Skip to main content
×
Home

High Proportion of False-Positive Clostridium difficile Enzyme Immunoassays for Toxin A and B in Pediatric Patients

  • Philip Toltzis (a1), Michelle M. Nerandzic (a2), Elie Saade (a2), Mary Ann O'Riordan (a1), Sarah Smathers (a3), Theoklis Zaoutis (a3), Jason Kim (a3) and Curtis J. Donskey (a4)...
Abstract
Objectives.

To determine the frequency of false-positive Clostridium difficile toxin enzyme immunoassay (EIA) results in hospitalized children and to examine potential reasons for this false positivity.

Design.

Nested case-control.

Setting.

Two tertiary care pediatric hospitals.

Methods.

As part of a natural history study, prospectively collected EIA-positive stools were cultured for toxigenic C. difficile, and characteristics of children with false-positive and true-positive EIA results were compared. EIA-positive/culture-negative samples were recultured after dilution and enrichment steps, were evaluated for presence of the tcdB gene by polymerase chain reaction (PCR), and were further cultured for Clostridium sordellii, a cause of false-positive EIA toxin assays.

Results.

Of 112 EIA-positive stools cultured, 72 grew toxigenic C. difficile and 40 did not, indicating a positive predictive value of 64% in this population. The estimated prevalence of C. difficile infection (CDI) in the study sites among children tested for this pathogen was 5%–7%. Children with false-positive EIA results were significantly younger than those with true-positive tests but did not differ in other characteristics. No false-positive specimens yielded C. difficile when cultured after enrichment or serial dilution, 1 specimen was positive for tcdB by PCR, and none grew C. sordellii.

Conclusions.

Approximately one-third of EIA tests used to evaluate pediatric inpatients for CDI were falsely positive. This finding was likely due to the low prevalence of CDI in pediatric hospitals, which diminishes the test's positive predictive value. These data raise concerns about the use of EIA assays to diagnosis CDI in children.

Infect Control Hosp Epidemiol 2012;33(2):175-179

Copyright
Corresponding author
Division of Pharmacology and Critical Care, Rainbow Babies and Children's Hospital, 11100 Euclid Avenue, Cleveland, OH 44106 (pxt2@case.edu)
References
Hide All
1.McDonald LC, Killgore GE, Thompson A, et al. An epidemic, toxin gene-variant strain of Clostridium difficile. N Engl J Med 2005;353:24332441.
2.Kim J, Smathers SA, Prasad P, Leckerman KH, Coffin S, Zaoutis T. Epidemiological features of Clostridium difficile–associated disease among inpatients at children's hospitals in the United States, 2001–2006. Pediatrics 2008;122:12661270.
3.Nylund CM, Goudie A, Garza JM, Fairbrother G, Cohen MB. Clostridium difficile infection in hospitalized children in the United States. Arch Pediatr Adolesc Med 2011;165:451457.
4.Zilberberg MD, Tillotson GS, McDonald C. Clostridium difficile infections among hospitalized children, United States, 1997–2006. Emerg Infect Dis 2010;16:604609.
5.Loo VG, Poirier L, Miller MA, et al. A predominantly clonal multi-institutional outbreak of Clostridium difficile–associated diarrhea with high morbidity and mortality. N Engl J Med 2005;353:24422449.
6.Muto CA, Blank MK, Marsh JW, et al. Control of an outbreak of infection with the hypervirulent Clostridium difficile BI strain in a university hospital using a comprehensive “bundle” approach. Clin Infect Dis 2007;45:12661273.
7.Toltzis P, Kim J, Dul M, Zoltanski J, Smathers S, Zaoutis T. Presence of the epidemic North American pulsed-field type 1 Clostridium difficile strain in hospitalized children. J Pediatr 2009;154:607608.
8.Luna RA, Boyanton BL Jr, Mehta S, et al. Rapid stool-based diagnosis of Clostridium difficile infection by real-time PCR in a children's hospital. J Clin Microbiol 2011;49:851857.
9.Peterson LR, Robicsek A. Does my patient have Clostridium difficile infection? Ann Intern Med 2009;151:176179.
10.Kim J, Shaklee JF, Smathers S, et al. Risk factors and outcomes associated with severe Clostridium difficile infection in children. Pediatr Infect Dis J (forthcoming).
11.Nerandzic MM, Donskey CJ. Effective and reduced-cost modified selective medium for isolation of Clostridium difficile. J Clin Microbiol 2009;47:397400.
12.Aldape MJ, Bryant AE, Stevens DL. Clostridium sordellii infection: epidemiology, clinical findings, and current perspectives on diagnosis and treatment. Clin Infect Dis 2006;43:14361446.
13.Fischer M, Bhatnagar J, Guarner J, et al. Fatal toxic shock syndrome associated with Clostridium sordellii after medical abortion. N Engl J Med 2005;353:23522360.
14.Planche T, Aghaizu A, Holliman R, et al. Diagnosis of Clostridium difficile infection by toxin detection kits: a systematic review. Lancet Infect Dis 2008;8:777784.
15.Donta ST, Myers MG. Clostridium difficile toxin in asymptomatic neonates. J Pediatr 1982;100:431434.
16.Larson HE, Barclay FE, Honour P, Hill ID. Epidemiology of Clostridium difficile in infants. J Infect Dis 1982;146:727733.
17.Sherertz RJ, Sarubbi FA. 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;100:435439.
18.Al-Nassir WN, Sethi AK, Li Y, Pultz MJ, Riggs MM, Donskey CJ. Both oral metronidazole and oral vancomycin promote persistent overgrowth of vancomycin-resistant enterococci during treatment of Clostridium difficile–associated disease. Antimicrob Agents Chemother 2008;52:24032406.
19.Cardona DM, Rand KH. Evaluation of repeat Clostridium difficile enzyme immunoassay testing. J Clin Microbiol 2008;46:36863689.
20.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;31:431455.
21.Mohan SS, McDermott BP, Parchuri S, Cunha BA. Lack of value of repeat stool testing for Clostridium difficile toxin. Am J Med 2006;119:356.
22.Aichinger E, Schleck CD, Harmsen WS, Nyre LM, Patel R. Non-utility of repeat laboratory testing for detection of Clostridium difficile by use of PCR or enzyme immunoassay. J Clin Microbiol 2008;46:37953797.
23.Litvin M, Reske KA, Mayfield J, et al. Identification of a pseudo-outbreak of Clostridium difficile infection (CDI) and the effect of repeated testing, sensitivity, and specificity on perceived prevalence of CDI. Infect Control Hosp Epidemiol 2009;30:11661171.
24.Mayer J, South B, Mooney B, et al. Surveillance of Clostridium difficile–associated disease (CDAD) based on toxin enzyme immunoassay (EI) results: did a problem with testing lead to a pseudo-outbreak? In: Programs and Abstracts of the Society for Healthcare Epidemiology of America (SHEA) Annual Meeting; Orlando, FL: SHEA; 2008. Abstract 56.
25.Bobulsky GS, Al-Nassir WN, Riggs MM, Sethi AK, Donskey CJ. Clostridium difficile skin contamination in patients with C. difficile–associated disease. Clin Infect Dis 2008;46:447450.
26.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 cyto-toxigenic culture methods. J Clin Microbiol 2009;47:32113217.
27.Ticehurst JR, Aird DZ, Dam LM, Borek AP, Hargrove JT, Carroll KC. Effective detection of toxigenic Clostridium difficile by a two-step algorithm including tests for antigen and cytotoxin. J Clin Microbiol 2006;44:11451149.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Infection Control & Hospital Epidemiology
  • ISSN: 0899-823X
  • EISSN: 1559-6834
  • URL: /core/journals/infection-control-and-hospital-epidemiology
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Metrics

Full text views

Total number of HTML views: 0
Total number of PDF views: 12 *
Loading metrics...

Abstract views

Total abstract views: 137 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 12th December 2017. This data will be updated every 24 hours.