By June 2006 the problem had spread to seven provinces with estimates of 13 cases per 1000 admissions.
Between 20 it was estimated that over 14 000 patients had been affected in the province of Quebec, with high mortality and relapse rates. 11, 12, 13 Perforations, toxic megacolon and colectomy rates had also increased. Over the next two years several investigations were performed: rates of CDAD were ∼28/1000 admissions (five times the national average of 1997) with an extra 10.7 days in hospital and 30‐day attributed mortality rates of 6.9%, these being 0.8–2% in 1997. Increased numbers of patients requiring colectomy alerted a hospital in Montreal, Quebec, Canada in 2002 to the possibility of CDAD with a higher severity, mortality and relapse rate. 8 Although CDAD is seen mainly inside hospitals and other healthcare settings, community CDAD is also described, although more epidemiological information is required. 7 It is presumed that increased gastric pH leads to decreased destruction of spores, but colonic receptors do exist for some proton pump inhibitors. 5 Other independent risk factors described more recently comprise proton pump inhibitors which increase the risk threefold. 6 CDAD is a disease predominantly of the aged, but other factors include recent gastrointestinal surgery and immunosuppressive therapy, including cytotoxics. Clindamycin historically had a particularly infamous relationship to CDAD animal work showed that following its use there was a particularly long period of gut susceptibility to the disease when challenged with C difficile spores. Almost all antibiotics have been associated with CDAD, although it is less often associated with some-for example, metronidazole, aminoglycosides, trimethoprim and the quinolones (but see below). Risk factors for CDAD comprise those that affect the gut microbial flora, the most common being exposure to antibiotics. However, significant mortality can also occur in the aged, even without colitis. Early intervention and aggressive management are key factors to recovery. Toxic megacolon, with a mortality of 6–30%, can also occur narcotic use may increase its likelihood, and immunocompromised status and delayed diagnosis appear to result in higher mortality. However, a right‐sided colitis is also described, featuring fever, pain, and decreased gut motility often with only mild diarrhoea.
Pseudomembranous colitis is the most severe manifestation of disease, and is usually a pancolitis affecting especially the distal colon and rectum. Asymptomatic colonisation can occur and diarrhoea ( Clostridium difficile associated diarrhoea (CDAD)) which varies in severity from mild to extremely severe. It has been isolated widely in the soil and the gut of many animals and, although a known cause of colitis in animals such as cats, dogs, birds, rodents and neonatal pigs, it was not until 1978 2 that it was found to also cause human disease (pseudomembranous colitis). 1 The designated name related to how difficult the original investigators found it to culture. The anaerobic, gram‐positive, spore‐forming bacterium Clostridium difficile was first isolated in 1935. An emerging theme is the importance of aspects of healthcare delivery in contributing to the problem this includes poorly maintained and cleaned healthcare premises, overcrowded hospitals and increased staffing workloads leading to poor compliance with infection control. There are also environmental factors relating to treatment such as antimicrobials, cytotoxics and proton pump inhibitors. There are many subtypes of the strain and more sophisticated typing and virulence assessment systems need to be developed using isolates carefully collected to test different epidemiological hypotheses. However, its association with increased virulence is not straightforward, probably reflecting the interactions with differing patient case mix. One strain (ribotype O27) is described in detail and, like other emerging strains, is demonstrating increasing antimicrobial resistance, notably to quinolone antibiotics. This is also described in Northern Europe and surveillance systems are being developed or improved to monitor the situation. North America has seen increasing numbers of hospitalised patients and others in nursing homes and the community, with more severe Clostridium difficile associated diarrhoea.