The full content of Annals is available to subscribers

Subscribe/Learn More  >
Improving Patient Care |

Does My Patient Have Clostridium difficile Infection?

Lance R. Peterson, MD; and Ari Robicsek, MD
[+] Article, Author, and Disclosure Information

From Northwestern University and NorthShore University HealthSystem, Evanston, Illinois.

Grant Support: There was no sponsorship or funding outside of the authors' organization, NorthShore University HealthSystem, for this work. The authors are solely responsible for this report.

Potential Financial Conflicts of Interest:Consultancies: L.R. Peterson (BD-GeneOhm, Cepheid, MicroPhage, Nanosphere, Roche). Honoraria: L.R. Peterson (BD-GeneOhm; Cepheid; Roche; as well as numerous universities, scientific/professional organizations, and governmental bodies for lectures on rapid diagnostic testing), A. Robicsek (Becton Dickinson). Grants received: L.R. Peterson (BD-GeneOhm, Cepheid, MicroPhage, Nanogen, Nanosphere, National Institute of Allergy and Infectious Diseases, Roche, 3M, Washington Square Health Foundation), A. Robicsek (Becton Dickinson). Grants pending: L.R. Peterson (BD-GeneOhm, Cepheid, MicroPhage, Nanosphere, National Institute of Allergy and Infectious Diseases, Roche, The Retirement Research Foundation).

Reproducible Research Statement:Study protocol: Available from Dr. Peterson (e-mail, lancer@northwestern.edu). Statistical code and data set: None.

Requests for Single Reprints: Lance R. Peterson, MD, NorthShore University HealthSystem, Department of Pathology and Laboratory Medicine, Walgreen SB525, 2650 Ridge Avenue, Evanston, IL 60201; e-mail, lancer@northwestern.edu.

Current Author Addresses: Dr. Peterson: NorthShore University HealthSystem, Department of Pathology and Laboratory Medicine, Walgreen SB525, 2650 Ridge Avenue, Evanston, IL 60201.

Dr. Robicsek: NorthShore University HealthSystem, Department of Infection Control, Burch 124, 2650 Ridge Avenue, Evanston, IL 60201.

Author Contributions: Conception and design: L.R. Peterson, A. Robicsek.

Analysis and interpretation of the data: L.R. Peterson, A. Robicsek.

Drafting of the article: L.R. Peterson.

Critical revision of the article for important intellectual content: L.R. Peterson, A. Robicsek.

Final approval of the article: L.R. Peterson, A. Robicsek.

Provision of study materials or patients: L.R. Peterson.

Statistical expertise: L.R. Peterson.

Administrative, technical, or logistic support: L.R. Peterson.

Collection and assembly of data: L.R. Peterson.

Ann Intern Med. 2009;151(3):176-179. doi:10.7326/0003-4819-151-3-200908040-00005
Text Size: A A A

The standard for suspecting CDI is clinically significant diarrhea, usually defined as 3 or more loose stools per day for at least 1 to 2 days (5). For example, in our recent study of patients suspected of having CDI, one third had fewer than 3 loose stools for 1 day and then had no additional symptoms of CDI during their hospitalization, but two thirds had 3 or more loose stools per day that continued until they were treated if found to have CDI (6). Thus, simply asking about the number of loose stools on the first day of possible CDI readily identifies persons at high risk for having CDI. Other studies have found that 29% to 39% of patients would not need testing if simple similar rules were followed (78). Judicious use of C. difficile testing is important because a C. difficile colonization state exists and can be common. More than a decade ago, Johnson and Gerding (9) observed that very few patients had C. difficile in their stool at the time of hospital admission, but nearly 50% had C. difficile in their stool by the end of 4 weeks even though they had no symptoms of CDI. Clostridium difficile testing in patients without symptoms of disease is thus analogous to culturing other nonsterile body sites where colonization cannot be distinguished from infection without clinical evidence of disease.

First Page Preview

View Large
First page PDF preview





Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).


Submit a Comment/Letter
No Title
Posted on August 12, 2009
Giorgio Costantino
Medicina II, Ospedale L. Sacco, Milan, Italy
Conflict of Interest: None Declared
No Comment
No Title
Posted on August 25, 2009
Jongoh Kim
Albert Einstein Medical Center
Conflict of Interest: None Declared

Peterson et al. discussed a proper way of diagnosing C.difficile infection (CDI). They pointed out that the use of more sensitive test under appropriate clinical situations will help reach correct diagnosis effectively. However, their argument against repeating EIA needs more explanation (table 2). The reason behind repeating diagnostics tests with not high enough sensitivity is to increase sensitivity so that serious conditions may not be missed. In other words, physicians want to increase sensitivity of the diagnostic process and thus negative predictive value. In reality, physicians usually repeat EIA up to three times if they get negative results but they have high suspicion. In this case, testing up to three times actually makes a single diagnostic test. The table below indicates sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the whole set of tests as EIA is repeated (with the same assumption of prevalence 10%, sensitivity 73.3%, and specificity 97.6%). As EIA was repeated, both sensitivity and NPV increased. When repeated up to three times, sensitivity was 98.0% and NPV was 0.998. On the other hand, specificity and PPV, as expected, decreased with repeating tests. The real argument against repeating diagnostic tests is when the performance of tests gets poorer each time they are repeated. To see if this is true, further studies are warranted rather than hypothetical calculations.































Conflict of Interest:

None declared

Does my patient have Clostridium difficile infection?
Posted on September 1, 2009
Farrin A Manian
St. John's Mercy Medical Center
Conflict of Interest: None Declared

In their recent timely article concerning testing for Clostridium difficile infection (CDI) (1), Peterson and Robicsek recommend against retesting of stool for the presence of this organism or its toxin for 7 to 14 days in patients with diarrhea and an initially negative test. Several caveats concerning such a rule may be worthy of further discussion.

First, such a rule appears to ignore the frequent de novo acquisition of C. difficile from extrinsic sources among hospitalized patients, often with a relatively brief period of less than 7 days from exposure to symptomatic infection (2). Thus, it is quite plausible that some hospitalized patients with diarrhea (e.g. caused by enteral tube feeding) and a negative initial CDT may acquire CDI during the "no repeat" test period of 7-14 days while the cause of their diarrhea is mistakenly attributed to some other etiology. Second, the yield of repeat CDT during the 7-14 day period following an initially negative test may potentially be influenced by factors such as the baseline endemic rate of CDI or the presence of an outbreak (suspected or not) in a particular healthcare facility. Of interest, in one hospital experiencing an outbreak of CDI (3), 8 (53%) of 15 patients with an originally negative CDT by a rapid immunoassay tested positive within one week, a rate that is much higher than those commonly reported in the literature (1). Third, the "7 to 14 day" rule does not distinguish between the 7 to 14 day period immediately following admission to the hospital and subsequent periods. Because the risk of CDI may increase with hospitalization of 7 days or longer (4), it is plausible that the yield of a positive repeat CDT may also be higher in patients with longer hospital stay, at least in some centers.

Of interest, one study involving 2 hospitals (5) reported a rate of CDT positivity by immunoassay of 5.4% or less when repeated during the first 6 days following a negative test compared to 10.6% on days 7 to 10. Lastly, given the expected variation in the reported rates of a positive CDT after an initially negative test among healthcare facilities, possibly related to the rate of endemic transmission of C. difficile and patient mix, it may be prudent to encourage hospitals and other healthcare facilities to study their own yield of a positive CDT following a negative test before embracing any published rule.


1. Peterson LR, Robicsek Ari. Does my patient have Clostridium difficile infection? Ann Intern Med 2009;151:176-179

2. Samore MH, DeGirolami PC, Tlucko A, et al. Clostridium difficile colonization and diarrhea at a tertiary care hospital. Clin Infect Dis 1994; 18:181-187.

3. Debast SB, van Kregten EV, Oskam KMG, et al. Effect on diagnostic yield of repeated stool testing during outbreaks of Clostridium difficile- associated disease. Clin Microbiol Infect 2008;14:622-624.

4. Manian FA, Aradhyula S, Greisnauer S, et al. Is it Clostridium difficile infection or something else? A case control study of 352 hospitalized patients with new-onset diarrhea. S Med J 2007;100:782-786.

5. Cardona DM, Rand KH. Evaluation of repeat Clostridium difficile enzyme immunoassay testing. J Clin Microbiol 2008; 46: 3686-3689.

Conflict of Interest:

None declared

Submit a Comment/Letter

Summary for Patients

Clinical Slide Sets

Terms of Use

The In the Clinic® slide sets are owned and copyrighted by the American College of Physicians (ACP). All text, graphics, trademarks, and other intellectual property incorporated into the slide sets remain the sole and exclusive property of the ACP. The slide sets may be used only by the person who downloads or purchases them and only for the purpose of presenting them during not-for-profit educational activities. Users may incorporate the entire slide set or selected individual slides into their own teaching presentations but may not alter the content of the slides in any way or remove the ACP copyright notice. Users may make print copies for use as hand-outs for the audience the user is personally addressing but may not otherwise reproduce or distribute the slides by any means or media, including but not limited to sending them as e-mail attachments, posting them on Internet or Intranet sites, publishing them in meeting proceedings, or making them available for sale or distribution in any unauthorized form, without the express written permission of the ACP. Unauthorized use of the In the Clinic slide sets will constitute copyright infringement.


Buy Now for $32.00

to gain full access to the content and tools.

Want to Subscribe?

Learn more about subscription options

Related Articles
Journal Club
Related Point of Care
Topic Collections
PubMed Articles
Forgot your password?
Enter your username and email address. We'll send you a reminder to the email address on record.