltrials.gov/ct2/show/NCT01226992].
  33. 33.
    ••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. Randomized control trial demonstrating the efficacy of monoclonal antibodies against C. difficile toxins as an adjunct to antimicrobial agents for reducing recurrence.PubMedCrossRefGoogle Scholar
  34. 34.
    Mastroianni A, Coronado O, Nanetti A, et al. Nosocomial Clostridium difficile-associated diarrhea in patients with AIDS: a three-year survey and review. Clin Infect Dis. 1997;25 Suppl 2:S204–5.PubMedCrossRefGoogle Scholar
  35. 35.
    Zulu I, Kelly P, Mwansa J, et al. Contrasting incidence of Clostridium difficile and other enteropathogens in AIDS patients in London and Lusaka. Trans R Soc Trop Med Hyg. 2000;94(2):167–8.PubMedCrossRefGoogle Scholar
  36. 36.
    Mathewson JJ, Salameh BM, DuPont HL, et al. HEp-2 cell-adherent Escherichia coli and intestinal secretory immune response to human immunodeficiency virus (HIV) in outpatients with HIV-associated diarrhea. Clin Diagn Lab Immunol. 1998;5(1):87–90.PubMedGoogle Scholar
  37. 37.
    Anastasi JK, Capili B. HIV and diarrhea in the era of HAART: 1998 New York State hospitalizations. Am J Infect Control. 2000;28(3):262–6.PubMedCrossRefGoogle Scholar
  38. 38.
    Sanchez TH, Brooks JT, Sullivan PS, et al. Bacterial diarrhea in persons with HIV infection, United States, 1992–2002. Clin Infect Dis. 2005;41(11):1621–7.PubMedCrossRefGoogle Scholar
  39. 39.
    Pulvirenti J, Mehra T, Hafiz I, et al. Epidemiology and outcome of Clostridium difficile infection and diarrhea in HIV infected inpatients. Diagn Microbiol Infect Dis. 2002;44(4):325–30.PubMedCrossRefGoogle Scholar
  40. 40.
    Gordon MA, Kankwatira AM, Mwafulirwa G, et al. Invasive non-typhoid salmonellae establish systemic intracellular infection in HIV-infected adults: an emerging disease pathogenesis. Clin Infect Dis. 2010;50(7):953–62.PubMedCrossRefGoogle Scholar
  41. 41.
    Larsen IK, Gradel KO, Helms M, et al. Non-typhoidal Salmonella and Campylobacter infections among HIV-positive patients in Denmark. Scand J Infect Dis. 2011;43(1):3–7.PubMedCrossRefGoogle Scholar
  42. 42.
    Barbut F, Meynard JL, Guiguet M, et al. Clostridium difficile-associated diarrhea in HIV-infected patients: epidemiology and risk factors. J Acquir Immune Defic Syndr Hum Retrovirol. 1997;16(3):176–81.PubMedCrossRefGoogle Scholar
  43. 43.
    Hutin Y, Molina JM, Casin I, et al. Risk factors for Clostridium difficile-associated diarrhoea in HIV-infected patients. AIDS. 1993;7(11):1441–7.PubMedCrossRefGoogle Scholar
  44. 44.
    Tumbarello M, Tacconelli E, Leone F, et al. Clostridium difficile-associated diarrhoea in patients with human immunodeficiency virus infection: a case–control study. Eur J Gastroenterol Hepatol. 1995;7(3):259–63.PubMedGoogle Scholar
  45. 45.
    Bouza E, Padilla B, Catalan P, et al. Diarrhea associated with Clostridium difficile: one-year experience in a general hospital. Rev Clin Esp. 1996;196(7):424–30.PubMedGoogle Scholar
  46. 46.
    Dallal RM, Harbrecht BG, Boujoukas AJ, et al. Fulminant Clostridium difficile: an underappreciated and increasing cause of death and complications. Ann Surg. 2002;235(3):363–72.PubMedCrossRefGoogle Scholar
  47. 47.
    Mody LR, Smith SM, Dever LL. Clostridium difficile-associated diarrhea in a VA medical center: clustering of cases, association with antibiotic usage, and impact on HIV-infected patients. Infect Control Hosp Epidemiol. 2001;22(1):42–5.PubMedCrossRefGoogle Scholar
  48. 48.
    Buchner AM, Sonnenberg A. Medical diagnoses and procedures associated with clostridium difficile colitis. Am J Gastroenterol. 2001;96(3):766–72.PubMedCrossRefGoogle Scholar
  49. 49.
    Saddi VR, Glatt AE. Clostridium difficile-associated diarrhea in patients with HIV: a 4-year survey. J Acquir Immune Defic Syndr. 2002;31(5):542–3.PubMedCrossRefGoogle Scholar
  50. 50.
    Sherer R, Pulvirenti J, Stieglitz K, et al. Hospitalization in HIV in Chicago. J Int Assoc Physicians AIDS Care (Chic). 2002;1(1):26–33.CrossRefGoogle Scholar
  51. 51.
    Palella Jr FJ, Chmiel JS, Moorman AC, et al. Durability and predictors of success of highly active antiretroviral therapy for ambulatory HIV-infected patients. AIDS. 2002;16(12):1617–26.CrossRefGoogle Scholar
  52. 52.
    Pavie J, Menotti J, Porcher R, et al. Prevalence of opportunistic intestinal parasitic infections among HIV-infected patients with low CD4 cells counts in France in the combination antiretroviral therapy era. Int J Infect Dis. 2012;16(9):e677–9.PubMedCrossRefGoogle Scholar
  53. 53.
    Samie A, Obi CL, Franasiak J, et al. PCR detection of Clostridium difficile triose phosphate isomerase (tpi), toxin A (tcdA), toxin B (tcdB), binary toxin (cdtA, cdtB), and tcdC genes in Vhembe District, South Africa. AmJTrop Med Hyg. 2008;78(4):577–85.Google Scholar
  54. 54.
    Willingham FF, Ticona Chavez E, Taylor DN, et al. Diarrhea and Clostridium difficile infection in Latin American patients with AIDS. Working Group on AIDS in Peru. Clin Infect Dis. 1998;27(3):487–93.PubMedCrossRefGoogle Scholar
  55. 55.
    Onwueme K, Fadairo Y, Idoko L, et al. High prevalence of toxinogenic Clostridium difficile in Nigerian adult HIV patients. Trans R Soc Trop Med Hyg. 2011;105(11):667–9.PubMedCrossRefGoogle Scholar
  56. 56.
    Jha AK, Uppal B, Chadha S, et al. Clinical and Microbiological Profile of HIV/AIDS Cases with Diarrhea in North India. J Pathog. 2012;2012:971958.PubMedGoogle Scholar
  57. 57.
    Cappell MS, Philogene C. Clostridium difficile infection is a treatable cause of diarrhea in patients with advanced human immunodeficiency virus infection: a study of seven consecutive patients admitted from 1986 to 1992 to a university teaching hospital. Am J Gastroenterol. 1993;88(6):891–7.PubMedGoogle Scholar
  58. 58.
    Lu SS, Schwartz JM, Simon DM, et al. Clostridium difficile-associated diarrhea in patients with HIV positivity and AIDS: a prospective controlled study. Am J Gastroenterol. 1994;89(8):1226–9.PubMedGoogle Scholar
  59. 59.
    Zuckerman E, Kanel G, Ha C, et al. Low albumin gradient ascites complicating severe pseudomembranous colitis. Gastroenterology. 1997;112(3):991–4.PubMedCrossRefGoogle Scholar
  60. 60.
    Beaugerie L, Ngo Y, Goujard F, et al. Etiology and management of toxic megacolon in patients with human immunodeficiency virus infection. Gastroenterology. 1994;107(3):858–63.PubMedCrossRefGoogle Scholar
  61. 61.
    DeMarais PL, Gertzen J, Weinstein RA. Nosocomial infections in human immunodeficiency virus-infected patients in a long-term-care setting. Clin Infect Dis. 1997;25(5):1230–2.PubMedCrossRefGoogle Scholar
  62. 62.
    Olofinlade O, Chiang C. Cytomegalovirus infection as a cause of pseudomembrane colitis: a report of four cases. J Clin Gastroenterol. 2001;32(1):82–4.PubMedCrossRefGoogle Scholar
  63. 63.
    Younus F, Steigbigel RT. Images in clinical medicine. Nodular Clostridium difficile colitis. N Engl J Med. 2004;350(10):e9.PubMedCrossRefGoogle Scholar
  64. 64.
    Cozart JC, Kalangi SS, Clench MH, et al. Clostridium difficile diarrhea in patients with AIDS versus non-AIDS controls. Methods of treatment and clinical response to treatment. J Clin Gastroenterol. 1993;16(3):192–4.PubMedCrossRefGoogle Scholar
  65. 65.
    Pepin J, Valiquette L, Gagnon S, et al. Outcomes of Clostridium difficile-associated disease treated with metronidazole or vancomycin before and after the emergence of NAP1/027. Am J Gastroenterol. 2007;102(12):2781–8.PubMedCrossRefGoogle Scholar
  66. 66.
    Alonso R, Gros S, Pelaez T, et al. Molecular analysis of relapse vs re-infection in HIV-positive patients suffering from recurrent Clostridium difficile associated diarrhoea. J Hosp Infect. 2001;48(2):86–92.PubMedCrossRefGoogle Scholar
  67. 67.
    Ricciardi R, Rothenberger DA, Madoff RD, et al. Increasing prevalence and severity of Clostridium difficile colitis in hospitalized patients in the United States. Arch Surg. 2007;142(7):624–31. discussion 31.PubMedCrossRefGoogle Scholar
  68. 68.
    • Saxena D, Li Y, Yang L, et al. Human microbiome and HIV/AIDS. Curr HIV/AIDS Rep. 2012;9(1):44–51. Review article summarizing what is known about the effect of HIV on the microbiome.PubMedCrossRefGoogle Scholar
  69. 69.
    Qiao X, He B, Chiu A, et al. Human immunodeficiency virus 1 Nef suppresses CD40-dependent immunoglobulin class switching in bystander B cells. Nat Immunol. 2006;7(3):302–10.PubMedCrossRefGoogle Scholar
  70. 70.
    Sullivan A, Edlund C, Nord CE. Effect of antimicrobial agents on the ecological balance of human microflora. Lancet Infect Dis. 2001;1(2):101–14.PubMedCrossRefGoogle Scholar
  71. 71.
    Tvede M, Rask-Madsen J. Bacteriotherapy for chronic relapsing Clostridium difficile diarrhoea in six patients. Lancet. 1989;1(8648):1156–60.PubMedCrossRefGoogle Scholar
  72. 72.
    Gori A, Tincati C, Rizzardini G, et al. Early impairment of gut function and gut flora supporting a role for alteration of gastrointestinal mucosa in human immunodeficiency virus pathogenesis. J Clin Microbiol. 2008;46(2):757–8.PubMedCrossRefGoogle Scholar
  73. 73.
    Ellis CL, Ma ZM, Mann SK, et al. Molecular characterization of stool microbiota in HIV-infected subjects by panbacterial and order-level 16S ribosomal DNA (rDNA) quantification and correlations with immune activation. J Acquir Immune Defic Syndr. 2011;57(5):363–70.PubMedCrossRefGoogle Scholar
  74. 74.
    Pérez-Santiago J, Weir C, Karris M, et al. Higher CD4 is associated with specific gut bacterial flora during HIV acute infection. Abstract 546, 19th Conference on Retroviruses and Opportunistic Infections. Seattle; 2012; Available from: http://www.retroconference.org/2012b/Abstracts/43386.htm. Accessed 31 Mar 2013.
  75. 75.
    Mainardi JL, Lacassin F, Guilloy Y, et al. Low rate of Clostridium difficile colonization in ambulatory and hospitalized HIV-infected patients in a hospital unit: a prospective survey. J Infect. 1998;37(2):108–11.PubMedCrossRefGoogle Scholar
  76. 76.
    Hutin Y, Casin I, Lesprit P, et al. Prevalence of and risk factors for Clostridium difficile colonization at admission to an infectious diseases ward. Clin Infect Dis. 1997;24(5):920–4.PubMedCrossRefGoogle Scholar
  77. 77.
    Poxton IR, McCoubrey J, Blair G. The pathogenicity of Clostridium difficile. Clin Microbiol Infect. 2001;7(8):421–7.PubMedCrossRefGoogle Scholar
  78. 78.
    Epple HJ, Zeitz M. HIV infection and the intestinal mucosal barrier. Ann N Y Acad Sci. 2012;1258:19–24.PubMedCrossRefGoogle Scholar
  79. 79.
    Varin A, Manna SK, Quivy V, et al. Exogenous Nef protein activates NF-kappa B, AP-1, and c-Jun N-terminal kinase and stimulates HIV transcription in promonocytic cells. Role in AIDS pathogenesis. J Biol Chem. 2003;278(4):2219–27.PubMedCrossRefGoogle Scholar
  80. 80.
    Vilhardt F, Plastre O, Sawada M, et al. The HIV-1 Nef protein and phagocyte NADPH oxidase activation. J Biol Chem. 2002;277(44):42136–43.PubMedCrossRefGoogle Scholar
  81. 81.
    Viscidi R, Laughon BE, Yolken R, et al. Serum antibody response to toxins A and B of Clostridium difficile. J Infect Dis. 1983;148(1):93–100.PubMedCrossRefGoogle Scholar
  82. 82.
    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):390–7.PubMedCrossRefGoogle Scholar
  83. 83.
    Moir S, Malaspina A, Ogwaro KM, et al. HIV-1 induces phenotypic and functional perturbations of B cells in chronically infected individuals. Proc Natl Acad Sci USA. 2001;98(18):10362–7.PubMedCrossRefGoogle Scholar
  84. 84.
    Ryan A, Lynch M, Smith SM, et al. A Role for TLR4 in Clostridium difficile Infection and the Recognition of Surface Layer Proteins. PLoS Pathog. 2011;7(6):e1002076.PubMedCrossRefGoogle Scholar
  85. 85.
    Modi N, Gulati N, Solomon K, et al. Differential binding and internalization of Clostridium difficile toxin A by human peripheral blood monocytes, neutrophils and lymphocytes. Scand J Immunol. 2011;74(3):264–71.Google Scholar
  86. 86.
    Mahida YR, Galvin A, Makh S, et al. Effect of Clostridium difficile toxin A on human colonic lamina propria cells: early loss of macrophages followed by T-cell apoptosis. Infect Immun. 1998;66(11):5462–9.PubMedGoogle Scholar
  87. 87.
    Dockrell DH. The multiple roles of Fas ligand in the pathogenesis of infectious diseases. Clin Microbiol Infect. 2003;9(8):766–79.PubMedCrossRefGoogle Scholar
  88. 88.
    Hensgens MP, Goorhuis A, Dekkers OM, et al. Time interval of increased risk for Clostridium difficile infection after exposure to antibiotics. J Antimicrob Chemother. 2012;67(3):742–8.PubMedCrossRefGoogle Scholar
  89. 89.
    Dockrell DH, Edwards S, Fisher M, et al. Evolving controversies and challenges in the management of opportunistic infections in HIV-seropositive individuals. J Infect. 2011;63(3):177–86.PubMedCrossRefGoogle Scholar
  90. 90.
    Spencer RC. The role of antimicrobial agents in the aetiology of Clostridium difficile-associated disease. J Antimicrob Chemother. 1998;41(Suppl C):21–7.PubMedCrossRefGoogle Scholar
  91. 91.
    Reiss P. HIV, co-morbidity and ageing. J Int AIDS Soc. 2012;15 Suppl 4:18073.Google Scholar
  92. 92.
    Terhes G, Urban E, Soki J, et al. Community-acquired Clostridium difficile diarrhea caused by binary toxin, toxin A, and toxin B gene-positive isolates in Hungary. J Clin Microbiol. 2004;42(9):4316–8.PubMedCrossRefGoogle Scholar
  93. 93.
    Astellas Pharma Ltd. Dificlir (fidaxomicin). Summary of product characteristics. 2012; Available from: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002087/WC500119705.pdf. Accessed 31 Mar 2013.
  94. 94.
    Bakken JS, Borody T, Brandt LJ, et al. Treating Clostridium difficile infection with fecal microbiota transplantation. Clin Gastroenterol Hepatol. 2011;9(12):1044–9.PubMedCrossRefGoogle Scholar
  95. 95.
    Zainah H, Silverman A. Fecal bacteriotherapy: a case report in an immunosuppressed patient with ulcerative colitis and recurrent clostridium difficile infection. Case Rep Infect Dis. 2012;2012:810943.PubMedGoogle Scholar
  96. 96.
    Neemann K, Eichele DD, Smith PW, et al. Fecal microbiota transplantation for fulminant Clostridium difficile infection in an allogeneic stem cell transplant patient. Transpl Infect Dis. 2012;14(6):E161–5.PubMedCrossRefGoogle Scholar
  97. 97.
    Hoffmann C, Schmid H, Muller M, et al. Improved outcome with rituximab in patients with HIV-associated multicentric Castleman disease. Blood. 2011;118(13):3499–503.PubMedCrossRefGoogle Scholar
  98. 98.
    Foglia G, Shah S, Luxemburger C, et al. Clostridium difficile: development of a novel candidate vaccine. Vaccine. 2012;30(29):4307–9.PubMedCrossRefGoogle Scholar
  99. 99.
    Geretti AM, Brook G, Cameron C, et al. British HIV Association guidelines for immunization of HIV-infected adults 2008. HIV Med. 2008;9(10):795–848.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Paul J. Collini
    • 1
  • Ed Kuijper
    • 2
  • David H. Dockrell
    • 3
  1. 1.Department of Infection and ImmunityThe University of Sheffield Medical School & Sheffield Teaching HospitalsSheffieldUK
  2. 2.Department of Medical MicrobiologyLeiden University Medical CenterLeidenNetherlands
  3. 3.Department of Infection and ImmunityThe University of Sheffield Medical School & Sheffield Teaching HospitalsSheffieldUK

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