Clostridium difficile: past, present and future

Clostridium difficile was originally recovered from the faeces of newborn infants by Hall and O’Toole in 1935.1 A hamster model proved essential in the early work where the toxin of C. difficile was shown to be the ‘agent’ of disease. The main contributors to this work included Keighley et al.2and Larsson et al.3 in the UK, and Bartlett et al.4 and Lusk et al.5 in the USA. In 1977, Bartlett and his co-workers showed that a cell cytotoxicity assay used to detect toxin in the faeces of affected patients was a useful diagnostic laboratory tool to establish the presence of disease.

In 1996, Braun et al.6 determined the nucleotide sequence 3.8 kb upstream and 5.2 kb downstream of the toxin genes A and B of C. difficile. They found nine open reading frames (ORFs), two of which were attributed to the pathogenicity locus (PaLoc). Further sequencing confirmed high conservation of the PaLoc borders, allowing the locus to be defined as a distinct genetic element.

Clostridium difficile Infection
The most common clinical presentation of C. difficile infection (CDI) is diarrhoea associated with antibiotic use. Diarrhoea can occur within a few days of the start of therapy but can equally occur up to eight weeks after therapy has ended. Patients with mild to moderate disease usually experience diarrhoea as the only symptom, with up to 10 bowel movements a day. More severe disease includes abdominal pain or cramps, fever and leucocytosis. The faeces are watery with a foul odour. The presence of blood is rare. Severely diseased patients also demonstrate hypoalbuminaemia and altered creatinine and lactate levels.