Clostridium difficile: when antibiotics push the gut over the edge

Clostridium difficile: When Antibiotics Cause the Gut to Overreact

Clostridium difficile, often shortened to C. difficile or simply C. diff, is a bacterium that lives in many people's intestines without causing problems. However, if the balance in the gut is disrupted, most often after a course of antibiotics, the bacterium can take over and trigger a severe inflammation of the large intestine called pseudomembranous colitis. In Denmark, it is the most common hospital-acquired gut infection, and the number of cases has steadily increased over the past twenty years.

The disease doesn't only affect elderly hospital patients. Younger, otherwise healthy patients can also contract it, and infection can occur outside of a hospital setting.

What are the symptoms?

Symptoms typically begin days to weeks after a course of antibiotics. The classic presentation includes:

• Watery, often foul-smelling diarrhoea, often many times a day
• Abdominal pain or cramps
• Low-grade fever
• Nausea and reduced appetite
• Fatigue and dehydration

In severe cases, high fever, blood in the stool, increasing abdominal pain, bloating, and in the worst cases, toxic megacolon can occur, where the large intestine dramatically expands and may rupture. Toxic megacolon requires urgent hospital admission and may necessitate surgical removal of the large intestine.

Why does it happen?

C. difficile produces two toxins (toxin A and toxin B) that attack the intestinal lining. The bacterium is only able to proliferate when the normal gut flora is weakened. This most often occurs after:

• Antibiotic treatment, particularly cephalosporins, clindamycin, ciprofloxacin, and broad-spectrum penicillins
• Hospitalisation, where exposure to spores from the environment is common
• Older age
• Use of acid-suppressing medication (PPIs like omeprazole, pantoprazole)
• Weakened immune system
• Chronic inflammatory bowel disease

The bacterium forms spores that are extremely resistant. They survive cleaning with ordinary disinfectants and can remain for weeks on bed rails, door handles, or toilets. This is why alcohol-based hand sanitisers are ineffective against C. difficile. Only thorough hand washing with soap and water removes the spores.

How is it diagnosed?

Diagnosis rests on symptoms that fit the picture, especially new watery diarrhoea, combined with microbiological testing of a stool sample. As a rule only loose stool is tested, because many healthy people carry the bacterium without being ill. The exception is suspected ileus or toxic megacolon, where the patient can be severely ill without diarrhoea and the doctor may choose to test anyway.

The tests measure three different things, and they do not mean the same:

1. GDH antigen (glutamate dehydrogenase) shows that C. difficile is present, but not whether it produces toxin.
2. Toxin test (enzyme immunoassay) detects free toxin A/B in the stool, that is, the substance that makes the bowel ill.
3. Nucleic acid test (PCR) detects the toxin gene, that is, that the bacterium can produce toxin. A positive PCR alone does not prove disease and must always be interpreted alongside the symptoms, since asymptomatic carriage is common.

Many laboratories therefore use a stepwise approach combining GDH and toxin testing, with PCR used when results disagree. The exact sequence varies between laboratories, and the local laboratory sets its own method. The American IDSA/SHEA guideline describes the principle (IDSA/SHEA guideline on C. difficile).

Sigmoidoscopy or colonoscopy is not a routine requirement for the diagnosis. Endoscopy is used only in selected cases, for example diagnostic doubt or suspicion of another disease, and may then show the white pseudomembranes that gave the disease its name.

CT scans are used in severe cases to assess the appearance of the bowel and rule out megacolon.

Treatment

First-line treatment has changed in recent years. Today, the recommendations are:

• First: if possible, stop the offending antibiotic
• First episode: antibiotics directed at the bacterium, typically vancomycin tablets or fidaxomicin. Metronidazole is used less often first line than it once was. The choice of drug and the length of treatment are set by the treating doctor, and we do not state doses or durations here.
• First recurrence: fidaxomicin or vancomycin in a pulsed/tapered regimen
• Repeated recurrences: microbiota-based therapy, including faecal microbiota transplantation (FMT), is recommended for selected adults with recurrent C. difficile infection after standard treatment. It is delivered in specialist care using screened donor material or approved products (AGA 2024). Reported efficacy depends on the patient group, the number of prior recurrences, the route of administration and the endpoint measured, so a single success figure does not apply to every situation. There is a risk of transmitting infectious organisms, which is why validated donor and product screening is required. FMT should not be used outside approved indications or clinical trials, and there is no safe way to do it at home.

Probiotics are not a treatment for C. difficile infection. The evidence for probiotics in preventing antibiotic-associated diarrhoea is strain- and situation-specific, and professional societies grade it differently.

In cases of severe colitis, septic shock, or toxic megacolon, emergency surgery may be necessary.

When should you seek medical attention?

Contact your GP or an emergency department if:

• You have watery diarrhoea that lasts for more than a week, especially after a course of antibiotics
• You have blood in your stool
• You have a high fever accompanied by abdominal pain
• You are very tired, have difficulty drinking enough, or are losing weight rapidly

For elderly or frail individuals, do not wait. Seek assessment early.

Frequently Asked Questions

Can I get C. diff without having taken antibiotics? Yes, but it is rare. Antibiotics are by far the most common trigger, but the elderly, immunocompromised individuals, and those on proton pump inhibitors can also contract it without prior antibiotic use.

Can it spread to my relatives? The bacterial spores can spread. Wash hands with soap and water (not alcohol gel), thoroughly clean bathrooms and toilets, and use separate towels as long as you have diarrhoea.

How long does the treatment last? The length of treatment is set by the treating doctor and depends on the drug, the severity of the illness and whether this is a first episode or a recurrence. Many feel better during the first few days, but diarrhoea can drag on. Recurrence is a recognised problem, and how often it happens varies between series and patient groups, so we do not give a single figure here.

What is faecal transplantation, and is it unpleasant? It involves transferring carefully screened stool from a healthy donor into your gut, most often during a colonoscopy. It might sound unusual, but it is used precisely for repeated recurrences where standard treatment has not held. Donors are rigorously screened for infections and diseases.

References

1. Johnson S, Lavergne V, Skinner AM, et al. Clinical Practice Guideline by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA): 2021 Focused Update Guidelines on Management of Clostridioides difficile Infection in Adults. Clin Infect Dis. 2021;73(5):e1029-e1044. PubMed
2. van Prehn J, Reigadas E, Vogelzang EH, et al. European Society of Clinical Microbiology and Infectious Diseases: 2021 update on the treatment guidance document for Clostridioides difficile infection in adults. Clin Microbiol Infect. 2021;27 Suppl 2:S1-S21. PubMed
3. Sundhed.dk. Clostridium difficile tarminfektion (lægehåndbogen).
4. Kelly CR, Fischer M, Allegretti JR, et al. ACG clinical guidelines: prevention, diagnosis, and treatment of Clostridioides difficile infections. Am J Gastroenterol. 2021;116(6):1124-1147. PubMed

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This article provides general information and does not replace a medical consultation. Please contact your GP if you experience symptoms.