Both Martin and Jon wanted to post a blog about the same article, so thought we’d put our hands together, so to speak, into a pro-con format! We hope you find it useful.
I like it when a paper comes along that confirms my view that we have not reached rock bottom with transmission of C. difficile in UK hospitals. I’ve been saying to anyone that would listen that the Walker paper suggesting that the minority of C. difficile cases detected in hospitals result from transmission in that setting had underestimated the effect of asymptomatic carriers and had caused some to think that hospital transmission was almost a thing of the past in the UK at least. Anyone reading the original paper however would have noted that the authors did comment on this aspect; unfortunately, there was no mention of this in the abstract, which is where I think most people stop reading. Others have suggested that the asymptomatic carrier is a significant unrecognized problem.
In a new quasi-experimental study just published in JAMA Internal Medicine, Longtin and colleagues studied the effect of screening new admissions for carriage, targeting the tcdB gene, subsequently placing all those that were positive under enhanced infection control precautions that had a minimal effect on bed management, for example a shared bay was acceptable however the curtains had to be drawn and staff did not have to wear isolation gowns. Other organisations in the area were used as controls and the effect of the intervention on the rate of C. difficile infections /10,000 patient days was studied. During the study period, 4.8% of patients were identified as carriers (368 in total). The effect of the intervention was not immediate, however there was a progressive effect over time leading to a 7% reduction for each four week period during the intervention. The authors estimated from ‘expected’ infections that 63% were prevented.
Could we do this in the UK? Well we do not have the side rooms in which to isolate all carriers, that is for sure. However it might be possible to undertake at least a risk assessment of anyone testing positive and at the merest slide down the Bristol stool chart, incontinence, antibiotic use etc could form part of a bundle of care that might help reduce transmission from this unheralded source of transmission. If nothing else it would prove to be a useful source of information on carriage rates in the local population.
There have been mutterings that we are now at the ‘irreducible minimum’ of CDI in the UK. I disagree. There are a number of papers suggesting that the role of the asymptomatic carrier is significant and this paper suggests that a minimal intervention may be of great benefit in a high-prevalence locality.
I have always had a hard time explaining to friends at dinner parties why we don’t do any asymptomatic screening for C. difficile, when it’s such an embedded IPC approach for other pathogens (MRSA, VRE, CPE and on and on). The reason I usually state is that the pathogenesis of C. difficile is different to the others – it commonly hangs around in the bowel and doesn’t cause a problem until antibiotics are administered. But is this so different from MRSA on the skin or CPE in the GI tract waiting for an opportunity to cause an infection?
The Longtin study is a great read and I enjoyed it immensely, along with the thoughtful accompanying editorial. Congratulations and thanks to the study team. They show that on the face of it, introducing an ambitious programme to screen and isolate asymptomatic carriers of C. difficile with the toxin gene present reduced the rate of HA-CDI from 6.9 to 3.0 per 10,000 patient days. This sounds impressive. But…
- This argument is won before it is even begun: there was a significant increase in hand hygiene compliance during the intervention (from 37% to 50%)! How can you possibly attribute any reduction observed wholly to another intervention?! Whilst I take the point that most of this was alcohol gel usage, which may not be effective against C. difficile, there’s no getting around the fact that an improvement in hand hygiene is a vial confounder.
- Is the study strong enough scientifically to draw solid conclusions? It is a single centre study, without randomization, with no evidence of pre-specified outcomes or a statistical analysis plan, including only a ‘natural control’. I accept that many of the practice-changing studies in IPC are designed like this, but surely this calls for a multi-centre cluster-RCT?
- Are the authors riding a downward trending epi curve to glory? If you take the annotations off the epi curve in the paper and look at the trend it seems to be a continual progression downwards from the epidemic period, which perhaps accelerates a little after the intervention (if you squint). Indeed, there was a significantly decreasing change of rate during the pre-intervention period!
- Even if the reductions observed were due to the intervention, how transferrable is this study? This was performed in a fairly small hospital with a fairly high rate of HA-CDI (the 6.9 cases per 10,000 patient days is higher than the 2.2 per 10,000 patient days reported at Imperial in the past financial year – which is in line with the national average).
- Related to this, England has managed to effect an impressive reduction in national rate of CDI (to a level lower than reported in the intervention phase of this study) without detecting and isolating asymptomatic carriers!
- The NHS – and many hospitals worldwide – have a chronic shortage of single rooms. So can we really implement effective isolation measures if another 5% of patients require isolation (5% of patients screened in this study carried C. difficile with the toxin gene)? In the study, they used ‘isolation-lite’, which could be performed in either a single room, or in a bay with privacy curtains drawn without the use of gowns. But then I begin to wonder whether you are eroding what is the plausible mechanism of isolation preventing transmission! Also, there’s a risk of “isolation fatigue”, where the intervention becomes progressively less effective the more patients are isolated.
- Who should be included in a screening programme for asymptomatic carriage of C. difficile? In the study, only patients admitted via the ED who stayed >24 hours were screened. It has taken us decades to work out the optimal group to screen for MRSA! Also, what is the sensitivity of rectal swabs for detecting carriage? And how good is the naked presence of one of the toxin genes in identifying the presence of toxigenic C. difficile?
- The authors report an exceptionally high rate of compliance with screening (92.5%). If this level of compliance is necessary to deliver clinical benefit, then I question the long-term effectiveness of this intervention.
- If the intervention is effective in both the short and long-term, is it cost effective? The authors include a “scrap paper” cost-effectiveness sum in the discussion, but this requires a full assessment of cost-effectiveness.
- From the patient perspective, rectal swabbing is not going to be well-received. Also, how will patients feel about being cooped up in a bay with a curtain permanently drawn?
- There is a real risk of over-diagnosis and over-treatment of C. difficile resulting from widespread detection of asymptomatic C. difficile carriage. For example, you have a patient who is screen positive who goes on to develop diarrhoea. This would increase the index of suspicion that the patient has CDI, even though in many cases, they will not. This will lead to collateral for the individual, and unnecessary use of antibiotics, which we can ill afford as we come towards the end of antibiotics!
- I am not going to make an argument that we should be going for universal interventions rather than targeted approaches to IPC; I think targeted interventions (including screening and isolation) are in many cases the best use of our limited resources. But, in the context of managing diarrhoea, the key IPC measures need to be in place BEFORE any pathogen is diagnosed. We need robust protocols for dealing with patients manifesting diarrhoea, not just those who turn out to have CDI.
Ultimately, I agree with the final conclusion of the study authors that: ‘Additional studies are warranted to further investigate this promising strategy.’ So, I don’t think it’s time to pull the asymptomatic screening trigger for C. difficile!
Now that you have heard both arguments, it’s time to cast your vote: