When should a patient be tested for Clostridioides difficile (C. diff) infection in the absence of recent antibiotic use?

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Last updated: June 1, 2025View editorial policy

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From the Guidelines

Testing for Clostridioides difficile (C. diff) infection should be considered in patients with unexplained new-onset diarrhea that persists for more than 24-48 hours, regardless of recent antibiotic use, especially if accompanied by abdominal pain or fever, as recommended by the 2017 Infectious Diseases Society of America guidelines 1. When evaluating a patient for C. diff infection, it's essential to consider the clinical presentation and risk factors, rather than solely relying on recent antibiotic use. The 2017 guidelines suggest testing for C. diff in people >2 years of age who have a history of diarrhea following antimicrobial use and in people with healthcare-associated diarrhea 1. Key considerations for testing include:

  • Unexplained new-onset diarrhea (three or more loose stools within 24 hours) that persists for more than 24-48 hours
  • Abdominal pain or fever
  • Recent hospitalization
  • Advanced age (>65 years)
  • Immunocompromised status
  • Inflammatory bowel disease
  • Recent gastrointestinal surgery
  • Contact with healthcare facilities or known C. diff cases Only diarrheal stool samples should be tested, as asymptomatic colonization is common and testing formed stool can lead to false positives 1. The preferred testing method is a single diarrheal stool specimen for detection of toxin or a toxigenic C. difficile strain, such as nucleic acid amplification testing (NAAT) 1.

From the Research

Testing for C. diff Infection

  • The decision to test for Clostridioides difficile (C. diff) infection should be based on clinical presentation, regardless of recent antibiotic use 2.
  • C. diff infection can occur in the absence of recent antibiotic use, and testing should be considered in patients with symptoms such as diarrhea, even if they have not recently taken antibiotics 3, 4.

Risk Factors for C. diff Infection

  • Risk factors for C. diff infection include hospital or nursing home stay, old age, and antibiotic therapy, but the absence of these risk factors does not rule out the possibility of infection 2.
  • Patients with symptoms of C. diff infection, such as diarrhea, should be tested regardless of their medical history or recent antibiotic use 3, 4.

Diagnostic Testing

  • Diagnostic testing for C. diff infection typically involves direct detection of C. difficile toxins in feces, using tests such as enzyme immunoassay (EIA) or polymerase chain reaction (PCR) 3, 2.
  • A two-step assay combining an enzyme immunoassay for glutamate dehydrogenase and the C. difficile toxin may be used to reduce the risk of clinical false-positive results 3.

Treatment and Management

  • Treatment for C. diff infection typically involves antibiotics such as vancomycin or fidaxomicin, and may also include fecal microbiota transplantation or other novel treatments for recurrent infection 3, 5, 4.
  • Management of C. diff infection requires a comprehensive approach, including diagnosis, treatment, and prevention of recurrence, as well as consideration of the patient's overall health and medical history 3, 4.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Clostridium difficile infection: review.

European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology, 2019

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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