Winter 2012 - Douglass Hanly Moir Pathology

Clostridium difficile InfectionClostridium difficile is an anaerobic Gram-positive, spore-formingbacillus, identified first as normal bowel flora in healthy neonatesbut, over time, recognised as a potential gastrointestinal pathogen ofmajor clinical and cross-infection significance. Disease is related tothe production of two potent exotoxins: toxin A ("enterotoxin") andtoxin B ("cytotoxin"), which cause intestinal fluid secretion, mucosalinjury and inflammation.Toxin B is the essential virulence factor of C. difficile, however, beingapproximately ten times more potent than toxin A.Dr Ian ChambersMicrobiologistC. difficile is the causative organismof antibiotic-associated colitis anddiarrhoea, and is a cause of significantmorbidity (and occasional mortality)especially, but not exclusively, amonghospitalized patients. Antibioticadministration is the most widelyrecognized risk factor for C. difficileassociateddiarrhoea (CDAD) but otherrisk factors include hospitalization,advanced age, concurrent severeillness, chemotherapy etc. CDAD canalso occur without any risk factor beingidentifiable.The main clinical features ofC. difficile infection are waterydiarrhoea, abdominal pain, lowgrade fever and leucocytosis,although the clinical spectrumranges from asymptomatic carriageto severe fulminant disease andtoxic megacolon. Illness is generallyin the setting of current or recentantibiotic administration, butonset may be days or weeks afterantibiotic treatment has stopped. Theantibiotics most frequently implicatedare fluoroquinolones, clindamycin,cephalosporins, and penicillins,but virtually all antibiotics, includingmetronidazole and vancomycin, havebeen associated with CDAD.Over the last decade, hospital-acquiredC. difficile infection has become a majorproblem worldwide, with the incidenceand severity of healthcare-associateddisease increasing dramatically. Severalfactors are involved in this, includingthe high carriage rates of C. difficilein hospitalised adults (~30%) and itseasy transmissibility via fomites. A morevirulent strain of C. difficile has alsoemerged in that time. This strain(C. difficile ribotype 027) causes a moresevere illness which can be refractoryto standard therapy and is more likelyto relapse than that caused by otherstrains. Its hypervirulence may bedue to its substantially greater toxinproduction compared to conventionalstrains, and a strong correlationexists between its emergence andthe increased use of fluoroquinoloneantibiotics.5