1887

Chapter 15 : Infection

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

Ebook: Choose a downloadable PDF or ePub file. Chapter is a downloadable PDF file. File must be downloaded within 48 hours of purchase

Buy this Chapter
Digital (?) $15.00

Preview this chapter:
Zoom in
Zoomout

Infection, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555819453/9781555819446_Chap15-1.gif /docserver/preview/fulltext/10.1128/9781555819453/9781555819446_Chap15-2.gif

Abstract:

The primary virulence factors that are known to cause clinical disease in infection (CDI) are the two large toxins: TcdA (toxin A; 308 kDa) and TcdB (toxin B; 270 kDa) ( ). Both toxins are glucosyltransferases that inactivate Rho, Rac, and Cdc42 and result in actin condensation and subsequent cytoskeletal changes, apoptosis, and cell death of target cells. These toxins also induce an intense inflammatory response characterized by infiltration of inflammatory cells, especially neutrophils; activation of submucosal neurons; secretion of cytokines, chemokines, and arachidonic acid metabolites; and production of substance P and reactive oxygen intermediates ( ). We have published previously that mediators of inflammation such as COX2 and angiotensin II, inflammatory cytokines such as interleukin-8 (IL-8), and immune cells such as neutrophils are significantly elevated in intestinal loops treated with TcdA ( ). Similarly, we see in our patients’ histopathology mucosal disruption, intense inflammatory cell infiltration, and thick fibrinous exudates of degenerating cells (pseudomembranes), which are the hallmarks of pseudomembranous colitis (PMC) ( ) ( Fig. 1 ). Increased fecal lactoferrin, IL-1β, and IL-8 were observed in patients with CDI ( ). The link between glucosylation of the small GTPases and induction of the inflammatory cascade is unclear. This raises the possibility that the host inflammatory response is not a direct effect of the toxins on intracellular signaling but a concerted response by the cells surrounding the “intoxicated” cell to the changes that occurred in the latter.

Citation: Shin J, Chaves-Olarte E, Warren C. 2016. Infection, p 265-294. In Scheld W, Hughes J, Whitley R (ed), Emerging infections 10. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.EI10-0007-2015
Highlighted Text: Show | Hide
Loading full text...

Full text loading...

Figures

Image of Figure 1
Figure 1

Gross pathology of pseudomembranous colitis. Histopathology of pseudomembranous colitis.

Citation: Shin J, Chaves-Olarte E, Warren C. 2016. Infection, p 265-294. In Scheld W, Hughes J, Whitley R (ed), Emerging infections 10. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.EI10-0007-2015
Permissions and Reprints Request Permissions
Download as Powerpoint

References

/content/book/10.1128/9781555819453.chap15
1. Voth DE,, Ballard JD . 2005. Clostridium difficile toxins: mechanism of action and role in disease. Clin Microbiol Rev 18 : 247263.[PubMed] [CrossRef]
2. Sun X,, Savidge T,, Feng H . 2010. The enterotoxicity of Clostridium difficile toxins. Toxins (Basel) 2 : 18481880.[PubMed] [CrossRef]
3. Alcantara C,, Stenson WF,, Steiner TS,, Guerrant RL . 2001. Role of inducible cyclooxygenase and prostaglandins in Clostridium difficile toxin A-induced secretion and inflammation in an animal model. J Infect Dis 184 : 648652.[PubMed] [CrossRef]
4. Alcantara CS,, Jin X-H,, Brito GAC,, Carneiro-Filho BA,, Barrett LJ,, Carey RM,, Guerrant RL . 2005. Angiotensin II subtype 1 receptor blockade inhibits Clostridium difficile toxin A-induced intestinal secretion in a rabbit model. J Infect Dis 191 : 20902096.[PubMed] [CrossRef]
5. Warren CA,, Calabrese GM,, Li Y,, Pawlowski SW,, Figler RA,, Rieger J,, Ernst PB,, Linden J,, Guerrant RL . 2012. Effects of adenosine A2A receptor activation and alanyl-glutamine in Clostridium difficile toxin-induced ileitis in rabbits and cecitis in mice. BMC Infect Dis 12 : 13. [PubMed] [CrossRef]
6. Guerrant RL,, Walker DH,, Weller PF (ed). 2011. Tropical Infectious Diseases: Principles, Pathogens and Practice, 3rd ed. Saunders/Elsevier, Edinburgh, Scotland.
7. Steiner TS,, Flores CA,, Pizarro TT,, Guerrant RL . 1997. Fecal lactoferrin, interleukin-1beta, and interleukin-8 are elevated in patients with severe Clostridium difficile colitis. Clin Diagn Lab Immunol 4 : 719722.[PubMed]
8. Schwan C,, Stecher B,, Tzivelekidis T,, van Ham M,, Rohde M,, Hardt W-D,, Wehland J,, Aktories K . 2009. Clostridium difficile toxin CDT induces formation of microtubule-based protrusions and increases adherence of bacteria. PLoS Pathog 5 : e1000626. doi:10.1371/journal.ppat.1000626. [PubMed] [CrossRef]
9. Lanis JM,, Barua S,, Ballard JD . 2010. Variations in TcdB activity and the hypervirulence of emerging strains of Clostridium difficile . PLoS Pathog 6 : e1001061. doi:10.1371/journal.ppat.1001061. [PubMed] [CrossRef]
10. Lanis JM,, Heinlen LD,, James JA,, Ballard JD . 2013. Clostridium difficile 027/BI/NAP1 encodes a hypertoxic and antigenically variable form of TcdB. PLoS Pathog 9 : e1003523. doi:10.1371/journal.ppat.1003523. [PubMed] [CrossRef]
11. Chaves-Olarte E,, Löw P,, Freer E,, Norlin T,, Weidmann M,, von Eichel-Streiber C,, Thelestam M . 1999. A novel cytotoxin from Clostridium difficile serogroup F is a functional hybrid between two other large clostridial cytotoxins. J Biol Chem 274 : 1104611052.[PubMed] [CrossRef]
12. Mattila E,, Arkkila P,, Mattila PS,, Tarkka E,, Tissari P,, Anttila V-J . 2013. Extraintestinal Clostridium difficile infections. Clin Infect Dis 57 : e148e153. [PubMed] [CrossRef]
13. Wanahita A,, Goldsmith EA,, Marino BJ,, Musher DM . 2003. Clostridium difficile infection in patients with unexplained leukocytosis. Am J Med 115 : 543546.[PubMed] [CrossRef]
14. Mao EJ,, Kelly CR,, Machan JT . 2015. Racial differences in Clostridium difficile infection rates are attributable to disparities in health care access. Antimicrob Agents Chemother 59 : 62836287.[PubMed] [CrossRef]
15. McDonald LC,, Owings M,, Jernigan DB . 2006. Clostridium difficile infection in patients discharged from US short-stay hospitals, 1996-2003. Emerg Infect Dis 12 : 409415.[PubMed] [CrossRef]
16. Muto CA,, Pokrywka M,, Shutt K,, Mendelsohn AB,, Nouri K,, Posey K,, Roberts T,, Croyle K,, Krystofiak S,, Patel-Brown S,, Pasculle AW,, Paterson DL,, Saul M,, Harrison LH . 2005. A large outbreak of Clostridium difficile-associated disease with an unexpected proportion of deaths and colectomies at a teaching hospital following increased fluoroquinolone use. Infect Control Hosp Epidemiol 26 : 273280.[PubMed] [CrossRef]
17. Zilberberg MD,, Shorr AF,, Kollef MH . 2008. Increase in adult Clostridium difficile-related hospitalizations and case-fatality rate, United States, 2000-2005. Emerg Infect Dis 14 : 929931.[PubMed] [CrossRef]
18. Labbé A-C,, Poirier L,, Maccannell D,, Louie T,, Savoie M,, Béliveau C,, Laverdière M,, Pépin J . 2008. Clostridium difficile infections in a Canadian tertiary care hospital before and during a regional epidemic associated with the BI/NAP1/027 strain. Antimicrob Agents Chemother 52 : 31803187.[PubMed] [CrossRef]
19. Loo VG,, Poirier L,, Miller MA,, Oughton M,, Libman MD,, Michaud S,, Bourgault A-M,, 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.[PubMed] [CrossRef]
20. Pépin J,, Valiquette L,, Alary M-E,, Villemure P,, Pelletier A,, Forget K,, Pépin K,, Chouinard D . 2004. Clostridium difficile-associated diarrhea in a region of Quebec from 1991 to 2003: a changing pattern of disease severity. CMAJ 171 : 466472.[PubMed] [CrossRef]
21. Kuijper EJ,, Coignard B,, Tüll P . 2006. ESCMID Study Group for Clostridium difficile, EU Member States, European Centre for Disease Prevention and Control. Emergence of Clostridium difficile-associated disease in North America and Europe. Clin Microbiol Infect 12(Suppl 6): 218.[PubMed] [CrossRef]
22. Kuijper EJ,, Barbut F,, Brazier JS,, Kleinkauf N,, Eckmanns T,, Lambert ML,, Drudy D,, Fitzpatrick F,, Wiuff C,, Brown DJ,, Coia JE,, Pituch H,, Reichert P,, Even J,, Mossong J,, Widmer AF,, Olsen KE,, Allerberger F,, Notermans DW,, Delmée M,, Coignard B,, Wilcox M,, Patel B,, Frei R,, Nagy E,, Bouza E,, Marin M,, Akerlund T,, Virolainen-Julkunen A,, Lyytikäinen O,, Kotila S,, Ingebretsen A,, Smyth B,, Rooney P,, Poxton IR,, Monnet DL . 2008. Update of Clostridium difficile infection due to PCR ribotype 027 in Europe, 2008. Euro Surveill 13 : 18942. [PubMed]
23. 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.[PubMed] [CrossRef]
24. Fernandez Canigia L,, Nazar J,, Arce M,, Dadamio J,, Smayevsky J,, Bianchini H . 2001. Clostridium difficile diarrhea: frequency of detection in a medical center in Buenos Aires, Argentina. Rev Argent Microbiol 33 : 101107. [In Spanish.][PubMed]
25. Souza Dias MB,, Yamashiro J,, Borrasca VL,, Stempliuk VA,, Araújo MRE,, Costa SF,, Levin AS . 2010. Pseudo-outbreak of Clostridium difficile associated diarrhea (CDAD) in a tertiary-care hospital. Rev Inst Med Trop Sao Paulo 52 : 133137.[PubMed] [CrossRef]
26. Zumbado-Salas R,, Gamboa-Coronado MM,, Rodríguez-Cavallini E,, Chaves-Olarte E . 2008. Clostridium difficile in adult patients with nosocomial diarrhea in a Costa Rican hospital. Am J Trop Med Hyg 79 : 164165.[PubMed]
27. Lopardo G,, Morfin-Otero R,, Moran-Vazquez II,, Noriega F,, Zambrano B,, Luxemburger C,, Foglia G,, Rivas EE . 2015. Epidemiology of Clostridium difficile: a hospital-based descriptive study in Argentina and Mexico. Braz J Infect Dis 19 : 814.[PubMed] [CrossRef]
28. Spadão F,, Gerhardt J,, Guimarães T,, Dulley F,, Almeida JN, Jr,, Batista MV,, Shikanai-Yasuda MA,, Levin AS,, Costa SF . 2014. Incidence of diarrhea by Clostridium difficile in hematologic patients and hematopoietic stem cell transplantation patients: risk factors for severe forms and death. Rev Inst Med Trop Sao Paulo 56 : 325331.[PubMed] [CrossRef]
29. Dumyati G,, Stevens V,, Hannett GE,, Thompson AD,, Long C,, Maccannell D,, Limbago B . 2012. Community-associated Clostridium difficile infections, Monroe County, New York, USA. Emerg Infect Dis 18 : 392400.[PubMed] [CrossRef]
30. Khanna S,, Pardi DS,, Aronson SL,, Kammer PP,, Orenstein R,, St Sauver JL,, Harmsen WS,, Zinsmeister AR . 2012. The epidemiology of community-acquired Clostridium difficile infection: a population-based study. Am J Gastroenterol 107 : 8995.[PubMed] [CrossRef]
31. Pai S,, Aliyu SH,, Enoch DA,, Karas JA . 2012. Five years experience of Clostridium difficile infection in children at a UK tertiary hospital: proposed criteria for diagnosis and management. PLoS One 7 : e51728. doi:10.1371/journal.pone.0051728. [CrossRef]
32. Sandora TJ,, Fung M,, Flaherty K,, Helsing L,, Scanlon P,, Potter-Bynoe G,, Gidengil CA,, Lee GM . 2011. Epidemiology and risk factors for Clostridium difficile infection in children. Pediatr Infect Dis J 30 : 580584.[PubMed] [CrossRef]
33. Sailhamer EA,, Carson K,, Chang Y,, Zacharias N,, Spaniolas K,, Tabbara M,, Alam HB,, DeMoya MA,, Velmahos GC . 2009. Fulminant Clostridium difficile colitis: patterns of care and predictors of mortality. Arch Surg 144 : 433439; discussion 439–440.[PubMed] [CrossRef]
34. Zilberberg MD,, Shorr AF,, Micek ST,, Doherty JA,, Kollef MH . 2009. Clostridium difficile-associated disease and mortality among the elderly critically ill. Crit Care Med 37 : 25832589.[PubMed] [CrossRef]
35. Balassiano IT,, Miranda KR,, Boente RF,, Pauer H,, Oliveira ICM,, Santos-Filho J,, Amorim ELT,, Caniné GA,, Souza CF,, Gomes MZR,, Ferreira EO,, Brazier JS,, Domingues RMCP . 2009. Characterization of Clostridium difficile strains isolated from immunosuppressed inpatients in a hospital in Rio de Janeiro, Brazil. Anaerobe 15 : 6164.[PubMed] [CrossRef]
36. Legaria MC,, Lumelsky G,, Rosetti S . 2003. Clostridium difficile-associated diarrhea from a general hospital in Argentina. Anaerobe 9 : 113116.[CrossRef]
37. Pires RN,, Monteiro AA,, Carneiro LC,, Baethgen LF,, Tavares R,, Lincho CS,, Park S,, Perlin D,, Rodrigues Filho EM,, Pasqualotto AC . 2014. Clostridium difficile infection in Brazil: a neglected problem? Am J Infect Control 42 : 459460.[PubMed] [CrossRef]
38. Balassiano IT,, Dos Santos-Filho J,, de Oliveira MPB,, Ramos MC,, Japiassu AM,, Dos Reis AM,, Brazier JS,, de Oliveira Ferreira E,, Domingues RMCP . 2010. An outbreak case of Clostridium difficile-associated diarrhea among elderly inpatients of an intensive care unit of a tertiary hospital in Rio de Janeiro, Brazil. Diagn Microbiol Infect Dis 68 : 449455.[PubMed] [CrossRef]
39. Camacho-Ortiz A,, Ponce-de-León A,, Sifuentes-Osornio J . 2009. Clostridum difficile associated disease in Latin America. Gac Med Mex 145 : 223229. [In Spanish.][PubMed]
40. Quesada-Gómez C,, Vargas P,, López-Ureña D,, Gamboa-Coronado MM,, Rodríguez-Cavallini E . 2012. Community-acquired Clostridium difficile NAP1/027-associated diarrhea in an eighteen month old child. Anaerobe 18 : 581583.[PubMed] [CrossRef]
41. Quesada-Gómez C,, Mulvey MR,, Vargas P,, Gamboa-Coronado MM,, Rodríguez C,, Rodríguez-Cavillini E . 2013. Isolation of a toxigenic and clinical genotype of Clostridium difficile in retail meats in Costa Rica. J Food Prot 76 : 348351.[PubMed] [CrossRef]
42. Silva ROS,, Santos RLR,, Pires PS,, Pereira LC,, Pereira ST,, Duarte MC,, de Assis RA,, Lobato FCF . 2013. Detection of toxins A/B and isolation of Clostridium difficile and Clostridium perfringens from dogs in Minas Gerais, Brazil. Braz J Microbiol 44 : 133137.[PubMed] [CrossRef]
43. Silva ROS,, Ribeiro de Almeida L,, Oliveira Junior CA,, de Magalhães Soares DF,, Pereira PLL,, Rupnik M,, Lobato FCF . 2014. Carriage of Clostridium difficile in free-living South American coati (Nasua nasua) in Brazil. Anaerobe 30 : 99101.[PubMed] [CrossRef]
44. Quesada-Gómez C,, Rodríguez C,, Gamboa-Coronado MM,, Rodríguez-Cavallini E,, Du T,, Mulvey MR,, Villalobos-Zúñiga M,, Boza-Cordero R . 2010. Emergence of Clostridium difficile NAP1 in Latin America. J Clin Microbiol 48 : 669670.[PubMed] [CrossRef]
45. 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.[PubMed] [CrossRef]
46. López-Ureña D,, Quesada-Gómez C,, Miranda E,, Fonseca M,, Rodríguez-Cavallini E . 2014. Spread of epidemic Clostridium difficile NAP1/027 in Latin America: case reports in Panama. J Med Microbiol 63 : 322324.[PubMed] [CrossRef]
47. Aguayo C,, Flores R,, Lévesque S,, Araya P,, Ulloa S,, Lagos J,, Hormazabal JC,, Tognarelli J,, Ibáñez D,, Pidal P,, Duery O,, Olivares B,, Fernández J . 2015. Rapid spread of Clostridium difficile NAP1/027/ST1 in Chile confirms the emergence of the epidemic strain in Latin America. Epidemiol Infect 143 : 30693073.[PubMed] [CrossRef]
48. Camacho-Ortiz A,, López-Barrera D,, Hernández-García R,, Galván-De Los Santos AM,, Flores-Treviño SM,, Llaca-Díaz JM,, Maldonado-Garza HJ,, Bosques-Padilla FJ,, Garza-González E . 2015. First report of Clostridium difficile NAP1/027 in a Mexican hospital. PLoS One 10 : e0122627. doi:10.1371/journal.pone.0122627. [CrossRef]
49. Goorhuis A,, Legaria MC,, van den Berg RJ,, Harmanus C,, Klaassen CHW,, Brazier JS,, Lumelsky G,, Kuijper EJ . 2009. Application of multiple-locus variable-number tandem-repeat analysis to determine clonal spread of toxin A-negative Clostridium difficile in a general hospital in Buenos Aires, Argentina. Clin Microbiol Infect 15 : 10801086.[PubMed] [CrossRef]
50. Quesada-Gómez C,, López-Ureña D,, Acuña-Amador L,, Villalobos-Zúñiga M,, Du T,, Freire R,, Guzmán-Verri C,, del Mar Gamboa-Coronado M,, Lawley TD,, Moreno E,, Mulvey MR,, de Castro Brito GA,, Rodríguez-Cavallini E,, Rodríguez C,, Chaves-Olarte E . 2015. Emergence of an outbreak-associated Clostridium difficile variant with increased virulence. J Clin Microbiol 53 : 12161226.[PubMed] [CrossRef]
51. Kim H,, Jeong SH,, Roh KH,, Hong SG,, Kim JW,, Shin M-G,, Kim M-N,, Shin HB,, Uh Y,, Lee H,, Lee K . 2010. Investigation of toxin gene diversity, molecular epidemiology, and antimicrobial resistance of Clostridium difficile isolated from 12 hospitals in South Korea. Korean J Lab Med 30 : 491497.[PubMed] [CrossRef]
52. Honda H,, Yamazaki A,, Sato Y,, Dubberke ER . 2014. Incidence and mortality associated with Clostridium difficile infection at a Japanese tertiary care center. Anaerobe 25 : 510.[PubMed] [CrossRef]
53. Kato H,, Kato N,, Watanabe K,, Yamamoto T,, Suzuki K,, Ishigo S,, Kunihiro S,, Nakamura I,, Killgore GE,, Nakamura S . 2001. Analysis of Clostridium difficile isolates from nosocomial outbreaks at three hospitals in diverse areas of Japan. J Clin Microbiol 39 : 13911395.[PubMed] [CrossRef]
54. Sawabe E,, Kato H,, Osawa K,, Chida T,, Tojo N,, Arakawa Y,, Okamura N . 2007. Molecular analysis of Clostridium difficile at a university teaching hospital in Japan: a shift in the predominant type over a five-year period. Eur J Clin Microbiol Infect Dis 26 : 695703.[PubMed] [CrossRef]
55. Collins DA,, Hawkey PM,, Riley TV . 2013. Epidemiology of Clostridium difficile infection in Asia. Antimicrob Resist Infect Control 2 : 21. [PubMed] [CrossRef]
56. Kim YS,, Han DS,, Kim YH,, Kim WH,, Kim JS,, Kim HS,, Kim HS,, Park YS,, Song HJ,, Shin SJ,, Yang SK,, Ye BD,, Eun CS,, Lee KM,, Lee SH,, Jang BI,, Jung SA,, Cheon JH,, Choi CH,, Huh KC . 2013. Incidence and clinical features of Clostridium difficile infection in Korea: a nationwide study. Epidemiol Infect 141 : 189194.[PubMed] [CrossRef]
57. Shin B-M,, Kuak EY,, Yoo HM,, Kim EC,, Lee K,, Kang J-O,, Whang DH,, Shin J-H . 2008. Multicentre study of the prevalence of toxigenic Clostridium difficile in Korea: results of a retrospective study 2000-2005. J Med Microbiol 57 : 697701.[PubMed] [CrossRef]
58. Shin B-M,, Kuak EY,, Yoo SJ,, Shin WC,, Yoo HM . 2008. Emerging toxin A-B+ variant strain of Clostridium difficile responsible for pseudomembranous colitis at a tertiary care hospital in Korea. Diagn Microbiol Infect Dis 60 : 333337.[PubMed] [CrossRef]
59. Kim J,, Kang JO,, Pai H,, Choi TY . 2012. Association between PCR ribotypes and antimicrobial susceptibility among Clostridium difficile isolates from healthcare-associated infections in South Korea. Int J Antimicrob Agents 40 : 2429.[PubMed] [CrossRef]
60. Hawkey PM,, Marriott C,, Liu WE,, Jian ZJ,, Gao Q,, Ling TKW,, Chow V,, So E,, Chan R,, Hardy K,, Xu L,, Manzoor S . 2013. Molecular epidemiology of Clostridium difficile infection in a major Chinese hospital: an underrecognized problem in Asia? J Clin Microbiol 51 : 33083313.[PubMed] [CrossRef]
61. Galaydick J,, Xu Y,, Sun L,, Landon E,, Weber SG,, Sun D,, Zhou J,, Sherer R . 2015. Seek and you shall find: prevalence of Clostridium difficile in Wuhan, China. Am J Infect Control 43 : 301302.[PubMed] [CrossRef]
62. Chung C-H,, Wu C-J,, Lee H-C,, Yan J-J,, Chang C-M,, Lee N-Y,, Chen P-L,, Lee C-C,, Hung Y-P,, Ko W-C . 2010. Clostridium difficile infection at a medical center in southern Taiwan: incidence, clinical features and prognosis. J Microbiol Immunol Infect 43 : 119125.[CrossRef]
63. Lai C-C,, Lin S-H,, Tan C-K,, Liao C-H,, Huang Y-T,, Hsueh P-R . 2014. Clinical manifestations of Clostridium difficile infection in a medical center in Taiwan. J Microbiol Immunol Infect 47 : 491496.[PubMed] [CrossRef]
64. Chia J-H,, Lai H-C,, Su L-H,, Kuo A-J,, Wu T-L . 2013. Molecular epidemiology of Clostridium difficile at a medical center in Taiwan: persistence of genetically clustering of AB+ isolates and increase of A+B+ isolates. PLoS One 8 : e75471. doi:10.1371/journal.pone.0075471. [CrossRef]
65. Hung Y-P,, Cia C-T,, Tsai B-Y,, Chen P-C,, Lin H-J,, Liu H-C,, Lee J-C,, Wu Y-H,, Tsai P-J,, Ko W-C . 2015. The first case of severe Clostridium difficile ribotype 027 infection in Taiwan. J Infect 70 : 98101.[PubMed] [CrossRef]
66. Lai M-J,, Chiueh T-S,, Huang Z-Y,, Lin J-C . 2015. The first Clostridium difficile ribotype 027 strain isolated in Taiwan. J Formos Med Assoc Taiwan 115 : 210212.[PubMed] [CrossRef]
67. Liao T-L,, Lin C-F,, Chiou C-S,, Shen G-H,, Wang J . 2015. Clostridium difficile PCR ribotype 027 emerges in Taiwan. Jpn J Infect Dis 68 : 338340.[PubMed] [CrossRef]
68. Cheng VCC,, Yam WC,, Lam OTC,, Tsang JLY,, Tse EYF,, Siu GKH,, Chan JFW,, Tse H,, To KKW,, Tai JWM,, Ho PL,, Yuen KY . 2011. Clostridium difficile isolates with increased sporulation: emergence of PCR ribotype 002 in Hong Kong. Eur J Clin Microbiol Infect Dis 30 : 13711381.[PubMed] [CrossRef]
69. Cheng VCC,, Yam WC,, Chan JFW,, To KKW,, Ho PL,, Yuen KY . 2009. Clostridium difficile ribotype 027 arrives in Hong Kong. Int J Antimicrob Agents 34 : 492493.[PubMed] [CrossRef]
70. Warren CA,, Labio E,, Destura R,, Sevilleja JE,, Jamias JD,, Daez MLO . 2012. Clostridium difficile and Entamoeba histolytica infections in patients with colitis in the Philippines. Trans R Soc Trop Med Hyg 106 : 424428.[PubMed] [CrossRef]
71. Hassan SA,, Othman N,, Idris FM,, Abdul Rahman Z,, Maning N,, Abdul Rahman R,, Tiong CG . 2012. Prevalence of Clostridium difficile toxin in diarhoeal stool samples of patients from a tertiary hospital in North Eastern Penisular Malaysia. Med J Malaysia 67 : 402405.[PubMed]
72. Oyofo BA,, Subekti D,, Tjaniadi P,, Machpud N,, Komalarini S,, Setiawan B,, Simanjuntak C,, Punjabi N,, Corwin AL,, Wasfy M,, Campbell JR,, Lesmana M . 2002. Enteropathogens associated with acute diarrhea in community and hospital patients in Jakarta, Indonesia. FEMS Immunol Med Microbiol 34 : 139146.[PubMed] [CrossRef]
73. Rupnik M,, Kato N,, Grabnar M,, Kato H . 2003. New types of toxin A-negative, toxin B-positive strains among Clostridium difficile isolates from Asia. J Clin Microbiol 41 : 11181125.[PubMed] [CrossRef]
74. Thamlikitkul V,, Danpakdi K,, Chokloikaew S . 1996. Incidence of diarrhea and Clostridium difficile toxin in stools from hospitalized patients receiving clindamycin, beta-lactams, or nonantibiotic medications. J Clin Gastroenterol 22 : 161163.[PubMed] [CrossRef]
75. Wongwanich S,, Ramsiri S,, Vanasin B,, Khowsaphit P,, Tantipatayangkul P,, Phan-urai R . 1990. Clostridium difficile associated disease in Thailand. Southeast Asian J Trop Med Public Health 21 : 367372.[PubMed]
76. Putsathit P,, Kiratisin P,, Ngamwongsatit P,, Riley TV . 2015. Clostridium difficile infection in Thailand. Int J Antimicrob Agents 45 : 17.[PubMed] [CrossRef]
77. Kumarasinghe G,, Lim YS,, Chow C,, Bassett DC . 1992. Prevalence of bacterial agents of diarrhoeal disease at the National University Hospital, Singapore and their resistance to antimicrobial agents. Trop Geogr Med 44 : 229232.[PubMed]
78. Koh TH,, Tan AL,, Tan ML,, Wang G,, Song KP . 2007. Epidemiology of Clostridium difficile infection in a large teaching hospital in Singapore. Pathology 39 : 438442.[PubMed] [CrossRef]
79. Hsu L-Y,, Tan TY,, Koh TH,, Kwa AL,, Krishnan P,, Tee NW,, Jureen R . 2011. Decline in Clostridium difficile-associated disease rates in Singapore public hospitals, 2006 to 2008. BMC Res Notes 4 : 77. [PubMed] [CrossRef]
80. Lim PL,, Ling ML,, Lee HY,, Koh TH,, Tan AL,, Kuijper EJ,, Goh SS,, Low BS,, Ang LP,, Harmanus C,, Lin RT,, Krishnan P,, James L,, Lee CE . 2011. Isolation of the first three cases of Clostridium difficile polymerase chain reaction ribotype 027 in Singapore. Singapore Med J 52 : 361364.[PubMed]
81. Ayyagari A,, Sharma P,, Venkateswarlu,, Mehta S,, Agarwal KC . 1986. Prevalence of Clostridium difficile in pseudomembranous and antibiotic-associated colitis in north India. J Diarrhoeal Dis Res 4 : 157160.[PubMed]
82. Dhawan B,, Chaudhry R,, Sharma N . 1999. Incidence of Clostridium difficile infection: a prospective study in an Indian hospital. J Hosp Infect 43 : 275280.[PubMed] [CrossRef]
83. Joshy L,, Chaudhry R,, Dhawan B . 2009. Detection and characterization of Clostridium difficile from patients with antibiotic-associated diarrhoea in a tertiary care hospital in North India. J Med Microbiol 58 : 16571659.[PubMed] [CrossRef]
84. Niyogi SK,, Bhattacharya SK,, Dutta P,, Naik TN,, De SP,, Sen D,, Saha MR,, Datta D,, Nair GB,, Mitra U,, Rasaily R,, and Chandra Pal S . 1991. Prevalence of Clostridium difficile in hospitalised patients with acute diarrhoea in Calcutta. J Diarrhoeal Dis Res 9 : 1619.[PubMed]
85. Ingle M,, Deshmukh A,, Desai D,, Abraham P,, Joshi A,, Rodrigues C,, Mankeshwar R . 2011. Prevalence and clinical course of Clostridium difficile infection in a tertiary-care hospital: a retrospective analysis. Indian J Gastroenterol 30 : 8993.[PubMed] [CrossRef]
86. Albert MJ,, Faruque AS,, Faruque SM,, Sack RB,, Mahalanabis D . 1999. Case-control study of enteropathogens associated with childhood diarrhea in Dhaka, Bangladesh. J Clin Microbiol 37 : 34583464.[PubMed]
87. Thomas C,, Stevenson M,, Williamson DJ,, Riley TV . 2002. Clostridium difficile-associated diarrhea: epidemiological data from Western Australia associated with a modified antibiotic policy. Clin Infect Dis 35 : 14571462.[PubMed] [CrossRef]
88. Ferguson JK,, Cheng AC,, Gilbert GL,, Gottlieb T,, Korman T,, McGregor A,, Richards M,, Roberts S,, Robson J,, Van Gessel H,, Riley TV . 2011. Clostridium difficile laboratory testing in Australia and New Zealand: national survey results and Australasian Society for Infectious Diseases recommendations for best practice. Pathology 43 : 482487.[PubMed] [CrossRef]
89. Slimings C,, Armstrong P,, Beckingham WD,, Bull AL,, Hall L,, Kennedy KJ,, Marquess J,, McCann R,, Menzies A,, Mitchell BG,, Richards MJ,, Smollen PC,, Tracey L,, Wilkinson IJ,, Wilson FL,, Worth LJ,, Riley TV . 2014. Increasing incidence of Clostridium difficile infection, Australia, 2011-2012. Med J Aust 200 : 272276.[PubMed] [CrossRef]
90. Furuya-Kanamori L,, Robson J,, Soares Magalhães RJ,, Yakob L,, McKenzie SJ,, Paterson DL,, Riley TV,, Clements ACA . 2014. A population-based spatio-temporal analysis of Clostridium difficile infection in Queensland, Australia over a 10-year period. J Infect 69 : 447455.[PubMed] [CrossRef]
91. Jackson T,, Nghiem HS,, Rowell D,, Jorm C,, Wakefield J . 2011. Marginal costs of hospital-acquired conditions: information for priority-setting for patient safety programmes and research. J Health Serv Res Policy 16 : 141146.[PubMed] [CrossRef]
92. Foster NF,, Collins DA,, Ditchburn SL,, Duncan CN,, van Schalkwyk JW,, Golledge CL,, Keed ABR,, Riley TV . 2014. Epidemiology of Clostridium difficile infection in two tertiary-care hospitals in Perth, Western Australia: a cross-sectional study. New Microbes New Infect 2 : 6471.[PubMed] [CrossRef]
93. Cheknis AK,, Sambol SP,, Davidson DM,, Nagaro KJ,, Mancini MC,, Hidalgo-Arroyo GA,, Brazier JS,, Johnson S,, Gerding DN . 2009. Distribution of Clostridium difficile strains from a North American, European and Australian trial of treatment for C. difficile infections: 2005-2007. Anaerobe 15 : 230233.[PubMed] [CrossRef]
94. Wilson R,, Beerbaum P,, Giglio S . 2015. Community and hospital acquired Clostridium difficile in South Australia: ribotyping of isolates and a comparison of laboratory detection methods. Lett Appl Microbiol 60 : 3336.[PubMed] [CrossRef]
95. Knight DR,, Giglio S,, Huntington PG,, Korman TM,, Kotsanas D,, Moore CV,, Paterson DL,, Prendergast L,, Huber CA,, Robson J,, Waring L,, Wehrhahn MC,, Weldhagen GF,, Wilson RM,, Riley TV . 2015. Surveillance for antimicrobial resistance in Australian isolates of Clostridium difficile, 2013-14. J Antimicrob Chemother 70 : 29922999.[PubMed] [CrossRef]
96. Huber CA,, Hall L,, Foster NF,, Gray M,, Allen M,, Richardson LJ,, Robson J,, Vohra R,, Schlebusch S,, George N,, Nimmo GR,, Riley TV,, Paterson DL . 2014. Surveillance snapshot of Clostridium difficile infection in hospitals across Queensland detects binary toxin producing ribotype UK 244. Commun Dis Intell Q Rep 38 : E279E284.[PubMed]
97. Lim SK,, Stuart RL,, Mackin KE,, Carter GP,, Kotsanas D,, Francis MJ,, Easton M,, Dimovski K,, Elliott B,, Riley TV,, Hogg G,, Paul E,, Korman TM,, Seemann T,, Stinear TP,, Lyras D,, Jenkin GA . 2014. Emergence of a ribotype 244 strain of Clostridium difficile associated with severe disease and related to the epidemic ribotype 027 strain. Clin Infect Dis 58 : 17231730.[PubMed] [CrossRef]
98. Eyre DW,, Tracey L,, Elliott B,, Slimings C,, Huntington PG,, Stuart RL,, Korman TM,, Kotsiou G,, McCann R,, Griffiths D,, Fawley WN,, Armstrong P,, Dingle KE,, Walker AS,, Peto TE,, Crook DW,, Wilcox MH,, Riley TV . 2015. Emergence and spread of predominantly community-onset Clostridium difficile PCR ribotype 244 infection in Australia, 2010 to 2012. Euro Surveill 20 : 21059. http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=21059. [PubMed] [CrossRef]
99. Elliott B,, Squire MM,, Thean S,, Chang BJ,, Brazier JS,, Rupnik M,, Riley TV . 2011. New types of toxin A-negative, toxin B-positive strains among clinical isolates of Clostridium difficile in Australia. J Med Microbiol 60 : 11081111.[PubMed] [CrossRef]
100. Riley TV,, Thean S,, Hool G,, Golledge CL . 2009. First Australian isolation of epidemic Clostridium difficile PCR ribotype 027. Med J Aust 190 : 706708.[PubMed]
101. Richards M,, Knox J,, Elliott B,, Mackin K,, Lyras D,, Waring LJ,, Riley TV . 2011. Severe infection with Clostridium difficile PCR ribotype 027 acquired in Melbourne, Australia. Med J Aust 194 : 369371.[PubMed]
102. Bull AL,, Worth LJ,, Richards MJ . 2012. Implementation of standardised surveillance for Clostridium difficile infections in Australia: initial report from the Victorian Healthcare Associated Infection Surveillance System. Intern Med J 42 : 715718.[PubMed] [CrossRef]
103. Samie A,, Obi CL,, Franasiak J,, Archbald-Pannone L,, Bessong PO,, Alcantara-Warren C,, Guerrant RL . 2008. PCR detection of Clostridium difficile triose phosphate isomerase (tpi), toxin A (tcdA), toxin B (tcdB), binary toxin (cdtA, cdtB), and tcdC genes in Vhembe District, South Africa. Am J Trop Med Hyg 78 : 577585.[PubMed]
104. Lekalakala MR,, Lewis E,, Hoosen AA . 2010. Clostridium difficile infections in a tertiary hospital: value of surveillance. J Hosp Infect 75 : 328329.[PubMed] [CrossRef]
105. Kullin B,, Meggersee R,, D’Alton J,, Galvao B,, Rajabally N,, Whitelaw A,, Bamford C,, Reid SJ,, Abratt VR . 2015. Prevalence of gastrointestinal pathogenic bacteria in patients with diarrhoea attending Groote Schuur Hospital, Cape Town, South Africa. S Afr Med J 105 : 121125.[PubMed] [CrossRef]
106. Mwachari C,, Batchelor BI,, Paul J,, Waiyaki PG,, Gilks CF . 1998. Chronic diarrhoea among HIV-infected adult patients in Nairobi, Kenya. J Infect 37 : 4853.[PubMed] [CrossRef]
107. Zulu I,, Kelly P,, Mwansa J,, Veitch A,, Farthing MJ . 2000. Contrasting incidence of Clostridium difficile and other enteropathogens in AIDS patients in London and Lusaka. Trans R Soc Trop Med Hyg 94 : 167168.[PubMed] [CrossRef]
108. Onwueme K,, Fadairo Y,, Idoko L,, Onuh J,, Alao O,, Agaba P,, Lawson L,, Ukomadu C,, Idoko J . 2011. High prevalence of toxinogenic Clostridium difficile in Nigerian adult HIV patients. Trans R Soc Trop Med Hyg 105 : 667669.[PubMed] [CrossRef]
109. Simango C,, Uladi S . 2014. Detection of Clostridium difficile diarrhoea in Harare, Zimbabwe. Trans R Soc Trop Med Hyg 108 : 354357.[PubMed] [CrossRef]
110. Tedesco FJ,, Barton RW,, Alpers DH . 1974. Clindamycin-associated colitis. A prospective study. Ann Intern Med 81 : 429433.[PubMed] [CrossRef]
111. Deshpande A,, Pasupuleti V,, Thota P,, Pant C,, Rolston DDK,, Sferra TJ,, Hernandez AV,, Donskey CJ . 2013. Community-associated Clostridium difficile infection and antibiotics: a meta-analysis. J Antimicrob Chemother 68 : 19511961.[PubMed] [CrossRef]
112. Pakyz AL,, Moczygemba LR,, Wang H,, Stevens MP,, Edmond MB . 2015. An evaluation of the association between an antimicrobial stewardship score and antimicrobial usage. J Antimicrob Chemother 70 : 15881591.[PubMed] [CrossRef]
113. Slimings C,, Riley TV . 2014. Antibiotics and hospital-acquired Clostridium difficile infection: update of systematic review and meta-analysis. J Antimicrob Chemother 69 : 881891.[PubMed] [CrossRef]
114. Zacharioudakis IM,, Zervou FN,, Pliakos EE,, Ziakas PD,, Mylonakis E . 2015. Colonization with toxinogenic C. difficile upon hospital admission, and risk of infection: a systematic review and meta-analysis. Am J Gastroenterol 110 : 381390, quiz 391.[PubMed] [CrossRef]
115. Clabots CR,, Johnson S,, Olson MM,, Peterson LR,, Gerding DN . 1992. Acquisition of Clostridium difficile by hospitalized patients: evidence for colonized new admissions as a source of infection. J Infect Dis 166 : 561567.[PubMed] [CrossRef]
116. 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.[PubMed] [CrossRef]
117. Eyre DW,, Cule ML,, Wilson DJ,, Griffiths D,, Vaughan A,, O’Connor L,, Ip CLC,, Golubchik T,, Batty EM,, Finney JM,, Wyllie DH,, Didelot X,, Piazza P,, Bowden R,, Dingle KE,, Harding RM,, Crook DW,, Wilcox MH,, Peto TEA,, Walker AS . 2013. Diverse sources of C. difficile infection identified on whole-genome sequencing. N Engl J Med 369 : 11951205.[PubMed] [CrossRef]
118. Kim K-H,, Fekety R,, Batts DH,, Brown D,, Cudmore M,, Silva J Jr,, Waters D . 1981. Isolation of Clostridium difficile from the environment and contacts of patients with antibiotic-associated colitis. J Infect Dis 143 : 4250.[CrossRef]
119. McFarland LV,, Mulligan ME,, Kwok RY,, Stamm WE . 1989. Nosocomial acquisition of Clostridium difficile infection. N Engl J Med 320 : 204210.[PubMed] [CrossRef]
120. Dubberke ER,, Reske KA,, Noble-Wang J,, Thompson A,, Killgore G,, Mayfield J,, Camins B,, Woeltje K,, McDonald JR,, McDonald LC,, Fraser VJ . 2007. Prevalence of Clostridium difficile environmental contamination and strain variability in multiple health care facilities. Am J Infect Control 35 : 315318.[PubMed] [CrossRef]
121. Bobulsky GS,, Al-Nassir WN,, Riggs MM,, Sethi AK,, Donskey CJ . 2008. Clostridium difficile skin contamination in patients with C. difficile-associated disease. Clin Infect Dis 46 : 447450.[PubMed] [CrossRef]
122. Lucado J,, Gould C,, Elixhauser A . 2012. Clostridium difficile infections (CDI) in hospital stays, 2009. Statistical brief 124. Healthcare Cost and Utilization Project (HCUP) Statistical Briefs [Internet]. Agency for Health Care Policy and Research, Rockville, MD. http://www.ncbi.nlm.nih.gov/books/NBK92613/.
123. Miller M,, Gravel D,, Mulvey M,, Taylor G,, Boyd D,, Simor A,, Gardam M,, McGeer A,, Hutchinson J,, Moore D,, Kelly S . 2010. Health care-associated Clostridium difficile infection in Canada: patient age and infecting strain type are highly predictive of severe outcome and mortality. Clin Infect Dis 50 : 194201.[PubMed] [CrossRef]
124. Pépin J,, Valiquette L,, Cossette B . 2005. Mortality attributable to nosocomial Clostridium difficile-associated disease during an epidemic caused by a hypervirulent strain in Quebec. CMAJ 173 : 10371042.[PubMed] [CrossRef]
125. Miniño AM,, Murphy SL,, Xu J,, Kochanek KD . 2011. Deaths: final data for 2008. Natl Vital Stat Rep 59 : 1126.[PubMed]
126. Lessa FC,, Mu Y,, Bamberg WM,, Beldavs ZG,, Dumyati GK,, Dunn JR,, Farley MM,, Holzbauer SM,, Meek JI,, Phipps EC,, Wilson LE,, Winston LG,, Cohen JA,, Limbago BM,, Fridkin SK,, Gerding DN,, McDonald LC . 2015. Burden of Clostridium difficile infection in the United States. N Engl J Med 372 : 825834.[PubMed] [CrossRef]
127. Henrich TJ,, Krakower D,, Bitton A,, Yokoe DS . 2009. Clinical risk factors for severe Clostridium difficile-associated disease. Emerg Infect Dis 15 : 415422.[PubMed] [CrossRef]
128. Kyne L,, Warny M,, Qamar A,, Kelly CP . 2001. Association between antibody response to toxin A and protection against recurrent Clostridium difficile diarrhoea. Lancet 357 : 189193.[PubMed] [CrossRef]
129. Pepin J,, Alary M-E,, Valiquette L,, Raiche E,, Ruel J,, Fulop K,, Godin D,, Bourassa C . 2005. Increasing risk of relapse after treatment of Clostridium difficile colitis in Quebec, Canada. Clin Infect Dis 40 : 15911597.[PubMed] [CrossRef]
130. Kyne L,, Merry C,, O’Connell B,, Kelly A,, Keane C,, O’Neill D . 1999. Factors associated with prolonged symptoms and severe disease due to Clostridium difficile . Age Ageing 28 : 107113.[PubMed] [CrossRef]
131. Cohen SH,, Gerding DN,, Johnson S,, Kelly CP,, Loo VG,, McDonald LC,, Pepin J,, Wilcox MH , Society for Healthcare Epidemiology of America, Infectious Diseases Society of America . 2010. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA). Infect Control Hosp Epidemiol 31 : 431455.[PubMed] [CrossRef]
132. Kelly CP,, Pothoulakis C,, LaMont JT . 1994. Clostridium difficile colitis. N Engl J Med 330 : 257262.[PubMed] [CrossRef]
133. Freiler JF,, Durning SJ,, Ender PT . 2001. Clostridium difficile small bowel enteritis occurring after total colectomy. Clin Infect Dis. 33 : 14291431.[PubMed] [CrossRef]
134. Cheng AC,, Ferguson JK,, Richards MJ,, Robson JM,, Gilbert GL,, McGregor A,, Roberts S,, Korman TM,, Riley TV , Australasian Society for Infections Diseases . 2011. Australasian Society for Infectious Diseases guidelines for the diagnosis and treatment of Clostridium difficile infection. Med J Aust 194 : 353358.[PubMed]
135. Debast SB,, Bauer MP,, Kuijper EJ , European Society of Clinical Microbiology and Infectious Diseases . 2014. European Society of Clinical Microbiology and Infectious Diseases: update of the treatment guidance document for Clostridium difficile infection. Clin Microbiol Infect 20(Suppl 2): 126.[PubMed] [CrossRef]
136. Surawicz CM,, Brandt LJ,, Binion DG,, Ananthakrishnan AN,, Curry SR,, Gilligan PH,, McFarland LV,, Mellow M,, Zuckerbraun BS . 2013. Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. Am J Gastroenterol 108 : 478498, quiz 499.[PubMed] [CrossRef]
137. Feuerstadt P,, Das R,, Brandt LJ . 2014. The evolution of urban C. difficile infection (CDI): CDI in 2009-2011 is less severe and has better outcomes than CDI in 2006-2008. Am J Gastroenterol 109 : 12651276.[PubMed] [CrossRef]
138. Karas JA,, Enoch DA,, Aliyu SH . 2010. A review of mortality due to Clostridium difficile infection. J Infect 61 : 18.[PubMed] [CrossRef]
139. Hu MY,, Katchar K,, Kyne L,, Maroo S,, Tummala S,, Dreisbach V,, Xu H,, Leffler DA,, Kelly CP . 2009. Prospective derivation and validation of a clinical prediction rule for recurrent Clostridium difficile infection. Gastroenterology 136 : 12061214.[PubMed] [CrossRef]
140. Planche T,, Wilcox MH . 2015. Diagnostic pitfalls in Clostridium difficile infection. Infect Dis Clin North Am 29 : 6382.[PubMed] [CrossRef]
141. Gerding DN,, Olson MM,, Peterson LR,, Teasley DG,, Gebhard RL,, Schwartz ML,, Lee JT, Jr . 1986. Clostridium difficile-associated diarrhea and colitis in adults. A prospective case-controlled epidemiologic study. Arch Intern Med 146 : 95100.[CrossRef]
142. 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.[PubMed] [CrossRef]
143. Berrington A,, Settle CD . 2007. Which specimens should be tested for Clostridium difficile toxin? J Hosp Infect 65 : 280282.[PubMed] [CrossRef]
144. Kundrapu S,, Sunkesula VCK,, Jury LA,, Sethi AK,, Donskey CJ . 2012. Utility of perirectal swab specimens for diagnosis of Clostridium difficile infection. Clin Infect Dis 55 : 15271530.[PubMed] [CrossRef]
145. Gerding DN,, Johnson S,, Peterson LR,, Mulligan ME,, Silva J, Jr . 1995. Clostridium difficile-associated diarrhea and colitis. Infect Control Hosp Epidemiol 16 : 459477.[PubMed] [CrossRef]
146. Am J Health Syst Pharm . 1998. ASHP therapeutic position statement on the preferential use of metronidazole for the treatment of Clostridium difficile-associated disease. Am J Health Syst Pharm 55 : 14071411.[PubMed]
147. Musher DM,, Aslam S,, Logan N,, Nallacheru S,, Bhaila I,, Borchert F,, Hamill RJ . 2005. Relatively poor outcome after treatment of Clostridium difficile colitis with metronidazole. Clin Infect Dis 40 : 15861590.[PubMed] [CrossRef]
148. Zar FA,, Bakkanagari SR,, Moorthi KMLST,, Davis MB . 2007. A comparison of vancomycin and metronidazole for the treatment of Clostridium difficile-associated diarrhea, stratified by disease severity. Clin Infect Dis 45 : 302307.[PubMed] [CrossRef]
149. Johnson S,, Louie TJ,, Gerding DN,, Cornely OA,, Chasan-Taber S,, Fitts D,, Gelone SP,, Broom C,, Davidson DM , Polymer Alternative for CDI Treatment (PACT) investigators . 2014. Vancomycin, metronidazole, or tolevamer for Clostridium difficile infection: results from two multinational, randomized, controlled trials. Clin Infect Dis 59 : 345354.[PubMed] [CrossRef]
150. Rokas KEE,, Johnson JW,, Beardsley JR,, Ohl CA,, Luther VP,, Williamson JC . 2015. The addition of intravenous metronidazole to oral vancomycin is associated with improved mortality in critically ill patients with Clostridium difficile infection. Clin Infect Dis 61 : 934941.[PubMed] [CrossRef]
151. Wenisch JM,, Schmid D,, Kuo H-W,, Allerberger F,, Michl V,, Tesik P,, Tucek G,, Laferl H,, Wenisch C . 2012. Prospective observational study comparing three different treatment regimes in patients with Clostridium difficile infection. Antimicrob Agents Chemother 56 : 19741978.[PubMed] [CrossRef]
152. Keighley MR,, Burdon DW,, Arabi Y,, Williams JA,, Thompson H,, Youngs D,, Johnson M,, Bentley S,, George RH,, Mogg GA . 1978. Randomised controlled trial of vancomycin for pseudomembranous colitis and postoperative diarrhoea. BMJ 2 : 16671669.[PubMed] [CrossRef]
153. Fekety R,, Silva J,, Kauffman C,, Buggy B,, Deery HG . 1989. Treatment of antibiotic-associated Clostridium difficile colitis with oral vancomycin: comparison of two dosage regimens. Am J Med 86 : 1519.[PubMed] [CrossRef]
154. Gonzales M,, Pepin J,, Frost EH,, Carrier JC,, Sirard S,, Fortier L-C,, Valiquette L . 2010. Faecal pharmacokinetics of orally administered vancomycin in patients with suspected Clostridium difficile infection. BMC Infect Dis 10 : 363. [PubMed] [CrossRef]
155. Teasley DG,, Gerding DN,, Olson MM,, Peterson LR,, Gebhard RL,, Schwartz MJ,, Lee JT, Jr . 1983. Prospective randomised trial of metronidazole versus vancomycin for Clostridium-difficile-associated diarrhoea and colitis. Lancet 2 : 10431046.[CrossRef]