Difficulties with Clostridium difficile.

by recent antibiotic use, watery diarrhea, and abdominal cramps, Clostridium difficile infection is a common cause of nosocomial diarrhea. For both medical and surgical patients, the optimal therapy for Clostridium difficile-associated disease (CDAD) has become more controversial in the face of the increasing prevalence and disease severity that have been well documented in the literature. In this issue of Surgical Infections, Zerey et al. analyzed post-operative inpatients using the Agency for Healthcare Research and Quality (AHRQ) National Inpatient Sample Database from 1999 to 2003. They found that a discharge diagnosis of C. difficile infection was an independent predictor of longer hospitalization and a higher mortality rate, with an estimated annual cost of $750 million [1]. During an epidemic in 2002, Pépin et al. analyzed 1,721 cases of CDAD retrospectively at a university hospital in Sherbrooke, Québec [2]. From 1991 to 1992, the incidence of CDAD among elderly patients (age 65 years) was 102/100,000, with a 30-day mortality rate of 4.7%. In 2003, the incidence was 866/100,000, with a mortality rate of 13.8%. These data correspond to the broader analysis of American hospitals by Zerey et al. for both the five-year period and the epidemic of 2002. Of note, the U.S. regions closest to Québec, the Northeast and the Midwest, were primarily responsible for the increase in incidence and severity of CDAD [1]. More recent studies from Québec document an incidence of 22.5 cases/1,000 admissions, with an attributable mortality rate of 6.9% [3]. These hospital trends are mirrored in the community. In the United Kingdom, the incidence of community-associated CDAD (among patients not hospitalized in the preceding year) increased from 1 to 18 cases per 100,000 persons from 1994 to 2004 [4]. Recent reports have described severe CDAD in patients with minimal healthcare exposure: One series documented 8 of 33 infected persons as having no previous antibiotic exposure [5]. Addressing these trends, physicians have suggested that the emergence of alcohol-based hand sanitizers has contributed to the higher incidence because these agents are not sporicidal [1]. Dial et al. postulated that concomitant gastric acid suppression may triple the relative risk of community-acquired CDAD [6]. Considering that as many as two-thirds of patients can be asymptomatic “fecal excretors,” these prevalence data are potentially underestimates [7], although current guidelines do not recommend treatment of C. difficile carriers. Other factors may contribute to low incidence reporting. For example, several centers test stool samples only for toxin A, with a sensitivity of approximately 80% [8], even though the prevalence of pathogenic A /B C. difficile strains ranges from 0.2% to 12% [9]. The lower sensitivity of such tests introduces the potential for more falsenegative results and, more importantly, delayed therapy. The increase in disease severity has been associated with the North American pulsed-field gel electrophoresis type 1 (NAP1)/027 ribotype. A mutation in the tcdC gene, a suppressor of toxin A and B production, causes this strain to secrete toxin at a rate 15to 20-fold higher than previous strains. In one comparative study, the hypervirulent ribotype inSURGICAL INFECTIONS Volume 8, Number 6, 2007 © Mary Ann Liebert, Inc. DOI: 10.1089/sur.2007. 9978