The article in JAMA that I was going to review unfortunately for me (good for them) is exceptionally well written and will be difficult to distill further for everyone. That’s okay! I am going to use this article to guide us through a few high yield questions about Clostridium difficile (C diff) that will provide a “10,000 foot view” of important characteristics of the infection. So that’s what I’m going to do, or at least attempt, and if you have additional questions go ahead and ask them and I will see what I can do. Thinking about explaining scientific articles to the public, and actually doing it are two very different things I’m realizing, it’s pretty tricky so bear with me. Hopefully I improve with some practice, and don’t completely ruin your opinion of science! Also I have appointments with doctors going on today so I will be posting this in chunks throughout the day. Anyways here we go.
What is Clostridium difficile and how does it cause problems?
C. diff is a gram positive, anaerobic, spore forming bacteria that is ubiquitous in nature, even among the normal healthy/’good’ bacteria (called normal flora) in healthy individuals. That’s a loaded sentence so let’s deconstruct it a bit…First, bacteria are most broadly described by the architecture of their cell walls specifically whether they “trap” a chemical in their cell walls. Gram positive bacteria trap this chemical in their walls which tend to be thicker and have distinct properties that further differentiate them from gram negative bacteria. The cell wall has many functions but most simply you can think of it as the bacteria’s protective surface from the external environment, things like antibiotics. Some groups of bacteria can form “colonies” called biofilms where bacteria, even of different species, can communicate chemically in a process called “quorum sensing.” Bacteria in these groups will further differentiate to have specialized functions based on their location. For instance the bacteria on the surface may all have antibiotic resistance whereas the interior bacteria may specialize solely on producing energy. The world of bacteria is very cool.
Secondly, C. diff is an anaerobic bacteria meaning that it will not grow in the presence of oxygen. This has important implications for how infection is spread so keep it in mind. Bacteria are smart and over millions of years of evolving they have found ways to circumvent pretty much any problem. If you think about where in the body this bacteria will be able to grow you quickly can eliminate some sites i.e. our lungs or skin simply by the fact that we know it is anaerobic. However in oxygen deprived environments like the gastrointestinal tract the bacteria feel at home. Interestingly, C diff is estimated to be present in 2-5% of the general population (1) and 16-35% of hospital inpatients (2) however it does not cause symptomatic infections in everyone. If you could tell me why this is the case I would appreciate it, and so would the whole scientific community! Anyways, closely related to its anaerobic growth patterns is the ability to form spores which remain viable in oxygenated environments but don’t divide. These spores are a serious problem because they can remain viable basically indefinitely (there are reports out there of bacterial spores millions of years old). If they are reintroduced to the appropriate environment they can begin to divide and cause disease.
Basically these spores can simplistically be thought of as potential progeny that remain in hibernation in oxygen rich enviornment and they’re shed by the bacteria continuously. Remember the bacteria in a person’s GI tract (whether they have the disease or not) are producing these spores by the millions and invariably they escape because of poor hygiene to the environment. That’s a little gross but it’s the truth, the oral fecal route of transmission is extremely common for a lot of diseases.
So if you can imagine a person may be walking along in a hospital, touch a surface with C. diff spores, not wash their hands, eat a sandwich and reintroduce the spore into an anaerobic environment where it will begin to divide. This is how C. diff is spread around the population. Now we also know that certain people are particularly at risk for developing symptoms rather than just carrying the bacteria. There are several groups at risk for infection but the most common and who we will focus on in subsequent posts people who have recently been in the hospital on certain antibiotics (3).
A final important characteristic of disease causing strains of bacteria is that they produce toxins aiding their virulence. Once a spore has been reintroduced to the GI tract it will reproduce, it will produce what is called an A and B toxins. The Toxin A causes fluid to accumulate in the bowel and cytotoxin B causes cell death in the GI tract. Ultimately patients have an all too familiar presentation characterized severe diarrhea, fever and abdominal pain. These symptoms are exactly like a Crohn’s flare so there is more testing we will discuss later that is important in diagnosing C. diff infection. Some patients will also have a “pseudomembranous colitis” which is seen upon colonoscopy. There are other more severe complications from C. diff but they’re relatively uncommon and no need to induce more panic.
- Ryan KJ, Ray CG (editors) (2004).Sherris Medical Microbiology (4th ed.). McGraw Hill. pp. 322–4
Aslam S, Hamill RJ, Musher DM. Treatment of Clostridium difficile-associated disease: old therapies and new strategies. Lancet Infect Dis. 2005 Sep;5(9):549-57. Review.
Bagdasarian N, Rao K, Malani PN. Diagnosis and treatment of Clostridium
difficile in adults: a systematic review. JAMA. 2015 Jan 27;313(4):398-408. doi: 10.1001/jama.2014.17103.