Repeated stool toxin testing for diagnosing difficile colitis is still valid.

We would like to thank the authors for this interesting and practical article, especially regarding the assertion that Clostridium difficile is becoming a major health concern in many institutions; however, we would like to comment on several points mentioned in this article. Firstly, C. difficile causes about 15 to 25% of all cases of antibiotic-associated diarrhea. It is estimated that the rate of C. difficile is about 3–25/10,000 patient days in acute care facilities, and the carriage rate is about 5 to 7% of patients in long-term facilities. However, the reported incidence of three million cases of C. difficile per year in the article might be an overestimation. According to surveillance for community-associated C. difficile in Connecticut and Philadelphia in 2006 and 2007, the incidence was about 7 per 100,000 cases. For a better understanding, we compared the incidence of C. difficile to the incidence of the flu. From September 28, 2008 to April 4, 2009, the World Health Organization and National Respiratory and Enteric Virus Surveillance System’s collaborating laboratories in the United States tested 173,397 respiratory specimens for influenza viruses; 24,793 (14.3%) of these were positive. These numbers are far less than the numbers reported by the authors. Secondly, we agree with the authors that C. difficile is a disturbing cause for morbidity and mortality; however, an overall mortality rate of 20% and up to 30% in intensive care units may not reflect an accurate number in today’s standard of care. In a large outbreak with an unexpected proportion of deaths and colectomies, nosocomial C. difficile infections increased from 2.7 to 6.8 cases per 1,000 discharges. There were 253 nosocomial C. difficile infections; of these, 26 resulted in colectomies and 18 resulted in death. Although these numbers as stated are unexpectedly high, they are still much lower than those reported in this article. According to the Surveillance for Community-Associated Clostridium difficile in Connecticut, only 2% of the patients developed toxic megacolon and required a colectomy, and another 2% died of complications related to C. difficile infection. Even among the “oldest” old patients (over 80 years old), C. difficile infection was the direct cause of death in only in 1 out of 70 patients, although these patients had a high all-cause mortality of 8.6% at 30 days and 17% at 90 days because of other comorbid conditions. In one other study of 40 patients with C. difficile by Kyne et al, C. difficile–associated diarrhea was not associated with an excess of 3-month or 1-year mortality after adjustment for age, comorbidity, and disease severity. In addition, Zilberberg et al reported an increase of the C. difficile–related, age-adjusted, casefatality rate from 1.2% in 2000 to 2.2% in 2004, which is much less than the rate reported in this article. Thirdly, looking at the sensitivity of the enzyme-linked immunoassay (EIA) test ranging anywhere from 50 to 90% (depending on the different studies) and looking at the sensitivity of this particular study falling near the higher end of the spectrum (at 84%), one wonders if these results (negative predictive value NPV of 94%) with two samples can be reproduced in institutions where sensitivity is at the lower spectrum (such as at 50%). A third sample would be very helpful in these cases to increase the NPV. The results of this study are in agreement with the previous studies, which show that repeat C. difficile testing increases the NPV (from 96 to 99% in this study). In another way, repeat C. difficile testing is of value, as opposed to the authors’ conclusion. While we agree that a repeat third sample is not needed if the clinical suspicion is low or if the patient is already improving, a third sample is required in many cases if C. difficile is still a possibility. Spreading out the time of testing might be a useful tool to increase the sensitivity without adding frequent testing, even though it is more time consuming. In some cases, where the clinical suspicion remains high despite three negative samples, an endoscopy or a computed tomography (CT) scan (which are more invasive and less sensitive than stool sampling) may be required before ruling out C. difficile colitis. We do not feel that financial considerations should stop clinicians from testing when it is indicated. According to this study, at least 4 out of 100 cases will be missed if only two samples are used. The financial burden of these missed cases will truly justify more aggressive diagnostic testing. In 2000, it was estimated that the mean cost of admission with a primary diagnosis of C. difficile was as high as $10,212 and C. difficile as a secondary diagnosis increased the cost by up to $13,675 per admission, with the annual US cost for C. difficile-associated disease management at $3.2 billion dollars. Less aggressive diagnosing standards for C. difficile would most likely lead to more C. difficile cases and increased costs. Lastly, we also feel that the comparison between the value of repeat C. difficile testing and rapid flu testing is not well balanced. In most cases, Influenza is a self-limited disease and treatment only mildly affects morbidity and mortalFrom the Departments of Internal Medicine and Infectious Diseases, Henry Ford Hospital, Detroit, MI.