A New Way of Thinking About Microbes: Clostridium difficile as a Case Study
Young presented a “case study” of Clostridium difficile infection to illustrate this change in paradigm. Clostridium difficile was associated with disease in the 1970s, when researchers fulfilled Koch’s postulates to identify C. difficile as the causative agent of clindamycin-associated colitis (Bartlett et al., 1977). The case involved a 56-year-old man with chronic obstructive pulmonary disease (COPD) due to long-term cigarette use. The man was admitted with probable pneumonia and, as is standard of care for patients with suspected pneumonia, he was treated with broad-spectrum antibiotics. Although his pulmonary disease improved with antibiotics, on hospital day 3, the patient developed abdominal pain, diarrhea, and hypotension and was transferred to the intensive care unit, all as a result of a C. difficile infection. This is a “typical case,” of C. difficile infection, Young said, where antibiotic treatment for one infection results in infection with the intestinal pathogen.
The “dogma” regarding C. difficile that Young was taught as a medical student was that the indigenous microbiota somehow prevents colonization by C. difficile. Accordingly, C. difficile erupts when antibiotics disturb the indigenous microbiota; colonization resistance against C. difficile is lost; and the patient is susceptible to spores of the pathogen, which are present in the hospital environment. When patients start showing signs of C. difficile infection, they are typically prescribed yet another antibiotic, usually metronidazole or vancomycin. Although this antibiotic treatment directed against C. difficile generally results in improvement, there can be problems with recurrence, with about 25 percent of patients redeveloping symptoms after ending antibiotic treatment. Importantly, recurrence can develop even in the absence of any further original antibiotic treatment and is thought to reflect continued imbalance in the microbiota that does not correct after stopping antibiotics. Although these hypotheses regarding the relationship between C. difficile and the indigenous microbiota were proposed shortly after it was proven that the pathogen caused antibiotic-associated colitis, they have only recently been examined experimentally.
Young challenges his students to consider other ways to think about C. difficile, reminding them that the indigenous gut microbiome not only has massive metabolic capacity, but also serves many vital functions. Importantly, it has been proposed that one of those functions is a protective one and that indigenous microbiota confer on the gut what Young called “colonization resistance.” Without any additional insult to the microbiota, an estimated 25 percent of treated C. difficile patients do not have enough colonization resistance to withstand continued exposure to C. difficile