Treating C. difficile

In their comprehensive review of Clostridium difficile-associated diarrhea (CDAD), Susan Poutanen and Andrew Simor1 refer to the use of anion-binding resins (colestipol or cholestyramine). It is important to highlight the timing of administration of these agents in relation to other oral therapeutic agents (metronidazole or vancomycin). In addition to binding the toxin and spores of C. difficile, the binding agents may also bind orally administered therapeutic agents to various degrees, thereby negating their effect. Ideally, resin binders should be given either an hour before or 4 to 6 hours after administration of the oral antibiotics2 to avoid this problem. However, in clinical practice, especially in hospitals, I have found that the binders and other agents are often given simultaneously; many of the patients have recurrent disease, are described as being resistant to metronidazole (an otherwise rare situation) and are subsequently given oral vancomycin, which is more costly. I believe that this is a common cause of iatrogenic resistance to oral metronidazole.

There are no studies of this phenomenon (i.e., no evidence in this era of evidenced-based and “evidence-made”3 medicine), but on the basis of a theoretical understanding of the pathophysiology of CDAD, I often administer 10 to 14 days of oral metronidazole followed by 5 to 7 days of oral cholestyramine (to bind the remaining spores in the gut) and have observed a very low rate of recurrence. It is time to prospectively evaluate this simple strategy of sequential therapy in the management of CDAD in a randomized trial.