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Infectious Diseases

Multistep Testing Algorithms for Clostridioides difficile Infection

Educational Objective
To understand how to interpret the results of diagnostic tests and apply them clinically.

1 Credit CME

JAMA

Published Online: August 21, 2023

JAMA Diagnostic Test Interpretation

Article Information and Disclosures

Maribeth R. Nicholson, MD, MPH¹;

Curtis J. Donskey, MD²

Author Affiliations

¹Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Monroe Carell Jr Children’s Hospital at Vanderbilt, Nashville, Tennessee
²Geriatric Research, Education, and Clinical Center, Louis Stokes Cleveland VA Medical Center, Cleveland, Ohio

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A 10-year-old female with spina bifida and neurogenic bowel was hospitalized for abdominal pain, dehydration, and more than 20 episodes of watery diarrhea per day. Her symptoms began 5 days after completing a course of amoxicillin for streptococcal pharyngitis. Results of a gastrointestinal pathogen panel that included 18 bacterial, viral, and parasitic pathogens were negative. A stool sample result was positive for Clostridioides difficile by polymerase chain reaction (PCR) testing and an enzyme immunoassay test for C difficile toxin A and B had a negative result.

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A 10-year-old female with spina bifida and neurogenic bowel was hospitalized for abdominal pain, dehydration, and more than 20 episodes of watery diarrhea per day. Her symptoms began 5 days after completing a course of amoxicillin for streptococcal pharyngitis. Results of a gastrointestinal pathogen panel that included 18 bacterial, viral, and parasitic pathogens were negative. A stool sample result was positive for Clostridioides difficile by polymerase chain reaction (PCR) testing and an enzyme immunoassay test for C difficile toxin A and B had a negative result.

B. Antibiotic treatment for C difficile infection is warranted.

Few studies are available to guide best testing practices for the diagnosis of C difficile infection (CDI) in children.¹ Colonization with toxigenic and nontoxigenic C difficile affects 3% to 40% of children younger than 3 years and 3% to 26% of hospitalized children and adults.² Therefore, diarrhea from causes other than CDI, such as laxatives, viral infections, and prior antibiotic use, should be considered.³

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Article Information

Corresponding Author: Maribeth R. Nicholson, MD, MPH, Monroe Carell Jr Children’s Hospital at Vanderbilt, 2200 Children’s Way, Nashville, TN 37232 (maribeth.r.nicholson@vumc.org).

Published Online: August 21, 2023. doi:10.1001/jama.2023.15875

Conflict of Interest Disclosures: Dr Nicholson reported being supported by a National Institute of Allergy and Infectious Diseases K23 award (No.1K23AI156132-01). Dr Donskey reported grants to his institution from Pfizer, Clorox, and Ecolab outside the submitted work. No other disclosures were reported.

References

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(11):936-945. doi:10.1016/S1473-3099(13)70200-7 PubMed Google Scholar Crossref

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). Nephrol Dial Transplant. 2018;66(7):e1-e48. doi:10.1093/cid/cix1085 PubMed Google Scholar Crossref

Crobach MJ , Planche T , Eckert C , et al. European Society of Clinical Microbiology and Infectious Diseases: update of the diagnostic guidance document for Clostridium difficile infection. Clin Microbiol Infect. 2016;22 Suppl 4:S63-S81. doi:10.1016/j.cmi.2016.03.010 PubMed Google Scholar Crossref

Kelly CR , Fischer M , Allegretti JR , et al. ACG clinical guidelines: prevention, diagnosis, and treatment of Clostridioides difficile infections. Am J Gastroenterol. 2021;116(6):1124-1147. doi:10.14309/ajg.0000000000001278 PubMed Google Scholar Crossref

Gerding DN . Is the healthcare facility level sufficient for assessing the impact of two-step Clostridioides difficile testing? Clin Infect Dis. 2023;ciad332. doi:10.1093/cid/ciad332 PubMed Google Scholar Crossref

Parnell JM , Fazili I , Bloch SC , et al. Two-step testing for Clostridioides difficile is inadequate in differentiating infection from colonization in children. J Pediatr Gastroenterol Nutr. 2021;72(3):378-383. doi:10.1097/MPG.0000000000002944 PubMed Google Scholar Crossref

Ng Wong YK , Gonzalez-Orta M , Saldana C , Cadnum JL , Jencson AL , Donskey CJ . Frequency of positive enzyme immunoassay for toxin in stool of asymptomatic carriers of Clostridium difficile. Nephrol Dial Transplant. 2019;68(4):711. doi:10.1093/cid/ciy701 PubMed Google Scholar Crossref

Polage CR , Gyorke CE , Kennedy MA , et al. Overdiagnosis of Clostridium difficile infection in the molecular test era. JAMA Intern Med. 2015:175(11):1792-1801. doi:10.1001/jamainternmed.2015.4114 PubMed Google Scholar Crossref

Hecker MT , Son AH , Zuccaro P , Conti J , Donskey CJ . Real-world evaluation of a two-step testing algorithm for Clostridioides difficile infection. Infect Control Hosp Epidemiol. Published online February 8, 2023. doi:10.1017/ice.2022.313 PubMed Google Scholar Crossref

Miller R , Morillas JA , Brizendine KD , Fraser TG . Predictors of Clostridioides difficile infection-related complications and treatment patterns among nucleic acid amplification test-positive/toxin enzyme immunoassay-negative patients. J Clin Microbiol. 2020;58(3):e01764-19. doi:10.1128/JCM.01764-19 PubMed Google Scholar Crossref

AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
1.00 credit toward the CME [and Self-Assessment requirements] of the American Board of Surgery’s Continuous Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.