Chapter 53 : Clostridium*

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Zoom in

Clostridium*, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555817381/9781555817381.ch53-1.gif /docserver/preview/fulltext/10.1128/9781555817381/9781555817381.ch53-2.gif


Severe infections caused by species have been described in the medical literature for centuries—largely because of their fulminant nature, distinctive clinical presentations, and complex management issues. The pathogenesis of these infections is attributable to the production of potent extracellular toxins, many of which are also diagnostically important. This review highlights the microbiological, epidemiological, and clinical characteristics of these infections, with emphasis on both classical and state-of-the-art identification methods and typing systems. The rapid and severe course of these infections mandates clear communication between the clinical microbiology laboratory and the health care provider in order to institute early interventions and appropriate antimicrobial treatment. Current antimicrobial susceptibilities among the clostridia are also presented, as are the evaluation, interpretation, and reporting of clinical microbiology laboratory results. Application of this integrated body of knowledge can reduce the incidence, lessen the severity, and improve outcomes of these devastating clostridial infections.

Citation: Stevens D, Bryant A, Carroll K. 2015. Clostridium*, p 940-966. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch53
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of FIGURE 1

(top row, left) Gram stain of . Note the thin, Gram stain-variable bacilli with distinct spores. Reprinted with permission from . doi:10.1128/9781555817381.ch53.f1

Citation: Stevens D, Bryant A, Carroll K. 2015. Clostridium*, p 940-966. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch53
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 2

(top row, right) Lecithinase reaction on egg yolk agar. Note the opacity of the agar surrounding colonies due to precipitation of complex fats. Reprinted with permission from . doi:10.1128/9781555817381.ch53.f2

Citation: Stevens D, Bryant A, Carroll K. 2015. Clostridium*, p 940-966. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch53
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 3

(middle row, left) on CCFA. Note the yellow, ground-glass appearance of colonies. Reprinted with permission from . doi:10.1128/9781555817381.ch53.f3

Citation: Stevens D, Bryant A, Carroll K. 2015. Clostridium*, p 940-966. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch53
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 4

(middle row, right) on blood agar showing a double zone of beta-hemolysis. Reprinted with permission from . doi:10.1128/9781555817381.ch53.f4

Citation: Stevens D, Bryant A, Carroll K. 2015. Clostridium*, p 940-966. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch53
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 5

(bottom row, left) on blood agar after 12 h of incubation. Note the spreading colonies. Courtesy of E. J. Baron. doi:10.1128/9781555817381.ch53.f5

Citation: Stevens D, Bryant A, Carroll K. 2015. Clostridium*, p 940-966. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch53
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 6

(bottom row, right) Gram stain of . Note the long, filamentous bacilli with rare spores. Courtesy of E. J. Baron. doi:10.1128/9781555817381.ch53.f6

Citation: Stevens D, Bryant A, Carroll K. 2015. Clostridium*, p 940-966. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch53
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Collins MD,, Lawson PA,, Willems A,, Cordoba JJ,, Fernandez-Garayzabal J,, Garcia P,, Cai J,, Hippe H,, Farrow JA. 1994. The phylogeny of the genus Clostridium: proposal of five new genera and eleven new species combinations. Int J Syst Bacteriol 44: 812826.
2. Johnson JL,, Francis BS. 1975. Taxonomy of the clostridia: ribosomal ribonucleic acid homologies among the species. J Gen Microbiol 88: 229244.
3. Stackebrandt E,, Rainey FA,. 1997. Phylogenic relationships, p 319. In Rood JI,, McClane BA,, Songer JG,, Titball RW ( ed), The Clostridia: Molecular Biology and Pathogenesis. Academic Press, New York, NY.
4. Steer T,, Collins MD,, Gibson GR,, Hippe H,, Lawson PA. 2001. Clostridium hathewayi sp. nov., from human faeces. Syst Appl Microbiol 24: 353357.
5. Song Y,, Liu C,, Molitoris DR,, Tomzynski TJ,, Lawson PA,, Collins MD,, Finegold SM. 2003. Clostridium bolteae sp. nov., isolated from human sources. Syst Appl Microbiol 26: 8489.
6. Finegold SM,, Song Y,, Liu C,, Hecht DW,, Summanen P,, Könönen E,, Allen SD. 2005. Clostridium clostridioforme: a mixture of three clinically important species. Eur J Clin Microbiol Infect Dis 24: 319324.
7. Song YL,, Liu CX,, McTeague M,, Summanen P,, Finegold SM. 2004. Clostridium bartlettii sp. nov., isolated from human faeces. Anaerobe 10: 179184.
8. Alfa MJ,, Robson D,, Davi M,, Bernard K,, Van Caeseele P,, Harding GK. 2002. An outbreak of necrotizing enterocolitis associated with a novel Clostridium species in a neonatal intensive care unit. Clin Infect Dis 35: S101S105.
9. Lawson PA,, Song Y,, Liu C,, Molitoris DR,, Vaisanen ML,, Collins MD,, Finegold SM. 2004. Anaerotruncus colihominis gen. nov., sp. nov., from human faeces. Int J Syst Evol Microbiol 54: 413417.
10. Lau SK,, Woo PC,, Woo GK,, Fung AM,, Ngan AH,, Song Y,, Liu C,, Summanen P,, Finegold SM,, Yuen K. 2006. Bacteraemia caused by Anaerotruncus colihominis and emended description of the species. J Clin Pathol 59: 748752.
11. Carlier JP,, Bedora-Faure M,, K’ouas G,, Alauzet C,, Mory F. 2009. Proposal to unify Clostridium orbiscindens Winter et al. 1991 and Eubacterium plautii (Séguin 1928) Hofstad and Aasjord 1982, with description of Flavonifractor plautii gen. nov., comb. nov., and reassignment of Bacteroides capillosus to Pseudoflavonifractor capillosus gen. nov., comb. nov. Int J Syst Evol Microbiol 60: 585590.
12. Holdeman LV,, Cato EP,, Moore WEC. 1977. Anaerobe Laboratory Manual. Virginia Polytechnic Institute and State University, Blacksburg, VA.
13. Stevens DL,, Musher DM,, Watson DA,, Eddy H,, Hamill RJ,, Gyorkey F,, Rosen H,, Mader J. 1990. Spontaneous, nontraumatic gangrene due to Clostridium septicum. Rev Infect Dis 12: 286296.
14. Smith LDS,. 1975. Clostridium, p 109114. In Smith LDS ( ed), The Pathogenic Anaerobic Bacteria. Charles C Thomas, Springfield, IL.
15. Bruggemann H,, Gottschalk G. 2004. Insights in metabolism and toxin production from the complete genome sequence of Clostridium tetani. Anaerobe 10: 5368.
16. Shimizu T,, Ohtani K,, Hirakawa H,, Ohshima K,, Yamashita A,, Shiba T,, Ogasawara N,, Hattori M,, Kuhara S,, Hayashi H. 2002. Complete genome sequence of Clostridium perfringens, an anaerobic flesh-eater. Proc Natl Acad Sci U S A 99: 9961001.
17. Barth H,, Aktories K,, Popoff MR,, Stiles BG. 2004. Binary bacterial toxins: biochemistry, biology, and applications of common Clostridium and Bacillus proteins. Microbiol Mol Biol Rev 68: 373402.
18. Smedley JG III,, Fisher DJ,, Sayeed S,, Chakrabarti G,, McClane BA. 2004. The enteric toxins of Clostridium perfringens. Rev Physiol Biochem Pharmacol 152: 183204.
19. Smith LDS,, Williams BL. 1984. The Pathogenic Anaerobic Bacteria. Charles C Thomas, Springfield, IL.
20. Mulligan ME,, Peterson LR,, Kwok RY,, Clabots CR,, Gerding DN. 1988. Immunoblots and plasmid fingerprints compared with serotyping and polyacrylamide gel electrophoresis for typing Clostridium difficile. J Clin Microbiol 26: 4146.
21. Leal J,, Gregson DB,, Ross T,, Church DL,, Laupland KB. 2008. Epidemiology of Clostridium species bacteremia in Calgary, Canada, 2000–2006. J Infect 57: 198203.
22. Simmon KE,, Mirrett S,, Reller LB,, Petti CA. 2008. Genotypic diversity of anaerobic isolates from bloodstream infections. J Clin Microbiol 46: 15961601.
23. Lassmann B,, Gustafson DR,, Wood CM,, Rosenblatt JE. 2007. Reemergence of anaerobic bacteremia. Clin Infect Dis 44: 895900.
24. Smith-Slatas CL,, Bourque M,, Salazar JC. 2006. Clostridium septicum infections in children: a case report and review of the literature. Pediatrics 117: e796e805.
25. Kudsk KA. 1992. Occult gastrointestinal malignancies producing metastatic Clostridium septicum infections in diabetic patients. Surgery 112: 765770.
26. Stevens DL,, Aldape MJ,, Bryant AE. 2012. Life-threatening clostridial infections. Anaerobe 18: 254259.
27. Goon PK,, O’Brien M,, Titley OG. 2005. Spontaneous Clostridium septicum septic arthritis of the shoulder and gas gangrene. a case report. J Bone Joint Surg Am 87: 874877.
28. Chen YM,, Lee HC,, Chang CM,, Chuang YC,, Ko WC. 2001. Clostridium bacteremia: emphasis on the poor prognosis in cirrhotic patients. J Microbiol Immunol Infect 34: 113118.
29. Leegaard TM,, Sandven P,, Gaustad P. 2005. Clostridium tertium: 3 case reports. Scand J Infect Dis 37: 230232.
30. Cohen AL,, Bhatnagar J,, Reagan S,, Zane SB,, D’Angeli MA,, Fischer M,, Killgore G,, Kwan-Gett TS,, Blossom DB,, Shieh WJ,, Guarner J,, Jernigan J,, Duchin JS,, Zaki SR,, McDonald LC. 2007. Toxic shock associated with Clostridium sordellii and Clostridium perfringens after medical and spontaneous abortion. Obstet Gynecol 110: 10271033.
31. Aldape MJ,, Bryant AE,, Stevens DL. 2006. Clostridium sordellii infection: epidemiology, clinical findings, and current perspectives on diagnosis and treatment. Clin Infect Dis 43: 14361446.
32. Woo PC,, Lau SK,, Teng JL,, Tse H,, Yuen KY. 2008. Then and now: use of 16S rDNA gene sequencing for bacterial identification and discovery of novel bacteria in clinical microbiology laboratories. Clin Microbiol Infect 14: 908934.
33. Wilson JR,, Limaye AP. 2004. Risk factors for mortality in patients with anaerobic bacteremia. Eur J Clin Microbiol Infect Dis 23: 310316.
34. Woo PC,, Lau SK,, Woo GK,, Fung AM,, Yiu VP,, Yuen KY. 2004. Bacteremia due to Clostridium hathewayi in a patient with acute appendicitis. J Clin Microbiol 42: 59475949.
35. Borriello SP,, Barclay FE,, Welch AR,, Stringer MF,, Watson GN,, Williams RK,, Seal DV,, Sullens K. 1985. Epidemiology of diarrhoea caused by enterotoxigenic Clostridium perfringens. J Med Microbiol 20: 363372.
36. Olsen SJ,, MacKinnon LC,, Goulding JS,, Bean NH,, Slutsker L. 2000. Surveillance for foodborne-disease outbreaks—United States, 1993-1997. MMWR CDC Surveill Summ 49: 162.
37. Johansson A,, Aspan A,, Bagge E,, Båverud V,, Engström BE,, Johansson KE. 2006. Genetic diversity of Clostridium perfringens type A isolates from animals, food poisoning outbreaks and sludge. BMC Microbiol 6: 47. 10.1186/1471-2180-6-47.
38. Miyamoto K,, Li J,, McClane BA. 2012. Enterotoxigenic Clostridium perfringens: detection and identification. Microbes Environ 27: 343349.
39. Bos J,, Smithee L,, McClane B,, Distefano RF,, Uzal F,, Songer JG,, Mallonee S,, Crutcher JM. 2005. Fatal necrotizing colitis following a foodborne outbreak of enterotoxigenic Clostridium perfringens type A infection. Clin Infect Dis 40: e78e83.
40. Brynestad S,, Sarker MR,, McClane BA,, Granum PE,, Rood JI. 2001. Enterotoxin plasmid from Clostridium perfringens is conjugative. Infect Immun 69: 34833487.
41. Fisher DJ,, Miyamoto K,, Harrison B,, Akimoto S,, Sarker MR,, McClane BA. 2005. Association of beta2 toxin production with Clostridium perfringens type A human gastrointestinal disease isolates carrying a plasmid enterotoxin gene. Mol Microbiol 56: 747762.
42. Songer JG,. 1997. Molecular and immunological methods for the diagnosis of clostridial diseases, p 491503. In Rood JI,, McClane BA,, Songer JG,, Titball RW ( ed), The Clostridia: Molecular Biology and Pathogenesis. Academic Press, New York, NY.
43. Sayeed S,, Uzal FA,, Fisher DJ,, Saputo J,, Vidal JE,, Chen Y,, Gupta P,, Rood JI,, McClane BA. 2008. Beta toxin is essential for the intestinal virulence of Clostridium perfringens type C disease isolate CN3685 in a rabbit ileal loop model. Mol Microbiol 67: 1530.
44. Lawrence GW,, Lehmann D,, Anian G,, Coakley CA,, Saleu G,, Barker MJ,, Davis MW. 1990. Impact of active immunisation against enteritis necroticans in Papua New Guinea. Lancet 336: 11651167.
45. Petrillo TM,, Beck-Sagué CM,, Songer JG,, Abramowsky C,, Fortenberry JD,, Meacham L,, Dean AG,, Lee H,, Bueschel DM,, Nesheim SR. 2000. Enteritis necroticans (pigbel) in a diabetic child. N Engl J Med 342: 12501253.
46. Matsuda T,, Okada Y,, Inagi E,, Tanabe Y,, Shimizu Y,, Nagashima K,, Sakurai J,, Nagahama M,, Tanaka S. 2007. Enteritis necroticans ‘pigbel’ in a Japanese diabetic adult. Pathol Int 57: 622626.
47. Li DY,, Scheimann AO,, Songer JG,, Person RE,, Horwitz M,, Resar L,, Schwarz KB. 2004. Enteritis necroticans with recurrent enterocutaneous fistulae caused by Clostridium perfringens in a child with cyclic neutropenia. J Pediatr Gastroenterol Nutr 38: 213215.
48. Sobel J,, Mixter CG,, Kolhe P,, Gupta A,, Guarner J,, Zaki S,, Hoffman NA,, Songer JG,, Fremont-Smith M,, Fischer M,, Killgore G,, Britz PH,, MacDonald C. 2005. Necrotizing enterocolitis associated with Clostridium perfringens type A in previously healthy North American adults. J Am Coll Surg 201: 4856.
49. Obladen M. 2009. Necrotizing enterocolitis—150 years of fruitless search for the cause. Neonatology 96: 203210.
50. Kliegman RM,, Fanaroff AA. 1984. Necrotizing enterocolitis. N Engl J Med 310: 10931103.
51. Kyne L,, Hamel MB,, Polavaram R,, Kelly CP. 2002. Health care costs and mortality associated with nosocomial diarrhea due to Clostridium difficile. Clin Infect Dis 34: 346353.
52. Sunenshine RH,, McDonald LC. 2006. Clostridium difficile-associated disease: new challenges from an established pathogen. Cleve Clin J Med 73: 187197.
53. McFarland LV,, Mulligan ME,, Kwok RY,, Stamm WE. 1989. Nosocomial acquisition of Clostridium difficile infection. N Engl J Med 320: 204210.
54. Braun V,, Hundsberger T,, Leukel P,, Sauerborn M,, von Eichel-Streiber C. 1996. Definition of the single integration site of the pathogenicity locus in Clostridium difficile. Gene 181: 2938.
55. Reineke J,, Tenzer S,, Rupnik M,, Koschinski A,, Hasselmayer O,, Schrattenholz A,, Schild H,, von Eichel-Streiber C. 2007. Autocatalytic cleavage of Clostridium difficile toxin B. Nature 446: 415419.
56. Matamouros S,, England P,, Dupuy B. 2007. Clostridium difficile toxin expression is inhibited by the novel regulator TcdC. Mol Microbiol 64: 12741288.
57. Johnson S,, Kent SA,, O’Leary KJ,, Merrigan MM,, Sambol SP,, Peterson LR,, Gerding DN. 2001. Fatal pseudomembranous colitis associated with a variant Clostridium difficile strain not detected by toxin A immunoassay. Ann Intern Med 135: 434438.
58. Lyerly DM,, Neville LM,, Evans DT,, Fill J,, Allen S,, Greene W,, Sautter R,, Hnatuck P,, Torpey DJ,, Schwalbe R. 1998. Multicenter evaluation of the Clostridium difficile TOX A/B TEST. J Clin Microbiol 36: 184190.
59. Lyras D,, O’Connor JR,, Howarth PM,, Sambol SP,, Carter GP,, Phumoonna T,, Poon R,, Adams V,, Vedantam G,, Johnson S,, Gerding DN,, Rood JI. 2009. Toxin B is essential for virulence of Clostridium difficile. Nature 458: 11761179.
60. Peniche AG,, Savidge TC,, Dann SM. 2013. Recent insights into Clostridium difficile pathogenesis. Curr Opin Infect Dis 26: 447453.
61. von Eichel-Streiber C,, Boquet P,, Sauerborn M,, Thelestam M. 1996. Large clostridial cytotoxins—a family of glycosyltransferases modifying small GTP-binding proteins. Trends Microbiol 4: 375382.
62. Just I,, Selzer J,, Wilm M,, von Eichel-Streiber C,, Mann M,, Aktories K. 1995. Glucosylation of Rho proteins by Clostridium difficile toxin B. Nature 375: 500503.
63. Hundsberger T,, Braun V,, Weidmann M,, Leukel P,, Sauerborn M,, von Eichel-Streiber C. 1997. Transcription analysis of the genes tcdA-E of the pathogenicity locus of Clostridium difficile. Eur J Biochem 244: 735742.
64. Warny M,, Pepin J,, Fang A,, Killgore G,, Thompson A,, Brazier J,, Frost E,, McDonald LC. 2005. Toxin production by an emerging strain of Clostridium difficile associated with outbreaks of severe disease in North America and Europe. Lancet 366: 10791084.
65. Loo VG,, Poirier L,, Miller MA,, Oughton M,, Libman MD,, Michaud S,, Bourgault AM,, Nguyen T,, Frenette C,, Kelly M,, Vibien A,, Brassard P,, Fenn S,, Dewar K,, Hudson TJ,, Horn R,, René P,, Monczak Y,, Dascal A. 2005. A predominantly clonal multi-institutional outbreak of Clostridium difficile-associated diarrhea with high morbidity and mortality. N Engl J Med 353: 24422449.
66. McDonald LC,, Killgore GE,, Thompson A,, Owens RC Jr,, Kazakova SV,, Sambol SP,, Johnson S,, Gerding DN. 2005. An epidemic, toxin gene-variant strain of Clostridium difficile. N Engl J Med 353: 24332441.
67. Bartlett JG,, Gerding DN. 2008. Clinical recognition and diagnosis of Clostridium difficile infection. Clin Infect Dis 46( Suppl 1): S12S18.
68. Valiquette L,, Cossette B,, Garant MP,, Diab H,, Pépin J. 2007. Impact of a reduction in the use of high-risk antibiotics on the course of an epidemic of Clostridium difficile-associated disease caused by the hypervirulent NAP1/027 strain. Clin Infect Dis 45( Suppl 2): S112S121.
69. Kuijper EJ,, Coignard B,, Brazier JS,, Suetens C,, Drudy D,, Wiuff C,, Pituch H,, Reichert P,, Schneider F,, Widmer AF,, Olsen KE,, Allerberger F,, Notermans DW,, Barbut F,, Delmée M,, Wilcox M,, Pearson A,, Patel BC,, Brown DJ,, Frei R,, Akerlund T,, Poxton IR,, Tüll P. 2007. Update of Clostridium difficile-associated disease due to PCR ribotype 027 in Europe. Euro Surveill 12: E1E2.
70. Spigaglia P,, Barbanti F,, Mastrantonio P,, Brazier JS,, Barbut F,, Delmée M,, Kuijper E,, Poxton IR,, European Study Group on Clostridium difficile (ESGCD). 2008. Fluoroquinolone resistance in Clostridium difficile isolates from a prospective study of C. difficile infections in Europe. J Med Microbiol 57: 784789.
71. Johnson S. 2009. Recurrent Clostridium difficile infection: a review of risk factors, treatments, and outcomes. J Infect 58: 403410.
72. Martin J,, Mawer D,, Wilcox MH. 2013. Clostridium difficile: biological therapies. Curr Opin Infect Dis 26: 454460.
73. Ritter AS,, Petri WA Jr. 2013. New developments in chemotherapeutic options for Clostridium difficile colitis. Curr Opin Infect Dis 26: 461470.
74. Gerding DN,, Muto CA,, Owens RC Jr. 2008. Treatment of Clostridium difficile infection. Clin Infect.Dis. 46 Suppl 1: S32S42.
75. Eyre DW,, Cule ML,, Wilson DJ,, Griffiths D,, Vaughan A,, O’Connor L,, Ip CL,, Golubchik T,, Batty EM,, Finney JM,, Wyllie DH,, Didelot X,, Piazza P,, Bowden R,, Dingle KE,, Harding RM,, Crook DW,, Wilcox MH,, Peto TE,, Walker AS. 2013. Diverse sources of C. difficile infection identified on whole-genome sequencing. N Engl J Med 369: 11951205.
76. Curry SR,, Muto CA,, Schlackman JL,, Pasculle AW,, Shutt KA,, Marsh JW,, Harrison LH. 2013. Use of multilocus variable number of tandem repeats analysis genotyping to determine the role of asymptomatic carriers in Clostridium difficile transmission. Clin Infect Dis 57: 10941102.
77. Bartlett JG. 2002. Clinical practice. Antibiotic-associated diarrhea. N Engl J Med 346: 334339.
78. Wilkins TD,, Lyerly DM. 2003. Clostridium difficile testing: after 20 years, still challenging. J Clin Microbiol 41: 531534.
79. Abrahao C,, Carman RJ,, Hahn H,, Liesenfeld O. 2001. Similar frequency of detection of Clostridium perfringens enterotoxin and Clostridium difficile toxins in patients with antibiotic-associated diarrhea. Eur J Clin Microbiol Infect Dis 20: 676677.
80. Asha NJ,, Tompkins D,, Wilcox MH. 2006. Comparative analysis of prevalence, risk factors, and molecular epidemiology of antibiotic-associated diarrhea due to Clostridium difficile, Clostridium perfringens, and Staphylococcus aureus. J Clin Microbiol 44: 27852791.
81. Stevens DL,, Bisno AL,, Chambers HF,, Everett ED,, Dellinger P,, Goldstein EJ,, Gorbach SL,, Hirschmann JV,, Kaplan EL,, Montoya JG,, Wade JC,, Infectious Diseases Society of America. 2005. Practice guidelines for the diagnosis and management of skin and soft-tissue infections. Clin Infect Dis 41: 13731406.
82. Centers for Disease Control and Prevention (CDC). 2000. Update: Clostridium novyi and unexplained illness among injecting-drug users—Scotland, Ireland, and England, April–June 2000. MMWR Morb Mortal Wkly Rep 49: 543545.
83. Centers for Disease Control and Prevention (CDC). 2001. Soft tissue infections among injection drug users—San Francisco, California, 1996–2000. MMWR Morb Mortal Wkly Rep 50: 381384.
84. Bangsberg DR,, Rosen JI,, Aragón T,, Campbell A,, Weir L,, Perdreau-Remington F. 2002. Clostridial myonecrosis cluster among injection drug users: a molecular epidemiology investigation. Arch Intern Med 162: 517522.
85. Brazier JS,, Gal M,, Hall V,, Morris T. 2004. Outbreak of Clostridium histolyticum infections in injecting drug users in England and Scotland. Euro Surveill 9: 1516.
86. Kimura AC,, Higa JI,, Levin RM,, Simpson G,, Vargas Y,, Vugia DJ. 2004. Outbreak of necrotizing fasciitis due to Clostridium sordellii among black-tar heroin users. Clin Infect Dis 38: e87e91.
87. MacLennan JD. 1962. The histotoxic clostridial infections of man. Bacteriol Rev 26: 177276.
88. Bryant AE,, Chen RY,, Nagata Y,, Wang Y,, Lee CH,, Finegold S,, Guth PH,, Stevens DL. 2000. Clostridial gas gangrene. I. Cellular and molecular mechanisms of microvascular dysfunction induced by exotoxins of Clostridium perfringens. J Infect Dis 182: 799807.
89. Bryant AE,, Chen RY,, Nagata Y,, Wang Y,, Lee CH,, Finegold S,, Guth PH,, Stevens DL. 2000. Clostridial gas gangrene. II. Phospholipase C–induced activation of platelet gpIIbIIIa mediates vascular occlusion and myonecrosis in Clostridium perfringens gas gangrene. J Infect Dis 182: 808815.
90. Johnson S,, Driks MR,, Tweten RK,, Ballard J,, Stevens DL,, Anderson DJ,, Janoff EN. 1994. Clinical courses of seven survivors of Clostridium septicum infection and their immunologic responses to α toxin. Clin Infect Dis 19: 761764.
91. Assadian O,, Assadian A,, Senekowitsch C,, Makristathis A,, Hagmüller G. 2004. Gas gangrene due to Clostridium perfringens in two injecting drug users in Vienna, Austria. Wien Klin Wochenschr 116: 264267.
92. Zink JM,, Singh-Parikshak R,, Sugar A,, Johnson MW. 2004. Clostridium sordellii endophthalmitis after suture removal from a corneal transplant. Cornea 23: 522523.
93. Hsu HY,, Lee SF,, Hartstein ME,, Harocopos GJ. 2008. Clostridium perfringens keratitis leading to blinding panophthalmitis. Cornea 27: 12001203.
94. Stevens DL,, Bryant AE,. 2005. Clostridial gas gangrene: clinical correlations, microbial virulence factors, and molecular mechanisms of pathogenesis, p 313335. In Proft T ( ed), Microbial Toxins: Molecular and Cellular Biology. Horizon Bioscience, Norfolk, United Kingdom.
95. Alouf JE,, Popoff MR. 2006. The Comprehensive Sourcebook of Bacterial Protein Toxins. Elsevier, New York, NY.
96. Williamson ED,, Titball RW. 1993. A genetically engineered vaccine against the alpha-toxin of Clostridium perfringens protects mice against experimental gas gangrene. Vaccine 11: 12531258.
97. Sugahara T,, Takahashi T,, Yamaya S,, Ohsaka A. 1976. In vitro aggregation of platelets induced by alpha-toxin (phospholipase C) of Clostridium perfringens. Jpn J Med Sci Biol 29: 255263.
98. Shepard LA,, Heuck AP,, Hamman BD,, Rossjohn J,, Parker MW,, Ryan KR,, Johnson AE,, Tweten RK. 1998. Identification of a membrane-spanning domain of the thiol-activated pore-forming toxin Clostridium perfringens perfringolysin O: an α-helical to β-sheet transition identified by fluorescence spectroscopy. Biochemistry 37: 1456314574.
99. Dowd KJ,, Tweten RK. 2012. The cholesterol-dependent cytolysin signature motif: a critical element in the allosteric pathway that couples membrane binding to pore assembly. PLoS Pathog 8: e1002787. 10.1371/journal .ppat.1002787.
100. Bryant AE,, Bergstrom R,, Zimmerman GA,, Salyer JL,, Hill HR,, Tweten RK,, Sato H,, Stevens DL. 1993. Clostridium perfringens invasiveness is enhanced by effects of theta toxin upon PMNL structure and function: the roles of leukocytotoxicity and expression of CD11/CD18 adherence glycoprotein. FEMS Immunol Med Microbiol 7: 321336.
101. Stevens DL,, Tweten RK,, Awad MM,, Rood JI,, Bryant AE. 1997. Clostridial gas gangrene: evidence that α and θ toxins differentially modulate the immune response and induce acute tissue necrosis. J Infect Dis 176: 189195.
102. Ballard J,, Bryant A,, Stevens D,, Tweten RK. 1992. Purification and characterization of the lethal toxin (alpha-toxin) of Clostridium septicum. Infect Immun 60: 784790.
103. Aldape MJ,, Bryant AE,, Ma Y,, Stevens DL. 2007. The leukemoid reaction in Clostridium sordellii infection: neuraminidase induction of promyelocytic cell proliferation. J Infect Dis 195: 18381845.
104. Arnon SS,, Schechter R,, Inglesby TV,, Henderson DA,, Bartlett JG,, Ascher MS,, Eitzen E,, Fine AD,, Hauer J,, Layton M,, Lillibridge S,, Osterholm MT,, O’Toole T,, Parker G,, Perl TM,, Russell PK,, Swerdlow DL,, Tonat K,, Working Group on Civilian Biodefense. 2001. Botulinum toxin as a biological weapon: medical and public health management. JAMA 285: 10591070.
105. Lacy DB,, Stevens RC. 1999. Sequence homology and structural analysis of the clostridial neurotoxins. J Mol Biol 291: 10911104.
106. Macdonald TE,, Helma CH,, Ticknor LO,, Jackson PJ,, Okinaka RT,, Smith LA,, Smith TJ,, Hill KK. 2008. Differentiation of Clostridium botulinum serotype A strains by multiple-locus variable-number tandem-repeat analysis. Appl Environ Microbiol 74: 875882.
107. Barash JR,, Arnon SS. 2014. A novel strain of Clostridium botulinum that produces type B and type H botulinum toxins. J Infect Dis 209: 183191.
108. Hatheway CI,. 2009. Botulism, p 111133. In Balows A,, Hausler WJ, Jr,, Ohashi M,, Turano A ( ed), Laboratory Diagnosis of Infectious Diseases: Principles and Practice. Springer-Verlag, New York, NY.
109. Fenicia L,, Da Dalt L,, Anniballi F,, Franciosa G,, Zanconato S,, Aureli P. 2002. A case if infant botulism due to neurotoxigenic Clostridium butyricum type E associated with Clostridium difficile colitis. Eur J Clin Microbiol Infect Dis 21: 736738.
110. Barash JR,, Tang TW,, Arnon SS. 2005. First case of infant botulism caused by Clostridium baratii type F in California. J Clin Microbiol 43: 42804282.
111. Paisley JW,, Lauer BA,, Arnon SS. 1995. A second case of infant botulism type F caused by Clostridium baratii. Pediatr Infect Dis J 14: 912914.
112. Hall JD,, McCroskey LM,, Pincomb BJ,, Hatheway CL. 1985. Isolation of an organism resembling Clostridium baratii which produces type F botulinal toxin from an infant with botulism. J Clin Microbiol 21: 654655.
113. Chaudhry R,, Dhawan B,, Kumar D,, Bhatia R,, Gandhi JC,, Patel RK,, Purohit BC. 1998. Outbreak of suspected Clostridium butyricum botulism in India. Emerg Infect Dis 4: 506507.
114. Johnson EA,, Goodnough MC,. 1998. Botulism, p 723741. In Collier L,, Mahy BW,, Balows A ( ed), Topley and Wilson’s Microbiology and Microbial Infections, 9th ed. Arnold Publishing, London, United Kingdom.
115. Smith GR,. 1987. Botulism in water birds and its relation to comparative medicine, p 7386. In Elklund MW,, Dowell VR Jr ( ed), Avian Botulism. Charles C Thomas, Springfield, IL.
116. Johnson EA,, Bradshaw M. 2001. Clostridium botulinum and its neurotoxins: a metabolic and cellular perspective. Toxicon 39: 17031722.
117. Bradshaw M,, Dineen SS,, Maks ND,, Johnson EA. 2004. Regulation of neurotoxin complex expression in Clostridium botulinum strains 62A, Hall A-hyper, and NCTC 2916. Anaerobe 10: 321333.
118. Eklund MW,, Poysky FT,, Habig WH,. 1989. Bacteriophages and plasmids in Clostridium botulinum and Clostridium tetani and their relationship to production of toxins, p 2551. In Simpson LL ( ed), Botulinum Toxin and Tetanus Toxin. Academic Press, San Diego, CA.
119. Arnon SS,. 2004. Infant botulism, p 17581766. In Feigen RD,, Cherry JD,, Demmler G,, Kaplan S ( ed), Textbook of Pediatric Infectious Diseases. W. B. Saunders, Philadelphia, PA.
120. Fenicia L,, Anniballi F,, Pulitano S,, Genovese O,, Polidori G,, Aureli P. 2004. A severe case of infant botulism caused by Clostridium botulinum type A with concomitant intestinal viral infections. Eur J Pediatr 163: 501502.
121. Griffin PM,, Hatheway CL,, Rosenbaum RB,, Sokolow R. 1997. Endogenous antibody production to botulinum toxin in an adult with intestinal colonization botulism and underlying Crohn’s disease. J Infect Dis 175: 633637.
122. Sheth AN,, Wiersma P,, Atrubin D,, Dubey V,, Zink D,, Skinner G,, Doerr F,, Juliao P,, Gonzalez G,, Burnett C,, Drenzek C,, Shuler C,, Austin J,, Ellis A,, Maslanka S,, Sobel J. 2008. International outbreak of severe botulism with prolonged toxemia caused by commercial carrot juice. Clin Infect Dis 47: 12451251.
123. Koussoulakos S. 2009. Botulinum neurotoxin: the ugly duckling. Eur Neurol 61: 331342.
124. Cherington M. 2004. Botulism: update and review. Semin Neurol 24: 155163.
125. Lalli G,, Bohnert S,, Deinhardt K,, Verastegui C,, Schiavo G. 2003. The journey of tetanus and botulinum neurotoxins in neurons. Trends Microbiol 11: 431437.
126. Schiavo G,, Matteoli M,, Montecucco C. 2000. Neurotoxins affecting neuroexocytosis. Physiol Rev 80: 717766.
127. Lacy DB,, Tepp W,, Cohen AC,, DasGupta BR,, Stevens RC. 1998. Crystal structure of botulinum neurotoxin type A and implications for toxicity. Nat Struct Biol 5: 898902.
128. Swaminathan S,, Eswaramoorthy S. 2000. Structural analysis of the catalytic and binding sites of Clostridium botulinum neurotoxin B. Nat Struct Biol 7: 693699.
129. Brett MM,, Hallas G,, Mpamugo O. 2004. Wound botulism in the UK and Ireland. J Med Microbiol 53: 555561.
130. Maselli RA,, Ellis W,, Mandler RN,, Sheikh F,, Senton G,, Knox S,, Salari-Namin H,, Agius M,, Wollmann RL,, Richman DP. 1997. Cluster of wound botulism in California: clinical, electrophysiologic, and pathologic study. Muscle Nerve 20: 12841295.
131. Kudrow DB,, Henry DA,, Haake DA,, Marshall G,, Mathisen GE. 1988. Botulism associated with Clostridium botulinum sinusitis after intranasal cocaine abuse. Ann Intern Med 109: 984985.
132. Chertow DS,, Tan ET,, Maslanka SE,, Schulte J,, Bresnitz EA,, Weisman RS,, Bernstein J,, Marcus SM,, Kumar S,, Malecki J,, Sobel J,, Braden CR. 2006. Botulism in 4 adults following cosmetic injections with an unlicensed, highly concentrated botulinum preparation. JAMA 296: 24762479.
133. Weber JT,, Goodpasture HC,, Alexander H,, Werner SB,, Hatheway CL,, Tauxe RV. 1993. Wound botulism in a patient with a tooth abscess: case report and review. Clin Infect Dis 16: 635639.
134. Paerregaard A,, Angen O,, Lisby M,, Mølbak K,, Clausen ME,, Christensen JJ. 2008. Denmark: botulism in an infant or infant botulism? Euro Surveill 13: pii19072. http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19072.
135. Domingo RM,, Haller JS,, Gruenthal M. 2008. Infant botulism: two recent cases and literature review. J Child Neurol 23: 13361346.
136. Underwood K,, Rubin S,, Deakers T,, Newth C. 2007. Infant botulism: a 30-year experience spanning the introduction of botulism immune globulin intravenous in the intensive care unit at Childrens Hospital Los Angeles. Pediatrics 120: e1380e1385.
137. Fox CK,, Keet CA,, Strober JB. 2005. Recent advances in infant botulism. Pediatr Neurol 32: 149154.
138. Franciosa G,, Aureli P,, Schechter R,. 2003. Clostridium botulinum, p 6189. In Bier MD,, Miliotis JW ( ed), International Handbook of Foodborne Pathogens. Marcel Dekker, Inc, New York, NY.
139. Smith LDS,, Sugiyama H. 1988. Botulism. The Organism, Its Toxins, the Diseases. Charles C Thomas, Springfield, IL.
140. Arnon SS,, Schechter R,, Maslanka SE,, Jewell NP,, Hatheway CL. 2006. Human botulism immune globulin for the treatment of infant botulism. N Engl J Med 354: 462471.
141. Chalk CH,, Benstead TJ,, Keezer M. 2014. Medical treatment for botulism. Cochrane Database Syst Rev 2:CD008123. 10.1002/14651858.CD008123.pub3.
142. Shukla HD,, Sharma SK. 2005. Clostridium botulinum: a bug with beauty and weapon. Crit Rev Microbiol 31: 1118.
143. Pitt ML,, LeClaire RD,. 2005. Pathogenesis by aerosol, p 6578. In Lindler LE,, Lebeda FJ,, Korch GW ( ed), Biological Weapons Defense. Infectious Diseases and Counterbioterrorism. Humana Press, Inc, Totowa, NJ.
144. Wein LM,, Liu Y. 2005. Analyzing a bioterror attack on the food supply: the case of botulinum toxin in milk. Proc Natl Acad Sci U S A 102: 99849989.
145. Holzer E. 1962. Botulism caused by inhalation. Med Klin 57: 17351738. (In German.)
146. Bleck TP. 1991. Tetanus: pathophysiology, management, and prophylaxis. Dis Mon 37: 545603.
147. Wagner KS,, White JM,, Andrews NJ,, Borrow R,, Stanford E,, Newton E,, Pebody RG. 2012. Immunity to tetanus and diphtheria in the UK in 2009. Vaccine 30: 71117117.
148. Barsam A,, Kerins M,, Jaye P. 2005. Tetanus and intravenous drug use. Eur J Clin Microbiol Infect Dis 24: 497498.
149. Hahné SJ,, White JM,, Crowcroft NS,, Brett MM,, George RC,, Beeching NJ,, Roy K,, Goldberg D. 2006. Tetanus in injecting drug users, United Kingdom. Emerg Infect Dis 12: 709710.
150. Lambo JA,, Anokye EA. 2013. Prognostic factors for mortality in neonatal tetanus: a systematic review and meta-analysis. Int J Infect Dis 17: e1100e1110.
151. Ackermann G,, Tang YJ,, Jang SS,, Silva J,, Rodloff AC,, Cohen SH. 2001. Isolation of Clostridium innocuum from cases of recurrent diarrhea in patients with prior Clostridium difficile associated diarrhea. Diagn Microbiol Infect Dis 40: 103106.
152. Brook I. 1995. Clostridial infection in children. J Med Microbiol 42: 7882.
153. Coleman N,, Speirs G,, Khan J,, Broadbent V,, Wight DG,, Warren RE. 1993. Neutropenic enterocolitis associated with Clostridium tertium. J Clin Pathol 46: 180183.
154. Kourtis AP,, Weiner R,, Belson K,, Richards FO Jr. 1997. Clostridium tertium meningitis as the presenting sign of a meningocele in a twelve-year-old child. Pediatr Infect Dis J 16: 527529.
155. Steyaert S,, Peleman R,, Vaneechoutte M,, De Baere T,, Claeys G,, Verschraegen G. 1999. Septicemia in neutropenic patients infected with Clostridium tertium resistant to cefepime and other expanded-spectrum cephalosporins. J Clin Microbiol 37: 37783779.
156. Linscott AJ,, Flamholtz RB,, Shukla D,, Song Y,, Liu C,, Finegold SM. 2005. Fatal septicemia due to Clostridium hathewayi and Campylobacter hominis. Anaerobe 11: 9798.
157. Elsayed S,, Zhang K. 2005. Bacteremia caused by Clostridium intestinale. J Clin Microbiol 43: 20182020.
158. Elsayed S,, Zhang K. 2004. Bacteremia caused by Clostridium symbiosum. J Clin Microbiol 42: 43904392.
159. Hausmann R,, Albert F,, Geissdörfer W,, Betz P. 2004. Clostridium fallax associated with sudden death in a 16-year-old boy. J Med Microbiol 53: 581583.
160. Glazunova OO,, Raoult D,, Roux V. 2005. First identification of Clostridium celerecrescens in liquid drained from an abscess. J Clin Microbiol 43: 30073008.
161. Wang RF,, Beggs ML,, Erickson BD,, Cerniglia CE. 2004. DNA microarray analysis of predominant human intestinal bacteria in fecal samples. Mol Cell Probes 18: 223234.
162. Statius van Eps RG,, LaMuraglia GM. 1997. Photodynamic therapy inhibits transforming growth factor beta activity associated with vascular smooth muscle cell injury. J Vasc Surg 25: 10441052.
163. Modi N,, Wilcox MH. 2001. Evidence for antibiotic induced Clostridium perfringens diarrhoea. J Clin Pathol 54: 748751.
164. Forward LJ,, Tompkins DS,, Brett MM. 2003. Detection of Clostridium difficile cytotoxin and Clostridium perfringens enterotoxin in cases of diarrhoea in the community. J Med Microbiol 52: 753757.
165. Carroll KC. 2011. Tests for the diagnosis of Clostridium difficile infection: the next generation. Anaerobe 17: 170174.
166. Burnham CA,, Carroll KC. 2013. Diagnosis of Clostridium difficile infection: an ongoing conundrum for clinicians and for clinical laboratories. Clin Microbiol Rev 26: 604630.
167. Stevens V,, van Wijngaarden E. 2013. Proton pump inhibitor use may be associated with an increased risk of Clostridium difficile infection. Evid Based Med 18: 193194.
168. Planche TD,, Davies KA,, Coen PG,, Finney JM,, Monahan IM,, Morris KA,, O’Connor L,, Oakley SJ,, Pope CF,, Wren MW,, Shetty NP,, Crook DW,, Wilcox MH. 2013. Differences in outcome according to Clostridium difficile testing method: a prospective multicentre diagnostic validation study of C difficile infection. Lancet Infect Dis 13: 936945.
169. Brecher SM,, Novak-Weekley SM,, Nagy E. 2013. Laboratory diagnosis of Clostridium difficile infections: there is light at the end of the colon. Clin Infect Dis 57: 11751181.
170. Dubberke ER,, Han Z,, Bobo L,, Hink T,, Lawrence B,, Copper S,, Hoppe-Bauer J,, Burnham CA,, Dunne WM Jr. 2011. Impact of clinical symptoms on interpretation of diagnostic assays for Clostridium difficile infections. J Clin Microbiol 49: 28872893.
171. Larson AM,, Fung AM,, Fang FC. 2010. Evaluation of tcdB real-time PCR in a three-step diagnostic algorithm for detection of toxigenic Clostridium difficile. J Clin Microbiol 48: 124130.
172. Babady NE,, Stiles J,, Ruggiero P,, Khosa P,, Huang D,, Shuptar S,, Kamboj M,, Kiehn TE. 2010. Evaluation of the Cepheid Xpert Clostridium difficile Epi assay for diagnosis of Clostridium difficile infection and typing of the NAP1 strain at a cancer hospital. J Clin Microbiol 48: 45194524.
173. Peterson LR,, Robicsek A. 2009. Does my patient have Clostridium difficile infection? Ann Intern Med 151: 176179.
174. Allen SD,, Emery CL,, Siders JA,. 2002. Anaerobic bacteriology, p 5081. In Truant AL ( ed), Manual of Commercial Methods in Clinical Microbiology. ASM Press, Washington, DC.
175. Woodruff BA,, Griffin PM,, McCroskey LM,, Smart JF,, Wainwright RB,, Bryant RG,, Hutwagner LC,, Hatheway CL. 1992. Clinical and laboratory comparison of botulism from toxin types A, B, and E in the United States, 1975–1988. J Infect Dis 166: 12811286.
176. Centers for Disease Control and Prevention. 1998. Botulism in the United States 1899–1996. Handbook for Epidemiologists, Clinicians, and Laboratory Workers. U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, Atlanta, GA.
177. Downes FP,, Ito K. 2001. Compendium of Methods for the Microbiological Examination of Foods. American Public Health Association, Washington, DC.
178. Wheeler C,, Inami G,, Mohle-Boetani J,, Vugia D. 2009. Sensitivity of mouse bioassay in clinical wound botulism. Clin Infect Dis 48: 16691673.
179. Hall YH,, Chaddock JA,, Moulsdale HJ,, Kirby ER,, Alexander FC,, Marks JD,, Foster KA. 2004. Novel application of an in vitro technique to the detection and quantification of botulinum neurotoxin antibodies. J Immunol Methods 288: 5560.
180. Dong M,, Tepp WH,, Johnson EA,, Chapman ER. 2004. Using fluorescent sensors to detect botulinum neurotoxin activity in vitro and in living cells. Proc Natl Acad Sci U S A 101: 1470114706.
181. Sharma SK,, Whiting RC. 2005. Methods for detection of Clostridium botulinum toxin in foods. J Food Prot 68: 12561263.
182. Akbulut D,, Grant KA,, McLauchlin J. 2005. Improvement in laboratory diagnosis of wound botulism and tetanus among injecting illicit-drug users by use of real-time PCR assays for neurotoxin gene fragments. J Clin Microbiol 43: 43424348.
183. De Medici D,, Anniballi F,, Wyatt GM,, Lindström M,, Messelhäusser U,, Aldus CF,, Delibato E,, Korkeala H,, Peck MW,, Fenicia L. 2009. Multiplex PCR to detect botulinum neurotoxin-producing clostridia in clinical, food and environmental samples. Appl Environ Microbiol 75: 64576461.
184. Jousimies-Somer H,, Summanen P,, Citron DM,, Baron EJ,, Wexler H,, Finegold SM. 2002. Wadsworth-KTL Anaerobic Bacteriology Manual, 6th ed. Star Publishing Co., Belmont, CA.
185. Winn WC,, Allen SD,, Janda WM,, Koneman EW,, Procop G,, Schrechenberger PC,, Woods G. 2005. Koneman’s Color Atlas and Textbook of Diagnostic Microbiology. Lippincott Williiams & Wilkins, Philadelphia, PA.
186. Atlas RM. 2004. Handbook of Microbiological Media. CRC Press, Boca Raton, FL.
187. Koransky JR,, Allen SD,, Dowell VR Jr. 1978. Use of ethanol for selective isolation of sporeforming microorganisms. Appl Environ Microbiol 35: 762765.
188. George WL,, Sutter VL,, Citron D,, Finegold SM. 1979. Selective and differential medium for isolation of Clostridium difficile. J Clin Microbiol 9: 214219.
189. Bliss DZ,, Johnson S,, Clabots CR,, Savik K,, Gerding DN. 1997. Comparison of cycloserine-cefoxitin-fructose agar (CCFA) and taurocholate-CCFA for recovery of Clostridium difficile during surveillance of hospitalized patients. Diagn Microbiol Infect Dis 29: 14.
190. Carson KC,, Boseiwaqa LV,, Thean SK,, Foster NF,, Riley TV. 2013. Isolation of Clostridium difficile from faecal specimens—a comparison of chromID C. difficile agar and cycloserine-cefoxitin-fructose agar. J Med Microbiol 62: 14231427.
191. Arroyo LG,, Rousseau J,, Willey BM,, Low DE,, Staempfli H,, McGeer A,, Weese JS. 2005. Use of a selective enrichment broth to recover Clostridium difficile from stool swabs stored under different conditions. J Clin Microbiol 43: 53415343.
192. Hink T,, Burnham CA,, Dubberke ER. 2013. A systematic evaluation of methods to optimize culture-based recovery of Clostridium difficile from stool specimens. Anaerobe 19: 3943.
193. Allen SD,, Siders JA,, Riddell MJ,, Fill JA,, Wegener WS. 1995. Cellular fatty acid analysis in the differentiation of Clostridium in the clinical microbiology laboratory. Clin Infect Dis 20( Suppl 2): S198S201.
194. Ghanem FM,, Ridpath AC,, Moore WE,, Moore LV. 1991. Identification of Clostridium botulinum, Clostridium argentinense, and related organisms by cellular fatty acid analysis. J Clin Microbiol 29: 11141124.
195. Belmares J,, Gerding DN,, Parada JP,, Miskevics S,, Weaver F,, Johnson S. 2007. Outcome of metronidazole therapy for Clostridium difficile disease and correlation with a scoring system. J Infect 55: 495501.
196. Citron DM,, Appelbaum PC. 1993. How far should a clinical laboratory go in identifying anaerobic isolates, and who should pay? Clin Infect Dis 16( Suppl 4): S435S438.
197. Alexander CJ,, Citron DM,, Brazier JS,, Goldstein EJ. 1995. Identification and antimicrobial resistance patterns of clinical isolates of Clostridium clostridioforme, Clostridium innocuum, and Clostridium ramosum compared with those of clinical isolates of Clostridium perfringens. J Clin Microbiol 33: 32093215.
198. Cresci A,, Orpianesi C,, La Rosa F,, Pannelli F,, Saltalamacchia G,, Scaloni G,, Trotta F,, Mastrandrea V. 1988. Characterization of some Clostridium species by gas-liquid chromatography using numerical analysis. Microbiologica 11: 179199.
199. Pepersack F,, Labbe M,, Nonhoff C,, Schoutens E. 1983. Use of gas-liquid chromatography as a screening test for toxigenic Clostridium difficile in diarrhoeal stools. J Clin Pathol 36: 12331236.
200. Marler LM,, Siders JA,, Wolters LC,, Pettigrew Y,, Skitt BL,, Allen SD. 1991. Evaluation of the new RapID-ANA II system for the identification of clinical anaerobic isolates. J Clin Microbiol 29: 874878.
201. Lindström MK,, Jankola HM,, Hielm S,, Hyytiä EK,, Korkeala HJ. 1999. Identification of Clostridium botulinum with API 20 A, Rapid ID 32 A and RapID ANA II. FEMS Immunol Med Microbiol 24: 267274.
202. Schreckenberger PC,, Celig DM,, Janda WM. 1988. Clinical evaluation of the Vitek ANI card for identification of anaerobic bacteria. J Clin Microbiol 26: 225230.
203. Rennie RP,, Brosnikoff C,, Turnbull L,, Reller LB,, Mirrett S,, Janda W,, Ristow K,, Krilcich A. 2008. Multicenter evaluation of the Vitek 2 anaerobe and Corynebacterium identification card. J Clin Microbiol 46: 26462651.
204. Cavallaro JJ,, Wiggs LS,, Miller JM. 1997. Evaluation of the BBL Crystal Anaerobe identification system. J Clin Microbiol 35: 31863191.
205. Mory F,, Alauzet C,, Matuszeswski C,, Riegel P,, Lozniewski A. 2009. Evaluation of the new Vitek 2 ANC card for identification of medically relevant anaerobic bacteria. J Clin Microbiol 47: 19231926.
206. Everley RA,, Mott TM,, Toney DM,, Croley TR. 2009. Characterization of Clostridium species utilizing liquid chromatography/mass spectrometry of intact proteins. J Microbiol Methods 77: 152158.
207. Bloedt K,, Riecker M,, Poppert S,, Wellinghausen N. 2009. Evaluation of new selective culture media and a rapid fluorescence in situ hybridization assay for identification of Clostridium difficile from stool samples. J Med Microbiol 58: 874877.
208. Shimizu S,, Ootsubo M,, Kubosawa Y,, Fuchizawa I,, Kawai Y,, Yamazaki K. 2009. Fluorescent in situ hybridization in combination with filter cultivation (FISHFC) method for specific detection and enumeration of viable Clostridium perfringens. Food Microbiol 26: 425431.
209. Grosse-Herrenthey A,, Maier T,, Gessler F,, Schaumann R,, Böhnel H,, Kostrzewa M,, Krüger M. 2008. Challenging the problem of clostridial identification with matrix-assisted laser desorption and ionization–time-of-flight mass spectrometry (MALDI-TOF MS). Anaerobe 14: 242249.
210. Nagy E,, Becker S,, Kostrzewa M,, Barta N,, Urban E. 2012. The value of MALDI-TOF MS for the identification of clinically relevant anaerobic bacteria in routine laboratories. J Med Microbiol 61: 13931400.
211. Fournier R,, Wallet F,, Grandbastien B,, Dubreuil L,, Courcol R,, Neut C,, Dessein R. 2012. Chemical extraction versus direct smear for MALDI-TOF mass spectrometry identification of anaerobic bacteria. Anaerobe 18: 294297.
212. Fedorko DP,, Drake SK,, Stock F,, Murray PR. 2012. Identification of clinical isolates of anaerobic bacteria using matrix-assisted laser desorption ionization-time of flight mass spectrometry. Eur J Clin Microbiol Infect Dis 31: 22572262.
213. Barreau M,, Pagnier I,, La Scola B. 2013. Improving the identification of anaerobes in the clinical microbiology laboratory through MALDI-TOF mass spectrometry. Anaerobe 22: 123125.
214. Schmitt BH,, Cunningham SA,, Dailey AL,, Gustafson DR,, Patel R. 2013. Identification of anaerobic bacteria by Bruker Biotyper matrix-assisted laser desorption ionization–time of flight mass spectrometry with on-plate formic acid preparation. J Clin Microbiol 51: 782786.
215. Justesen US,, Holm A,, Knudsen E,, Andersen LB,, Jensen TG,, Kemp M,, Skov MN,, Gahrn-Hansen B,, Møller JK. 2011. Species identification of clinical isolates of anaerobic bacteria: a comparison of two matrix-assisted laser desorption ionization–time of flight mass spectrometry systems. J Clin Microbiol 49: 43144318.
216. Veloo AC,, Knoester M,, Degener JE,, Kuijper EJ. 2011. Comparison of two matrix-assisted laser desorption ionisation-time of flight mass spectrometry methods for the identification of clinically relevant anaerobic bacteria. Clin Microbiol Infect 17: 15011506.
217. Jamal WY,, Shahin M,, Rotimi VO. 2013. Comparison of two matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry methods and API 20AN for identification of clinically relevant anaerobic bacteria. J Med Microbiol 62: 540544.
218. Barbut F,, Mastrantonio P,, Delmee M,, Brazier J,, Kuijper E,, Poxton I. 2007. Prospective study of Clostridium difficile infections in Europe with phenotypic and genotypic characterisation of the isolates. Clin Microbiol Infect 13: 10481057.
219. Killgore G,, Thompson A,, Johnson S,, Brazier J,, Kuijper E,, Pepin J,, Frost EH,, Savelkoul P,, Nicholson B,, van den Berg RJ,, Kato H,, Sambol SP,, Zukowski W,, Woods C,, Limbago B,, Gerding DN,, McDonald LC. 2008. Comparison of seven techniques for typing international epidemic strains of Clostridium difficile: restriction endonuclease analysis, pulsed-field gel electrophoresis, PCR-ribotyping, multilocus sequence typing, multilocus variable-number tandem-repeat analysis, amplified fragment length polymorphism, and surface layer protein A gene sequence typing. J Clin Microbiol 46: 431437.
220. Tenover FC,, Akerlund T,, Gerding DN,, Goering RV,, Boström T,, Jonsson AM,, Wong E,, Wortman AT,, Persing DH. 2011. Comparison of strain typing results for Clostridium difficile isolates from North America. J Clin Microbiol 49: 18311837.
221. Huber CA,, Foster NF,, Riley TV,, Paterson DL. 2013. Challenges for standardization of Clostridium difficile typing methods. J Clin Microbiol 51: 28102814.
222. Clabots CR,, Johnson S,, Bettin KM,, Mathie PA,, Mulligan ME,, Schaberg DR,, Peterson LR,, Gerding DN. 1993. Development of a rapid and efficient restriction endonuclease analysis typing system for Clostridium difficile and correlation with other typing systems. J Clin Microbiol 31: 18701875.
223. Alonso R,, Martín A,, Peláez T,, Marín M,, Rodríguez-Creixéms M,, Bouza E. 2005. An improved protocol for pulsed-field gel electrophoresis typing of Clostridium difficile. J Med Microbiol 54: 155157.
224. Wilcox MH,, Shetty N,, Fawley WN,, Shemko M,, Coen P,, Birtles A,, Cairns M,, Curran MD,, Dodgson KJ,, Green SM,, Hardy KJ,, Hawkey PM,, Magee JG,, Sails AD,, Wren MW. 2012. Changing epidemiology of Clostridium difficile infection following the introduction of a national ribotyping-based surveillance scheme in England. Clin Infect Dis 55: 10561063.
225. He M,, Miyajima F,, Roberts P,, Ellison L,, Pickard DJ,, Martin MJ,, Connor TR,, Harris SR,, Fairley D,, Bamford KB,, D’Arc S,, Brazier J,, Brown D,, Coia JE,, Douce G,, Gerding D,, Kim HJ,, Koh TH,, Kato H,, Senoh M,, Louie T,, Michell S,, Butt E,, Peacock SJ,, Brown NM,, Riley T,, Songer G,, Wilcox M,, Pirmohamed M,, Kuijper E,, Hawkey P,, Wren BW,, Dougan G,, Parkhill J,, Lawley TD. 2013. Emergence and global spread of epidemic healthcare-associated Clostridium difficile. Nat Genet 45: 109113.
226. Eyre DW,, Golubchik T,, Gordon NC,, Bowden R,, Piazza P,, Batty EM,, Ip CL,, Wilson DJ,, Didelot X,, O’Connor L,, Lay R,, Buck D,, Kearns AM,, Shaw A,, Paul J,, Wilcox MH,, Donnelly PJ,, Peto TE,, Walker AS,, Crook DW. 2012. A pilot study of rapid benchtop sequencing of Staphylococcus aureus and Clostridium difficile for outbreak detection and surveillance. BMJ Open 2: e001124. 10.1136/bmjopen-2012-001124.
227. Jacobson MJ,, Lin G,, Whittam TS,, Johnson EA. 2008. Phylogenetic analysis of Clostridium botulinum type A by multi-locus sequence typing. Microbiology 154: 24082415.
228. Chalmers G,, Bruce HL,, Hunter DB,, Parreira VR,, Kulkarni RR,, Jiang YF,, Prescott JF,, Boerlin P. 2008. Multilocus sequence typing analysis of Clostridium perfringens isolates from necrotic enteritis outbreaks in broiler chicken populations. J Clin Microbiol 46: 39573964.
229. Neumann AP,, Rehberger TG. 2009. MLST analysis reveals a highly conserved core genome among poultry isolates of Clostridium septicum. Anaerobe 15: 99106.
230. Leclair D,, Pagotto F,, Farber JM,, Cadieux B,, Austin JW. 2006. Comparison of DNA fingerprinting methods for use in investigation of type E botulism outbreaks in the Canadian Arctic. J Clin Microbiol 44: 16351644.
231. Sawires YS,, Songer JG. 2005. Multiple-locus variable-number tandem repeat analysis for strain typing of Clostridium perfringens. Anaerobe 11: 262272.
232. Chalmers G,, Martin SW,, Prescott JF,, Boerlin P. 2008. Typing of Clostridium perfringens by multiple-locus variable number of tandem repeats analysis. Vet Microbiol 128: 126135.
233. Brook I,, Wexler HM,, Goldstein EJ. 2013. Antianaerobic antimicrobials: spectrum and susceptibility testing. Clin Microbiol Rev 26: 526546.
234. Wybo I,, Van den Bossche D,, Soetens O,, Vekens E,, Vandoorslaer K,, Claeys G,, Glupczynski Y,, Ieven M,, Melin P,, Nonhoff C,, Rodriguez-Villalobos H,, Verhaegen J,, Piérard D. 2014. Fourth Belgian multicentre survey of antibiotic susceptibility of anaerobic bacteria. J Antimicrob Chemother 69: 155161.
235. Jenkins SG,, Schuetz AN. 2012. Current concepts in laboratory testing to guide antimicrobial therapy. Mayo Clin Proc 87: 290308.
236. Roberts SA,, Shore KP,, Paviour SD,, Holland D,, Morris AJ. 2006. Antimicrobial susceptibility of anaerobic bacteria in New Zealand: 1999–2003. J Antimicrob Chemother 57: 992998.
237. Finegold SM,, Molitoris D,, Väisänen ML. 2009. Study of the in vitro activities of rifaximin and comparator agents against 536 anaerobic intestinal bacteria from the perspective of potential utility in pathology involving bowel flora. Antimicrob Agents Chemother 53: 281286.
238. Mory F,, Lozniewski A,, David V,, Carlier JP,, Dubreuil L,, Leclercq R. 1998. Low-level vancomycin resistance in Clostridium innocuum. J Clin Microbiol 36: 17671768.
239. Ackermann G,, Schaumann R,, Pless B,, Claros MC,, Goldstein EJ,, Rodloff AC. 2000. Comparative activity of moxifloxacin in vitro against obligately anaerobic bacteria. Eur J Clin Microbiol Infect Dis 19: 228232.
240. Liebetrau A,, Rodloff AC,, Behra-Miellet J,, Dubreuil L. 2003. In vitro activities of a new des-fluoro(6) quinolone, garenoxacin, against clinical anaerobic bacteria. Antimicrob Agents Chemother 47: 36673671.
241. Ackermann G,, Tang YJ,, Kueper R,, Heisig P,, Rodloff AC,, Silva J Jr,, Cohen SH. 2001. Resistance to moxifloxacin in toxigenic Clostridium difficile isolates is associated with mutations in gyrA. Antimicrob Agents Chemother 45: 23482353.
242. Clinical and Laboratory Standards Institute. 2012. Methods for Antimicrobial Susceptibility Testing of Anaerobic Bacteria; Approved Standard—8th Edition. CLSI Document M11-A8. Clinical and Laboratory Standards Institute, Wayne, PA.
243. Clinical and Laboratory Standards Institute. 2014. Performance Standards for Antimicrobial Susceptibility Testing; 24th Informational Supplement. CLSI Document M100-S24. Clinical and Laboratory Standards Institute, Wayne, PA.
244. Ferraris L,, Butel MJ,, Aires J. 2010. Antimicrobial susceptibility and resistance determinants of Clostridium butyricum isolates from preterm infants. Int J Antimicrob Agents 36: 420423.
245. Johnson EA,, Summanen P,, Finegold SM,. 2006. Clostridium. In Murray PR,, Baron EJ,, Jorgensen JH,, Landry ML,, Pfaller MA ( ed), Manual of Clinical Microbiology, 9th ed. ASM Press, Washington, DC.


Generic image for table

Characteristics of species of clinical significance

Citation: Stevens D, Bryant A, Carroll K. 2015. Clostridium*, p 940-966. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch53
Generic image for table

Characteristics of species of clinical significance

Citation: Stevens D, Bryant A, Carroll K. 2015. Clostridium*, p 940-966. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch53
Generic image for table

Commonly used tests for the diagnosis of disease

Citation: Stevens D, Bryant A, Carroll K. 2015. Clostridium*, p 940-966. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch53
Generic image for table

Rapid identification of some lecithinase-positive and/or swarming spp. of clinical significance

Citation: Stevens D, Bryant A, Carroll K. 2015. Clostridium*, p 940-966. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch53
Generic image for table

Activities of various drugs against spp. (Wadsworth agar dilution procedure)

Citation: Stevens D, Bryant A, Carroll K. 2015. Clostridium*, p 940-966. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch53

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error