Clostridioides difficile infection

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Clostridioides difficile is a spore-forming anaerobic bacterium that colonises some healthy adults without disease. Antimicrobial disruption of the gut microbiome permits expansion of toxigenic strains, whose toxins injure colonic epithelium and cause diarrhoea and colitis.

Risk rises with recent antibiotics, healthcare or care-home exposure, older age, severe comorbidity, immunosuppression and acid suppression. Community-associated infection also occurs, so absence of recent admission does not exclude it.

Diagnosis requires compatible symptoms plus laboratory evidence interpreted through the local algorithm. A positive nucleic-acid or glutamate-dehydrogenase screening test without toxin may represent colonisation, particularly when another cause of diarrhoea exists.

Management combines transmission control, medication review, oral antimicrobial therapy, hydration and repeated severity assessment. Clinical deterioration, not stool frequency alone, determines escalation because ileus can stop diarrhoea while toxin-mediated colitis worsens.

Key points

Test only symptomatic patients with new unformed stool and interpret organism and toxin results through the local two-stage or multistage laboratory algorithm.
Do not perform a test of cure: C difficile can remain detectable after symptoms resolve.
Isolate promptly, use gloves and aprons, wash hands with soap and water and clean the environment with a sporicidal agent.
Stop the precipitating antibiotic where safe; review proton-pump inhibitors, laxatives, opioids and other medicines worsening diarrhoea or ileus.
For a first episode, NICE first-line treatment is vancomycin 125 mg orally four times daily for 10 days.
For a first recurrence within 12 weeks of symptom resolution, use fidaxomicin 200 mg orally twice daily for 10 days.
For life-threatening infection, use vancomycin 500 mg orally or by nasogastric tube four times daily plus metronidazole 500 mg intravenously three times daily for 10 days.
Seek specialist advice for further recurrence and consider faecal microbiota transplant after two or more previous episodes.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Antibiotic disruption

Broad-spectrum and prolonged antimicrobials reduce protective gut diversity, allowing toxigenic C difficile spores to germinate and expand.

Spore exposure

Durable spores contaminate healthcare and community environments, survive routine cleaning and reach the bowel through faecal–oral transfer.

Host susceptibility

Older age, frailty, immunosuppression, severe illness and reduced gastric acidity impair resistance to colonisation and toxin injury.

Healthcare transmission

Shared facilities, contaminated hands, equipment and repeated antibiotic exposure amplify spread among hospital and care-home residents.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Microbiome loss
Reduced colonisation resistance removes competition for nutrients and bile-acid signals that normally suppress C difficile growth.
2
Toxin production
Toxins A and B disrupt epithelial cytoskeleton and tight junctions, causing cell death, secretion and intense inflammation.
3
Pseudomembrane formation
Necrotic epithelium, fibrin, mucus and neutrophils coat injured colon and produce characteristic plaques. during active invasive disease.
4
Colonic dilatation
Severe inflammation paralyses smooth muscle, causing ileus, toxic megacolon, bacterial translocation and perforation risk. during active invasive disease.
5
Spore-mediated recurrence
Antimicrobials kill vegetative organisms but not spores, which germinate before the microbiome has recovered. during active invasive disease.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Typical diarrhoeal illness

New frequent watery stool, cramping, fever and recent antibiotic or healthcare exposure form the usual presentation.

Severe inflammatory diseaseRed flag

High fever, marked leukocytosis, kidney injury, hypoalbuminaemia or severe abdominal tenderness indicates higher failure and complication risk.

Ileus presentationRed flag

Progressive distension, pain, vomiting and reduced or absent stool may reflect colonic paralysis despite ongoing severe toxin injury.

Toxic megacolonRed flag

Systemic toxicity with colonic dilatation, tenderness and organ dysfunction requires immediate medical, surgical and critical-care coordination.

Recurrence

Return of diarrhoea after initial resolution, especially within 12 weeks, may be relapse or reinfection and uses a different treatment pathway.

Red flags requiring action

Hypotension, rising lactate, altered mental state or organ dysfunction marks life-threatening colitis even if stool frequency falls.
Abdominal distension, ileus or absent stool can reflect worsening toxic megacolon rather than recovery.
Guarding, rebound tenderness or free air suggests perforation and requires emergency surgery.
White cell count above 15 × 10⁹/L, temperature above 38.5°C, creatinine rise above 50% from baseline or severe imaging features indicate severe disease.
Continuing unnecessary broad-spectrum antibiotics increases failure and recurrence risk and should be reviewed immediately.
Immunosuppression, frailty, inflammatory bowel disease and repeated recurrence warrant early specialist involvement.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Local stool C difficile algorithmFirst step
Why
Identify toxigenic organism and evidence of free toxin in a symptomatic unformed specimen.
Interpretation and limitations
Follow the local screening and toxin sequence; toxin positivity with compatible diarrhoea supports active disease, while discordant results need clinical interpretation.
02
Full blood count
Why
Measure leukocytosis and anaemia and help classify disease severity.
Interpretation and limitations
A white cell count above 15 × 10⁹/L is one NICE marker of severe infection; very high or falling counts with deterioration can be ominous.
03
Urea, electrolytes and creatinine
Why
Assess dehydration, kidney injury, electrolyte loss and the severity criterion of a creatinine rise.
Interpretation and limitations
A rise above 50% from baseline supports severe infection; correct volume loss while avoiding overload in frailty or cardiac disease.
04
CRP, albumin, lactate and venous gas
Why
Assess systemic inflammation, nutritional reserve, perfusion and metabolic deterioration.
Interpretation and limitations
Rising lactate or acidosis despite treatment is a life-threatening sign and prompts surgical and critical-care escalation.
05
Abdominal CT
Why
Define severe colitis, bowel-wall thickening, dilatation, ileus, perforation or an alternative diagnosis.
Interpretation and limitations
Use urgently in severe or life-threatening features without delaying treatment; imaging evidence of severe disease can determine severity category.
06
Plain abdominal radiograph
Why
Rapidly assess colonic dilatation or perforation when toxic megacolon is suspected.
Interpretation and limitations
A normal film does not exclude severe colitis; CT and surgical review may still be needed based on physiology.
07
Medication and microbiology review
Why
Identify precipitating agents, prior episodes, prior regimens and other stool pathogens or outbreak context.
Interpretation and limitations
Document exact antibiotic dates and recurrence interval because treatment differs for failure, early recurrence and later recurrence.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Asymptomatic colonisation

Organism or gene detection occurs without toxin-mediated diarrhoea and should not trigger treatment in a well carrier.

Medication-related diarrhoea

Laxatives, enteral feed, metformin and other drugs cause loose stool and can coexist with positive colonisation tests.

Viral gastroenteritis

Vomiting and linked cases may suggest norovirus, requiring similar isolation but no C difficile antimicrobial regimen.

Inflammatory bowel flare

Ulcerative colitis or Crohn disease causes severe diarrhoea and bleeding, while C difficile can simultaneously trigger worsening.

Ischaemic colitis

Abrupt pain and bleeding in a vascular-risk adult requires urgent imaging and does not follow the usual antibiotic-exposure pattern.

Additional chapter-specific clues

Alternative diarrhoea

Tube feeds, laxatives, viral outbreaks, inflammatory bowel disease and other antibiotics may explain symptoms despite asymptomatic C difficile carriage.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01ISOLATEConfirm symptomatic infectionFirst stepAn adult develops otherwise unexplained unformed diarrhoea with antibiotic, healthcare or community risk.

1Place the patient in enteric isolation, use gloves and aprons and start soap-and-water and sporicidal environmental measures.
2AlternativeSend one unformed stool sample through the local C difficile algorithm and assess alternative drug, feed and infectious causes.
3Record baseline stool count, abdominal examination, full blood count, creatinine, temperature, albumin and haemodynamic status.
4EscalationDo not wait for a result to escalate a patient with toxic colitis, and do not repeat testing merely to demonstrate cure.

02FIRSTTreat the first episodeCompatible symptoms and microbiology support a first C difficile episode without life-threatening features.

1AlternativeStop the inciting antibiotic if clinically safe or replace it with the narrowest effective lower-risk alternative.
2First lineGive vancomycin 125 mg orally four times daily for 10 days as NICE first-line treatment.
3Review fluid, electrolytes, nutrition, proton-pump inhibitor, laxatives, opioids and medicines affected by acute kidney injury.
4Second lineReassess daily; if vancomycin is ineffective, use NICE second-line fidaxomicin 200 mg orally twice daily for 10 days after specialist review.

03FULMINANTEscalate life-threatening colitisEscalationHypotension, ileus, toxic megacolon, perforation, severe CT features or rapidly progressive organ failure is present.

1Use ABCDE, begin careful crystalloid resuscitation, monitor lactate and involve critical care, infection, gastroenterology and colorectal surgery immediately.
2Give vancomycin 500 mg orally or via nasogastric tube four times daily for 10 days.
3Add metronidazole 500 mg intravenously three times daily for 10 days and discuss additional rectal vancomycin if ileus prevents colonic delivery.
4Reassess repeatedly for early operative intervention; do not wait for perforation or irreversible shock before surgical decision-making.

04RECURRENCEBreak the relapse cycleSymptoms and testing support recurrent infection after initial clinical resolution.

1For a first recurrence within 12 weeks, give fidaxomicin 200 mg orally twice daily for 10 days.
2For recurrence more than 12 weeks later, use vancomycin 125 mg four times daily for 10 days or fidaxomicin 200 mg twice daily for 10 days according to NICE.
3Seek microbiology or infection advice for a second or later recurrence and reconsider avoidable antibiotics and acid suppression.
4Consider faecal microbiota transplant after two or more previous episodes through an accredited specialist service.

Key medicines and prescribing safety4 treatments · regimens, roles and cautions

NICE first-line therapy delivers high intraluminal activity against vegetative C difficile.

Vancomycin for first episode

Give 125 mg orally four times daily for 10 days for an initial C difficile infection, including severe disease without life-threatening features.

Oral vancomycin treats colonic infection rather than systemic sepsis; review swallowing and ileus, and escalate dose and combination only for life-threatening disease.

Provides narrow intraluminal therapy with lower recurrence risk in selected treatment pathways.

Fidaxomicin

Give 200 mg orally twice daily for 10 days for a first recurrence within 12 weeks, or as NICE-directed second-line or later-recurrence therapy.

Confirm whether the episode is treatment failure or recurrence, check interactions and swallowing, and use specialist advice for repeated disease.

Provides increased intraluminal treatment during fulminant colitis as part of combined medical and surgical management.

Life-threatening oral vancomycin

Give 500 mg orally or through a nasogastric tube four times daily for 10 days in life-threatening C difficile infection.

Ileus may prevent distal delivery; discuss rectal administration with specialists and never delay surgical review because doses have begun.

Adds systemic delivery when severe inflammation or ileus may limit luminal distribution.

Intravenous metronidazole adjunct

Give 500 mg intravenously three times daily for 10 days alongside high-dose enteral vancomycin in life-threatening infection.

Not monotherapy for severe colonic disease; monitor liver function, neurological toxicity, alcohol interaction and warfarin effect.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Toxic megacolon

Systemic toxicity and non-obstructive colonic dilatation cause ileus, perforation, shock and emergency colectomy risk. without timely definitive management.

Bowel perforation

Full-thickness necrosis releases colonic contents into the peritoneum, producing severe sepsis and urgent operative need. without timely definitive management.

Acute kidney injury

Fluid loss, sepsis and nephrotoxic exposure reduce renal function and complicate resuscitation and concurrent medicines. without timely definitive management.

Recurrent infection

Persistent spores and incomplete microbiome recovery lead to repeated toxin-mediated episodes after apparent resolution. without timely definitive management.

Malnutrition and deconditioning

Prolonged diarrhoea, isolation and repeated admissions reduce intake, muscle strength and functional independence. without timely definitive management.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Record stool number and consistency while also tracking distension, pain and bowel sounds because ileus can reduce diarrhoea falsely.
Measure temperature, pulse, blood pressure, mental state, urine output and fluid balance at a frequency matched to severity.
Repeat full blood count, creatinine, electrolytes, albumin and lactate during severe or deteriorating disease.
Review the necessity and spectrum of every concurrent antimicrobial each day.
Check abdominal examination and imaging for colonic dilatation, perforation or failure to respond.
Monitor adherence and ability to receive oral or nasogastric doses, particularly with vomiting or ileus.
At resolution give recurrence advice, avoid test of cure and document the episode prominently for future antibiotic decisions.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Less stool can mean worse disease

When ileus develops, diarrhoea may stop while toxin, inflammation and colonic dilatation progress.

Colonisation complicates PCR

Highly sensitive organism detection can remain positive without toxin-mediated symptoms, so test only appropriate unformed stool.

Vancomycin is luminal

Oral dosing achieves colonic concentration but does not treat an unrelated bloodstream infection requiring systemic therapy.

The precipitating drug matters

Continuing an unnecessary broad-spectrum antibiotic sustains microbiome disruption and undermines an otherwise correct C difficile regimen.

Recurrence is expected biology

Spores persist and microbiome recovery is incomplete, so return of symptoms is not automatically non-adherence or resistance.

Surgery is time dependent

Outcomes deteriorate once profound shock and multiorgan failure develop; early colorectal involvement precedes definitive operative thresholds.

11Common pitfallsFrequent interpretation and management errors.

01
Do not test formed stool or perform routine microbiological tests of cure.
02
Do not treat a positive screening assay without compatible symptoms and clinical interpretation.
03
Do not give loperamide, codeine or other antimotility treatment during active C difficile colitis.
04
Do not regard reduced stool frequency with increasing distension as improvement.
05
Do not continue an avoidable precipitating antibiotic or proton-pump inhibitor without review.
06
Do not delay surgical referral until perforation in rapidly worsening life-threatening colitis.