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Clinical heterogeneity of patients with stool samples testing PCR+/Tox− from a two-step Clostridium difficile diagnostic algorithm

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Abstract

The clinical significance of indeterminate (PCR+/Tox−) results for patients tested with a two-step algorithm for Clostridium difficile infection (CDI) is uncertain. We aimed to evaluate the clinical presentation and 8-week outcomes of patients with indeterminate test results. Patients with stool samples testing positive by PCR and negative by toxin A/B immunoassay between February 1, 2017, and April 30, 2018, were assessed by antimicrobial stewardship program (ASP) clinicians and classified as colonized or infected. Retrospective chart review was performed to obtain outcomes occurring within 8 weeks of testing, including recurrent C. difficile diarrhea, subsequent treatment for CDI, follow-up C. difficile testing, all-cause mortality, and CDI-related complications. In total, 110 PCR+/Tox− patients were evaluated. ASP classified 54% of patients as infected and 46% as colonized. Patients assessed and classified as colonized did not have increased adverse outcomes by 8 weeks compared to those assessed as infected, despite not receiving treatment for CDI. We conclude that PCR+/Tox− patients are heterogeneous with respect to clinical presentation. Negative toxin A/B immunoassay in a two-step algorithm should not be interpreted in isolation to distinguish colonization from infection as many PCR+/Tox− results may be clinically significant for CDI.

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References

  1. Bogaty C, Levesque S, Garenc C, Frenette C, Bolduc D, Galarneau LA, Lalancette C, Loo V, Tremblay C, Trudeau M, Vachon J, Dionne M, Villeneuve J, Longtin J, Longtin Y (2017) Trends in the use of laboratory tests for the diagnosis of Clostridium difficile infection and association with incidence rates in Quebec, Canada, 2010-2014. Am J Infect Control 45(9):964–968. https://doi.org/10.1016/j.ajic.2017.04.002

    Article  CAS  PubMed  Google Scholar 

  2. Polage CR, Gyorke CE, Kennedy MA, Leslie JL, Chin DL, Wang S, Nguyen HH, Huang B, Tang YW, Lee LW, Kim K, Taylor S, Romano PS, Panacek EA, Goodell PB, Solnick JV, Cohen SH (2015) Overdiagnosis of Clostridium difficile infection in the molecular test era. JAMA Intern Med 175(11):1792–1801. https://doi.org/10.1001/jamainternmed.2015.4114

    Article  PubMed  PubMed Central  Google Scholar 

  3. McDonald LC, Gerding DN, Johnson S, Bakken JS, Carroll KC, Coffin SE, Dubberke ER, Garey KW, Gould CV, Kelly C, Loo V, Shaklee Sammons J, Sandora TJ, Wilcox MH (2018) Clinical practice guidelines for Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis 66(7):987–994. https://doi.org/10.1093/cid/ciy149

    Article  PubMed  Google Scholar 

  4. Wilcox MH (2012) Overcoming barriers to effective recognition and diagnosis of Clostridium difficile infection. Clin Microbiol Infect 18(Suppl 6):13–20. https://doi.org/10.1111/1469-0691.12057

    Article  PubMed  Google Scholar 

  5. Fang FC, Polage CR, Wilcox MH (2017) Point-counterpoint: what is the optimal approach for detection of Clostridium difficile infection? J Clin Microbiol 55(3):670–680. https://doi.org/10.1128/jcm.02463-16

    Article  PubMed  PubMed Central  Google Scholar 

  6. Wilmer A, Lloyd-Smith E, Leung V, Wong T, Ritchie G, Hoang L, Champagne S, Romney MG (2013) Polymerase chain reaction assay to detect Clostridium difficile tcdC variants is valuable in characterizing hospital epidemiology. J Hosp Infect 84(3):252–255. https://doi.org/10.1016/j.jhin.2013.04.002

    Article  CAS  PubMed  Google Scholar 

  7. Loo VG, Davis I, Embil J, Evans GA, Hota S, Lee C, Lee TC, Longtin Y, Louie T, Moayyedi P, Poutanen S, Simor AE, Steiner T, Thampi N, Valiquette L (2018) Association of Medical Microbiology and Infectious Disease Canada treatment practice guidelines for Clostridium difficile infection. JAMMI 3(2):71–92. https://doi.org/10.3138/jammi.2018.02.13

    Article  Google Scholar 

  8. Sullivan KM, Dean A, Soe MM (2009) OpenEpi: a web-based epidemiologic and statistical calculator for public health. Public Health Rep 124(3):471–474

    Article  PubMed  PubMed Central  Google Scholar 

  9. Avni T, Babich T, Ben-Zvi H, Atamna A, Yahav D, Shepshelovich D, Leibovici-Weissman Y, Bishara J (2018) Molecular-based diagnosis of Clostridium difficile infection is associated with reduced mortality. Eur J Clin Microbiol Infect Dis 37(6):1137–1142. https://doi.org/10.1007/s10096-018-3228-4

    Article  CAS  PubMed  Google Scholar 

  10. Baker I, Leeming JP, Reynolds R, Ibrahim I, Darley E (2013) Clinical relevance of a positive molecular test in the diagnosis of Clostridium difficile infection. J Hosp Infect 84(4):311–315. https://doi.org/10.1016/j.jhin.2013.05.006

    Article  CAS  PubMed  Google Scholar 

  11. Patel H, Randhawa J, Nanavati S, Marton LR, Baddoura WJ, DeBari VA (2015) Laboratory and clinical features of EIA toxin-positive and EIA toxin-negative community-acquired Clostridium difficile infection. Ann Clin Lab Sci 45(3):333–339

    CAS  PubMed  Google Scholar 

  12. Origuen J, Corbella L, Orellana MA, Fernandez-Ruiz M, Lopez-Medrano F, San Juan R, Lizasoain M, Ruiz-Merlo T, Morales-Cartagena A, Maestro G, Parra P, Villa J, Delgado R, Aguado JM (2018) Comparison of the clinical course of Clostridium difficile infection in glutamate dehydrogenase-positive toxin-negative patients diagnosed by PCR to those with a positive toxin test. Clin Microbiol Infect 24(4):414–421. https://doi.org/10.1016/j.cmi.2017.07.033

    Article  CAS  PubMed  Google Scholar 

  13. Crobach MJ, Planche T, Eckert C, Barbut F, Terveer EM, Dekkers OM, Wilcox MH, Kuijper EJ (2016) European Society of Clinical Microbiology and Infectious Diseases: update of the diagnostic guidance document for Clostridium difficile infection. Clin Microbiol Infect 22(Suppl 4):S63–S81. https://doi.org/10.1016/j.cmi.2016.03.010

    Article  PubMed  Google Scholar 

  14. Gerding DN, Meyer T, Lee C, Cohen SH, Murthy UK, Poirier A, Van Schooneveld TC, Pardi DS, Ramos A, Barron MA, Chen H, Villano S (2015) Administration of spores of nontoxigenic Clostridium difficile strain M3 for prevention of recurrent C. difficile infection: a randomized clinical trial. JAMA 313(17):1719–1727. https://doi.org/10.1001/jama.2015.3725

    Article  PubMed  Google Scholar 

  15. Lee YJ, Arguello ES, Jenq RR, Littmann E, Kim GJ, Miller LC, Ling L, Figueroa C, Robilotti E, Perales MA, Barker JN, Giralt S, van den Brink MRM, Pamer EG, Taur Y (2017) Protective factors in the intestinal microbiome against Clostridium difficile infection in recipients of allogeneic hematopoietic stem cell transplantation. J Infect Dis 215(7):1117–1123. https://doi.org/10.1093/infdis/jix011

    Article  PubMed  PubMed Central  Google Scholar 

  16. Lewis BB, Buffie CG, Carter RA, Leiner I, Toussaint NC, Miller LC, Gobourne A, Ling L, Pamer EG (2015) Loss of microbiota-mediated colonization resistance to Clostridium difficile infection with oral vancomycin compared with metronidazole. J Infect Dis 212(10):1656–1665. https://doi.org/10.1093/infdis/jiv256

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank the St. Paul’s Hospital microbiology laboratory staff for their commitment to quality testing. We are also grateful to the Infection Prevention and Control staff at Providence Health Care for supporting this project and their dedication to excellent C. difficile surveillance.

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Correspondence to Christopher F. Lowe.

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Ethics approval was obtained for this study by the University of British Columbia – Providence Health Care Research Institute research ethics board.

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The authors declare that they have no conflicts of interest.

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Zou, J., Leung, V., Champagne, S. et al. Clinical heterogeneity of patients with stool samples testing PCR+/Tox− from a two-step Clostridium difficile diagnostic algorithm. Eur J Clin Microbiol Infect Dis 37, 2355–2359 (2018). https://doi.org/10.1007/s10096-018-3383-7

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  • DOI: https://doi.org/10.1007/s10096-018-3383-7

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