October 1, 2007

Treatment Options for C. difficile

With the emergence of a binary toxin positive strain (BI/NAP1/027), the face of Clostridium difficile infection (CDI) has changed since the late 1980s. CDI is now more prevalent and virulent. Meanwhile, the effectiveness of metronidazole has decreased, leaving fewer antimicrobial options for treatment. At the 45th Annual Meeting of IDSA, in San Diego, a large audience of ID specialists gathered to hear experts discuss current and emerging treatment options, which include antibiotics as well as some rather unconventional methods to repair broken ecosystems in the colon.  

According to L. Clifford McDonald, MD, of the Centers for Disease Control and Prevention, BI/NAP1/027 is now present in at least 28 states and most European countries. “Although we’ve identified C. difficile in 28 states, it’s probably in every state,” he added. A study of a Quebec outbreak in 2004 showed that the 30-day attributable mortality rate was 6.9 percent, with a 12-month direct and indirect attributable mortality of 16.7 percent—compared with an attributable mortality of less than 1 percent in a 1988 Boston hospital in 1998. Mortality and prevalence are highest in the elderly.

Problems with CDI Management

With recurrence rates of 20 to 30 percent, CDI is difficult to manage. Dale N. Gerding, MD, FIDSA, of the Hines VA Hospital in Hines, Ill. presented data that suggest a changing response to metronidazole. “Vancomycin appears to be superior for severely ill patients,” he said. A recent study by F.A. Zar et al. suggests a statistically significant superiority in the response rate of vancomycin over metronidazole for severe disease but not for mild disease, although relapse rates associated with the two drugs appear to be similar.

With vancomycin as the only FDA-approved drug for CDI and the off-label use of metronidazole less effective than it once was, presenters at the session discussed potential strategies to improve CDI treatment. One is to use antimicrobial treatment that spares normal flora. Rifaximin, one such drug, is being studied in a Phase III trial for CDI, as is OPT-80, an investigational agent from Optimer.

Nonpharmacologic Approaches

A presentation from Tom Moore, MD, with Infectious Disease Consultants in Wichita, Kansas, included a number of alternative treatment methods for recurrent CDI. These treatments restore the normal colonic bacterial flora. Such methods include prebiotics and probiotics as well as the somewhat controversial method of fecal bacteriotherapy, which restores colon homeostasis by reintroducing normal bacterial flora from stool obtained from a healthy donor. Benefits of fecal bacteriotherapy include reducing the risk of antibiotic-associated resistance, cost savings when compared to repeated courses of antibiotic therapy, and high success rate. Of 80 published reports, the success rate was 94 to 100 percent. Although the benefits are apparently great, there are potential obstacles and risks, which include limitations that might be imposed by the local institutional review board and lack of Medicare coverage for donor stool screening and instillation procedure. Physicians with experience using fecal bacteriotherapy were encouraged to publish their findings.

Slides from this session and many others from IDSA 2007 are available online. 

Audio files, including a full-conference CD-ROM, are available for purchase from Sound Images.

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