Prevention is key in treating C. difficile infections

April 14, 2008

An effective control program includes active monitoring of antibiotic use, prescribing shorter durations, avoiding broad-spectrum drug use, using automatic stop orders, and employing antibiotic pharmacists.

Over the last decade, the incidence of Clostridium difficile-associated disease (CDAD) has steadily increased. CDAD ranges in severity from mild diarrhea to life-threatening pseudomembranous colitis.

A review of recent developments in the prevention and management of acute and recurrent CDAD was published in the February 5 Online First issue of Gut. "Emerging reports of CDAD in North America have been associated with the use of fluoroquinolones and more severe disease than that seen previously, especially in those over the age of 65 years," noted Tanya Monaghan, University of Nottingham and Nottingham University Hospitals in United Kingdom, and lead author of the article. Since 2001, several outbreaks of infection due to a hypervirulent and possibly resistant C. difficile strain have been reported.

The document emphasizes that prior antimicrobial therapy has been shown to be a major risk factor for CDAD. Key components of an effective control program include active monitoring of antibiotic use, prescribing shorter durations of antibiotics, avoiding broad-spectrum drug use if possible, using automatic stop orders, and employing antibiotic pharmacists.

As a first step, Timothy Riley, Pharm.D., clinical pharmacy coordinator at Monmouth Medical Center, Long Branch, N.J., suggests that pharmacists be familiar with the Infectious Diseases Society of America (IDSA) guidelines for developing an institutional program to enhance antimicrobial stewardship (available at http://www.idsociety.org/). Stewardship programs have shown to reduce the rates of CDAD. "Through a multidisciplinary approach, pharmacists can help implement specific elements of the program to minimize CDAD," stated Riley. "For instance, pharmacists at my institution assist physicians in selecting appropriate empirical antimicrobial therapy, streamlining antibiotics based on culture and sensitivity data, reducing the duration of antimicrobial use, and switching from parenteral to oral therapy when indicated," he said.

Treatment options

The authors suggest that patients with mild CDAD may respond to discontinuation of offending antibiotics and not require specific antimicrobial treatment. The review also discusses established and emerging treatment options for those patients requiring therapy. Monaghan pointed out that many guidelines recommend the use of metronidazole for treatment of CDAD based on the equivalent efficacy of metronidazole and oral vancomycin in clinical studies and risk of colonization with vancomycin-resistant enterococci (VRE).

Nitazoxanide (Alinia, Romark), an antibiotic used for the treatment of intestinal parasites, has been shown to be as effective as metronidazole for CDAD in a double-blind study. Rifaximin (Xifaxan, Salix), an FDA-approved agent for traveler's diarrhea, has demonstrated in vitro activity against C. difficile and is as effective as vancomycin in resolving initial CDAD symptoms.

On the horizon

Ramoplanin, a first member of a novel class of antibiotics known as glycolipodepsipeptides, has bactericidal activity against aerobic and anaerobic gram-positive bacteria, including C. difficile. In a Phase II study, ramoplanin 200 mg and 400 mg twice daily were compared with oral vancomycin 125 mg four times daily in patients with CDAD. The clinical cure rates for evaluable patients in both ramoplanin groups were comparable to vancomycin. Other investigational agents include tolevamer, an anion-exchange resin, which has demonstrated non-inferiority to vancomycin in a trial.

Despite appropriate initial treatment, the disease may recur in 15%-30% of patients with CDAD. Treatment with "tapered" or "pulsed-dose" vancomycin has been demonstrated to be beneficial for recurrent CDAD. The authors explained that the rationale for such treatment is that antibiotic-resistant spores may convert to antibiotic-sensitive vegetative forms during gradual withdrawal of antibiotics (tapered) and given on alternate days (pulsed). Other treatments include sequential vancomycin followed by rifaximin, intravenous immunoglobulin, and fecal enemas prepared from healthy donor stools.

THE AUTHOR is a writer and hospital pharmacist based in New Jersey.