Of the 140 or so human pathogens that have emerged in the past half-century, few are as remarkable as the bacterium, Clostridioides difficile (formerly Clostridium difficile), or C. diff for short. You would think a microbe that is the most common cause of bacterial gastroenteritis in the U.S. (about 500,000 cases per year with an estimated annual mortality of 15,000) would qualify it for instant name recognition. But, unless you work in a healthcare facility, chances are you haven’t heard of C. diff. In hospitals, on the other hand, C. diff is a bane of existence for everyone involved in infection control and patient safety. That’s because hospitals harbor people who are at greatest risk of developing C. difficile infection (CDI)—those receiving antibiotics and the elderly.
In addition to its clinical significance, I believe C. diff deserves everyone’s attention because of four closely related lessons it teaches.
1. Be thankful if your gut microbiome is balanced (eubiosis).
Few areas of medicine are witness to as many discoveries in the past decade as is research on the gut microbiome. (The term microbiome refers to microbes that share our body’s surfaces.) Because of the National Institute of Health-supported Human Microbiome Project initiated in 2008, researchers have determined significant associations between the composition of the microbes we harbor in our gastrointestinal tract (or gut) and good health as well as with a variety of diseases.
Incredibly, the human gut contains about 40 trillion bacteria (the remainder of the entire human body contains around 37 trillion cells). And more than 2,000 different bacterial species call the gut their home. On top of this, the gut contains an even larger number of viruses (the virome) and a substantial number of fungi (the fungiome).
While correlations between the gut microbiome and many medical conditions have been found (for example, see one of the previous Germ Gems blogs on obesity), the role of a disturbed balance between beneficial and harmful bacteria (a condition called dysbiosis) and a particular disease hasn’t been causally established in most instances. But in the case of CDI, it is clear that “good” bacteria keep C. diff in check. No single microbial species, however, protects the colon against C. difficile gaining a foothold. Rather, resistance against colonization with C. diff is associated with a cooperative interaction of several different groups of bacteria.
2. Use antibiotics judiciously.
There are many reasons you shouldn’t take an antibiotic unless you have a bacterial infection known to respond to an antibiotic. The risk of developing CDI, however, is one of the most important reasons. Because virtually all antibiotics can eradicate the good bacteria in your gut that protect against C diff. they can all set you up for increased risk of CDI.
Most hospitals in the U.S. currently have antibiotic stewardship teams (usually including an infectious diseases specialist and a pharmacist) that oversee antibiotic use. Preventing CDI is one of their major goals. In recent years, CDI has moved into the community where monitoring of antibiotic use is more difficult. Nonetheless, if you have a viral infection (e.g., a common cold, sinusitis, or bronchitis), be wary of those who prescribe antibiotics, as these drugs don’t work and they put you at risk of CDI.
3. If you are a victim of recurrent bouts of CDI, a fecal microbiota transplant (FMT) is the way to go.
After a decade of clinical research on various treatments of recurrent (two or more episodes) CDI, it is now clear that the most effective treatment, believe it or not, is—human stool. That is nature knows best. The goal of FMT is to address the dysbiosis caused by antibiotics through repopulating the gut with bacteria that will eradicate C. diff. While FMT isn’t always effective and isn’t risk-free, it is better than alternative therapies. Donor stool samples, carefully assessed for potential pathogens, can be delivered from below by a colonoscope or from above by a device or a pill. It is crucial, however, that the management is guided by a gastroenterologist with expertise with FMT.
4. A new species of C. difficile is evolving that likes sweets.
C diff is very clever. One of the reasons C. diff is so successful as a pathogen is that it has the capacity to form spores. Spores are dormant forms of the bacteria that can withstand harsh conditions and long periods of nutritional deprivation. When the time is right, (for example, an antibiotic has eliminated bacterial competitors,) spores blossom into bacterial forms. If by chance the bacterial form produces toxins that damage the colon, look out for CDI.
A recent study by Nitin Kumar and colleagues suggests that in response to exposure to simple dietary sugars (glucose and fructose), a new species of C. difficile is evolving that has high levels of resistant spores that make it particularly well suited for existence in patients in hospital environments. Kumar and his colleagues collected 906 different strains (or variants) of C. diff from humans, animals, and the environment and sequenced their DNA. They found that 70% of the strains collected from hospital patients shared distinct genetic traits, a group known as C. difficile clade A. They found that this group is “on the verge of becoming a different species,” meaning that they share more than 95% of their DNA. The emerging microbe has several traits that make it a perfect fit for living in hospitals: it’s resistant to antibiotics, difficult to kill with hospital disinfectants, and thrives on simple sugars that characterize a Western diet (and post-operative feedings of clear liquids and soft foods).
The lesson here: microbes evolve along with us and our environment. And an overarching principle that can be learned from the gut microbiome—the benefit of diversity.
