Hostname: page-component-586b7cd67f-2brh9 Total loading time: 0 Render date: 2024-11-29T09:29:51.576Z Has data issue: false hasContentIssue false

Sequential introduction of a multistep testing algorithm and nucleic acid amplification testing leading to an increase in Clostridioides difficile detection and a trend toward increased strain diversity

Published online by Cambridge University Press:  24 June 2020

Andrew M. Skinner*
Affiliation:
Edward Hines, Jr, Veterans’ Affairs Hospital, Hines, Illinois Loyola University Medical Center, Maywood, Illinois (Present affiliation: Metro Infectious Diseases Consultants, Burr Ridge, Illinois [B.Y.].)
Brian Yu
Affiliation:
Edward Hines, Jr, Veterans’ Affairs Hospital, Hines, Illinois Loyola University Medical Center, Maywood, Illinois (Present affiliation: Metro Infectious Diseases Consultants, Burr Ridge, Illinois [B.Y.].)
Adam Cheknis
Affiliation:
Edward Hines, Jr, Veterans’ Affairs Hospital, Hines, Illinois
Susan M. Pacheco
Affiliation:
Edward Hines, Jr, Veterans’ Affairs Hospital, Hines, Illinois Loyola University Medical Center, Maywood, Illinois (Present affiliation: Metro Infectious Diseases Consultants, Burr Ridge, Illinois [B.Y.].)
Dale N. Gerding
Affiliation:
Edward Hines, Jr, Veterans’ Affairs Hospital, Hines, Illinois
Stuart Johnson*
Affiliation:
Edward Hines, Jr, Veterans’ Affairs Hospital, Hines, Illinois Loyola University Medical Center, Maywood, Illinois (Present affiliation: Metro Infectious Diseases Consultants, Burr Ridge, Illinois [B.Y.].)
*
Authors for correspondence: Stuart Johnson, E-mail: [email protected]. Or Andrew Skinner, E-mail: [email protected]
Authors for correspondence: Stuart Johnson, E-mail: [email protected]. Or Andrew Skinner, E-mail: [email protected]

Abstract

Background:

Most clinical microbiology laboratories have replaced toxin immunoassay (EIA) alone with multistep testing (MST) protocols or nucleic acid amplification testing (NAAT) alone for the detection of C. difficile.

Objective:

Study the effect of changing testing strategies on C. difficile detection and strain diversity.

Design:

Retrospective study.

Setting:

A Veterans’ Affairs hospital.

Methods:

Initially, toxin EIA testing was replaced by an MST approach utilizing a glutamate dehydrogenase (GDH) and toxin EIA followed by tcdB NAAT for discordant results. After 18 months, MST was replaced by a NAAT-only strategy. Available patient stool specimens were cultured for C. difficile. Restriction endonuclease analysis (REA) strain typing and quantitative in vitro toxin testing were performed on recovered isolates.

Results:

Before MST (toxin EIA), 79 of 708 specimens (11%) were positive, and after MST (MST-A), 121 of 517 specimens (23%) were positive (P < .0001). Prior to NAAT-only testing (MST-B), 80 of the 490 specimens (16%) were positive by MST, and after NAAT-only testing was implemented, 67 of the 368 specimens (18%) were positive (P = nonsignificant). After replacing toxin EIA testing, REA strain group diversity increased (8, 13, 13, and 10 REA groups in the toxin EIA, MST-A, MST-B, and NAAT-only periods, respectively) and in vitro toxin concentration decreased. The average log10 toxin concentration of the isolates were 2.08, 1.88, 1.20 and 1.55 ng/mL for the same periods, respectively.

Conclusions:

MST and NAAT had similar detection rates for C. difficile. Compared to toxin testing alone, they detected increased diversity of C. difficile strains, many of which were low toxin producing.

Type
Original Article
Copyright
© 2020 by The Society for Healthcare Epidemiology of America. All rights reserved.

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

McDonald, LC, Gerding, DN, Johnson, S, et al.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 2018;66(7):e1e48.CrossRefGoogle Scholar
Burnham, CAD, Carroll, KC.Diagnosis of Clostridium difficile infection: an ongoing conundrum for clinicians and for clinical laboratories. Clin Microbiol Rev 2013;26:604630.CrossRefGoogle ScholarPubMed
De Jong, E, De Jong, AS, Bartels, CJMet al.Clinical and laboratory evaluation of a real-time PCR for Clostridium difficile toxin A and B genes. Eur J Clin Microbiol Infect Dis 2012;31:22192225.10.1007/s10096-012-1558-1CrossRefGoogle ScholarPubMed
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;47:32113217.10.1128/JCM.01082-09CrossRefGoogle Scholar
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.CrossRefGoogle ScholarPubMed
Voth, DE, Ballard, JD.Clostridium difficile toxins: mechanism of action and role in disease. Clin Microbiol Rev 2005;18:247263.10.1128/CMR.18.2.247-263.2005CrossRefGoogle Scholar
Denève, C, Janoir, C, Poilane, I, Fantinato, C, Collignon, A.New trends in clostridium difficile virulence and pathogenesis. Int J Antimicrob Agents 2009;33 suppl 1:S24S28.10.1016/S0924-8579(09)70012-3CrossRefGoogle ScholarPubMed
Koo, HL, Van, JN, Zhao, M, et al.Real-time polymerase chain reaction detection of asymptomatic Clostridium difficile colonization and rising C. difficile–associated disease rates. Infect Control Hosp Epidemiol 2014;35:667673.CrossRefGoogle Scholar
Clabots, CR, Johnson, S, Bettin, KM, et al.Development of a rapid and efficient restriction endonuclease analysis typing system for Clostridium difficile and correlation with other typing systems. J Clin Microbiol 1993;31:18701875.CrossRefGoogle ScholarPubMed
Wieczorkiewicz, JT, Lopansri, BK, Cheknis, A, et al.Fluoroquinolone and macrolide exposure predict Clostridium difficile infection with the highly fluoroquinolone- and macrolide-resistant epidemic C. difficile strain BI/NAP1/027. Antimicrob Agents Chemother 2016;60:418423.CrossRefGoogle ScholarPubMed
Gould, CV, Edwards, JR, Cohen, J, et al.Effect of nucleic acid amplification testing on population-based incidence rates of Clostridium difficile infection. Clin Infect Dis 2013;57:13041307.CrossRefGoogle ScholarPubMed
Moehring, RW, Lofgren, ET, Anderson, DJ.Impact of change to molecular testing for Clostridium difficile infection on healthcare facility–associated incidence rates. Infect Control Hosp Epidemiol 2013;34:10551061.10.1086/673144CrossRefGoogle ScholarPubMed
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;366:10791084.CrossRefGoogle ScholarPubMed
Killgore, G, Thompson, A, Johnson, S, et al.Comparison of seven techniques for typing international epidemic strains of Clostridium difficile: restriction endonuclease analysis, pulsed-field gel electrophoresis, PCR-ribotyping, multilocus sequence typing, multilocus variable-number tandem-repeat an. J Clin Microbiol 2008;46:431437.CrossRefGoogle Scholar
Cheknis, A, Johnson, S, Chesnel, L, et al.Molecular epidemiology of Clostridioides (Clostridium) difficile strains recovered from clinical trials in the US, Canada, and Europe from 2006–2009 to 2012–2015. Anaerobe. 2018;53:3842.10.1016/j.anaerobe.2018.05.009CrossRefGoogle ScholarPubMed
Vohra, P, Poxton, IR.Comparison of toxin and spore production in clinically relevant strains of Clostridium difficile. Microbiology 2011;157:13431353.CrossRefGoogle ScholarPubMed
Furuya-Kanamori, L, Riley, TV, Paterson, DL, et al.Comparison of Clostridium difficile ribotypes circulating in Australian hospitals and communities. J Clin Microbiol 2017;55:216225.CrossRefGoogle ScholarPubMed
Knight, DR, Squire, MM, Collins, DA, Riley, TV.Genome analysis of Clostridium difficile PCR ribotype 014 lineage in australian pigs and humans reveals a diverse genetic repertoire and signatures of long-range interspecies transmission. Front Microbiol 2017;7:2138.10.3389/fmicb.2016.02138CrossRefGoogle ScholarPubMed
Lalkhen, AG, McCluskey, A.Clinical tests: sensitivity and specificity. Contin Educ Anaesth Crit Care Pain 2008;8:221223.CrossRefGoogle Scholar
Planche, TD, Davies, KA, Coen, PG, 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;13:936945.CrossRefGoogle ScholarPubMed
Polage, CR, Gyorke, CE, Kennedy, MA, et al.Overdiagnosis of Clostridium difficile infection in the molecular test era. JAMA Intern Med 2015;175:17921801.CrossRefGoogle ScholarPubMed
Polage, CR, Solnick, JV, Cohen, SH.Nosocomial diarrhea: evaluation and treatment of causes other than clostridium difficile. Clin Infect Dis 2012;55:982989.CrossRefGoogle ScholarPubMed
Bartlett, JG, Gerding, DN.Clinical recognition and diagnosis of Clostridium difficile infection. Clin Infect Dis 2008;46 suppl 1:S12S18.CrossRefGoogle ScholarPubMed
McDonald, LC, Gerding, DN, Johnson, S, et al.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 2018;66(7):e1e48.CrossRefGoogle Scholar
Guh, AY, Hatfield, KM, Winston, LG, et al.Toxin enzyme immunoassays detect clostridioides difficile infection with greater severity and higher recurrence rates. Clin Infect Dis 2019;69:16671674.10.1093/cid/ciz009CrossRefGoogle ScholarPubMed