Clostridium difficile and PMC

OVERVIEW

  • Clostridium difficile enterocolitis and pseudomembranous colitis (PMC)
  • acute inflammatory disease of colon commonly associated with antibiotic use
  • C. difficile implicated as a causative organism in 1970’s

PATHOPHYSIOLOGY

Mechanism

  • antibiotic exposure -> overgrowth of C. difficile -> increased toxin production -> mucosal damage -> inflammation and necrosis
  • rarely other organisms have been implicated: Staph aureus, Salmonella, Clostridium perfringens, Yersinia, Shigella, Campylobacter, CMV, Entamoeba, Listeria

Complications related to diarrhoea

  • Hypovolaemia
  • Electrolyte disturbance: hypokalaemia, hypomagnesaemia

Complications related to intestinal infection

  • Sepsis and septic shock
  • Perforation
  • Toxic megacolon
  • Bleeding

CLINICAL FEATURES

  • diarrhoea 3-9 days post initiation of antibiotics
  • may start weeks after discontinuation of antibiotics
  • loose stools -> toxic megacolon and colonic perforation
  • profuse, watery/mucoid, foul-smelling stool
  • may contain blood and pseudomembranes
  • fever
  • rarely: oligoarthritis and iridocyclitis

RISK FACTORS

Antibiotic exposure – any antimicrobial can incite disease

  • Likely – beta-lactams, clindamycin
  • Uncommon – quinolones, aztreonam, imipenem, metronidazole
  • Rare – vancomycin, erythromycin, tetracycline, gentamicin

Other

  • age >65y
  • previous GI surgery
  • renal impairment
  • prolonged hospitalisation
  • gastric acid suppression
  • renal failure
  • immunocompromised and chemotherapy patients

INVESTIGATIONS

General

  • leucocytosis
  • low albumin
  • AXR: mucosal oedema, thumb-printing
  • CT: distension, diffuse and focal thickening of colonic wall

Specific

  • faecal leucocytosis
  • stool cultures
  • stool assay for C. difficile toxins (takes 2 days)
  • ELISA for toxin A and B (takes 2 hours)
  • PCR (false positives are problematic)
  • mucosal assessment: proctosigmoidoscopy, flexible sigmoidoscopy, colonoscopy

MARKERS OF SEVERITY

Clinical

  • fever T>38
  • peritonism
  • ileus
  • hemodynamic instability

Investigations

  • WBC >15 and <20% neutrophils
  • elevated lactate
  • 50% increase in baseline creatinine
  • albumin <25
  • megacolon on imaging

MANAGEMENT

Resuscitation

  • fluid therapy
  • extreme hypovolaemia and septic shock requiring fluid resuscitation and inotropes

Correct metabolic disturbance

Specific Therapy

  • antibiotics according to severity (See below)
  • early surgical referral if severe as colectomy may be needed
  • relapsing disease can be a problem – a variety of different antibiotics may be used
  • stool transplant aka fecal bacteriotherapy in resistant cases
  • a polymer called tolevamer was developed to bind enterotoxin directly, but is inferior to antibiotics in studies and is not used

Treat underlying cause

  • isolation
  • stop offending drugs
  • avoid antidiarrheal drugs and narcotics
  • toxic megacolon -> surgery

Prevention

  • avoid excessive antibiotic use; antibiotic stewardship
  • isolation
  • hand washing with soap and water

ANTIBIOTICS THERAPY

If mild to moderate disease:

  • metronidazole 400 mg (child: 10 mg/kg up to 400 mg) orally or via nasogastric tube, 8-hourly for 10 days
  • Metronidazole can be given intravenously in patients who cannot tolerate the oral formulation (see dose below)

If severe:

  • vancomycin 125 mg (child: 3 mg/kg up to 125 mg) orally or via nasogastric tube, 6-hourly for 10 days
  • Intravenous vancomycin is not effective against C. difficile

If complicated (eg hypotension or shock, ileus, megacolon), in addition to vancomycin, use:

  • metronidazole 500 mg (child: 12.5 mg/kg up to 500 mg) IV, 8-hourly for 10 days
  • if ileus present  vancomycin can be administered as a retention enema (500 mg in 100 mL sodium chloride 0.9% rectally, 6-hourly) in addition to oral or nasogastric vancomycin and intravenous metronidazole

References and Links

Journal articles

  • Dupont HL. Diagnosis and management of Clostridium difficile infection. Clin Gastroenterol Hepatol. 2013 Oct;11(10):1216-23; quiz e73. PMID: 23542332.

CCC 700 6

Critical Care

Compendium

Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also the Innovation Lead for the Australian Centre for Health Innovation at Alfred Health and Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.

After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.

He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE.  He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.

His one great achievement is being the father of two amazing children.

On Twitter, he is @precordialthump.

| INTENSIVE | RAGE | Resuscitology | SMACC

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