C difficile three-fer: Overdiagnosis with Multiplex Testing, Fidaxomicin Pediatric Approval, & Changing Incidence

Queen Elizabeth II -picture for the pandemic

JM Cotter et al. (J Pediatr 2020; 218: 157-65) reviewed 1214 C difficile positive results from a total of 6841 C difficile tests 2013-15 & 2015-17). Key findings:

  • In the later era of multiplex tests, there was a much higher rate of C difficile detection (1.7-2.3 times higher) and a much higher rate of detection.
  • However, 31% of the multiplex tests identified another organism which indicates a high likelihood of a false-positive test (C difficile colonization)
  • Many of these “C difficile infections” were detected simply due to ease of test ordering.  In addition, the test results should be viewed with suspicion particularly in low-risk individuals.
  • Nearly one-third of the C difficile infected patients were oncology patients who are known to have high rates of asymptomatic colonization.
  • In patients known to have high risk of asymptomatic colonization (eg. young, oncology, IBD), detection of C difficile infection may lead to anchoring bias resulting in diagnostic delays for other disorders.

My take: We know that we are approaching the diagnosis of C difficile infection the wrong way (see IDSA guidelines below), but it is so quick and easy.

Related blog posts:

  • Clostridium difficile Guidelines The diagnosis of CDI… Molecular tests (eg, nucleic acid amplification tests [NAATs], such as polymerase chain reaction), which do not differentiate colonization and infection, are now the most commonly used test for CDI among US hospitals. NAATs have the potential to misdiagnose patients with colonization as having CDI, particularly when used in patients with low likelihood of CDI. Thus, this guideline strongly reinforces the importance of practicing good diagnostic stewardship and limiting C difficile testing to patients with new-onset, unexplained, and clinically significant (ie, at least 3 unformed stools in a 24-hour period) diarrhea…formed stools should not be tested for C difficile, nor should patients be retested within 7 days of a previous negative C difficile test. In pediatric populations, because of the unclear role of C difficile as a cause of diarrhea in infants, children less than 12 months of age should not be tested…If diagnostic stewardship is not an achievable goal, use of NAAT alone is likely to lead to frequent misdiagnosis of CDI among patients with C difficile colonization. In these cases, NAAT alone should be avoided and a multistep algorithm that incorporates toxin testing is recommended.

From MDEdge Pediatrics: full link: FDA approves fidaxomicin for treatment of C. difficile-associated diarrhea

An excerpt:

Approval [by FDA] was based on results from SUNSHINE, a phase 3, multicenter, investigator-blind, randomized, parallel-group study in 142 pediatric patients aged between 6 months and 18 years with confirmed C. difficile infection who received either fidaxomicin or vancomycin for 10 days. Clinical response 2 days after the conclusion of treatment was similar in both groups (77.6% for fidaxomicin vs. 70.5% for vancomycin), and fidaxomicin had a superior sustained response 30 days after the conclusion of treatment (68.4% vs. 50.0%)…

The fidaxomicin pediatric trial was the first randomized, controlled trial of C. difficile infection treatment in children,” Larry K. Kociolek, MD

AY Guh et al. NEJM 2020; 382: 1320-30. The authors examined the U.S. Burden of CDI by using the Emerging Infections Program (35 counties in 10 states). Key findings:

  • 15,461 cases of CDI in 2011 and 15,5512 in 2017 detected which extrapolates to 476,000 national cases in 2011 and 462,400 national cases in 2017
  • When accounting for increased use of PCR assays, the authors estimate that the C difficile infectious burden decreased by 24% from 2011 to 2017 (due to a drop in health care-associated infections.

My wife has been receiving a lot of compliments for her daily jokes which she decided to post for all of the neighborhood walkers: “If number two pencils are so popular, why are they still number 2?”

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