Skip to main content
HHS Author Manuscripts logoLink to HHS Author Manuscripts
. Author manuscript; available in PMC: 2024 Feb 21.
Published in final edited form as: N Engl J Med. 2015 Jun 11;372(24):2369–2370. doi: 10.1056/NEJMc1505190

Re: Burden of Clostridium difficile Infection in the United States

Fernanda C Lessa 1, L Clifford McDonald 2; Emerging Infections Program C. difficile Surveillance Team
PMCID: PMC10880113  NIHMSID: NIHMS1965247  PMID: 26061850

The Authors Reply:

Banaei and colleagues express concern that Clostridium difficile infection (CDI) may be over diagnosed using PCR given that in their study only a third of patients had clinically significant diarrhea defined as 3 or more unformed stools in a 24-hour period, and half of these patients had recent exposure to laxatives. (1) Because positive predictive value is influenced by the prevalence of true disease, care must be taken to assure the appropriate population is tested; this is especially true with nucleic acid amplification tests (NAATs) where a C. difficile prevalence closer to 20% has been associated with a more accurate CDI diagnosis. (2) We included in the supplementary material of our report an evaluation of the impact of different NAAT usage rates on the U.S. burden of CDI. (3)

Meanwhile, Bouwknegt and colleagues are concerned that CDI may be under diagnosed in outpatient settings because C. difficile is frequently detected in diarrheal stool samples submitted by general practitioners for other diagnostic tests. (4) Although it is possible there is a hidden burden of CDI in the United States due to a lack of clinical suspicion, non-infectious conditions and brief, self-limited infections often cause diarrhea, and testing of non-clinically significant diarrheal specimens may lead to detection of C. difficile colonization rather than infection (5).

As outlined by the letters of Banaei and Bouwknegt, there are several limitations to the diagnosis of CDI that can impact disease burden estimates and consequently limitations to any surveillance definition or approach that is employed.

Footnotes

Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

Contributor Information

Fernanda C. Lessa, Centers for Disease Control and Prevention, Atlanta, GA, USA.

L. Clifford McDonald, Centers for Disease Control and Prevention, Atlanta, GA, USA.

References

  • 1.Banaei A Anikst V, Schroeder LF. Letter to the Editor. NEJM [Google Scholar]
  • 2.Deshpande A, Pasupuleti V, Rolston DD, et al. Diagnostic accuracy of real-time polymerase chain reaction in detection of Clostridium difficile in the stool samples of patients with suspected Clostridium difficile Infection: a meta-analysis. Clin Infect Dis. 2011;53:e81–90. [DOI] [PubMed] [Google Scholar]
  • 3.Lessa FC, Mu Y, Bamberg WM, et al. Burden of Clostridium difficile infection in the United States. N Engl J Med. 2015;372:825–34. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Hensgens MP, Dekkers OM, Demeulemeester A, et al. Diarrhoea in general practice: when should a Clostridium difficile infection be considered? Results of a nested case-control study. Clin Microbiol Infect. 2014; 20:O1067–74. [DOI] [PubMed] [Google Scholar]
  • 5.Dubberke ER, Han Z, Bobo L, et al. Impact of clinical symptoms on interpretation of diagnostic assays for Clostridium difficile infections. J Clin Microbiol 2011;49: 2887–93. [DOI] [PMC free article] [PubMed] [Google Scholar]

RESOURCES