Update on Clostridium difficile infection

Current Opinion in Gastroenterology

Volumn 27, Issue 1, 2011, Pages 38-47

  O'Donoghuea, C ^a   Kyne, L ^a  

^a MATER MISERICORDIAE UNIVERSITY HOSPITAL   (Ireland)

Author keywords

Clostridium difficile; Fidaxomicin; Hypervirulent strains; Monoclonal antibodies

Indexed keywords

BACTERIAL VACCINE; CLOSTRIDIUM DIFFICILE TOXIN A; CLOSTRIDIUM DIFFICILE TOXIN B; FIDAXOMICIN; IMMUNOGLOBULIN; MONOCLONAL ANTIBODY; NITAZOXANIDE; ORITAVANCIN; PROBIOTIC AGENT; RAMOPLANIN; RESTRICTION ENDONUCLEASE; RIFALAZIL; RIFAXIMIN; TIGECYCLINE; VANCOMYCIN; VIRULENCE FACTOR;

ARTICLE; BACTERIAL STRAIN; CLOSTRIDIUM DIFFICILE INFECTION; COMORBIDITY; DISEASE SEVERITY; DNA IMMUNIZATION; ENTERITIS; GENOTYPE; HEALTH CARE COST; HEALTH CARE FACILITY; HOSPITALIZATION; HUMAN; INFECTIOUS DIARRHEA; NORTH AMERICA; POLYMERASE CHAIN REACTION; PULSED FIELD GEL ELECTROPHORESIS; TREATMENT OUTCOME;

EID: 85028099832     PISSN: 02671379     EISSN: None     Source Type: Journal    
DOI: 10.1097/MOG.0b013e3283411634     Document Type: Article

References (120)

1. Kyne L, Warny M, Qamar A, Kelly CP. Asymptomatic carriage of Clostridium difficile and serum levels of IgG antibody against toxin A. N Engl J Med 2000; 342:390-397. (Pubitemid 30084537)
2. Bartlett JG. Antibiotic-associated colitis. Dis Mon 1984; 30:1-54.
3. Bartlett JG. Clinical practice. Antibiotic-associated diarrhea. N Engl J Med 2002; 346:334-349.
4. Kelly CP, LaMont JT. Clostridium difficile - More difficult than ever. N Engl J Med 2008; 359:1932-1940.
5. Rupnik M, Wilcox MH, Gerding DN. Clostridium difficile infection: New developments in epidemiology and pathogenesis. Nat Rev Microbiol 2009; 7:526-536. An excellent up-to-date review of new developments in the epidemiology and pathogenesis of CDI.
6. Miller MA, Hyland M, Ofner-Agostini M, et al. Morbidity, mortality, and healthcare burden of nosocomial Clostridium difficile-associated diarrhea in Canadian hospitals. Infect Control Hosp Epidemiol 2002; 23:137-140. (Pubitemid 34246541)
7. Gravel D, Miller M, Simor A, et al. Healthcare-associated Clostridium difficile infection in adults admitted to acute care hospitals in Canada: A Canadian nosocomial infections surveillance program study. Clin Infect Dis 2009; 48:565-576. The authors report the results of a 6-month survey conducted in 2004-2005 examining the incidence of healthcare-associated-CDI in 29 Canadian hospitals, with an emphasis on patient outcomes. Comparing the results to a previous survey completed in 1997, they find similar incidence rates but an almost four-fold increase in attributable mortality.
8. Bauer MP, Noretmans DW, van Benthem, et al. Clostridium difficile infection in Europe: A hospital-based survey. Lancet 2010 [Epub ahead of print]. A survey conducted in November 2008 involving 34 European countries demonstrated that the incidence of CDI varied across hospitals and countries (mean: 4.1 per 10 000 patient days; range 0-36.3). The prevalence of PCR ribotype 027 was 5%. PCR ribotype 078 was the third most frequently isolated ribotype.
9. Cohen SH, Gerding DN, Johnson S, et al. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA). Infect Control Hosp Epidemiol 2010; 31:431-455. This is an excellent review of CDI in adults. The comprehensive guidelines on diagnosis and management of CDI are invaluable reading for all healthcare providers.
10. Kuijper EJ, Coignard B, Tull P. ESCMID study group for Clostridium difficile. Emergence of Clostridium difficile-associated disease in North America and Europe. Clin Microbiol Infect 2006; 12 (Suppl 6):2-18. (Pubitemid 44362038)
11. Kutty PK, Woods CW, Sena AC, et al. Risk factors for and estimated incidence of community-associated Clostridium difficile infection, North Carolina, USA. Emerg Infect Dis 2010; 16:197-204. A study of the estimated incidence of CA-CDI at six hospitals in North Carolina in 2005, identifying patient risk factors.
12. Hirschhorn LR, Trnka Y, Onderdonk A, et al. Epidemiology of communityacquired Clostridium difficile-associated diarrhea. J Infect Dis 1994; 169: 127-133.
13. Centres for Disease Control and Prevention. Severe Clostridium difficileassociated disease in populations previously at low risk-four states, 2005. MMWR Morb Mortal Wkly Rep 2005; 54:1201-1205.
14. Centres for Disease Control and Prevention. Surveillance for community acquired Clostridium difficile infection-Connecticut, 2006. MMWR Morb Mortal Wkly Rep 2008; 57:340-343.
15. Lambert PJ, Dyck M, Thompson LH, Hammond GW. Population-based surveillance of Clostridium difficile infection in Manitoba, Canada, by using interim surveillance definitions. Infect Control Hosp Epidemiol 2009; 30:945-951. The authors use surveillance data from one Canadian province from 2005 to 2006, to categorize CDI by onset in the community or in a healthcare facility.
16. Barbut F, Gariazzo B, Bonné L, et al. Clinical features of Clostridium difficileassociated infections and molecular characterization of strains: Results of a retrospective study, 2000-2004. Infect Control Hosp Epidemiol 2007; 28:131-139. (Pubitemid 46374152)
17. Norén T, Akerlund T, Bäck E, et al. Molecular epidemiology of hospitalassociated and community-acquired Clostridium difficile infection in a Swedish county. J Clin Microbiol 2004; 42:3635-3643. (Pubitemid 39045692)
18. Kalström O, Fryklund B, Tullus K, Burman LG. A prospective nationwide study of Clostridium difficile-associated diarrhea in Sweden. The Swedish C. difficile study group. Clin Infect Dis 1998; 26:141-145. (Pubitemid 28068168)
19. Bauer MP, Veenendaal D, Verhoef L, et al. Clinical and microbiological characteristics of community-onset Clostridium difficile infection in The Netherlands. Clin Microbiol Infect 2009; 15:1087-1092. A survey of community-onset CDI in the Netherlands over a 3-month period spanning 2007-2008, with a description of the incidence, patient profiles, risk factors and strain types isolated from affected patients. The authors found that there was no history of recent antimicrobial use in 40% of cases.
20. Wilcox MH, Mooney L, Bendall R, et al. A case-control study of communityassociated Clostridium difficile infection. J Antimicrob Chemother 2008; 62:388-396. (Pubitemid 351984787)
21. McFarland LV, Beneda HW, Clarridge JE, Raugi GJ. Implications for the changing face of Clostridium difficile disease for healthcare practitioners. Am J Infect Control 2007; 35:237-253. (Pubitemid 46670518)
22. Kelly CP. A 76-year-old man with recurrent Clostridium difficile-associated diarrhea: Review of C. difficile infection. JAMA 2009; 301:954-962. The author presents a case vignette of recurrent CDI and a concise review of CDI.
23. Kyne L, Sougioultzis S, McFarland LV, Kelly CP. Underlying disease severity as a major risk factor for nosocomial Clostridium difficile diarrhea. Infect Control Hosp Epidemiol 2002; 23:653-659. (Pubitemid 35315987)
24. McFarland LV, Mulligan ME, Kwok RY, Stamm WE. Nosocomial acquisition of Clostridium difficile infection. N Engl J Med 1989; 320: 204-210. (Pubitemid 19034145)
25. Freeman J, Bauer MP, Baines SD, et al. The changing epidemiology of Clostridium difficile infections. Clin Microbiol Rev 2010; 23:529-549. An excellent and very extensive review of the changing epidemiology of CDI, including new information on the risk factors for CDI.
26. Dial S, Delaney JA, Barkun AN, Suissa S. Use of gastric acid-suppressive agents and the risk of community-acquired Clostridium difficile-associated disease. JAMA 2005; 294:2989-2995. 27 (Pubitemid 41817660)
27. Kim J, Lee KL, Jeong JB, et al. Proton pump inhibitors as a risk factor for recurrence of Clostridium difficile-associated diarrhea. World J Gastroenterol 2010; 16:3573-3577. This retrospective study of hospitalized patients with CDI in South Korea identified advanced age, hypoalbuminemia and proton pump inhibitor use as risk factors for recurrent CDI.
28. Jenkins PJ, Teoh K, Simpson PM, et al. Clostridium difficile in patients undergoing primary hip and knee replacement. J Bone Joint Surg Br 2010; 92:994-998. This case-controlled retrospective review of CDI patients in an orthopedic service between 1984 and 2000 failed to find an association between CDI and the use of gastroprotective agents.
29. Henrich TJ, Krakower D, Bitton A, Yokoe DS. Clinical risk factors for severe Clostridiumdifficile-associated disease.Emerg Infect Dis 2009; 15:415-422. In this retrospective chart review of all patients with a positive fecal C. difficile toxin result over a 12-month period from 2005 to 2006, the authors identified advanced age, high leukocyte count, low albumin levels, raised creatinine levels, small-bowel obstruction or ileus, and evidence of colorectal inflammation on computerized tomography scan to be significantly associated with severe CDI. Gastroprotective agents were not associated with severity.
30. Lowe DO, Mamdani MM, Kopp A, et al. Proton pump inhibitors and hospitalization for Clostridium difficile-associated disease: A population-based study. Clin Infect Dis 2006; 43:1272-1276. (Pubitemid 44706452)
31. Garey KW, Jiang ZD, Yadav Y, et al. Peripartum Clostridium difficile infection: Case series and review of the literature. Am J Obstet Gynecol 2008; 199:332-337.
32. Rouphael NG, O'Donnell JA, Bhatnagar J, et al. Clostridium difficile-associated diarrhea: An emerging threat to pregnant women. Am J Obstet Gynecol 2008; 198:6351-6356.
33. Zilberberg MD, Tillotson GS, McDonald LC. Clostridium difficile infections among hospitalized children, United States, 1997-2006. Emerg Infect Dis 2010; 16:604-609. Using the 1997-2006 Kids' Inpatient Database and the 2006 National Hospital Discharge Survey, the authors calculate rates of CDI in pediatric patients, and the increasing incidence over a decade. The authors also speculate that the increasing rates may be due to reporting bias for diarrheal illnesses as they also noted a concomitant increase in rotavirus-related hospitalizations.
34. Bryant K, McDonald LC. Clostridium difficile infections in children. Pediatr Infect Dis J 2009; 28:145-146. This is a concise review on CDI in children, with specific recommendations for testing for C. difficile.
35. Freedman SD, Uppot RN, Mino-Kenudson M. A 34-year-old man with cystic fibrosis with abdominal pain and distension. N Engl J Med 2009; 361:807-816. Freedman et al. present a very interesting case, followed by a comprehensive review of CDI in patients with CF.
36. Rosen JB, Schecter MG, Heinle JS, et al. Clostridium difficile colitis in children following lung transplantation. Pediatr Transplant 2010; 14:651-656. This is a case series and discussion of four patients with CF who develop C. difficile colitis after lung transplantation.
37. Pituch H. Clostridium difficile is no longer just a nosocomial infection or an infection of adults. Int J Antimicrob Agents 2009; 33(Suppl 1)S42-S45. This is a review of the increasing incidence of CDI in the community and previously 'low-risk' populations, with a mention of risk factors among these populations.
38. Wultańska D, Banaszkiewicz A, Radikowski A, et al. Clostridium difficile infection in Polish pediatric outpatients with inflammatory bowel disease. Eur J Clin Microbiol Infect Dis 2010; 29:1265-1270. In this prospective study the authors tested stool samples for C. difficile from outpatients with IBD and identified isolates by PCR ribotyping to estimate the incidence of CDI and recurrent CDI among this population.
39. Ananthakrishnan AN, Issa M, Binion DG. Clostridium difficile and inflammatory bowel disease. Med Clin North Am 2010; 38:711-728. This article presents an updated and extensive review of the complex subject of CDI in patients with IBD.
40. Nguyen GC, Kaplan GG, Harris ML, Brant SR. A national survey of the prevalence and impact of Clostridium difficile infection among hospitalized inflammatory bowel disease patients. Am J Gastroenterol 2008; 103:1443-1450. (Pubitemid 351813903)
41. Ananthakrishnan AN, McGinley EL, Saeian K, Binion DG. Temporal trends in disease outcomes related to Clostridium difficile infection in patients with inflammatory bowel disease. Inflamm bowel disease 2010 [Epub ahead of print]. The authors perform a retrospective study of the incidence of CDI complicating IBD-related hospitalizations in the years 1998, 2004 and 2007. They report an increased excess morbidity related to CDI in hospitalized patients with IBD over this time frame.
42. Powell N, Jung SE, Krishnan B. Clostridium difficile infection and inflammatory bowel disease: A marker for disease extent? Gut 2008; 57:1183-1184.
43. Ben-Horin S, Margalit M, Bossuyt P, et al. Combination immunomodulator and antibiotic treatment in patients with inflammatory bowel disease and Clostridium difficile infection. Clin Gastroenterol Hepatol 2009; 7:981- 987. In this retrospective review, the authors compare different treatment regimens for patients with flaring IBD and CDI and highlight the need for prospective controlled trials to establish best practice for managing these patients.
44. Stone CD. Prognosis in Clostridium difficile infection complicating inflammatory bowel disease. Gut 2008; 57:150-152. (Pubitemid 351158037)
45. Warny M, Pé pin J, Fang A, et al. Toxin production by an emerging strain of Clostridium difficile associated with outbreaks of severe disease in North America and Europe. Lancet 2005; 366:1079-1084. (Pubitemid 41338761)
46. Merrigan M, Venugopal A, Mallozzi M, et al. Human hypervirulent Clostridium difficile strains exhibit increased sporulation as well as robust toxin production. J Bacteriol 2010; 194:4904-4911. The authors examine toxin production and sporulation in hypervirulent C. difficile strains and compare them with nonhypervirulent strains.
47. Akerlund T, Persson I, Unemo M, et al. Increased sporulation rate of epidemic Clostridium difficile type 027/NAP1. J Clin Microbiol 2008; 46:1530-1533. (Pubitemid 351563610)
48. Dawson LF, Valiente E, Wren B. Clostridium difficile - a continually evolving and problematic pathogen. Infect Genet Evol 2009; 9:1410-1417. Dawson et al. provide an excellent review of the virulence factors of emerging strains. The issue of rapidly changing epidemiology on a global setting is well addressed.
49. Underwood S, Guan S, Vijayasubhash V, et al. Characterization of the sporulation initiation pathway of Clostridium difficile and its role in toxin production. J Bacteriol 2009; 191:7296-7305. Using ClosTron gene knockout technology the authors demonstrated that inactivation of genes involved in sporulation initiation in C. difficile resulted in an asporogeneous phenotype and also a reduction in toxin production. The authors discuss the implications of these findings for C. difficile sporulation, virulence and transmission.
50. Pé pin J, Saheb N, Coulombe MA, et al. Emergence of fluoroquinolones as the predominant risk factor for Clostridium difficile-associated diarrhea: A cohort study during an epidemic in Quebec. Clin Infect Dis 2005; 41:1254-1260. (Pubitemid 41532667)
51. Loo VG, Poirier L, Miller MA, et al. A predominantly clonal multiinstitutional outbreak of Clostridium difficile-associated diarrhea with high morbidity and mortality. N Engl J Med 2005; 353:2442-2449. (Pubitemid 41770165)
52. McDonald LC, Killgore GE, Thompson A, et al. An epidemic, toxin genevariant strain of Clostridium difficile. N Engl J Med 2005; 353:2433-2441. (Pubitemid 41770164)
53. Biller P, Shank B, Lind L, et al. Moxifloxacin therapy as a risk factor for Clostridium difficile-associated disease during an outbreak: Attempts to control a new epidemic strain. Infect Control Hosp Epidemiol 2007; 28:198-201. (Pubitemid 46374161)
54. Muto CA, Blank MK, Marsh JW, et al. Control of an outbreak of infection with the hypervirulent Clostridium difficile B1 strain in a university hospital using a comprehensive 'bundle' approach. Clin Infect Dis 2007; 45:1266-1273. (Pubitemid 351411898)
55. Smith A. Outbreak of Clostridium difficile infection in an English hospital linked to hypertoxin-producing strains in Canada and the US. Euro Surveill 2005; 10:E050630-E050632.
56. Kuijper EJ, Barbut F, Brazier JS, et al. Update of Clostridium difficile infection due to PCR ribotype 027 in Europe, 2008. Euro Surveill 2008; 13:18942.
57. Riley TV, Thean S, Hool G, Golledge CL. First Australian isolation of epidemic Clostridium difficile PCR ribotype 027. Med J Aust 2009; 190:706-708.
58. Tae CH, Jung SA, Song HJ, et al. The first case of antibiotic-associated colitis by Clostridium difficile PCR ribotype 027 in Korea. J Korean Med Sci 2009; 24:520-524.
59. Cheng VC, Yam WC, Chan JF, et al. Clostridium difficile ribotype 027 arrives in Hong Kong. Int J Antimicrob Agents 2009; 34:492-493.
60. Quesada-Gomez C, Rodriguez C, Gamboa-Coronado Mdel M, et al. Emergence of Clostridium difficile NAP1 in Latin America. J Clin Microbiol 2010; 48:669-670.
61. Clements AC, Magalhães RJ, Tatem AJ, et al. Clostridium difficile PCR ribotype 027: Assessing the risks of further worldwide spread. Lancet Infect Dis 2010; 10:395-404. The authors present a risk assessment framework for assessing risks of further worldwide spread of epidemic strains of C. difficile with a view to preventing outbreaks in previously unaffected countries. They raise the issue of the role of international trade and travel in disease dissemination.
62. Cheknis AK,Sambol SP,DavidsonDM, et al. Distribution of Clostridium difficile strains froma North American, European and Australian trial of treatment for C. difficile infections: 2005-2007. Anaerobe 2009; 15:230-233. In this study the authors present the results of C. difficile strain typing of stool samples collected from patients enrolled in two large phase III trials of Tolevamer in North America, Europe and Australia involving over 1000 patients. The authors highlight the importance of coordinating international surveillance to monitor the changing epidemiology of CDI.
63. Hensgens MP, Goorhuis A, Notermans DW, et al. Decrease of hypervirulent Clostridium difficile PCR ribotype 027 in the Netherlands. Euro Surveill 2009; 14:19402. Following the establishment of a national surveillance program for C. difficile in the Netherlands, Hensgens et al. report a reduction in the prevalence of PCR ribotype 027 to only 3% of all CDI cases, highlighting the role of surveillance and disease control and prevention measures.
64. Jhung MA, Thompson AD, Killgore GE, et al. Toxinotype V Clostridium difficile in humans and food animals. Emerg Infect Dis 2008; 14:1039-1045. (Pubitemid 351920432)
65. Rupnik M, Widmer A, Zimmermann O, et al. Clostridium difficile toxinotype V, ribotype 078, in animals and humans. J Clin Microbiol 2008; 46:2146. (Pubitemid 351831867)
66. Goorhuis A, Bakker D, Corver J, et al. Emergence of Clostridium difficile infection due to a new hypervirulent strain, polymerase chain reaction ribotype 078. Clin Infect Dis 2008; 47:1162-1170.
67. Limbago BM, Long CM, Thompson AD, et al. Clostridium difficile strains from community-associated infections. J Clin Microbiol 2009; 47:3004-3007. The authors collected stool samples from CA-CDI cases over a 3-month period in 2006 in nine states in the United States. They examined strain types and antimicrobial susceptibility profiles.
68. Keel K, Brazier JS, Post KW, et al. Prevalence of PCR ribotypes among Clostridium difficile isolates from pigs, calves, and other species. J Clin Microbiol 2007; 45:1963-1964. (Pubitemid 46933933)
69. Bakker D, Corver J, Harmanus C, et al. Relatedness of human and animal Clostridium difficile PCR ribotype 078 isolates based on multi locus variable number of tandem repeat analysis and tetracycline resistance. J Clin Microbiol 2010; 48:3744-3749. In this European study of 102 human and 56 porcine C. difficile PCR ribotype 078 strains, the investigators find high degrees of genetic relatedness.
70. Debast SB, van Leengoed LA, Goorhuis A, et al. Clostridium difficile PCR ribotype 078 toxinotype V found in diarrhoeal pigs identical to isolates from affected humans. Environ Microbiol 2009; 11:505-511. Debast et al. examined C. difficile PCR ribotype 078 strains from both diarrheal piglets and humans and found them indistinguishable in terms of genetic identity, toxin production and antimicrobial sensitivity.
71. Weese JS. Clostridium difficile in food-innocent bystander or serious threat? Clin Microbiol Infect 2010; 16:3-10. Weese reviews the literature to-date on C. difficile in food products and examines its possible role as a food-borne pathogen.
72. Gould LH, Limbago B. Clostridium difficile in food and domestic animals: A new foodborne pathogen? Clin Infect Dis 2010; 51:577-582. Gould presents a summary of the data on C. difficile in food and animals, contributing to the discussion on C. difficile as a potential food-borne pathogen.
73. Burns K, Skally M, Solomon K, et al. Clostridium difficile infection in the Republic of Ireland: Results of a 1-month national surveillance and ribotyping project, March 2009. Infect Control Hosp Epidemiol 2010; 31:1085-1087.
74. Burns K, Morris-Downes M, Fawley WN, et al. Infection due to C. difficile ribotype 078: First report of cases in the Republic of Ireland. J Hosp Infect 2010; 75:287-291. This report documents an outbreak of CDI in an Irish hospital associated with PCR ribotypes 027 and 078 affecting older patients.
75. Crobach MJ, Dekkers OM, Wilcox M, Kuijper EJ. European society of clinical microbiology and infectious diseases (ESCMID): Data review and recommendations for diagnosing Clostridium difficile-infection (CDI). Clin Microbiol Infect 2009; 15:1053-1066. An excellent review of current diagnostic tests for CDI and presentation of evidence-based guidelines for the diagnosis of CDI.
76. Planche T, Aghaizu A, Holliman R, et al. Diagnosis of Clostridium difficile infection by toxin detection kits: A systematic review. Lancet Infect Dis 2008; 8:777-784.
77. Eastwood K, Else P, Charlett A, Wilcox M. Comparison of nine commercially available Clostridium difficile toxin detection assays, a real-time PCR assay for C. difficile tcdB, and a glutamate dehydrogenase detection assay to cytotoxin testing and cytotoxigenic culture methods. J Clin Microbiol 2009; 47:3211-3217. Eastwood et al. compile a comprehensive review of various testing methods for C. difficile, in particular, comparing performances to both cytotoxin testing and cytotoxigenic culture at low (2%) and high (10%) prevalence of C. difficile. They found that PCR for the toxin B gene was the optimal rapid single test for the diagnosis of CDI because it had the highest NPV.
78. Gilligan PH. Is a two-step glutamate dehydrogenase antigen-cytotoxicity neutralization assay algorithm superior to the premier toxin A and B enzyme immunoassay for laboratory detection of Clostridium difficile? J Clin Microbiol 2008; 46:1523-1525. (Pubitemid 351563608)
79. Ticehurst JR, Aird DZ, Dam LM, et al. Effective detection of toxigenic Clostridium difficile by a two-step algorithm including tests for antigen and cytotoxin. J Clin Microbiol 2006; 44:1145-1149.
80. Schmidt ML, Gilligan PH. Clostridium difficile testing algorithms: What is practical and feasible? Anaerobe 2009; 15:270-273. A good mini-review and discussion of the strengths and weaknesses of the current reference standards for the diagnosis of CDI and a review of testing algorithms used in their institution.
81. Goldenberg SD, Dieringer T, French GL. Detection of toxigenic Clostridium difficile in diarrheal stools by rapid real-time polymerase chain reaction. Diagn Microbiol Infect Dis 2010; 67:304-307. The investigators found that the Cepheid Xpert PCR assay (Sunnyvale, CA) had a sensitivity of 100%, specificity of 96.7%, PPV of 90.5% and NPV of 100% compared to toxigenic culture for the diagnosis of CDI. This multiplex system could detect the tcdB gene, binary toxin gene and a deletion in the tcdC gene, making it useful for predicting the presence of PCR ribotype 027.
82. de Boer RF, Wijma JJ, Schuurman T, et al. Evaluation of a rapid molecular screening approach for the detection of toxigenic Clostridium difficile in general and subsequent identification of the tcdC delta117 mutation in human stools. J Microbiol Methods 2010; 83:59-65. In this article the authors evaluate a screening multiplex real-time PCR assay which detects the presence of tcdA and tcdB directly in feces and a separate multiplex real-time PCR typing assay targeting the tcdC gene.
83. Persson S, Torpdahl M, Olsen KEP. New multiplex PCR method for the detection of Clostridium difficile toxin A (tcdA) and toxin B (tcdB) and the binary toxin (cdtA/cdtB) genes applied to a Danish strain collection. Clin Microbiol Infect 2008; 14:1057-1064. (Pubitemid 352748847)
84. Doing KM, Hintz MS, Keefe C, et al. Reevaluation of the Premier Clostridium difficile toxin A and B immunoassay with comparison to glutamate dehydrogenase common antigen testing evaluating Bartels cytotoxin and Prodesse ProGastro Cd polymerase chain reaction as confirmatory procedures. Diagn Microbiol Infect Dis 2010; 66:129-134. In a large prospective study, the authors compared the performance of a commercial toxinA/B assay to a two-step algorithm that evaluated cytotoxin and PCR as confirmatory methods. The toxin A/B test missed 25% of truepositives. Once again, PCR for the toxin B gene was the most sensitive test. They concluded that molecular techniques, used either as a confirmatory or primary testing strategy, allowed same day reporting and had the highest correlation with toxigenic culture.
85. Arnold A, Pope C, Bray S, et al. Prospective assessment of two-stage testing for Clostridium difficile. J Hosp Infect 2010; 76:18-22. The authors report the results of the introduction of a two-step diagnostic algorithm for C. difficile using an EIA for toxin A and B followed by cell CTA and toxigenic culture as confirmatory techniques.
86. Goldenberg SD, Cliff PR, Smith S, et al. Two-step glutamate dehydrogenase antigen real-time polymerase chain reaction assay for detection of toxigenic Clostridium difficile. J Hosp Infect 2010; 74:48-54. Using culture cytotoxin neutralization as the reference standard, the authors compare EIA for toxin A and B with a two-step algorithm using a GDH screening test and confirmatory PCR assay. They conclude that screening for GDH before confirmation of positives by PCR is cheaper than screening all specimens by PCR. The discussion includes an interesting cost-benefit analysis of two-step testing based on UK costings.
87. Larson AM, Fung AM, Fang FC. Evaluation of tcdB real-time polymerase chain reaction in a three-step diagnostic algorithm for detection of toxigenic Clostridium difficile. J Clin Microbiol 2010; 48:124-130. Larson et al. found that a three-step algorithm in which direct stool PCR is used to analyze GDH-positive, toxin EIA negative specimens provided rapid results for 87.7% of specimens. They explore US costs and conclude that the additional annual costs associated with direct stool PCR or three-step algorithms are justified by the earlier detection of CDI.
88. Planche TD, Wilcox MH. Two-step testing for C. difficile: No answers yet. J Hosp Infect 2010; 75:325-326. In response to the article by Goldenberg et al. [86], Planche and Wilcox highlight the difficulties associated with the performance characteristics of the two-step algorithm and call for a large well designed prospective study to clarify optimal testing strategies for CDI.
89. Bauer MP, Kuijper EJ, van Dissel JT. European society of clinical microbiology and infectious diseases (ESCMID): Treatment guidance document for Clostridium difficile infection (CDI). Clin Microbiol Infect 2009; 15:1067-1079. An excellent review of the literature and presentation of treatment guidelines for CDI based on evidence and expert opinion.
90. Cloud J, Noddin L, Pressman A, et al. Clostridium difficile strain NAP-1 is not associated with severe disease in a non epidemic setting. Clin Gastroenterol Hepatol 2009; 7:868-873. Examining strain types and outcomes in CDI cases over a 13-month period, the authors identify risk factors for severe CDI and worse outcomes. They highlight the clinical significance of having a leukocyte count more than 20 000 cells/ml and a peak creatinine more than 2.3 mg/dl in predicting severe CDI and CDI-related deaths.
91. Lamontagne F, Labbé AC, Haeck O, et al. Impact of emergency colectomy on survival of patients with fulminant Clostridium difficile colitis during an epidemic caused by a hypervirulent strain. Ann Surg 2007; 245:267-272. (Pubitemid 46148486)
92. Aslam S, Hamill RJ, Musher DM. Treatment of Clostridium difficile-associated disease: Old therapies and new strategies. Lancet Infect Dis 2005; 5:549-557. (Pubitemid 41196754)
93. Kyne L, Warny M, Qamar A, Kelly CP. Association between antibody response to toxin A and protection against recurrent Clostridium difficile diarrhea. Lancet 2001; 357:189-193. (Pubitemid 32108091)
94. Hu MY, Katchar K, Kyne L, et al. Prospective derivation and validation of a clinical prediction rule for recurrent Clostridium difficile infection. Gastroenterology 2009; 136:1206-1214. Hu et al. prospectively derive and validate a clinical prediction rule for recurrent CDI incorporating age, Horns index of disease severity and additional antibiotic use after diagnosis of CDI.
95. Tannock G, Munro K, Taylor C, et al. A new macrocyclic antibiotic, Fidaxomicin (OPT-80), causes less alteration to the bowel microbiota of Clostridium difficile-infected patients than does vancomycin. Microbiol 2010; 156:3354-3359. The investigators compare the effects on the fecal microbiota of fidaxomicin with those of vancomycin.
96. Poxton IR. Fidaxomicin: A new macrocyclic, RNA polymerase-inhibiting antibiotic for the treatment of Clostridium difficile infection. Future Microbiol 2010; 5:539-548. This review covers the performance to-date of fidaxomicin in clinical trials.
97. Lu CL, Liu CY, Liao CH, et al. Severe and refractory Clostridium difficile infection successfully treated with tigecycline and metronidazole. Int J Antimicrob Agents 2010; 35:311-312. The authors report a case of successful treatment of severe and recurrent CDI with tigecycline.
98. Herpers BL, Vlaminckx B, Burkhardt O, et al. Intravenous tigecycline as adjunctive or alternative therapy for severe refractory Clostridium difficile infection. Clin Infect Dis 2009; 48:1732-1735. This series documents four cases of patients successfully treated with tigecycline.
99. Kopterides P, Papageorgiou C, Antoniadou A, et al. Failure of tigecycline to treat severe Clostridium difficile infection. Anaesth Intensive Care 2010; 38:755-758. In this case report, treatment of severe CDI with tigecycline is unsuccessful and complications of treatment, including the acquisition of other antimicrobial resistant organisms, are discussed.
100. Johnson S, Schriever C, Patel U, et al. Rifaximin Redux: Treatment of recurrent Clostridium difficile infections with rifaximin immediately postvancomycin treatment. Anaerobe 2009; 15:290-291. This article describes a case series of six patients treated for recurrent CDI with rifaximin.
101. Garey KW, Jiang ZD, Bellard A, Dupont HL. Rifaximin in treatment of recurrent Clostridium difficile-associated diarrhea: An uncontrolled pilot study. J Clin Gastroenterol 2009; 43:91-93.
102. Koo HL, Garey KW, DuPont HL. Future novel therapeutic agents for Clostridium difficile infection. Expert Opin Investig Drugs 2010; 19:825-836. The authors perform a thorough review of novel therapies for CDI, including the clinical evidence to support their efficacy.
103. Musher DM, Logan N, Bressler Am, et al. Nitazoxanide versus vancomycin in Clostridium difficile infection: A randomized, double blind study. Clin Infect Dis 2009; 48:e41-46. A randomized controlled trial of 50 participants comparing the efficacy of nitazoxanide with vancomycin in patients with CDI.
104. Musher DM, Logan N, Mehendiratta V, et al. Clostridium difficile colitis that fails conventional metronidazole therapy: Response to nitazoxanide. J Antimicrob Chemother 2007; 59:705-710. (Pubitemid 47073405)
105. Johnson AP. New antibiotics for selective treatment of gastrointestinal infection caused by Clostridium difficile. Expert Opin Ther Patents 2010; 20:1389-1399. This review discusses the use of fidaxomicin, REP3123, oritavancin, NVB302 and nitazoxanide for the treatment of CDI.
106. Rohlke F, Surawicz CM, Stollman N. Fecal flora reconstitution for recurrent Clostridium difficile infection: Results and methodology. J Clin Gastroenterol 2010; 44:567-570. Here the authors describe successful treatment of 19 patients with multiple episodes of recurrent CDI by infusing donor stool through a colonoscope.
107. Yoon SS, Brandt LJ. Treatment of refractory/recurrent Clostridium difficileassociated disease by donated stool transplanted via colonoscopy: A case series of 12 patients. J Clin Gastroenterol 2010; 44:562-566. Describtion of successful treatment of 12 patients with recurrent CDI by infusing donor stool through a colonoscope.
108. Bakken JS. Fecal bacteriotherapy for recurrent Clostridium difficile infection. Anaerobe 2009; 15:285-289. A thorough review of the topic of fecal transplantation for recurrent CDI. The authors describe selection of patients and donors, routes of instillation and success rates. They conclude that this low-tech procedure is easy to perform and is successful in approximately 90% of cases. They speculate on the future development of ''synthetic stool'' products.
109. van Nood E, Speelman P, Kuijper EJ, Keller JJ. Struggling with recurrent Clostridium difficile infections: Is donor faeces the solution? Euro Surveill 2009; 14:1-6. Another concise review of fecal transplant for recurrent CDI, with details of recruitment for the first randomized controlled study of donor feces instillation for recurrent CDI.
110. Merrigan MM, Sambol SP, Johnson S, Gerding D. New approach to the management of Clostridium difficile infection: Colonisation with nontoxigenic Clostridium difficile during daily ampicillin or ceftriaxone administration. Int J Antimicrob Agents 2009; 33:S46-S50. Merriganet al. detail their studyonthe role of colonization withnontoxigenic C. difficile strains in hamsters receiving antibiotics. They discuss scenarios of colonization and prevention success in hospitalized patients that are likely to occur depending on the susceptibility of the C. difficile strains to the antibiotic the patient is receiving.
111. McFarland LV. Evidence-based review of probiotics for antibiotic-associated diarrhea and Clostridium difficile infections. Anaerobe 2009; 15:274-280. This article provides a positive review of the role of probiotics, highlighting areas for further research and development.
112. Miller M. The fascination with probiotics for Clostridium difficile infection: Lack of evidence for prophylactic or therapeutic efficacy. Anaerobe 2009; 15:281-284. In contrast, this review of the literature on probiotics for the treatment of CDI finds that they have little role to play in the prevention or therapy of CDI.
113. Gao XW, Mubasher M, Fang CY, et al. Dose-response efficacy of proprietary probiotic formula of Lactobacillus acidophilus CL1285 and Lactobacillus casei LBC80R for antibiotic-associated diarrhea and Clostridium difficileassociated diarrhea prophylaxis in adult patients. Am J Gastroenterol 2010; 105:1636-1641. The investigators report the results of a double blind, randomized, placebo controlled study of BIO-K CL-1285 in an Asian population for the prophylaxis of antibiotic-associated diarrhea.
114. Juang P, Skledar SJ, Zgheib NK, et al. Clinical outcomes of intravenous immune globulin in severe Clostridium difficile-associated diarrhea. Am J Infect Control 2007; 35:131-137. (Pubitemid 46283599)
115. Abougergi MS, Broor A, Cui W, Jaar BG. Intravenous immunoglobulin for the treatment of severe Clostridium difficile colitis: An observational study and review of the literature. J Hosp Med 2010; 5:e1-e9. In this observational study the authors found that IVIG was not beneficial in the treatment of all patients with severe CDI. However, they did observe that benefit appeared to depend on the extent of systemic involvement, prompting a discussion on the optimal timing of IVIG.
116. Lowy I, Molrine DC, Leav BA, et al. Treatment with monoclonal antibodies against Clostridium difficile toxins. N Engl J Med 2010; 362: 197-205. Lowy et al. report promising results of a phase II clinical trial of two fully human, neutralizing mAbs against C. difficile toxins A and B for the treatment of recurrent CDI.
117. Giannasca PJ, Warny M. Active and passive immunization against Clostridium difficile diarrhea and colitis. Vaccine 2004; 22:848-856. (Pubitemid 38177385)
118. Sougioultzis S, Kyne L, Drudy D, et al. Clostridium difficile toxoid vaccine in recurrent C. difficile-associated diarrhea. Gastroenterology 2005; 128: 764-770. (Pubitemid 40585378)
119. Lee BY, Popovich MJ, Tian Y, et al. The potential value of Clostridium difficile vaccine: An economic computer simulation model. Vaccine 2010; 28:5245-5253. Lee et al. have developed an economic model evaluating the cost-effectiveness of a C. difficile vaccine for primary and secondary prevention of CDI.
120. Gardiner DF, Rosenberg T, Zaharatos J, et al. A DNA vaccine targeting the receptor-binding domain of Clostridium difficile toxin A. Vaccine 2009; 27:3598-3604. The authors describe the development of a DNA vaccine capable of inducing neutralizing antibodies to C. difficile toxin A, with evidence of protection in mice from death.