Learning path: After antibiotics · Chapter 1 of 5

After antibiotics: C. difficile and faecal transplants

A germ that can take over after antibiotics, and a treatment that works better than any drug.

How solid is the research? Established

C. difficile infections and the effectiveness of faecal transplants for recurrent infections are well established by randomised trials and guidelines.

Cause or consequence? Root cause

Antibiotics come first: they hit the gut flora broadly and open the door to C. difficile, fungi and other germs. What follows often traces back to this one treatment.

Healthy state

Clostridioides difficile A bacterium that can spread after antibiotics and cause severe diarrhoea with its toxins. occurs in small amounts in some healthy adults and in many infants without causing symptoms. The bacterium forms spores, resistant resting forms that survive stomach acid, drying out and many cleaning agents and can live for months on surfaces. That many people take up the germ regularly but only few fall ill is due to the defences in the gut.

Bile acids Substances made by the liver that make fat digestible. About 95 percent are reabsorbed in the last part of the small intestine; gut bacteria transform the rest. More in the chapter “Bile acids: when bile causes diarrhoea” are an important reason. C. difficile survives as a spore that only germinates when it detects certain primary bile acids such as taurocholate. Healthy gut bacteria convert these primary bile acids into secondary ones, which slow down the growth of C. difficile. More on this in the chapter on bile acids.

Location matters here. In the small intestine, bile is fresh and contains many primary bile acids, the germination signal. In the large intestine, where the germ multiplies, most bile acids in healthy people have already been converted: there they protect. Only when the converters are missing does the large intestine also become a germination site.

In mouse experiments, giving Clostridium scindens, one of the few bacteria that make secondary bile acids, was enough to clearly strengthen resistance. On top of this comes competition for food: the other bacteria use up the sugars and amino acids C. difficile would live on. Short-chain fatty acids Acids such as acetate, propionate and butyrate that gut bacteria make from fibre. They nourish the gut wall and act throughout the body. More in the chapter “Butyrate and other short-chain fatty acids”, the Mucus layer A gel layer of mucins on the gut wall that keeps bacteria at a distance. In the colon, the inner layer is almost free of microbes. More in the chapter “The mucus layer and additives” and IgA (secretory IgA) The antibody of the mucous membranes. It is released into the gut in large amounts, where it holds germs in the mucus without causing inflammation. More in the chapter “IgA: the antibody that keeps the gut clean, and what vitamin A, D and omega-3 have to do with it” are also part of the defence.

Not everyone is equally at risk. The risk rises with age (especially from 65), after hospital and care-home stays, with immune weakness, with Inflammatory bowel disease Umbrella term for Crohn’s disease and ulcerative colitis: long-term, relapsing inflammation of the gut that needs medical treatment. More in the chapter “Immune system and inflammation” and with severe underlying illness. But the infection also affects people outside hospitals who recently took antibiotics.

C. difficile spores rest while secondary bile acids and the other flora keep them in check.

Disrupted state: causes and effects

Broad-spectrum antibiotics wipe out large parts of the Microbiome, gut microbiota The community of all microbes in the gut, mainly bacteria, plus viruses, fungi and archaea. Most live in the colon. More in the chapter “Building microbial diversity”, including the bile acid converters. In one study, after vancomycin the stool contained almost only primary bile acids, an ideal environment for germination. A narrow-spectrum antibiotic that spared the rest of the microbiota, by contrast, preserved the bile acid profile.

Antibiotics with a broad spectrum, such as clindamycin, cephalosporins and fluoroquinolones, are considered especially risky. The risk is highest during treatment and in the weeks after, and stays raised for a few months. The longer and broader the treatment, the greater the risk. Even antibiotics not meant for gut germs, for example for a cold with a bacterial follow-on infection or at the dentist, can hit the microbiota.

Then the competition is missing, and C. difficile can multiply and produce toxins (toxin A and B). These damage the gut cells and trigger inflammation. The result is watery diarrhoea, often with cramps and fever, up to severe colitis with a coating on the mucosa. Rarely there are life-threatening courses with a greatly widened bowel. Most infections are, however, treatable.

In about one in five people, the infection comes back after treatment. The reasons: the microbiota has not yet recovered, remaining spores germinate again, or there is a new infection. The antibiotic against C. difficile also keeps the rest of the microbiota small. After one relapse the risk of further ones rises, a vicious circle that faecal transplant breaks.

Even without C. difficile, the gut microbiota needs weeks to months to recover after antibiotics. Not all species come back. Antibiotic-associated diarrhoea often has other causes: fewer short-chain fatty acids are made, which help the gut absorb water, and undigested carbohydrates are fermented differently. For perspective: a positive test only proves that the germ is there. In people without diarrhoea, a finding is often harmless colonisation, and after cure the test can stay positive for weeks.

Antibiotics wipe out the flora. The spores germinate and produce toxins.

Where it comes from and where it leads

The same symptoms can have different roots. This map shows what may be involved in this problem and what may follow from it.

Connections, not certainty: a link means “can”, not “must”. What applies to you is best clarified in a talk with your doctor.

What often helps

Lifestyle

Diet, exercise, sleep, social contact and dealing with stress.

Eat a varied diet after antibiotics A high-fibre, varied diet gives the remaining species food to spread again. Patience is part of it: recovery takes weeks to months. Plausible How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open.
Wash your hands C. difficile spores survive alcohol-based hand sanitisers. Thorough handwashing with soap is important around people who are ill. Well supported How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open.
Antibiotics only when needed The risk of C. difficile falls with every antibiotic course avoided. They do not help against colds and flu, which are caused by viruses. When needed, take them exactly as prescribed, and ask whether a narrower-spectrum drug is possible. Well supported How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open.
At home during an illness Anyone ill with C. difficile should if possible use their own toilet, clean the toilet and handles with a chlorine-based cleaner and wash laundry hot. This protects housemates, especially older or sick ones. Promising How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open.

Natural supplements

Supplements do not replace a medical check-up. Discuss dosage and interactions with your doctor or pharmacist.

Saccharomyces boulardii This yeast reduces the risk of antibiotic-associated diarrhoea. Against C. difficile, a meta-analysis found a statistically clear effect only in children, not in adults. The US specialist society nevertheless suggests it for adults at high risk of C. difficile while on antibiotics, as a weak recommendation, because the trend points the same way. Not with a central venous catheter, serious illness or severe immune weakness: the yeast can then, rarely, enter the blood and cause a serious infection. Well supported How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open. [1][2]
Not probiotics by default In a small study, probiotics after antibiotics delayed the return of the body's own gut microbiota. More probiotics are therefore not always better. Plausible How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open. [3]
Prebiotics after antibiotics Fibre powders and prebiotics might help recovery. For the time after antibiotics there are hardly any studies, though, and with acute diarrhoea they can make symptoms worse. Try slowly, at the earliest once symptoms have eased. Experimental How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open.

Medical treatments

Information, not a treatment recommendation. Decide together with a doctor. Approval and availability differ from country to country.

Faecal transplant for recurrent infection In recurrent C. difficile infection, a faecal transplant cured far more people than the antibiotic vancomycin in a randomised trial. Guidelines recommend it for this purpose, usually after at least two relapses. Part of its effect is probably due to bringing back the bile acid converters. Some countries now also have standardised products, ask in your country. Donor stool can transmit pathogens, so donors are strictly screened; long-term effects are still little studied. Established How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open. [4][5][6]
Get tested for diarrhoea after antibiotics Three or more new, unformed or watery stools within 24 hours during or after antibiotic treatment, with no other explanation such as laxatives, are a reason to see a doctor and get tested for C. difficile. Established How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open.
Which antibiotic against C. difficile? According to the 2021 US guideline, fidaxomicin is suggested over vancomycin in adults because relapses are less frequent afterwards. Vancomycin remains an accepted alternative, especially if fidaxomicin is too expensive or unavailable. The choice is made by the doctor, depending on country and severity. Well supported How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open. [6]
Do not stop diarrhoea on your own If C. difficile is suspected, drugs that slow the gut should be taken only after talking to a doctor. The gut needs to get rid of the toxin, and pain or a swollen belly need prompt assessment. Promising How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open.
After cure: recognise a relapse After successful treatment, a follow-up test in people without symptoms is usually not useful because it can stay positive. What matters are symptoms: if diarrhoea returns within the next weeks, contact a doctor promptly. Promising How we rate the evidence Established Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies. Well supported Several randomised studies in humans with largely consistent results. Promising Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies. Plausible Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms. Experimental Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open.

In the mood for something completely different? Another one, at random

How we rate the evidence

Trust score 5 of 5:Established: Recommended in medical guidelines or supported by several consistent meta-analyses of randomised human studies.
Trust score 4 of 5:Well supported: Several randomised studies in humans with largely consistent results.
Trust score 3 of 5:Promising: Single randomised or controlled studies in humans, not yet independently confirmed — or many consistent observational studies.
Trust score 2 of 5:Plausible: Two cases: first observational or pilot studies with small samples — or a settled basis that is not in dispute, such as movement, sleep or meal pauses. But not tested in humans for symptoms.
Trust score 1 of 5:Experimental: Barely studied in humans. Mainly lab and animal studies or theoretical reasoning; whether it helps is open.

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