Well S*#t

We are just going to keep talking about GI subjects until I get tired of them. Probably after this but who knows? I get to take care of a lot of GI/GU patients at work with some of the "Greatest Hits" of the gut. Diverticulitis, intestinal perforations, colorectal cancer, pancreatitis, bowel obstructions, abscesses, bleeds, and the like. I won't ever be a GI specialist but I do love infections and the big dog at the moment is everyone's favorite, Clostridioides difficile AKA Clostridium difficile maybe C. diff or in this mess of words, CD. 

CD is a Gram -positive, spore forming, obligate anaerobic, motile, "drumstick-shaped" bacillus. To expand on that, they need low-no oxygen environments (like the gut), create spores that are hardy and able to survive conditions that would kill the live bacteria, and CD creates toxins that cause many of the effects of a CD infection. Though we generally associate CD with the diseases it causes, sometimes called CDAD or C. diff associated diarrhea, colitis, toxic megacolon, perforation, and others, CD can also be part of our normal flora. Different sources put the rate of asymptomatic carriers between 5-11%, while ~1/2 million people in the U.S.A. are infected each year symptomatically with ~15,000-30,000 deaths per year. 

CD can be found in pigs, soil, sewage, meat, on surfaces not cleaned properly, and of course in humans. The fecal oral route is how you get CD, which is normally picked up from surfaces because people don't wash their hands enough and the spores are VERY hardy and not killed by normal alcohol hand sanitizer. Have we tried to wash with bourbon? Might work better. Though once you get the beastie inside of your insides, it is easily kept at low levels by your normal gut flora, that is until you get some antibiotics. 

Before we get to that, CD causes its disease via Toxin A & Toxin B, very original names. Toxin A is what causes the inflammation of the intestines when released. This can lead to ulceration, perforation, and increased intestinal permeability. Toxin B helps A do its work by increasing the gap between epithelial cells so A can get in the cracks and cause more damage. There is a -mab used to block Toxin B in efforts to prevent the effects of A and thus spare the afflicted from the disease, its name is bezlotoxumab. Say that 5 times fast. There are other toxins that don't seem to play as large of a role, and there is some debate over A or B being the more important for CD associated disease. Personally I root for Toxin J, the underdog who shares the first letter in my name. J probably doesn't exist outside my mind but who cares? 

So if the CD is sitting in your gut, maybe from some contaminated food or not washing your hands or any number of other methods. Normally, your normal gut flora keeps CD in check but once you get some antibiotics the normal flora gets killed off. This gives CD the opportunity to fill that niche and you move from colonized to infected. As the CD toxins take effect most people will have watery or bloody diarrhea with a smattering of anorexia, nausea, fever, abdominal pain, and arthritis though some have the inflammation without the diarrhea. 

The antibiotics most strongly linked to CD infections are cephalosporins, fluoroquinolones, clindamycin, and penicillins, though any may cause CD to take over. The diagnoses is first based off of 3 or more loose stools in 24 hours and subsequent CD toxin and PCR labs on a stool sample. The patient should then be put in an isolation room and all who enter must wash their hands with soap and water upon leaving (see the use of bourbon as my good idea) since normal hand sanitizer doesn't cut it. Generally medical staff will wear a gown and gloves for all patient interactions. 

For non-severe CD infections oral vancomycin or fidaxomicin is given, both of which have very poor absorption so they stay in the intestines without the same level of risk as parenteral versions. This first treatment is normally 10 days (like everything else, 5, 7, 10, 14, 21, etc...) with longer courses for subsequent infections. As the recurrences drag on (as is not uncommon) rifaximin may be added, fecal transplant, vancomycin enema, and/or IV metronidazole. These recurrences happen in around 20% of first time CD patients, and increase form there as high as a 60% recurrence rate. If the disease becomes severe enough (shock, toxic megacolon, perforations) surgery may be the next option. 

Of course, this may all be a moot point if CD becomes resistant to our weaponry. A January 2022 PLOS article looked at 15 studies and assessed average resistance in the U.S.A., China, the EU, Scotland, Thailand, Iran, and Poland. Resistance rates were vancomycin (3%), metronidazole (5%), clindamycin (61%), moxifloxacin (42%), tetracycline (35%), erythromycin (61%), and ciprofloxacin (64%). So, while some men wonder if the world will perish in fire or ice, I say nay, it shall perish in s*@t with drug resistant diarrhea. Actually, I don't think CD will be the first totally resistant bug that kills us all but it may be in the running. Taking bets? CD vs VRE vs XDRTB vs A. baumanii. vs N. gonorrhea. 

Anyway, that is CD and all of its glory. So wash your hands, much easier than intractable diarrhea.   

References 

Antibiotics Associated With Clostridium difficile Infection by Rafey et al., in Cureus 2023

Antimicrobial resistance in Clostridioides (Clostridium) difficile derived from humans: a systematic review and meta-analysis by Sholeh et a., in Antimicrobial Resistance & Infection Control 2020

Both Oral Metronidazole and Oral Vancomycin Promote Persistent Overgrowth of Vancomycin-Resistant Enterococci during Treatment of Clostridium difficile-Associated Disease by Al-Nassir et al., in Antimicrobial Agents and Chemotherapy 2008

Clostridium difficile infection and antibiotic-associated diarrhoea by Mullish & Williams in Clinical Medicine by the Royal College of Physicians 2018

Current Treatment Options for Severe Clostridium difficile–associated Disease by Shen & Surawicz in Gastroenterology & Hepatology 2008

Does Addition of Intravenous Metronidazole to Oral Vancomycin Improve Outcomes in Clostridioides difficile Infection? by Wang et al., in CID 2020

Prevalence and antimicrobial resistance pattern of Clostridium difficile among hospitalized diarrheal patients: A systematic review and meta-analysis from CID by McDonald et al., 2018

Fidaxomicin versus metronidazole, vancomycin and their combination for initial episode, first recurrence and severe Clostridioides difficile infection — An observational cohort study by Polivkova et al., in the International Journal of Infectious Diseases 2021

Image of a CD spore from the New Scientist

NIH and CDC pages on CD

Prevalence and antimicrobial resistance pattern of Clostridium difficile among hospitalized diarrheal patients: A systematic review and meta-analysis by Dilnessa et al., in PLOS One 2022

Prevalence and Risk Factors for Asymptomatic Clostridium difficile Carriage by Alasmari et al., in CID 2014

Screening of Clostridioides difficile carriers in an urban academic medical center: understanding implications of disease by Baron et al., in Infection Control Hosp Epidemiol 2020

The burden of CDI in the United States: a multifactorial challenge by Feuerstadt et al., in BMC Infectious Diseases 2023