• Clinical science

Clostridium difficile infection

Abstract

Clostridium difficile (C. difficile) is a gram-positive rod-shaped bacillus that is commonly involved in antibiotic-associated diarrhea. As the bacterial spores are difficult to eradicate and easily transmitted (via fecal-oral transmission), the C. difficile infection rate is particularly high among hospitalized patients and residents in long-term care facilities. Colonization with C. difficile occurs following antibiotic treatment of other diseases, as the bacteria is particularly resistant to antibiotics. The resulting damage to the intestinal flora promotes infection, which may be accompanied by high fever, abdominal pain, and characteristically foul-smelling diarrhea. The most severe form of C. difficile infection is pseudomembranous colitis, which may lead to ileus, sepsis, and toxic megacolon. In most cases, however, colonization results in asymptomatic carriage rather than symptomatic infection. Diagnosis is usually made via detection of the C. difficile toxin and/or corresponding genes in stool samples. C. difficile infections are treated with oral vancomycin or oral fidaxomicin. Following diagnosis, strict adherence to hygiene measures and patient isolation is essential, especially in hospitals and other healthcare settings.

Epidemiology

  • ∼ 3 million cases in the US per year, causing ∼ 14,000 deaths
  • Hospital-acquired infections especially affect the elderly (> 65 years)
  • Patients affected by community-acquired infections are typically younger (average age 50 years).
  • The incidence, severity, and likelihood of treatment-resistant C. difficile colitis are rising, both in healthcare-associated and community-associated settings.

References:[1][2][3]

Epidemiological data refers to the US, unless otherwise specified.

Etiology

C. difficile infection typically requires a combination of factors: fecal-oral contamination, colonization after the intestinal flora are compromised, and pathogenic toxin release.

  • Pathogen: Clostridium difficile
    • Gram-positive rod-shaped bacillus, obligate anaerobe, toxigenic organism
    • Forms environmentally resistant spores (capable of withstanding heat and acid)
    • Highly contagious
  • Route of infection: fecal-oral transmission of ubiquitous bacteria
    • Hospital-acquired infections: transmission via contaminated hands of healthcare workers or patients, contaminated surfaces/furniture, and medical equipment (see "Prevention" below)
  • Community-acquired infections
    • Emergence of severe cases in individuals without typical risk factors (antibiotic treatment, hospitalization)
  • Antibiotic treatment
  • Other risk factors

Colonization with C. difficile results in asymptomatic carriage more often than manifest disease, as symptomatic infection requires the presence of further risk factors. In both cases, individuals test positive for the toxin or the pathogen itself!References:[4][5][1]

Clinical features

Symptoms of C. difficile-associated diarrhea (CDAD) usually develop during antibiotic treatment or 2–10 days following its initiation; however, 25–40% of cases may manifest as late as 10 weeks following treatment.

  • Watery diarrhea, characteristically foul-smelling
    • Mild disease presents with ≥ 3 stools/day whereas patients with fulminant colitis may have up to 20 stools per day
    • May have traces of mucus or occult blood
    • Hematochezia or melena are rare
  • Cramping abdominal pain, nausea, anorexia
  • Fever and dehydration (especially in severe cases)
  • Fulminant colitis: abdominal distention and severe hypovolemia
  • Recurrent disease: reoccurrence of symptoms following end of treatment (10–40% of cases)

References:[1][6][7]

Diagnostics

The patient history and clinical presentation are usually strong indicators of the diagnosis, which is then confirmed with identification of the pathogen's genes or corresponding toxins in stool. Further diagnostics, such as blood tests or imaging, may be used to assess the severity of disease or the presence of complications.

History

  • Treatment with antibiotics in the last 3 months
  • Recent hospitalization

Stool tests

Blood tests

Imaging studies

Endoscopy

  • Colonoscopy (or sigmoidoscopy)
    • Not indicated if C. difficile is suspected based on clinical findings, laboratory tests, and/or response to empiric treatment
    • Approach cautiously (↑ risk of perforation)
    • Findings

References:[1][2][6][8][7][9]

Treatment

General measures

Medical therapy

C. difficile infection is one of the rare indications for oral administration of vancomycin!

Medical therapy in children

Fecal microbiota transplantation (FMT)

  • Indication: recurrent C. difficile infections with failure of at least two appropriate antibiotic regimens
  • Implementation: Sterile normal saline solution is added to donor stool and blended to a smooth, liquid consistency.
  • Administration
    • Enema
    • Colonoscopy
    • Nasogastric or jejunal tube

References:[1][7][4][8][9][10]

Complications

References:[11][6]

We list the most important complications. The selection is not exhaustive.

Prevention

  • Detection: C. difficile toxin stool test for at-risk patients with recent onset of diarrhea
  • Isolation
    • Single-bed room with designated bathroom facilities (up to 2 days after symptoms subside)
    • Cohort isolation is possible if control measures are implemented.
  • Control measures
    • Personal protective equipment/contact precautions: gloves and protective gown (change after each patient); a mask is not necessary
    • Hand hygiene (applies to caregivers, patients, and contact persons): thorough washing with soap and water
    • Consistent disinfection of possibly contaminated surfaces with sporicidal oxidants, such as peracetic acid or sodium hypochlorite
      • Autoclaving is also sporicidal and can be used to sterilize larger equipment