Clostridium difficile

From Ganfyd

A sporing bacterium that can be regarded as a normal part of the gut flora, and usually effectively kept in its place by other gut flora. Formation of p-cresol as the main fermentation product of tyrosine by C. difficile is unique among clostridial species and allows the organism to be often recognised by smell.

It generally causes a diarrhoeal disease due to pseudomembranous colitis, so named because of endoscopic appearances, but can rarely also affect the small bowel as well as seen by the accumulating number of case reports.^{[1][2][3][4][5][6][7]}

Aetiology

Ubiquitous environmental contaminant, with spores that are both resistant and excreted in massive quantities in an overgrowth situation such as can occur with. The spores are transfered by several routes including the hands.^[8] The ribotype O27 strain outbreaks in USA, Canada and Europe from 2003 onwards are associated with different antibiotic exposure patterns to other ribotypes and this is extremely important in controlling this pathogen.^[9]

Diffy silly not diffy seal. It is from the Latin rather than via French. Image:Difficile.wav

Clinical

Most cases present with characteristic profuse diarrhoea which many health care workers can diagnose by the distinctive p-cresol smell (you can only smell it if you have the right genetics!). Unhappily mortality is connected to ribotype and the public scandals where such issues have been brought to the fore at least concentrate minds.

Investigations

Stool tests

• Stool toxin assay is very useful but can be negative (especially early in infection) and very occasionally positive due to other Clostridium spp..
• Serotyping is effectively retrospective

Radiology

• Toxic megacolon is the feared complication

Treatment

C. difficile can be spread among hospital patients and isolation is important.

Medical

• First line Metronidazole PO TDS x7-10days (but give iv if patient can not take orally) for which there is high quality evidence
• Second line Vancomycin 250mg PO QDS x 7-10 days for which there is high quality evidence
• Third line: There is moderate quality evidence for prolonged courses of above
• Probiotics^[10]
  • low quality evidence for Saccharomyces boulardii in adults
  • low quality evidence for Lactobacillus rhamnosus GG in children
  • low quality evidence for immunoglobulin

Surgical

• Toxic megacolon may require urgent resection for which there is strong recommendation as it is life saving.

Stool Transfer

Donated stool from healthy individuals with normal flora can be transferred to afflicted patients.^[11]

Prevention

The proven interventions are:

C. difficile rates related to changes in antibiotic policy for a large acute hospital

• Good hygiene, infection control and cleaning practices has high quality evidence
• Reducing broad spectrum antibiotic load has high quality evidence. This requires removal of drugs like co-amoxiclav, Cephalosporins and ciprofloxacin from use in common indications like chest infections, exacerbation of COPD, soft tissue infections and urinary tract infections. Reversion to more narrow spectrum drugs which deal with the nastier pathogens and use of doxycycline and gentamicin reduces over all mortality and morbidity, something that those doctors who want to give the best possible therapy to the individual and have traditionally chosen the antibiotic that killed all known causes of the infection in question might bear in mind.

These can have a good sustained effect on C. difficile attack rates, even with the O27 ribotype.

• Probiotics have low quality evidence^[12]

There are a number of associations that may or may not translate into useful interventions:

• Initial reports that Clostridium difficile diarrhoea was associated with a higher rates of PPI use which makes some sense, then had to be tempered by the not unexpected discovery that use of H2-receptor blockers is also correlated with incidence. There is no evidence base to confirm that primary intervention works but in the context that PPIs increase the rate of recurrence by over four times there is a case for discontinuing PPIs on diagnosis of C difficile ^[13].

According to Bandolier, "the estimated cost of a case of Clostridium difficile diarrhoea in hospital usually to an older and sicker patient, is about £5000, and prolongs length of stay by 21 days. Reduction of PPI use may be an additional strategy to reduce the incidence of this infection, as vegetative cells are highly susceptible to acid." This is also relevant to observations such as that hospitals with higher rates of C. difficile infection tend to have higher bed occupancy.

There is high quality evidence that alcohol hand-rubs may be relatively ineffective in preventing cross-infection by spore-forming organisms such as C diff.

References