C. difficile and healthcare-associated infections

Contents

Overview

Healthcare-associated infections (HAIs) are infections acquired in a healthcare setting that were not present at the time of admission. They represent a major source of morbidity, mortality, and cost in the ICU. Clostridioides difficile (formerly Clostridium difficile) is one of the most important HAIs in the UK, responsible for thousands of deaths annually. ICU patients are at particularly high risk due to antibiotic exposure, immune suppression, and prolonged hospitalisation.

Clostridioides difficile Infection

Microbiology and Pathogenesis

C. difficile is an anaerobic, gram-positive, spore-forming bacillus. It is part of the normal gut flora in a minority of adults (<3%), but colonisation rates in healthcare settings are substantially higher.

CDI requires two conditions: disruption of the normal gut microbiome (most commonly by antibiotic exposure) and acquisition of a toxin-producing C. difficile strain.

Toxin production:

  • Toxin A (enterotoxin): disrupts tight junctions and attracts neutrophils
  • Toxin B (cytotoxin): causes direct cell death via glucosylation of Rho GTPases; the dominant virulence factor

The hypervirulent NAP1/BI/027 ribotype produces binary toxin in addition to A and B, and is associated with more severe disease, higher recurrence rates, and greater mortality.

Risk factors:

  • Antibiotic exposure (virtually any antibiotic; highest risk with clindamycin, fluoroquinolones, broad-spectrum beta-lactams, carbapenems)
  • Age >65 years
  • Proton pump inhibitor use (reduces gastric acid barrier)
  • Prolonged hospitalisation
  • Immunosuppression
  • Prior CDI

Clinical Spectrum

Asymptomatic carriage: Does not require treatment.

Mild-moderate CDI: Diarrhoea (≥3 loose stools in 24 hours, not explained by laxatives), abdominal cramps, low-grade fever. White cell count modestly elevated.

Severe CDI: White cell count >15 × 10⁹/L, creatinine above 1.5× baseline, temperature >38.5°C, signs of colitis (abdominal tenderness).

Complicated CDI (fulminant):

  • Hypotension or shock
  • Ileus (paradoxically, reduced diarrhoea — impaired peristalsis)
  • Toxic megacolon (colon diameter >6 cm with systemic toxicity)
  • Peritonitis or perforation
  • Requires ICU admission; mortality >30%

Diagnosis of CDI

Diagnosis requires:

  1. Clinical features (≥3 unformed stools in 24 hours not explained by other causes)
  2. Microbiological confirmation

UK guidance (Public Health England, now UKHSA) recommends a two-step laboratory testing algorithm:

Step 1 — Glutamate dehydrogenase (GDH) antigen test: detects all C. difficile, including non-toxigenic strains. High sensitivity (~99%), low specificity. A negative GDH excludes CDI.

Step 2 — Toxin A/B EIA (enzyme immunoassay) or NAAT (nucleic acid amplification test/PCR) for toxin genes. NAAT is more sensitive than EIA for toxin but detects toxin genes rather than free toxin and may over-diagnose. Positive toxin test confirms CDI.

CT abdomen: CT findings in severe CDI include marked colonic wall thickening, pericolonic fat stranding, and in fulminant disease, pneumatosis or pneumoperitoneum indicating perforation. Toxic megacolon is identified by colonic diameter >6 cm.

Flexible sigmoidoscopy: Characteristic pseudomembrane (raised yellow-white plaques on inflamed colonic mucosa) confirms the diagnosis in pseudomembranous colitis. Not routinely performed.

Management of CDI

General Measures

Stop the precipitating antibiotic if clinically possible. Isolate in a side room with contact precautions. Use soap and water for hand hygiene — alcohol gel does not kill spores.

Antibiotic Treatment

Mild-moderate CDI: Oral vancomycin 125 mg QDS for 10 days. Vancomycin remains the preferred agent over metronidazole, which is less effective (Cochrane meta-analyses show higher cure rates with vancomycin). Fidaxomicin 200 mg BD for 10 days is associated with lower recurrence rates and is used when recurrence prevention is a priority.

Severe CDI: Oral vancomycin 125–500 mg QDS for 10–14 days. Fidaxomicin is an alternative.

Fulminant CDI with ileus: Oral/NG vancomycin cannot reach the colon if ileus is present. Options:

  • Intracolonic vancomycin (administered via enema)
  • IV metronidazole (the only anticiostridial with IV penetration to the colon) — adds some activity
  • Combination: oral/rectal vancomycin + IV metronidazole

Surgical consultation: Urgent surgical review is required in fulminant CDI with toxic megacolon, perforation, peritonitis, or worsening despite maximal medical therapy. Total colectomy (or loop ileostomy with colonic lavage) is performed; colectomy carries high perioperative mortality in this population.

Recurrent CDI

Recurrence occurs in 20–30% after first episode, and in up to 60% after the second. Management:

  • Fidaxomicin (reduces recurrence vs vancomycin)
  • Extended tapering/pulsed vancomycin regimen for second and subsequent recurrences
  • Faecal microbiota transplant (FMT): Highly effective for recurrent CDI. Donor stool (screened for pathogens) is delivered via NG tube, enema, or colonoscopy. Restores normal gut flora and suppresses C. difficile. Cure rates for recurrent CDI exceed 80%.
  • Bezlotoxumab (anti-toxin B monoclonal antibody): single infusion given with antibiotic treatment reduces recurrence rate by ~40% in high-risk patients.

Prevention of CDI

  • Antibiotic stewardship: The most effective prevention. Reducing antibiotic use — particularly clindamycin, fluoroquinolones, and broad-spectrum beta-lactams — reduces CDI incidence. Duration of antibiotic courses should be minimised.
  • Hand hygiene: Soap and water (not alcohol gel — spores survive alcohol). Strict hand hygiene before and after patient contact.
  • Contact precautions: Apron and gloves for all contact with CDI patients; dedicated equipment; side room isolation.
  • Environmental decontamination: Hypochlorite-based cleaning agents (sporicidal) required for rooms of CDI patients. Standard quaternary ammonium compounds do not kill C. difficile spores.
  • PPI restriction: Unnecessary PPI prescribing increases CDI risk. Review and discontinue PPIs where not clearly indicated.

Other Healthcare-Associated Infections

Catheter-associated urinary tract infection (CAUTI): The most common HAI. Prevention: remove urinary catheters as soon as clinically indicated; aseptic insertion and maintenance; closed drainage system.

Central line-associated bloodstream infection (CLABSI): High mortality (10–30%). Prevention: care bundles — full sterile technique at insertion, chlorhexidine skin prep, optimal site selection (subclavian preferred over femoral), daily line necessity review.

Ventilator-associated pneumonia (VAP): Defined as pneumonia developing ≥48 hours after intubation. VAP care bundle: head-of-bed elevation 30–45°, daily sedation holds and extubation readiness assessment, subglottic secretion drainage, chlorhexidine oral care, tube cuff pressure maintenance.

Surgical site infection (SSI): Preventable with appropriate prophylactic antibiotics (given within 60 minutes of incision, appropriate spectrum, single dose in most cases), normothermia maintenance, and blood glucose control.

MRSA and CPE: Multidrug-resistant organisms (MDROs) require enhanced contact precautions, active screening, and decolonisation protocols. Carbapenem-resistant Enterobacterales (CRE/CPE) are a major emerging threat requiring cohorting, enhanced environmental cleaning, and specialist infection control input.

Viva Questions

How do you diagnose CDI in an ICU patient with diarrhoea and what is the initial management?

In an ICU patient with unexplained diarrhoea (three or more unformed stools in 24 hours not attributable to laxatives or enteral feeds), CDI must be tested for if there has been antibiotic exposure or hospitalisation in the preceding 12 weeks. Stool is sent for the two-step diagnostic algorithm: GDH antigen testing followed by toxin EIA or NAAT PCR. A positive GDH with positive toxin confirms CDI. Initial management involves stopping or narrowing precipitating antibiotics where clinically safe, isolating the patient in a side room with contact precautions, and implementing soap-and-water hand hygiene. Antibiotic treatment is with oral vancomycin 125 mg QDS for 10 days — metronidazole is no longer recommended as first-line therapy for CDI. If there are signs of severe disease (WBC >15, rising creatinine, fever, abdominal pain), vancomycin 500 mg QDS is used. CT abdomen is obtained if there is clinical concern about fulminant disease (megacolon, perforation, deteriorating haemodynamics).

What constitutes fulminant CDI and how is it managed in the ICU?

Fulminant CDI is characterised by hypotension or shock, ileus, toxic megacolon (colonic dilatation >6 cm with systemic toxicity), peritonitis, or perforation. Paradoxically, ileus may reduce diarrhoea, masking the severity. In the ICU, fulminant CDI requires ICU-level support for haemodynamic instability plus aggressive treatment of the infection. Because oral vancomycin cannot reach the colon in the presence of ileus, intracolonic vancomycin (enema) must be used to deliver drug directly to the affected colon. IV metronidazole (500 mg TDS) is added as it provides some activity in the colon via transmucosal secretion. Urgent surgical review is mandatory — total colectomy or diverting loop ileostomy with antegrade colonic lavage may be required, with the decision based on clinical trajectory. Perioperative mortality in this frail population is high (30–50%), but surgery may be life-saving. The decision for surgery should not be deferred until the point of perforation or arrest.

What is the role of faecal microbiota transplant in CDI and what are its limitations?

Faecal microbiota transplant (FMT) involves delivering screened donor stool to the recipient via NG tube, enema, or colonoscopy. The rationale is restoration of normal gut microbiome diversity, which suppresses C. difficile colonisation and prevents recurrence. FMT is highly effective for recurrent CDI — multiple randomised trials demonstrate cure rates exceeding 80% compared with 30–50% for antibiotic therapy alone in this indication. It is now recommended for second or subsequent CDI recurrences where fidaxomicin or extended vancomycin regimens have failed. Limitations include logistical requirements for donor screening (to exclude enteric pathogens, MDRO carriage, HIV, hepatitis), restricted availability outside specialist centres, and the need for active CDI to be treated with antibiotics beforehand. A small number of serious adverse events — including transmission of ESBL-producing organisms and COVID-19 — have been reported, leading to enhanced screening protocols. The mechanism of long-term benefit is not fully understood, and some patients relapse after an initial cure, requiring repeat FMT.