Tag Archives: clostridium difficile

“A Game-Changer…”

Every so often a piece of research comes out that significantly affects our practice. It is refreshing to see that such research is still occasionally published, amidst the plethora of commerce sponsored papers that can be useful, but more often than not, are simply adverts.

Diverse Sources of C. difficile Infection Identified on Whole-Genome Sequencing. David W. Eyre et al.N Engl J Med 2013; 369:1195-1205.

This paper involves sequencing Clostridium difficile isolates from symptomatic patients over a 4 year period between 2007 and 2011 in Oxford Hospitals. 45% of the isolates were genetically distinct enough to suggest that their source was not from other patients symptomatic from Clostridium difficile infection.

The bottom line of this research is that it suggests that the epidemiology of Clostridium difficile is multi-factorial and that Infection Control measures will only go so far in controlling Clostridium difficile rates in hospitals. We also need to take such research into account when setting realistic targets for Infection Control teams to attain when addressing organisms such as Clostridium difficile.

These findings should not really surprise us that much… We know from previous carriage studies that approximately 10% of the population carry Clostridium difficile, so there are bound to be significant reservoirs in the hospital, peri-hospital and community settings. It may even be that some patients become infected with their own endemic Clostridium difficile strains, which are allowed to proliferate and produce significant amounts of toxin when the patient is challenged with broad spectrum antibiotics, thus creating an ecological niche for the Clostridium difficile bacteria. 

This study and another recent one on the laboratory diagnosis of Clostridium difficile have real implications from both a clinical and laboratory point of view on how we think about Clostridium difficile. As both these papers challenge established thought, they may not be readily accepted. From a lab point of view there may be a few grumbles because we may have to change and possibly increase our testing in light of these findings.

Both these papers need to be discussed in detail at departmental journal clubs, and not the interesting but highly isoteric environmental bacterium isolated on the blood culture bench for the first time in 10 years…


“A test that is just a bit too good…”

On one of my rare forays through a research journal I surprised myself by finding a paper that interested me….

Clinical relevance of a positive molecular test in the diagnosis of Clostridium difficile infection. Baker I et al, Journal of Hospital Infection 84 (2013),311-315. Click here for a link to the abstract. Unfortunately the full text requires subscription.


Photo accredited to Dr Holdeman
Photo accredited to Dr Holdeman


It has long been thought that toxin assays for Clostridium difficile lack sensitivity. This has triggered a move towards PCR or other molecular testing for toxin producing Clostridium difficile strains.

This paper primarily looks at the clinical differences between patient cohorts who are PCR +ve and toxin EIA negative for C.difficile, and patients who are both PCR and toxin EIA positive.

The study showed increased mortality and prolonged duration of diarrhoea in the toxin EIA positive group, compared with the group that was PCR positive but toxin EIA negative. There was no obvious attributable mortality to Clostridium difficile in the group that was PCR positive but toxin EIA negative. (However this seemed to be only on examination of the death certificates as opposed to detailed review of the clinical notes)

The study shows nicely that by using a molecular test such as PCR for C. difficile detection, it may just be a little too good at detecting it, and thus produce positive results that are not clinically relevant (?mostly just colonising). However the study did not specify whether there was any clinical cases suggestive of severe CDAD in the PCR positive, toxin EIA negative group, which would have been nice to know before discounting this cohort altogether.

These findings confirm my clinical suspicions that we have moved to a test which is just a little too good, and that there is probably a continuing need/role for toxin EIA testing in diagnostic algorhythms for disease due to Clostridium difficile.

The only downside of the paper was the declaration of a conflict of interest by one of the authors, although it looks to be fairly minor.

Nice paper. Worth getting hold of and discussing further in your laboratory journal clubs etc.


p.s. Click here for a previous article on faecal transplantation to treat disease due to Clostridium difficile.

“Faecal Transplant for recurrent C. difficile Infection: An idea not to be sniffed at…”

A recent article in the New England Journal of Medicine demonstrates the usefulness of faecal transfer/transplant for treatment of recurrent Clostridium difficile infection.

Although anecdotal reports and case studies had suggested that this therapy was effective, this is the first randomised controlled trial that has been done on the treatment.

This treatment modality has been around for at least 20 years. However there are probably a few reasons why faecal transplant for recurrent Clostridium difficile infection has never really gained widespread popularity and acceptance:

1)Compared with giving a medication, it is quite a lot of work to find donors, screen donor stool, screen donor blood, prepare the donor stool etc etc.

2)Except in very large hospitals, the number of patients with Clostridium difficile infection who don’t resolve with one or two courses of conventional therapy (oral metronidazole or vancomycin) will actually be quite small.

3)Lastly is the fact that some patients and more worryingly, some doctors, find the nature of the treatment “off-putting”.

I hope that the publication of this research will encourage hospitals to develop standard protocols for this type of therapy so that it can be used when needed, instead of just being thought about.

Personally if I was suffering the unpleasant symptoms of recurrent Clostridium difficile infection, I would not hesitate to get a donor stool infusion to get things sorted out.