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Table of Contents
Vol. 16, No. 5, 1998
Issue release date: September–October 1998< (January 1999)
Section title: Paper
Dig Dis 1998;16:292–307
(DOI:10.1159/000016879)

Epidemiology, Risk Factors and Treatments for Antibiotic-Associated Diarrhea

McFarland L.V.
Department of Medicinal Chemistry, School of Pharmacy, University of Washington and Biocodex, Inc., Seattle Wash., USA

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Article / Publication Details

Published online: 1/25/1999

Number of Print Pages: 16
Number of Figures: 0
Number of Tables: 5

ISSN: 0257-2753 (Print)
eISSN: 1421-9875 (Online)

For additional information: http://www.karger.com/DDI

Abstract

Antibiotic-associated diarrhea (AAD) is a common complication of antibiotics and recent findings on the epidemiology, etiologies and treatment strategies are reviewed. Rates of AAD vary from 5 to 39% depending upon the specific type of antibiotic. The severity of AAD may include uncomplicated diarrhea, colitis or pseudomembranous colitis. The pathogenesis of AAD may be mediated through the disruption of the normal flora and overgrowth of pathogens or through metabolic imbalances. The impact of AAD is reflected by increased hospital stays, higher medical costs and increased rates of comorbidity. The key to decreasing these consequences is prompt diagnosis followed by effective treatment and institution of control measures.


Article / Publication Details

Published online: 1/25/1999

Number of Print Pages: 16
Number of Figures: 0
Number of Tables: 5

ISSN: 0257-2753 (Print)
eISSN: 1421-9875 (Online)

For additional information: http://www.karger.com/DDI


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. McGowan JE Jr, Gerding DN: Does antibiotic restriction prevent resistance? New Horiz 1996;4:370–376.
  2. Gleckman RA, Borrego F: Adverse reactions to antibiotics. Clues for recognizing, understanding and avoiding them. Postgrad Med 1997;101:97–98/101–104/107–108.
  3. Boehler M, Rustler T, Wolf D, Knahr K: Antibiotic‐associated colitis in orthopaedic patients. Int Orthop 1996;20:204–206.

    External Resources

  4. James AH, Katz VL, Dotters DJ, Rogers RG: Clostridium difficile infection in obstetric and gynecologic patients. South Med J 1997;90:889–892.

    External Resources

  5. McFarland LV, Surawicz CM, Greenberg RN, Ekmer GW, Moyer KA, Melcher SA, Bowen KE, Cox JL: Prevention of β‐lactam associated diarrhea by Saccharomyces boulardii compared with placebo. Am J Gastroenterol 1995;90:439–448.
  6. Cartmill TD, Panigrahi H, Worsley MA, McCann DC, Nice CN, Keith E: Management and control of a large outbreak of diarrhoea due to Clostridium difficile. J Hosp Infect 1994;27:1–15.

    External Resources

  7. Olson MM, Shanholtzer CJ, Lee JT Jr, Gerding DN: Ten years of prospective Clostridium difficile‐associated disease surveillance and treatment at the Minneapolis VA Medical Center, 1982–1991. Infect Control Hosp Epidemiol 1994;15:371–381.
  8. Samore MH, DeGirolami PC, Tlucko A, Lichtenberg DA, Melvin ZA, Karchmer AW: Clostridium difficile colonization and diarrhea at a tertiary care hospital. Clin Infect Dis 1994;18:181–187.

    External Resources

  9. Gorbach SL: Clostridium difficile settles in a nursing home. Hosp Pract 1989;24:145–149.
  10. Bentley DW: Clostridium difficile‐associated disease in long‐term care facilities. Infect Control Hosp Epidemiol 1990;11:434–438.

    External Resources

  11. Slevogt H, Ruf B: Antibiotic associated diarrhea in HIV‐infected patients. Infection 1997;25:189.

    External Resources

  12. Satin AJ, Harrison CR, Hancock KC, Zahn CM: Relapsing Clostridium difficile toxin‐associated colitis in ovarian cancer patients treated with chemotherapy. Obstet Gynecol 1989;74:487–489.

    External Resources

  13. Andrejak M, Lafon B, Decocq G, Chetaille E, Dupas JL, Ducroix JP, Capron JP: Antibiotic associated pseudomembranous colitis: Retrospective study of 48 cases diagnosed by colonscopy (in French). Thérapie 1996;51:81–86.

    External Resources

  14. Tedesco FJ, Barton RW, Alpers DH: Clindamycin‐associated colitis. Ann Intern Med 1974;81:429–433.

    External Resources

  15. Larson HF, Parry JV, Price AB, Davies DR, Dolby J, Tyrrell DAJ: Undescribed toxin in pseudomembranous colitis. Brit Med J 1977;i:1246–1248.
  16. Bartlett JG, Onderdonk AB, Cisneros RL, Kasper DL: Clindamycin‐associated colitis due to a toxin‐producing species of Clostridum in hamsters. J Infect Dis 1977;136:701–705.
  17. Rifkin GD, Fekety FR, Silva J Jr: Antibioticinduced colitis. Implication of a toxin neutralised by Clostridium sordelli antitoxin. Lancet 1977;ii:1103–1106.
  18. Bartlett JG, Moon N, Chang TW, Taylor N, Onderdonk AB: Role of Clostridium difficile in antibiotic associated PMC. Gastroenterology 1978;75:778–782.

    External Resources

  19. Viscidi R, Willey S, Bartlett JG: Isolation rates and toxigenic potential of Clostridium difficile isolates from various patient populations. Gastroenterology 1981;81:5–9.

    External Resources

  20. Silva J, Batts DH, Fekety R, Plouffe JF, Rifkin GD, Baird I: Treatment of Clostridium difficile colitis and diarrhea with vancomycin. Am J Med 1981;71:815–821.

    External Resources

  21. Rothman S, Borwn JE, Diecidue A, Foret DA: Differential cytotoxic effects of toxins A and B isolated from Clostridium difficile. Infect Immun 1984;46:324–331.
  22. Aronsson B, Mollby R, Nord CD: Antimicrobial agents and Clostridium difficile in acute enteric disease: Epidemiological data from Sweden, 1980–82. J Infect Dis 1985;151:476–481.
  23. Gerding DN, Olson MM, Peterson LR, Teasley DG, Gebhard RL, Schwartz ML, Lee JT Jr: Clostridium difficile‐associated diarrhea and colitis in adults. Arch Intern Med 1986;146:95–100.
  24. Bender BS, Laughon BE, Gaydos C, Forman MS, Bennett R, Greenough WB, Sears SD, Bartlett JG: Is Clostridium difficile endemic in chronic‐care facilities? Lancet 1986;ii:11–13.
  25. Borriello SP, Barclay FE: Colonisation resistance to Clostridium difficile infection. Microecol Ther 1987;17:53.
  26. McFarland LV, Mulligan ME, Kwok RYY, Stamm WE: Nosocomial acquisition of Clostridium difficile infection. N Engl J Med 1989;320:204–210.
  27. Brown E, Talbot GH, Axelrod P, Provencher M, Hoegg C: Risk factors for Clostridium difficile toxin‐associated diarrhea. Infect Control Hosp Epidemiol 1990;11:283–290.

    External Resources

  28. McFarland LV, Surawicz CM, Stamm WE: Risk factors for Clostridium difficile carriage and C. difficile‐associated diarrhea in a cohort of hospitalized patients. J Infect Dis 1990;162:678–684.
  29. Tabaqchali S, O’Farrell S, Holland D, Silman R: Typing scheme for Clostridium difficile: Its application in clinical and epidemiological studies. Lancet 1990;i:935–938.
  30. Johnson S, Gerding DN, Janoff EN: Systemic and mucosal antibody responses to toxin A in patients infected with Clostridium difficile. J Infect Dis 1992;166:1287–1294.

    External Resources

  31. Struelens MJ, Maas A, Nonhoff C, Deplano A, Rost F, Serruys E, Delmee M: Control of nosocomial transmission of Clostridium difficile based on sporadic case surveillance. Am J Med 1991;91(suppl>3B):138–144.
  32. Fekety R, Shah AB: Diagnosis and treatment of Clostridium difficile colitis. JAMA 1993;269:71–75.
  33. Nath SK, Thornley JH, Kelly M, Kucera B, On SLW, Holmes B, Costas M: A sustained outbreak of Clostridium difficile in a general hospital: Persistence of a toxigenic clone in four units. Infect Control Hosp Epidemiol 1994;15:382–389.

    External Resources

  34. Pear SM, Williamson TH, Bettin KM, Gerding DN, Galgiani JN: Decrease in nosocomial Clostridium difficile‐associated diarrhea by restricting clindamycin use. Ann Intern Med 1994;120:272–277.

    External Resources

  35. Cartmill TD, Shrimpton SB, Panigrahi H, Khanna V, Borwn R, Poxton IR: Nosocomial diarrhoea due to a single strain of Clostridium difficile: A prolonged outbreak in elderly patients. Age Ageing 1992;21:245–249.
  36. Gerding DN, Johnson S, Peterson LR, Mulligan ME, Silva J Jr: Clostridium difficile‐associated diarrhea and colitis. Infect Control Hosp Epidemiol 1995;16:459–477.

    External Resources

  37. Fekety R: Guidelines for the diagnosis and management of Clostridium difficile‐associated diarrhea and colitis. Am J Gastroenterol 1997;92:739–750.
  38. McFarland LV: Clostridium difficile‐associated disease; in Surawicz CM, Owen RL (eds): Gastrointestinal and Hepatic Infections. Philadelphia, Saunders, 1995, pp 153–175.
  39. Hastie KJ, Weymont G, Lewis DA: An outbreak of Clostridium difficile associated diarrhea in urological practice: A potential consequence of excessive antibiotic prophylaxis? J R Coll Surg Edinb 1989;34:146–148.

    External Resources

  40. >tbThibault A, Miller MA, Gaese C: Risk factors for the development of Clostridium difficile‐associated diarrhea during a hospital outbreak. Infect Control Hosp Epidemiol 1991;12:345–348.
  41. Talon D, Bailly P, Delmee M, Thouverez M, Mulin B, Tehl‐Robert M, Cailleaux V, MichelBriand Y: Use of pulsed‐field gel electrophoresis for investigation of an outbreak of Clostridium difficile infection among geriatric patients. Eur J Clin Microbiol Infect Dis 1995;14:987–993.

    External Resources

  42. Testore GP, Pantosti A, Cerquetti M, Babudieri S, Panichi G, Gianfrilli PM: Evidence for cross‐infection in an outbreak of Clostridium difficile‐associated diarrhoea in a surgical unit. J Med Microbiol 1988;26:125–128.

    External Resources

  43. Brooks SE, Veal RO, Kramer M, Dore L, Schupf N, Adachi M: Reduction in the incidence of Clostridium difficile‐associated diarrhea in an acute care hospital and a skilled nursing facility following replacement of electronic thermometers with single‐use disposables. Infect Control Hosp Epidemiol 1992;13:98–103.
  44. McFarland LV: Diarrhea acquired in the hospital. Gastroenterol Clin North Am 1993;22:563–577.
  45. Cone R, Mohan K, Thouless M, Corey L: Nosocomial transmission of rotavirus infection. Pediatr Infect Dis J 1988;7:103–109.
  46. Raad II, Sherertz RJ, Russell BA, Reuman PD: Uncontrolled nosocomial rotavirus transmission during a community outbreak. Am J Infect Control 1990;18:24–28.
  47. Ford‐Jones EL, Mindorff CM, Gold R, Petric M: The incidenceof viral‐associated diarrhea after admission to a pediatric hospital. Am J Epidemiol 1990;131:711–718.
  48. Adam J, Barret A, Barret‐Bellet C, Benedetti E, Calendini A, Darchen P et al: Clinical double‐blinded controlled studies with lyophilized Ultra‐levure: A multicentered study with 25 physicians and 388 cases (in French). Gaz Méd Fr 1977;84:2072–2078.
  49. DeBarbeyrac B, Guinet R, Quentin C, Cantet P, Bebear C: Clostridium difficile and its cytotoxin in diarrhoeic stools of hospitalized patients. Toxigenic potential of the isolates. Ann Biol Clin 1989;47:67–70.

    External Resources

  50. Dutta P, Niyogi SK, Mitra U, Rasaily R, Bhattacharya MK, Chakraborty, Mitra A: Clostridium difficile in antibiotic associated pediatric diarrhea. Indian Pediatr 1994;31:121–126.

    External Resources

  51. Zehnder D, Kunzi UP, Maibach R, Zoppi R, Halter F, Neftel KA, Muller U, Galeazzi RL, Hess T, Hoigne R: Frequency of antibiotics‐associated colitis in hospitalized patients in 1974–1991 in ‘Comprehensive Hospital Drug Monitoring’, Bern/St. Gallen (in German). Schweiz Med Wochenschr 1995;125:676–683.

    External Resources

  52. Hutin Y, Casin I, Lesprit P, Welker Y, Decazes J‐M, Lagrange P, Modai J, Molina J‐M: Prevalence of and risk factors for Clostridium difficile colonization at admission to an infectious disease ward. Clin Infect Dis 1997;24:920–924.
  53. Winston DJ, Winston GH, Bruckner DA, Champlin RE: Beta‐lactam antibiotic therapy in febrile granulocytopenic patients. Ann Intern Med 1991;115:849–859.
  54. Hirschhorn LR, Trnka Y, Onderdonk A, Lee M‐LT, Platt R: Epidemiology of communityacquired Clostridium difficile‐associated diarrhea. J Infect Dis 1994;169:127–133.
  55. Van der Waaij D, Hofstra H, Wiegersma N: Effect of β‐lactam antibiotics on the resistance of the digestive tract of mice to colonization. J Infect Dis 1982;146:417–422.
  56. Bongaerts GPA, Lyerly DM: Role of bacterial metabolism and physiology in the pathogenesis of Clostridium difficile disease. Microb Pathog 1997;22:253–256.
  57. Bartlett JG: Antibiotic‐associated diarrhea. Clin Infect Dis 1992;15:573–581.

    External Resources

  58. Thompson JW, Jacobs RF: Adverse effects of newer cephalosporins. An update. Drug Safety 1993;9:132–142.

    External Resources

  59. Grossman RF: The relationship of absorption characteristics and gastrointestinal side effects of oral antimicrobial agents. Clin Ther 1991;13:189–193.
  60. Finegold SM, Ingram‐Drake L, Gee R, Reinhardt J, Edelstein MAC, MacDonald K, Wexler H: Bowel flora changes in humans receiving cefixime (CL 284, 635) or cefaclor. Antimicrob Agents Chemother 1987;31:443–446.
  61. Soyletir G, Eskiturk A, Kilic G, Korten V, Tozun N: Clostridium difficile acquisition rate and its role in nosocomial diarrhoea at a university hospital in Turkey. Eur J Epidemiol 1996;12:391–394.

    External Resources

  62. Bartlett JG: Clostridium difficile: History of its role as an enteric pathogen and the current state of knowledge about the organism. Clin Infect Dis 1994;18(suppl>4):265–272.
  63. Surawicz CM, Elmer GW, Speelman P, McFarland LV, Chinn J, Van Belle G: Prevention of antibiotic‐associated diarrhea by Saccharomyces boulardii: A prospective study. Gastroenterology 1989;96:981–988.
  64. Knobel H, Salvado M, Plass E, Orfila A, Llorach I, Diez A: Nosocomial epidemic outbreak of diarrhea from Clostridium difficile. Comparative study of diarrhea associated with the use of antibiotics (in Spanish). Med Clin (Barc) 1994;102:165–168.

    External Resources

  65. Riegler M, Sedivy R, Pothoulakis C, Hamilton G, Zacheri J, Bischof G, Cosentini E, Feil W, Schiessel R, LaMont JT, Wenzl E: Clostridium difficile toxin B is more potent than toxin A in damaging human colonic epithelium in vitro. J Clin Invest 1995;95:2004–2011.
  66. Guerrant RL, Lima AAM, Thielman NM, Steiner TS, Fonteles MC: Diarrhea, demography and cell signaling: Lessons from microbial toxins. Trans Am Clin Climatol Assoc 1997;108:149–164.
  67. Just I, Fritz G, Aktories K, Giry M, Popoff MR, Boquet P, Hegenbarth S, Von Eighel‐Streiber C: Clostridium difficile toxin B acts on the GTP‐binding protein Rho. J Biol Chem 1994;269:10706–10712.
  68. Kelly CP, Becker S, Linevsky JK, Joshi MA, O’Kean JC, Dickey BF, LaMont JT, Pothoulakis C: Neutrophil recruitment in Clostridium difficile toxin A enteritis in the rabbit. J Clin Invest 1994;93:1257–1265.

    External Resources

  69. Branka JC, Vallette C, Jarry A, Boullana C, Lamarre P, Van PN, Laboisse CL: Early functional effects of Clostridium difficile toxin A on human colonocytes. Gastroenterology 1997;112:1887–1894.
  70. Levine J, Dykoski R, Janoff EN: Candida‐associated diarrhea: A syndrome in search of credibility. Clin Infect Dis 1995;21:881–886.

    External Resources

  71. Danna PL, Urban C, Bellin E, Rahal JJ: Role of candida in pathogenesis of antibiotic‐associated diarrhoea in elderly inpatients. Lancet 1991;337:511–514.
  72. Ponnuvel KM, Rajkumar R, Thangam Menon, Sankaranarayanan VS: Role of Candida in indirect pathogenesis of antibiotic associated diarrhoea in infants. Mycopathologia 1996;135:145–147.

    External Resources

  73. Dellaiche G, LePannec MP, Choudat L, Lay C, Slama JL: Value of sigmoidoscopy with bacteriological biopsy cultures for the diagnosis of antibiotic associated and haemorrhagic colitis due to Klebsiella oxytoca. Gastroenterol Clin Biol 1997;21:784–787.
  74. Benoit R, Dorval D, Loulergue J, Bacq Y, Oliver JM, Audurier A, Metman EH: Post‐antibiotic diarrheas: Role of Klebsiella oxytoca (in French). Gastroenterol Clin Biol 1992;16:860–864.
  75. Minami J, Katayama S, Matsushita O, Sakamoto H, Okabe A: Enterotoxic activity of Klebsiella oxytoca cytotoxin in rabbit intestinal loops. Infect Immun 1994;62:172–177.

    External Resources

  76. Yokoyama T, Kondo H, Yokota T, Tokue Y, Saito D, Shimada Y, Sugihara K: Colonscopy for frank bloody stools associated with cancer chemotherapy. Jpn J Clin Oncol 1997;27:111–114.

    External Resources

  77. Ishiyama M, Watanabe C, Utsunomiya K: Colitis caused by MRSA (in Japanese). Nippon Naika Gakkai Zasshi 1992;81:1629–1634.
  78. Inamatsu T, Ooshima H, Masuda Y, Fukayama M, Adachi K, Takeshima H, Hashimoto H: Clinical spectrum of antibiotic associated enterocolitis due to methicillin resistant Staphylococcus aureus (in Japanese). Nippon Rinsho 1992;50:1087–1092.
  79. Borriello SP, Larson HE, Welch AR: Enterotoxigenic Clostridum perfringens: A possible cause of antibiotic‐associated diarrhoea. Lancet 1984;i:305.
  80. Samuel SC, Hancock P, Leigh DA: An investigation into Clostridium perfringens enterotoxin‐associated diarrhoea. J Hosp Infect 1991;18:219–230.
  81. Kato S, Ebina K, Ozawa A, Naganuma H, Nakagawa H: Antibiotic‐associated hemorrhagic colitis without Clostridium difficile toxin in children. J Pediatr 1995;126:1008–1010.

    External Resources

  82. Clausen MR, Bonnen H, Tvede M, Mortensen PR: Colonic fermentation to short‐chain fatty acids is decreased in antibiotic associated diarrhea. Gastroenterology 1991;101:1497–1504.
  83. Hove H, Tvede M, Mortensen PB: Antibioticassociated diarrhoea, Clostridium difficile, and short chain fatty acids. Scand J Gastroenterol 1996;31:688–693.

    External Resources

  84. Ruppin H, Bar‐Meir S, Soergel KH, Wood CM, Schmitt MG Jr: Absorption of short‐chain fatty acids by the colon. Gastroenterology 1980;78:1500–1507.
  85. Firmansyah A, Penn D, Lebenthal E: Isolated colonocyte metabolism of glucose, glutamine, n‐butyrate and b‐hydroxybutyrate in malnutrition. Gastroenterology 1989;97:622–629.
  86. Rao SSC, Edwards CA, Austen CJ, Bruce C, Read NW: Impaired colonic fermentation of carbohydrate after ampicillin. Gastroenterology 1988;94:928–932.

    External Resources

  87. Pothoulakis C, Castagliuolo I, LaMont JT, Jaffer A, O’Keane JC, Snider M, Leeman SE: CP96,3445, a substance P antagonist, inhibits rat intestinal responses to Clostridium difficile toxin A but not cholera toxin. Proc Natl Acad Sci USA 1994;91:947–951.

    External Resources

  88. Percy WH, Christensen J: Antibiotic depression of evoked and spontaneous responses of opossum distal colonic muscularis mucosae in vitro: A factor in antibiotic‐associated colitis? Gastroenterology 1985;88:964–970.

    External Resources

  89. Burakoff R, Zhao L, Celifarco J, Rose KL, Donovan V, Pothoulakis C, Percy WH: Effects of purified Clostridium difficile toxin A on rabbit distal colon. Gastroenterology 1995;109:348–354.
  90. Charles F, Phillips SF, Camilleri M, Thomforde GM: Rapid gastric emptying in patients with functional diarrhea. Mayo Clin Proc 1997;72:323–328.
  91. Cron RQ, Gordon PV: Reactive arthritis to Clostridium difficile in a child. West J Med 1997;166:419–421.

    External Resources

  92. Rybolt AH, Bennett RG, Laughon BE et al: Protein‐losing enteropathy associated with Clostridium difficile infection. Lancet 1989;i:1353–1355.
  93. Dansinger ML, Johnson S, Jansen PC, Opstad NL, Bettin KM, Gerding DN: Protein‐losing enteropathy is associated with Clostridium difficile diarrhea but not with asymptomatic colonization: A prospective, case‐control study. Clin Infect Dis 1996;22:932–937.

    External Resources

  94. Anand A, Bashey B, Tanveer M, Mir T, Glatt AE: Epidemiology, clinical manifestations and outcome of Clostridium difficile‐associated diarrhea. Am J Gastroenterol 1994;89:519–523.
  95. Morris JB, Zollinger RM, Stellato TA: Role of surgery in antibiotic‐induced pseudomembranous enterocolitis. Am J Surg 1990;160:535–539.
  96. Hayward RS, Wensel RH, Kibsey P: Relapsing Clostridium difficile colitis and Reiter’s syndrome. Am J Gastroenterol 1990;85:752–756.

    External Resources

  97. McFarland LV, Surawicz CM, Greenberg RN, Fekety R, Elmer GW, Moyer KA, Melcher SA, Bowen KE, Cox JL, Noorani Z, Harrington G, Rubin M, Greenwald D: A randomized placebo‐controlled trial of Saccharomyces boulardii in combination with standard antibiotics for Clostridium difficile disease. JAMA1994;271:1913–1918.
  98. Jacobs J, Rudensky B, Dresdner J, Berman A, Sonnenblick M, van Dijk Y, Yinnon AM: Comparison of four laboratory tests for diagnosis of Clostridium difficile‐associated diarrhea. Eur J Clin Microbiol Infect Dis 1996;15:561–566.

    External Resources

  99. Thorne GM, Greatorex JS: Evaluation of diarrhea, including molecular diagnostic meth‐ ods and interpretation of diagnostic tests; in Surawicz CM, Owen RL (eds): Gastrointestinal and Hepatic Infections. Philadelphia, Saunders, 1995, pp 487–518.
  100. Marx CE, Morris A, Wilson ML, Reller LB: Fecal leukocytes in stool specimens submitted for C. difficile toxin assay. Diagn Microbiol Infect Dis 1993;16:313–315.
  101. Triadafilopoulous G, Hallstone AE: Acute abdomen as the first presentation of pseudomembranous colitis. Gastroenterology 1991;101:685–691.
  102. Burke GW, Wilson ME, Mehrez IO: Absence of diarrhea in toxic megacolon complicating Clostridium difficile pseudomembranous colitis. Am J Gastroenterol 1988;83:304–307.
  103. Tedesco FJ: Antibiotic‐associated pseudomembranous colitis with negative proctosigmoidoscopic examination. Gastroenterology 1979;77:295–297.

    External Resources

  104. Gebhard RL, Gerding DN, Olson MM, Peterson LR, McClain CJ, Ansel HJ, Shaw MJ, Schwartz ML: Clinical and endoscopic findings in patients early in the course of Clostridium difficile‐associated pseudomembranous colitis. Am J Med 1985;78:45–48.

    External Resources

  105. Nathan MA, Seabold JE, Brown BP, Bushnell DL: Colonic localization of labeled leukocytes in critically ill patients. Scintigraphic detection of PMC. Clin Nucl Med 1995;20:99–106.
  106. Lipsett PA, Samantaray DK, Tam ML, Bartlett JG, Lillemoe KD: Pseudomembranous colitis: A surgical disease? Surgery 1994;116:491–496.

    External Resources

  107. Lipscomb G, Loughrey G, Thakker M, Rees W, Nicholson D: A prospective study of abdominal computerized tomography and colonoscopy in the diagnosis of colonic disease in an elderly population. Eur J Gastroenterol Hepatol 1996;8:887–891.
  108. McFarland LV: Epidemiology of infectious and iatrogenic nosocomial diarrhea in a cohort of general medicine patients. Am J Infect Control 1995;23:295–305.
  109. Fekety R, McFarland LV, Surawicz CM, Greenberg RN, Elmer GW, Mulligan ME: Recurrent Clostridium difficile diarrhea: Characteristics of and risk factors for patients enrolled in a prospective, randomized, double‐blinded trial. Clin Infect Dis 1997;24:324–333.
  110. Lima NL, Guerrant RL, Kaiser DL, Germanson T, Farr BM: A retrospective cohort study of nosocomial diarrhea as a risk factor for nosocomial infection. J Infect Dis 1990;161:948–952.

    External Resources

  111. Settle CD, Wilcox MH: Review article: Antibiotic‐induced Clostridium difficile infection. Aliment Pharmacol Ther 1996;10:835–841.

    External Resources

  112. Gerding DN: Is there a relationship between vancomycin‐resistant enterococcal infection and Clostridium difficile infection? Clin Infect Dis 1997;25(suppl>2):206–210.
  113. Bulstrode NW, Bradbury AW, Barrett S, Stansby G, Mansfield AO, Nicolaides AN, Wolfe JH: Clostridium difficile colitis after aortic surgery. Eur J Vasc Endovasc Surg 1997;14:217–220.

    External Resources

  114. Cron RQ, Gordon PV: Reactive arthritis to Clostridium difficile in a child. West J Med 1997;166:419–421.

    External Resources

  115. Lowenkron SE, Waxner J, Khullar P, Ilowite JS, Niederman MS, Fein AM: Clostridium difficile infection as a cause of severe sepsis. Intensive Care Med 1996;22:990–994.
  116. Kofsky P, Rosen L, Reed J, Tolmie M, Ufberg D: Clostridium difficile – A common and costly colitis. Dis Colon Rectum 1991;34:244–248.
  117. Jobe BA, Grasley A, Deveney KE, Deveney CW, Sheppard BC: Clostridium difficile colitis: An increasing hospital‐acquired illness. Am J Surg 1995;169:480–483.

    External Resources

  118. McCarty JM, Phillips A, Wiisanen R: Comparative safety and efficacy of clarithromycin and amoxicillin/clavulanate in the treatment of acute otitis media in children. Pediatr Infect Dis J 1993;12(suppl):122–127.
  119. Lai KK, Melvin ZS, Menard MJ, Kotilainen HR, Baker S: Clostridium difficile‐associated diarrhea: Epidemiology, risk factors, and infection control. Infect Control Hosp Epidemiol 1997;18:628–632.

    External Resources

  120. Impallomeni M, Galletly NP, Wort SJ, Starr JM, Rogers TR: Increased risk of diarrhoea caused by Clostridium difficile in elderly patients receiving cefotaxime. BMJ 1995;311:1345–1346.
  121. Trexler MF, Fraser TG, Jones MP: Fulminant pseudomembranous colitis caused by clindamycin phosphate vaginal cream. Am J Gastroenterol 1997;92:2112–2113.

    External Resources

  122. Nelson DE, Auerbach SB, Baltch AL, Desjardin E, Beck‐Sague C, Rheal C, Smith RP, Jarvis WR: Epidemic Clostridium difficile‐associated diarrhea: Role of second‐ and thirdgeneration cephalosporins. Infect Control Hosp Epidemiol 1994;15:88–94.
  123. Mitchell DK, Van R, Mason EH, Norris DM, Pickering LK: Prospective study of toxigenic Clostridium difficile in children given amoxicillin/clavulanate for otitis media. Pediatr Infect Dis J 1996;15:514–519.
  124. Yee J, Dixon CM, McLean APH, Meakins JL: Clostridium difficile disease in a department of surgery. Arch Surg 1991;126:241–246.
  125. Marts BC, Longo WE, Vernava AM III, Kennedy DJ, Daniel GL, Jones I: Patterns and prognosis of Clostridium difficile colitis. Dis Colon Rectum 1994;37:837–845.

    External Resources

  126. Keighley MRB, Alexander‐Williams J, Arabi Y, Youngs D, Burdon DW, Shinagawa N, Thompson H, Benley S, George RH: Diarrhoea and pseudomembranous colitis after gastrointestinal operations. Lancet 1978;ii:8101–8102.
  127. Guenter PA, Settle RG, Perlmutter S, Marino PL, Desimone GA, Rolandelli RH: Tube feeding‐related diarrhea in acutely ill patients. J Parent Enteral Nutr 1991;15:277–280.
  128. Heimburger D: Diarrhea with enteral feeding: Will the real cause please stand up? Am J Med 1990;88:89–90.
  129. Bleichner G, Blehaut H, Mentec H, Moyse D: Saccharomyces boulardii> prevents diarrhea in critically ill tube‐fed patients: A multicenter, randomized, double‐blind placebo‐controlled trial. Intensive Care Med 1997;23:517–523.
  130. Hassett J, Meyers S, McFarland LV, Mulligan ME: Recurrent Clostridium difficile infection in a patient with selective IgG1 deficiency treated with intravenous immune globulin and Saccharomyces boulardii>. Clin Infect Dis 1995;20(suppl):266–268.
  131. Leung DY, Kelly CP, Boguniewicz M, Pothoulakis C, LaMont JT, Flores A: Treatment with intravenously administered gamma globulin of chronic relapsing colitis induced by Clostridium difficile toxin. J Pediatr 1991;118:633–637.

    External Resources

  132. Mulligan ME, Miller SD, McFarland LV, Fung HC, Kwok RYY: Elevated levels of serum immunoglobulins in asymptomatic carriers of Clostridium difficile. Clin Infect Dis 1993;16 (suppl 4):239–244.
  133. 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;88:891–897.
  134. Lu SS, Schwartz JM, Simon DM, Brandt LJ: Clostridium difficile‐associated diarrhea in patients with HIV positivity and AIDS: A prospective controlled study. Am J Gastroenterol 1994;89:1226–1229.
  135. Teasley DG, Gerding DN, Olson MM, Peterson LR, Gebhard RL, Schwartz MJ, Lee JT Jr: Prospective randomised trial of metronidazole versus vancomycin for Clostridium difficile‐associated diarrhoea and colitis. Lancet 1983;ii:1043–1046.
  136. Wenisch C, Parschalk B, Hasenhundl M, Hirschel AM, Graninger W: Comparison of vancomycin teicoplanin, metronidazole, and fusidic acid for the treatment of Clostridium difficile‐associated diarrhea. Clin Infect Dis 1996;22:813–818.
  137. Wilcox MH, Howe R: Diarrhoea caused by Clostridium difficile: Response time for treatment with metronidazole and vancomycin. J Antimicrob Chemother 1995;36:673–679.

    External Resources

  138. Elmer GW, Surawicz CM, McFarland LV: Biotherapeutic agents: A neglected modality for the treatment and prevention of selected intestinal and vaginal infections. JAMA 1996;275:870–876.
  139. McFarland LV, Elmer GW: Pharmaceutical probiotics for the treatment of anaerobic and other infections. Anaerobe 1997;3:73–78.
  140. >tb>dc10>Tankanow RM, Ross MB, Ertel IJ, Dickinson DG, McCormick LS, Garfinkel JF: A double‐ blind placebo‐controlled study of the efficacy of Lactinex in the prophylaxis of amoxicillininduced diarrhea. DICP 1990;24:382–384.
  141. Siitonen S, Vapaatalo H, Salminen S, Gordin A, Saxelin M, Wikberg R, Kirkkola A: Effect of Lactobacillus GG yoghurt in prevention of antibiotic associated diarrhoea. Ann Med 1990;22:57–59.
  142. Gronlund MM, Lehtonen OP, Kero P, Saxelin M, Salminen S: Lactobacillus GG supplemen‐ tation does not reduce faecal colonization of Klebsiella oxytoca in preterm infants (letter). Acta Paediatr 1997;86:440–441.

    External Resources

  143. Buts JP, Corthier G and Delmee M: Saccharomyces boulardii and C. difficile‐associated enteropathies in infants. J Pediatr Gastroenterol Nutr 1993;16:419–425.
  144. Biller JA, Katz AJ, Flores AF, Buie TM, Gorbach SL: Treatment of recurrent Clostridium difficile colitis with Lactobacillus GG. J Pediatr Gastroenterol Nutr 1995;21:224–226.
  145. Gorbach SL, Chang T‐W, Goldin B: Successful treatment of relapsing Clostridium difficile colitis with Lactobacillus GG (letter). Lancet 1987;ii:1519.
  146. Salcedo J, Keates S, Pothoulakis C, Warny M, Castagliuolo I, LaMont JT, Kelly CP: Intravenous immunoglobulin therapy for severe Clostridium difficile colitis. Gut 1997;41:366–370.
  147. Gaskins HR, Mackie R, May T, Garleb KA: Dietary fructo‐oligosaccharide modulates large intestinal inflammatory responses to Clostridium difficile in antibiotic‐compromised mice. Microb Ecol Health Dis 1996;9:157–166.
  148. Gonzales R, Steiner JF, Sande MA: Antibiotic prescribing for adults with colds, upper respiratory tract infection, and bronchitis in ambulatory care physicians. JAMA 1997;278:901–904.
  149. Guillemot D, Maison P, Carbon C, Balkau B, Vauzelle‐Kervroedan F, Sermet C, Bouvenot G, Eschwege: Trends in antimicrobial drug use in the community – France, 1981–1992. J Infect Dis 1998;117:492–497.
  150. Johnson S, Gerding DN, Olson MM, Weiler MD, Hughes RA, Clabots CR, Peterson LR: Prospective, controlled study of vinyl glove use to interrupt Clostridium difficile nosocomial transmission. Am J Med 1990;80:137–140.
  151. McFarland LV, Stamm WE: Nosocomial Clostridium difficile infections (letter). N Engl J Med 1989;321:190.
  152. Thamlikitkul V, Danpakdi K, Chokloikaew S: Incidence of diarrhea and Clostridium difficile toxin in stools from hospitalized patients receiving clindamycin, beta‐lactams, or nonantibiotic medications. J Clin Gastroenterol 1996;22:161–163.
  153. Fekety R, Silva J, Kauffman C, Buggy B, Deery HG: Treatment of antibiotic‐associated Clostridium difficile colitis with oral vancomycin: comparison of two dosage regimens. Am J Med 1989;86:15–19.
  154. De Lalla F, Nicolin R, Rinaldi E, Scarpellini P, Rigoli R, Manfrin V, Tramarin A: Prospective study of oral teicoplanin versus oral vancomycin for therapy of pseudomembranous colitis and Clostridium difficile‐associated diarrhea. Antimicrob Agents Chemother 1992;36:2192–2196.

    External Resources

  155. Wunderlich PF, Braun L, Fumagalli I, D’Apuzzo V, Heim F, Karly M, Lodi R, Politta G, Vonbank F, Zeltner L: Double‐blind report on the efficacy of lactic acid‐producing Enterococcus SF68 in the prevention of antibiotic‐associated diarrhoea and in the treatment of acute diarrhoea. J Int Med Res 1989;17:333–338.