Narrative Review: The New Epidemic of Clostridium difficile?Associated Enteric Disease

</NOBR><NOBR>John G. Bartlett, MD</NOBR>

21 November 2006 | Volume 145 Issue 10 | Pages 758-764

Antibiotic-associated diarrhea and colitis were well established<SUP> </SUP>soon after antibiotics became available. Early work implicated<SUP> </SUP>Staphylococcus aureus, but in 1978 Clostridium difficile became<SUP> </SUP>the established pathogen in the vast majority of cases. In the<SUP> </SUP>first 5 years (1978 through 1983), the most common cause was<SUP> </SUP>clindamycin, the standard diagnostic test was the cytotoxin<SUP> </SUP>assay, and standard management was to withdraw the implicated<SUP> </SUP>antibiotic and treat with oral vancomycin. Most patients responded<SUP> </SUP>well, but 25% relapsed when vancomycin was withdrawn. During<SUP> </SUP>the next 20 years (1983 through 2003), the most commonly implicated<SUP> </SUP>antibiotics were the cephalosporins, which reflected the rates<SUP> </SUP>of use; the enzyme immunoassay replaced the cytotoxin assay<SUP> </SUP>because of speed of results and technical ease of performance;<SUP> </SUP>and metronidazole replaced vancomycin as standard treatment,<SUP> </SUP>and principles of containment hospitals became infection control<SUP> </SUP>and antibiotic control. During the recent past (2003 to 2006),<SUP> </SUP>C. difficile has been more frequent, more severe, more refractory<SUP> </SUP>to standard therapy, and more likely to relapse. This pattern<SUP> </SUP>is widly distributed in the United States, Canada, and Europe<SUP> </SUP>and is now attributed to a new strain of C. difficile designated<SUP> </SUP>BI, NAP1, or ribotype 027 (which are synonymous terms). This<SUP> </SUP>strain appears more virulent, possibly because of production<SUP> </SUP>of large amounts of toxins, and fluoroquinolones are now major<SUP> </SUP>inducing agents along with cephalosporins, which presumably<SUP> </SUP>reflects newly acquired in vitro resistance and escalating rates<SUP> </SUP>of use. The recent experience does not change principles of<SUP> </SUP>management of the individual patient, but it does serve to emphasize<SUP> </SUP>the need for better diagnostics, early recognition, improved<SUP> </SUP>methods to manage severe disease and relapsing disease, and<SUP> </SUP>greater attention to infection control and antibiotic restraint.<SUP> </SUP>http://www.annals.org/cgi/content/abstract/145/10/758