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Infectious Diarrhea: An Overview

  • Large Intestine (B Cash, Section Editor)
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Abstract

Diarrheal disease, which is most often caused by infectious pathogens, is a significant cause of morbidity and mortality worldwide, especially in children. This is particularly true in developing countries. Recent outbreaks of infectious diarrhea in developed countries, including the USA, are often attributed to food handling and distribution practices and highlight the need for continued vigilance in this area. Another common cause of infectious diarrhea, Clostridium difficile infection (CDI), has historically been associated with the use of antibiotics and exposure to a health-care setting but is now increasingly common in the community in persons who lack the typical risk factors. Recent scientific advances have also led to new and proposed new therapies for infectious diarrhea, including fecal microbiota transplant (FMT) for recurrent C. difficile infection (RCDI), probiotics for prevention of antibiotic-associated diarrhea (AAD) and CDI, and the use of zinc supplementation in the treatment of acute diarrhea in children. Other therapies that have been in use for decades, such as the oral rehydration solution (ORS), continue to be the targets of scientific advancement in an effort to improve delivery and efficacy. Finally, post-infectious irritable bowel syndrome (PI-IBS) is an increasingly recognized occurrence. Attempts to understand the mechanism behind this phenomenon are underway and may provide insight into potential treatment options.

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References

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

  1. World Health Organization: Diarrhoeal disease. Available at http://www.who.int/mediacentre/factsheets/fs330/en/. Accesses April 4, 2014.

  2. Centers for Disease Control and Prevention (CDC). Incidence and trends of infection with pathogens transmitted commonly through food—foodborne diseases active surveillance network, 10 U.S. sites, 1996–2012. MMWR Morb Mortal Wkly Rep. 2013;62(15):283–7.

    Google Scholar 

  3. Gould LH, Demma L, Jones TF, et al. Hemolytic uremic syndrome and death in persons with Escherichia coli 0157:H7 infection, foodborne disease active surveillance network sites, 2000–2006. Clin Infect Dis. 2009;49:1480–5.

    Article  PubMed  Google Scholar 

  4. Frank C, Werber D, Cramer JP, et al. Epidemic profile of Shiga-toxin-producing Escherichia coli O104:H4 outbreak in Germany. N Eng J Med. 2011;365(19):1771–80.

    Article  CAS  Google Scholar 

  5. Mellmann A, Harmsen D, Cummings CA, et al. Prospective genomic characterization of the German enterohemorrhagic Escherichia coli O104:H4 outbreak by rapid next generation sequencing technology. PLoS ONE. 2011;6:e22751.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Rhode H, Qin J, Cui Y, et al. Open-source genomic analysis of Shiga-toxin-producing E. coli O104:H4. N Eng J Med. 2011;365:718–24.

    Article  Google Scholar 

  7. Barton Behravesh C, Jones TF, Vugia DJ, et al. Deaths associated with bacterial pathogens transmitted commonly through food: foodborne disease active surveillance network (FoodNet), 1996–2005. J Infect Dis. 2011;204:263–7.

    Article  PubMed  Google Scholar 

  8. McCollum JT, Cronquist AB, Silk BJ, et al. Multistate outbreak of listeriosis associated with cantaloupe. N Eng J Med. 2013;369(10):944–53.

    Article  CAS  Google Scholar 

  9. Arvelo W, Hinkle CJ, Nguyen TA, et al. Transmission risk factors and treatment of pediatric shigellosis during a large daycare center-associated outbreak of multidrug resistant Shigella sonnei: implications for the management of shigellosis outbreaks among children. Pediatr Infect Dis J. 2009;28:976–80.

    Article  PubMed  Google Scholar 

  10. CDC. Notes from the field: outbreak of infections caused by Shigella sonnei with decreased susceptibility to azithromycin—Los Angeles, California, 2012. MMWR Morb Mortal Wkly Rep. 2013;62(9):171.

    Google Scholar 

  11. McFarland LV. Emerging therapies for Clostridium difficile infections. Exp Opin Emerg Drugs. 2011;16:425–39.

    Article  Google Scholar 

  12. O’brien JA, Lahue BJ, Caro JJ, et al. The emerging infectious challenge of Clostridium difficile-associated disease in Massachusetts hospitals: clinical and economic consequences. Infect Control Hosp Epidemiol. 2007;28:1219–27.

    Article  PubMed  Google Scholar 

  13. O’Connor JR, Johnson S, Gerding D. Clostridium difficile infection caused by the epidemic BI/NAP1/027 strain. Gastroenterology. 2009;136(6):1913–24.

    Article  PubMed  Google Scholar 

  14. Pepin J, Saheb N, Coulombe MA, et al. Emergence of fluoroquinolones as the predominant risk factor for Clostridium difficile—associated diarrhea: a cohort study during an epidemic in Quebec. Clin Infect Dis. 2005;41(9):1254–60.

    Article  CAS  PubMed  Google Scholar 

  15. Gupta A, Khanna S. Community-acquired Clostridium difficile infection: an increasing public health threat. Infect Drug Resist. 2014;7:63–72.

    PubMed Central  PubMed  Google Scholar 

  16. Otten AM, Reid-Smith RJ, Fazil A, Weese JS. Disease transmission model for community-associated Clostridium difficile infection. Epidemiol Infect. 2010;138(6):901–14.

    Article  Google Scholar 

  17. Bavishi C, Dupont HL. Systematic review: the use of proton pump inhibitors and increased susceptibility to enteric infection. Aliment Pharmacol Ther. 2011;34(11–12):1269–81.

    Article  CAS  PubMed  Google Scholar 

  18. Ozaki E, Kato H, Kita H, et al. Clostridium difficile colonization in healthy adults: transient colonization and correlation with enterococcal colonization. J Med Microbiol. 2004;53(2):167–72.

    Article  PubMed  Google Scholar 

  19. Khanna S, Keddis M, Noheria A, et al. The epidemiology of Clostridium difficile infection in children: a population based study. Clin Infect Dis. 2013;56(10):1401–6.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Chitnis A, Holzbauer S, Belflower R, et al. Epidemiology of community-associated Clostridium difficile infection, 2009–2011. JAMA Intern Med. 2013;173:1359–67.

    Article  PubMed  Google Scholar 

  21. 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.

    Article  PubMed Central  PubMed  Google Scholar 

  22. Janarthanan S, Ditah I, Adler DG, et al. Clostridium difficile associated diarrhea and proton pump inhibitor therapy—a meta-analysis. Am J Gastroenterol. 2012;107:1001–10.

    Article  CAS  PubMed  Google Scholar 

  23. Kwok CS, Arthur AK, Anibueze CI, et al. Risk of Clostridium difficile infection with acid suppression agents and antibiotics: meta-analysis. Am J Gastroenterol. 2012;107:1011–9.

    Article  CAS  PubMed  Google Scholar 

  24. Barletta JF, El-Ibiary SY, Davis LE, et al. Proton pump inhibitors and the risk for hospital-acquired Clostridium difficile infection. Mayo Clin Proc. 2013;88(10):1085–90.

    Article  CAS  PubMed  Google Scholar 

  25. Buendgens L, Bruensing J, Matthes M, et al.: Administration of proton pump inhibitors in critically ill medical patients is associated with increased risk of developing Clostridium difficile-associated diarrhea. J Crit Care 2014, S0883-9441(14)00079-3. doi: 10.1016/j.jcrc.2014.03.002

  26. Drug Safety Communication - FDA Clostridium difficile-associated diarrhea (CDAD) can be associated with stomach acid drugs. http://www.fda.gov/Safety/MedWatch?SafetyInformation?Safety AlertsforHumanMedicalProducts/ucm290838.htm (assessed 2 April 2014).

  27. Freedberg DE, Salmasian H, Friedman C, Abrams JA. Proton pump inhibitors and risk for recurrent Clostridium difficile infection among inpatients. Am J Gastroenterol. 2013;108(11):1794–801.

    Article  PubMed  Google Scholar 

  28. Khanna S, Aronson S, Kammer P, et al. Gastric acid suppression and outcomes in Clostridium difficile infection: a population based study. Mayo Clin Proc. 2012;87(7):636–42.

    Article  PubMed Central  PubMed  Google Scholar 

  29. Surawicz CM, Brandt LJ, Binion DG, et al. Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. Am J Gastroenterol. 2013;108(4):478–9. New guidelines for the diagnosis and treatment of Clostridium difficile infections. A great resource for a comprehensive review of the subject.

    Article  CAS  PubMed  Google Scholar 

  30. Kelly C, Lamont J. Clostridium difficile—more difficult than ever. N Engl J Med. 2008;359:1932–40.

    Article  CAS  PubMed  Google Scholar 

  31. Louie TJ, Miller MA, Mullane KM, et al. Fidaxomicin versus vancomycin for Clostridium difficile-associated disease in Quebec, Canada. Clin Infect Dis. 2006;42:758–64.

    Article  Google Scholar 

  32. Taur Y, Pamer EG. Harnessing microbiota to kill a pathogen: fixing the microbiota to treat Clostridium difficile infections. Nat Med. 2014;20(3):246–7. An interesting article from Nature that highlights the need for greater understanding of the mechanism by which FMT is effective for recurrent CDI in order to potentially achieve the same effect as FMT but with greater ease of administration.

    Article  CAS  PubMed  Google Scholar 

  33. Tvede M, Rask-Madsen J. Bacteriotherapy for chronic relapsing Clostridium difficile diarrhoea in six patients. Lancet. 1989;1(8648):1156–60.

    Article  CAS  PubMed  Google Scholar 

  34. Hamilton M, Weingarden A, Sadowsky M, Khoruts A. Standardized frozen preparation for transplantation of fecal microbiota for recurrent Clostridium difficile infection. Am J Gastroenterol. 2012;107(5):761–7.

    Article  PubMed  Google Scholar 

  35. Matilla E, Uusitalo-Seppala R, Wuorela M, et al. Fecal transplantation, through colonoscopy, is effective therapy for recurrent Clostridium difficile infection. Gastroenterology. 2012;142:490–6.

    Article  Google Scholar 

  36. Gough E, Shaikh H, Manges A. Systematic review of intestinal microbiota transplantation (fecal bacteriotherapy) for recurrent Clostridium difficile infection. Clin Infect Dis. 2011;53:994–1002.

    Article  PubMed  Google Scholar 

  37. Van Nood E, Vrieze A, Nieuwdorp M, et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Eng J Med. 2013;368(5):407–15. First randomized controlled trial using fecal microbiota transplantation for the treatment of recurrent Clostridium difficile infection.

    Article  Google Scholar 

  38. Khoruts A, Dicksved J, Jansson JK, et al. Changes in the composition of the human fecal microbiome after bacteriotherapy for recurrent Clostridium difficile-associated diarrhea. J Clin Gastroenterol. 2010;44(5):354–60.

    PubMed  Google Scholar 

  39. Sorg JA, Sonenshein AL. Bile salts and glycine as cogerminants for Clostridium difficile spores. J Bacteriol. 2008;190(7):2505–12.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  40. Sorg JA, Sonenshein AL. Inhibiting the initiation of Clostridium difficile spore germination using analogs of chenodeoxycholic acid, a bile acid. J Bacteriol. 2012;192(19):4983–90.

    Article  Google Scholar 

  41. Smith PM, Howitt MR, Panikov N, et al. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science. 2013;341(6145):569–73.

    Article  CAS  PubMed  Google Scholar 

  42. Ley RE. Harnessing microbiota to kill a pathogen: the sweet tooth of Clostridium difficile. Nat Med. 2014;20(3):248–9.

    Article  CAS  PubMed  Google Scholar 

  43. Ng KM, Ferreyra JA, Higginbottom SK, et al. Microbiota-liberated host sugars facilitate post-antibiotic expansion of enteric pathogens. Nature. 2013;502(7469):96–9.

    Article  CAS  PubMed  Google Scholar 

  44. Binder HJ, Brown I, Ramakrishna BS, Young GP. Oral rehydration therapy in the second decade of the twenty-first century. Curr Gastroenterol Rep. 2014;16(3):376. An excellent review on the history of oral rehydration therapy, including improvements that have been made in the solution over time and current research efforts to further improve its efficacy and delivery.

    Article  PubMed Central  PubMed  Google Scholar 

  45. Desjeux JF, Briend A, Butzner JD. Oral rehydration solution in the year 2000: pathophysiology, efficacy and effectiveness. Baillieres Clin Gastroenterol. 1997;11:509–27.

    Article  CAS  PubMed  Google Scholar 

  46. Lin R, Murtazina R, Cha B, et al. D-glucose acts via sodium/glucose cotransporter 1 to increase NHE3 in mouse jejunal brush border by a Na+/H + exchange regulatory factor 2-dependent process. Gastroenterology. 2011;140:560–71.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  47. Duggan C, Fontaine O, Pierce NF, et al. Scientific rationale for a change in the composition of oral rehydration solution. JAMA. 2004;291:2628–31.

    Article  CAS  PubMed  Google Scholar 

  48. Ramakrishna BS, Venkataraman S, Srinivasan P, et al. Amylase-resistant starch plus oral rehydration solution for cholera. N Engl J Med. 2000;342:308–13.

    Article  CAS  PubMed  Google Scholar 

  49. Raghupathy P, Ramakrishna BS, Oommen SP, et al. Amylase-resistant starch as adjunct to oral rehydration therapy in children with diarrhea. J Pediatr Gastr Nutr. 2006;42:362–8.

    Article  CAS  Google Scholar 

  50. Balakrishnan BS, Venkataraman S, Mohen V, et al. Amylase resistant starch in hypo-osmolar oral rehydration solution for the treatment of acute severe watery diarrhea in adults. PLoS ONE. 2008;3:e1587.

    Article  Google Scholar 

  51. Subramanya S, Balakrishnan BS, Ramakrishna S, et al. Evaluation of oral rehydration solution by whole gut perfusion in rats: effects of osmolarity, sodium concentration and resistant starch. J Pediatr Gastroenterol Nutr. 2006;43:568–77.

    Article  CAS  PubMed  Google Scholar 

  52. Penny ME. Zinc supplementation in public health. Ann Nutr Metab. 2013;62(1):31–42.

    Article  CAS  PubMed  Google Scholar 

  53. WHO/UNICEF joint statement: clinical management of acute diarrhoea. The United Nations Children's Fund/World Health Organization, 2004. http://whqlibdoc.who.int.offcampus.lib.washington.edu/hq/2004/WHO_FCH_CAH_04.7.pdf (accessed April 3, 2014).

  54. Lazzerini M, Ronfani L. Oral zinc for treating diarrhoea in children. Cochrane Database Syst Rev. 2013;1, CD005436.

    PubMed  Google Scholar 

  55. Fasano A. Toxin and the gut: role in human disease. Gut. 2002;50:9–14.

    Article  Google Scholar 

  56. Surawicz CM. Mechanisms of Diarrhea. Curr Gastroenterol Rep. 2010;12(4):236–41.

    Article  PubMed  Google Scholar 

  57. Berni Canani R, Cirillo P, Buccigrossi V, et al. Zinc inhibits cholera toxin-induced, but not Escherichia coli heat-stable enterotoxin-induced, ion secretion in human enterocytes. J Infect Dis. 2006;191:1072–7.

    Article  Google Scholar 

  58. BerniCanani R, Secondo A, Passariello A, et al. Zinc inhibits calcium-mediated and nitric oxide-mediated ion secretion in human enterocytes. Eur J Pharmacol. 2010;626:266–70.

    Article  CAS  Google Scholar 

  59. Berni Canani R, Buccigrossi V, Passariello A. Mechanisms of action of zinc in acute diarrhea. Curr Opin Gastroenterol. 2011;27:8–12.

    Article  PubMed  Google Scholar 

  60. Salgueiro MJ, Zubillaga M, Lysionek A, et al. Zinc status and immune system relationship: a review. Biol Trace Elem Res. 2000;76:193–205.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  62. 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(12):878–88. Recent Cochrane review looking at the use of probiotics in the prevention of Clostridium difficile infection.

    Article  PubMed  Google Scholar 

  63. Allen SJ, Wareham K, Wang D, et al. Lactobacilli and bifidobacteria in the prevention of antibiotic-associated diarrhoea and Clostridium difficile diarrhoea in older patients (PLACIDE): a randomised, double-blind, placebo-controlled, multicentre trial. Lancet. 2013;382(9900):1249–57.

    Article  PubMed  Google Scholar 

  64. Spiller R, Garsed K. Postinfectious irritable bowel syndrome. Gastroenterology. 2009;136:1979–88.

    Article  PubMed  Google Scholar 

  65. Stewart GT. Post-dysenteric colitis. Br Med J. 1950;1:405–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  66. Ghoshal UC, Ranjan P. Post-infectious irritable bowel syndrome: the past, the present, the future. J Gastroenterol Hepatol. 2011;26(3):94–101.

    Article  PubMed  Google Scholar 

  67. Gorbach SL, Neale G, Levitan R, et al. Alterations in human intestinal microflora during experimental diarrhoea. Gut. 1970;11:1–6.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  68. Krogius-Kurikka L, Lyra A, Malinen E, et al. Microbial community analysis reveals high level phylogenetic alterations in the overall gastrointestinal microbiota of diarrhoea-predominant irritable bowel syndrome sufferers. BMC Gastroenterol. 2009;9:95.

    Article  PubMed Central  PubMed  Google Scholar 

  69. Gwee KA, Collins SM, Read NW, et al. Increased rectal mucosal expression of interleukin 1beta in recently acquired post-infectious irritable bowel syndrome. Gut. 2003;52:523–6.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  70. Pimentel M, Chatterjee S, Chang C, et al. A new rat model links two contemporary theories in irritable bowel syndrome. Dig Dis Sci. 2008;53(4):982–9.

    Article  PubMed  Google Scholar 

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Brandon Dickinson and Christina M. Surawicz have nothing to disclose.

Human and Animal Rights and Informed Consent

This article does not contain any studies with animal subjects performed by any of the authors. With regard to the authors’ research cited in this paper, all procedures were followed in accordance with the ethical standards of the responsible committee on human experimentation and with the Helsinki Declaration of 1975, as revised in 2000 and 2008.

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Correspondence to Christina M. Surawicz.

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Dickinson, B., Surawicz, C.M. Infectious Diarrhea: An Overview. Curr Gastroenterol Rep 16, 399 (2014). https://doi.org/10.1007/s11894-014-0399-8

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