C difficile-Associated Disease: Changing Epidemiology and Treatment
Philadelphia, Pennsylvania; Wednesday, October 17, 2007 -- Clostridium difficile infection is increasingly recognized as a serious consequence of antimicrobial treatment. In the past, the majority of cases were acquired nosocomially; however, outpatient cases are increasing in frequency. In addition, more cases are occurring in long-term-care facilities such as residential nursing homes and skilled nursing facilities. Treatment has changed little in the past 20 years; metronidazole (the only FDA-approved therapy for C difficile infection), followed by vancomycin if the former is ineffective, is still the standard of care. Passive immunization with immunoglobulin and the use of new antimicrobials are under intense investigation. At this year's meeting of the American College of Gastroenterology (ACG), several important abstracts related to the changing epidemiology and treatment of C difficile were presented.

 
A Review of Intravenous Immunoglobulin to Treat Severe C difficile Disease
Koulaouzidis and colleagues performed a systematic review of the available literature on the use of intravenous immunoglobulin (IVIG) for the treatment of refractory cases of C difficile colitis. It is believed that these patients have an impaired ability to mount antibody to C difficile toxin A. No controlled trials were identified. The authors found 7 case reports/series as well as 1 retrospective case-control study for a total of 46 patients treated with IVIG. Overall, 17.4% receiving this therapy died, 39.1% suffered relapse/recurrence, and 6.5% required colectomy. The authors appropriately recommend a randomized prospective trial to determine IVIG benefit in this setting.

 
Shift in C difficile Cases From the Hospital to the Community
Kumar and colleagues from Johns Hopkins University performed a retrospective analysis of 300 hospital records of patients with established C difficile colitis, seeking to determine the patient's probable location at the time of infection. They found that only 17.7% of cases were likely acquired in the acute hospital setting. Approximately 69% of cases were acquired in the community or while the patient resided at a nursing home. The authors correctly point out that the epidemiology of C difficile-associated disease appears to be shifting toward the outpatient setting. New approaches toward control of infection need to be considered.

 
Should Vancomycin Replace Metronidazole as First-line Treatment?
Thomas and colleagues performed an analysis to determine whether the current strategy of using metronidazole prior to vancomycin was the most cost-effective approach to the treatment of C difficile-associated diarrhea. The authors used complex modeling (Markov method), which factored in not only drug cost but also the potential cost of additional hospital days and repeat treatment due to differences in efficacy. The analysis still favored the use of metronidazole as the first-line treatment. Projected average cost for a course of metronidazole was $561, while vancomycin cost $910. The cost of vancomycin would need to be reduced by nearly 90% to make this drug relatively cost-effective.

 
Factors Associated With C difficile Colitis After Abdominal Surgery
Rahmani and colleagues retrospectively identified 1214 patients who had undergone an abdominal operation in 2006. Overall, 45 (4%) were found to have a stool toxin positive for C difficile. They used uninfected patients as controls for identifying risk. Preoperative risks included increasing age (odds ratio [OR] = 1.34), male sex (OR = 1.84), proton-pump inhibitor use (OR = 2.00), antibiotic use (OR = 2.04), length of stay before surgery (OR = 1.58), and low albumin level on admission (OR = 2.00). Postoperative risks for mortality related to C difficile disease were low serum albumin on admission (hazard ratio [HR] = 3.41) and high admission creatinine level (HR = 1.55). Many of the risks identified here have been reported in other studies, and therefore these results appear consistent with the published literature.

 
Rifaximin Enema for C difficile Colitis in an Immunocompromised Host
Oral rifaximin is currently under investigation for the treatment of C difficile colitis. Rifaximin is a nonabsorbable antibiotic with good in-vitro activity against Clostridium species. Donald David, MD, reported the case of a 37-year-old woman with severe C difficile colitis who was profoundly immunosuppressed after a bone marrow transplant. She failed to respond to oral vancomycin and IV metronidazole therapy, and thus underwent loop ileostomy without colectomy. Postoperatively the patient was treated with retention enemas of vancomycin and rifaximin (400 mg) thrice daily with good response. Eventually the ileostomy was successfully reversed. Although rifaximin holds promise in the treatment of C difficile-associated disease, there remains concern regarding the widespread use of this agent for this disease because of the reported emergence of resistant organisms.

 
How Good Are the Clinical Guidelines for Predicting C difficile Diarrhea?
Kaczanowski and others from Norwalk Hospital in Connecticut sought to test guidelines established by the ACG for predicting C difficile as the etiology of hospital-acquired diarrhea. They performed a retrospective chart review to identify all cases of C difficile-related diarrhea at their hospital over a 6-month period. They found that the ACG guidelines performed relatively well in their hospital. Overall, 33.3% of patients who met the guidelines on initial testing had a positive stool toxin. However, if the criteria were not met, only 17.6% of stools tested positive. The guidelines performed less well on subsequent stool studies for those who did not test positive initially. The authors point out the limitations of the guidelines: they are only marginally superior to clinical suspicion due to their poor positive and negative predictive value. Testing and empiric treatment should commence when the clinical suspicion for C difficile is high, regardless of meeting specific clinical criteria.

Supported by independent educational grants from Abbott and Shire