Pitfalls in Diagnosis of Pediatric Clostridium difficile Infection

Infectious Disease Clinics of North America

Volumn 29, Issue 3, 2015, Pages 465-476

  Sammons, Julia S ^a   Toltzis, Philip ^b  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b CASE WESTERN RESERVE UNIVERSITY   (United States)

Author keywords

Clostridium difficile; Diagnosis; Diarrhea; Pediatrics

Indexed keywords

BACTERIAL TOXIN; GLUTAMATE DEHYDROGENASE;

ADULTHOOD; BACTERIUM CULTURE; CHILDHOOD; CHILDHOOD DISEASE; CLOSTRIDIUM DIFFICILE INFECTION; COMMUNITY ACQUIRED INFECTION; CYTOTOXICITY ASSAY; CYTOTOXIGENIC CULTURE; DIAGNOSTIC ACCURACY; DIAGNOSTIC TEST; DIARRHEA; ENZYME IMMUNOASSAY; FALSE POSITIVE RESULT; HUMAN; INCIDENCE; LOOP MEDIATED ISOTHERMAL AMPLIFICATION; NONHUMAN; PEPTOCLOSTRIDIUM DIFFICILE; POLYMERASE CHAIN REACTION; PREDICTIVE VALUE; PREVALENCE; REVIEW; RISK FACTOR; CHILD; CLOSTRIDIUM INFECTIONS; FEMALE; INFANT; ISOLATION AND PURIFICATION; LABORATORY DIAGNOSIS; MALE; MICROBIOLOGY; PRESCHOOL CHILD;

CHILD; CHILD, PRESCHOOL; CLOSTRIDIUM DIFFICILE; CLOSTRIDIUM INFECTIONS; DIARRHEA; FALSE POSITIVE REACTIONS; FEMALE; HUMANS; INFANT; MALE; PREVALENCE; RISK FACTORS;

EID: 84952870595     PISSN: 08915520     EISSN: 15579824     Source Type: Journal    
DOI: 10.1016/j.idc.2015.05.010     Document Type: Review

References (79)

1. Cohen S.H., Gerding D.N., 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.
2. Dubberke E.R., Wertheimer A.I. Review of current literature on the economic burden of Clostridium difficile infection. Infect Control Hosp Epidemiol 2009, 30:57-66.
3. Miller B.A., Chen L.F., Sexton D.J., et al. Comparison of the burdens of hospital-onset, healthcare facility-associated Clostridium difficile infection and of healthcare-associated infection due to methicillin-resistant Staphylococcus aureus in community hospitals. Infect Control Hosp Epidemiol 2011, 32:387-390.
4. Magill S.S., Edwards J.R., Bamberg W., et al. Multistate point-prevalence survey of health care-associated infections. N Engl J Med 2014, 370:1198-1208.
5. Voth D.E., Ballard J.D. Clostridium difficile toxins: mechanism of action and role in disease. Clin Microbiol Rev 2005, 18:247-263.
6. Kaatz G.W., Gitlin S.D., Schaberg D.R., et al. Acquisition of Clostridium difficile from the hospital environment. Am J Epidemiol 1988, 127:1289-1294.
7. Shaughnessy M.K., Micielli R.L., DePestel D.D., et al. Evaluation of hospital room assignment and acquisition of Clostridium difficile infection. Infect Control Hosp Epidemiol 2011, 32:201-206.
8. Owens R.C., Donskey C.J., Gaynes R.P., et al. Antimicrobial-associated risk factors for Clostridium difficile infection. Clin Infect Dis 2008, 46(Suppl 1):S19-S31.
9. Seekatz A.M., Young V.B. Clostridium difficile and the microbiota. J Clin Invest 2014, 124:4182-4189.
10. Steiner C., Barrett M., Terrel L. HCUP projections: Clostridium difficile hospitalizations 2011 to 2012 2012, HCUP Projections Report # 2012-01, U.S. Agency for Healthcare Research and Quality, Rockville (MD).
11. 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.
12. Loo V.G., Poirier L., Miller M.A., et al. A predominantly clonal multi-institutional outbreak of Clostridium difficile-associated diarrhea with high morbidity and mortality. N Engl J Med 2005, 353:2442-2449.
13. Lessa F.C., Mu Y., Bamberg W.M., et al. Burden of Clostridium difficile infection in the United States. N Engl J Med 2015, 372:825-834.
14. Dubberke E.R., Olsen M.A. Burden of Clostridium difficile on the healthcare system. Clin Infect Dis 2012, 55(Suppl 2):S88-S92.
15. Kim J., Smathers S.A., Prasad P., et al. Epidemiological features of Clostridium difficile-associated disease among inpatients at children's hospitals in the United States, 2001-2006. Pediatrics 2008, 122:1266-1270.
16. Zilberberg M.D., Tillotson G.S., McDonald C. Clostridium difficile infections among hospitalized children, United States, 1997-2006. Emerg Infect Dis 2010, 16:604-609.
17. Nylund C.M., Goudie A., Garza J.M., et al. Clostridium difficile infection in hospitalized children in the United States. Arch Pediatr Adolesc Med 2011, 165:451-457.
18. Benson L., Song X., Campos J., et al. Changing epidemiology of Clostridium difficile-associated disease in children. Infect Control Hosp Epidemiol 2007, 28:1233-1235.
19. Zilberberg M.D., Shorr A.F., Kollef M.H. Increase in Clostridium difficile-related hospitalizations among infants in the United States, 2000-2005. Pediatr Infect Dis J 2008, 27:1111-1113.
20. Wendt J.M., Cohen J.A., Mu Y., et al. Clostridium difficile infection among children across diverse US geographic locations. Pediatrics 2014, 133:651-658.
21. Khanna S., Baddour L.M., Huskins W.C., et al. The epidemiology of Clostridium difficile infection in children: a population-based study. Clin Infect Dis 2013, 56:1401-1406.
22. Sammons J.S., Localio R., Xiao R., et al. Clostridium difficile infection is associated with increased risk of death and prolonged hospitalization in children. Clin Infect Dis 2013, 57:1-8.
23. Rhee S.M., Tsay R., Nelson D.S., et al. Clostridium difficile in the pediatric population of Monroe County, New York. J Pediatric Infect Dis Soc 2014, 3:183-188.
24. Centers for Disease Control and Prevention (CDC) Severe Clostridium difficile-associated disease in populations previously at low risk-four states, 2005. MMWR Morb Mortal Wkly Rep 2005, 54:1201-1205.
25. Centers for Disease Control and Prevention (CDC) Surveillance for community-associated Clostridium difficile-Connecticut, 2006. MMWR Morb Mortal Wkly Rep 2008, 57:340-343.
26. Centers for Disease Control and Prevention (CDC) Vital signs: preventing Clostridium difficile infections. MMWR Morb Mortal Wkly Rep 2012, 61:157-162.
27. Chitnis A.S., Holzbauer S.M., Belflower R.M., et al. Epidemiology of community-associated Clostridium difficile infection, 2009 through 2011. JAMA Intern Med 2013, 173:1359-1367.
28. Humphries R.M., Uslan D.Z., Rubin Z. Performance of Clostridium difficile toxin enzyme immunoassay and nucleic acid amplification tests stratified by patient disease severity. J Clin Microbiol 2013, 51:869-873.
29. Kaltsas A., Simon M., Unruh L.H., et al. Clinical and laboratory characteristics of Clostridium difficile infection in patients with discordant diagnostic test results. J Clin Microbiol 2012, 50:1303-1307.
30. Peterson L.R., Manson R.U., Paule S.M., et al. Detection of toxigenic Clostridium difficile in stool samples by real-time polymerase chain reaction for the diagnosis of C. difficile-associated diarrhea. Clin Infect Dis 2007, 45:1152-1160.
31. Planche T.D., Davies K.A., Coen P.G., et al. Differences in outcome according to Clostridium difficile testing method: a prospective multicentre diagnostic validation study of C difficile infection. Lancet Infect Dis 2013, 13:936-945.
32. Baker I., Leeming J.P., Reynolds R., et al. Clinical relevance of a positive molecular test in the diagnosis of Clostridium difficile infection. J Hosp Infect 2013, 84:311-315.
33. Longtin Y., Trottier S., Brochu G., et al. Impact of the type of diagnostic assay on Clostridium difficile infection and complication rates in a mandatory reporting program. Clin Infect Dis 2013, 56:67-73.
34. Guerrero D.M., Chou C., Jury L.A., et al. Clinical and infection control implications of Clostridium difficile infection with negative enzyme immunoassay for toxin. Clin Infect Dis 2011, 53:287-290.
35. Guerrero D.M., Becker J.C., Eckstein E.C., et al. Asymptomatic carriage of toxigenic Clostridium difficile by hospitalized patients. J Hosp Infect 2013, 85:155-158.
36. Crobach M.J., Dekkers O.M., Wilcox M.H., et al. 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.
37. 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.
38. O'Horo J.C., Jones A., Sternke M., et al. Molecular techniques for diagnosis of Clostridium difficile infection: systematic review and meta-analysis. Mayo Clin Proc 2012, 87:643-651.
39. Leslie J.L., Cohen S.H., Solnick J.V., et al. Role of fecal Clostridium difficile load in discrepancies between toxin tests and PCR: is quantitation the next step in C. difficile testing?. Eur J Clin Microbiol Infect Dis 2012, 31:3295-3299.
40. Dionne L.L., Raymond F., Corbeil J., et al. Correlation between Clostridium difficile bacterial load, commercial real-time PCR cycle thresholds, and results of diagnostic tests based on enzyme immunoassay and cell culture cytotoxicity assay. J Clin Microbiol 2013, 51:3624-3630.
41. Warny M., Pepin 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.
42. Tenover F.C., Novak-Weekley S., Woods C.W., et al. Impact of strain type on detection of toxigenic Clostridium difficile: comparison of molecular diagnostic and enzyme immunoassay approaches. J Clin Microbiol 2010, 48:3719-3724.
43. Sunkesula V.C., Kundrapu S., Muganda C., et al. Does empirical Clostridium difficile infection (CDI) therapy result in false-negative CDI diagnostic test results?. Clin Infect Dis 2013, 57:494-500.
44. Shetty N., Wren M.W., Coen P.G. The role of glutamate dehydrogenase for the detection of Clostridium difficile in faecal samples: a meta-analysis. J Hosp Infect 2011, 77:1-6.
45. Ticehurst J.R., Aird D.Z., Dam L.M., 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.
46. Selvaraju S.B., Gripka M., Estes K., et al. Detection of toxigenic Clostridium difficile in pediatric stool samples: an evaluation of Quik Check Complete Antigen assay, BD GeneOhm Cdiff PCR, and ProGastro Cd PCR assays. Diagn Microbiol Infect Dis 2011, 71:224-229.
47. Hart J., Putsathit P., Knight D.R., et al. Clostridium difficile infection diagnosis in a paediatric population: comparison of methodologies. Eur J Clin Microbiol Infect Dis 2014, 33:1555-1564.
48. Ota K.V., McGowan K.L. Clostridium difficile testing algorithms using glutamate dehydrogenase antigen and C. difficile toxin enzyme immunoassays with C. difficile nucleic acid amplification testing increase diagnostic yield in a tertiary pediatric population. J Clin Microbiol 2012, 50:1185-1188.
49. Kociolek L.K., Sandora T.J. National variability in surveillance, testing, and infection prevention for Clostridium difficile infection in pediatric populations. Am J Infect Control 2013, 41:933-935.
50. Sammons J.S., Gerber J.S., Tamma P.D., et al. Diagnosis and management of Clostridium difficile infection by pediatric infectious diseases physicians. J Pediatric Infect Dis Soc 2013, 3:43-48.
51. Deshpande A., Pasupuleti V., Rolston D.D., et al. Diagnostic accuracy of real-time polymerase chain reaction in detection of Clostridium difficile in the stool samples of patients with suspected Clostridium difficile infection: a meta-analysis. Clin Infect Dis 2011, 53:e81-e90.
52. Rutledge-Taylor K., Matlow A., Gravel D., et al. A point prevalence survey of health care-associated infections in Canadian pediatric inpatients. Am J Infect Control 2012, 40:491-496.
53. Campbell R.J., Giljahn L., Machesky K., et al. Clostridium difficile infection in Ohio hospitals and nursing homes during 2006. Infect Control Hosp Epidemiol 2009, 30:526-533.
54. Toltzis P., Nerandzic M.M., Saade E., et al. High proportion of false-positive Clostridium difficile enzyme immunoassays for toxin A and B in pediatric patients. Infect Control Hosp Epidemiol 2012, 33:175-179.
55. Donta S.T., Myers M.G. Clostridium difficile toxin in asymptomatic neonates. J Pediatr 1982, 100:431-434.
56. Larson H.E., Barclay F.E., Honour P., et al. Epidemiology of Clostridium difficile in infants. J Infect Dis 1982, 146:727-733.
57. Sherertz R.J., Sarubbi F.A. The prevalence of Clostridium difficile and toxin in a nursery population: a comparison between patients with necrotizing enterocolitis and an asymptomatic group. J Pediatr 1982, 100:435-439.
58. Rousseau C., Poilane I., De Pontual L., et al. Clostridium difficile carriage in healthy infants in the community: a potential reservoir for pathogenic strains. Clin Infect Dis 2012, 55:1209-1215.
59. Jangi S., Lamont J.T. Asymptomatic colonization by Clostridium difficile in infants: implications for disease in later life. J Pediatr Gastroenterol Nutr 2010, 51:2-7.
60. Kim J., Shaklee J.F., Smathers S., et al. Risk factors and outcomes associated with severe Clostridium difficile infection in children. Pediatr Infect Dis J 2012, 31:134-138.
61. Schutze G.E., Willoughby R.E., Committee on Infectious Disease, American Academy of Pediatrics Clostridium difficile infection in infants and children. Pediatrics 2013, 131:196-200.
62. Adler S.P., Chandrika T., Berman W.F. Clostridium difficile associated with pseudomembranous colitis. Occurrence in a 12-week-old infant without prior antibiotic therapy. Am J Dis Child 1981, 135:820-822.
63. Qualman S.J., Petric M., Karmali M.A., et al. Clostridium difficile invasion and toxin circulation in fatal pediatric pseudomembranous colitis. Am J Clin Pathol 1990, 94:410-416.
64. Singer D.B., Cashore W.J., Widness J.A., et al. Pseudomembranous colitis in a preterm neonate. J Pediatr Gastroenterol Nutr 1986, 5:318-320.
65. McDonald L.C., Coignard B., Dubberke E., et al. Recommendations for surveillance of Clostridium difficile-associated disease. Infect Control Hosp Epidemiol 2007, 28:140-145.
66. Pai S., Aliyu S.H., Enoch D.A., et al. Five years experience of Clostridium difficile infection in children at a UK tertiary hospital: proposed criteria for diagnosis and management. PLoS One 2012, 7:e51728.
67. de Blank P., Zaoutis T., Fisher B., et al. Trends in Clostridium difficile infection and risk factors for hospital acquisition of Clostridium difficile among children with cancer. J Pediatr 2013, 163:699-705.e1.
68. Tschudin-Sutter S., Tamma P.D., Naegeli A.N., et al. Distinguishing community-associated from hospital-associated Clostridium difficile infections in children: implications for public health surveillance. Clin Infect Dis 2013, 57:1665-1672.
69. Pascarella F., Martinelli M., Miele E., et al. Impact of Clostridium difficile infection on pediatric inflammatory bowel disease. J Pediatr 2009, 154:854-858.
70. Sandora T.J., Fung M., Flaherty K., et al. Epidemiology and risk factors for Clostridium difficile infection in children. Pediatr Infect Dis J 2011, 30:580-584.
71. Boenning D.A., Fleisher G.R., Campos J.M., et al. Clostridium difficile in a pediatric outpatient population. Pediatr Infect Dis 1982, 1:336-338.
72. Ellis M.E., Mandal B.K., Dunbar E.M., et al. Clostridium difficile and its cytotoxin in infants admitted to hospital with infectious gastroenteritis. Br Med J (Clin Res Ed) 1984, 288:524-526.
73. Vesikari T., Isolauri E., Maki M., et al. Clostridium difficile in young children. Association with antibiotic usage. Acta Paediatr Scand 1984, 73:86-91.
74. Denno D.M., Shaikh N., Stapp J.R., et al. Diarrhea etiology in a pediatric emergency department: a case control study. Clin Infect Dis 2012, 55:897-904.
75. Tang P., Roscoe M., Richardson S.E. Limited clinical utility of Clostridium difficile toxin testing in infants in a pediatric hospital. Diagn Microbiol Infect Dis 2005, 52:91-94.
76. El Feghaly R.E., Stauber J.L., Tarr P.I., et al. Viral co-infections are common and are associated with higher bacterial burden in children with clostridium difficile infection. J Pediatr Gastroenterol Nutr 2013, 57:813-816.
77. Valentini D., Vittucci A.C., Grandin A., et al. Coinfection in acute gastroenteritis predicts a more severe clinical course in children. Eur J Clin Microbiol Infect Dis 2013, 32:909-915.
78. Stockmann C., Rogatcheva M., Harrel B., et al. How well does physician selection of microbiologic tests identify Clostridium difficile and other pathogens in paediatric diarrhoea? Insights using multiplex PCR-based detection. Clin Microbiol Infect 2015, 21:179.e9-179.e15.
79. Vernacchio L., Vezina R.M., Mitchell A.A., et al. Diarrhea in American infants and young children in the community setting: incidence, clinical presentation and microbiology. Pediatr Infect Dis J 2006, 25:2-7.