European approaches to MDR-GNR prevention and control

HISME

I was privileged to be asked to speak at the inaugural Healthcare Infection Society Middle East Summit in Dubai this week on ‘European approaches to MDR-GNR prevention and control’. You can download my slides here.

I began with a (probably too lengthy) preamble outlining some overall points:

  • CRE is a big deal in Europe, especially in the UK, and has prompted unprecedented action on a national level in the form of a Toolkit, a Patient Safety Alert and a letter to all CEOs requesting (demanding?) an action plan. The political picture is similar elsewhere in Europe and in the USA. Although this level of government scrutiny can be challenging, on the whole I think it’s beneficial, and is probably a sizeable factor in the successes achieved with MRSA and CDI.
  • Do we go universal or targeted? There’s been much discussion recently about abandoning traditional targeted (aka vertical) approaches in favour of universal (aka horizontal). Interesting, all guidelines that I could lay my hands on favoured a targeted approach for MDR-GNR, centred around screening and isolation of carriers.
  • Where is the evidence? We are hamstrung by the lack of high quality studies telling us with any certainty what works to control MDR-GNR. Pretty much all studies to date are either performed in an outbreak setting (regression to the mean…) or include multiple interventions (which worked?), or both. The few studies that evaluated a single intervention in an endemic setting are underpowered to deliver a meaningful conclusion. So, we need bigger and better studies!
  • How do you produce good guidelines – who is on the guideline writing dream team, and what are the key pitfalls to avoid. Plus, importantly, how to good guidelines translate through a good policy into good practice?

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‘Crapsules’ spell the end for recurrent Clostridium difficile infection

Faecal microbiota transplantation (FMT) has shown remarkable efficacy for treating recurrent C. difficile infection (CDI). In fact, the randomized controlled trial to evaluate the effectiveness of FMT for recurrent CDI versus treatment with vancomycin was terminated early because FMT was so obviously superior, with a cure rate of more than 90% (see Figure 1, below).

Figure 1: Faecal microbiota transplant for recurrent CDI. Patients with recurrent CDI randomised to FMT (n=16), vancomycin (n=12) or vancomycin + bowel lavage (n=13). Colour scheme chosen carefully.van nood_blog

FMT is crude in every sense. You take donor stool, put it in a blender, sieve it, and deliver it to the recipient’s gut. I had the pleasure of watching a colleague prepare a dose of FMT in our laboratory in London last week. It really is a simple preparation. The delivery of the FMT to the recipient’s gut isn’t so much tricky as it is unpleasant for the recipient, with a tube required for the procedure.

So, could you deliver FMT orally? The answer according to a recent JAMA study is yes. The team from Boston in the US developed specially formulated capsules (aka ‘crapsules’) designed to deliver the FMT to the correct part of the gut. Of the 20 patients with recurrent CDI given a short 2 day course of ‘crapsules’, 14 (70%) resolved. The 6 non-responders were given a second course and 4 of these resolved, resulting in an overall resoluation rate of 90% (18/20). The quality of life benefits are obvious, and spelled out in the reduction in number of daily bowel movements (Figure 2, below). Although this wasn’t an RCT, so the patients knew they were getting the FMT and there could have been a placebo effect, the similarity in the rate of resolution between this study and the van Nood study (Figure 1) is striking.

Figure 2: Median number of bowel movements for 20 patients suffering from recurrent CDI treated with ‘crapsules’.Youngster blog

Oral FMT via ‘crapsules’ takes away the unpleasantness of the delivery for the recipient (if they can get over the ‘gross’ factor). But it doesn’t solve the lingering safety concerns associated with the procedure. We simply don’t have the tools to screen donor stool for problems we don’t yet know about. The experience from delivering hepatitis C virus to haemophiliacs in the 1980s in contaminated blood products from donors is salutary, and close to my heart since one of my good friends is still suffering the consequences of this. But, this risk has to be balanced against the urgent need of patients becoming increasingly desperate with recurrent CDI. If I had recurrent CDI, I’d be joining the queue for FMT.

The real solution to this problem is synthetic FMT. Lots of people are working on this at the moment – check our some of the work by Trevor Lawley on this. I am pretty certain that a simple bacterial cocktail will not make an effective synthetic FMT. There’s huge microbial and non-microbial diversity in the gut contents which will need to be replicated somehow. Clearly, some of this will be redundant, but it will take quite some time to pick through the constituent parts to derive an effective synthetic FMT. But I’m certain it will happen, and probably over the next decade.

Until then, ‘crapsules’ offer an alternative, effective way to deliver FMT, which is remarkably effective for resolving recurrent CDI. But recurrent CDI is just the start. There’s a host of other conditions that could potentially benefit from FMT. It may even be that ‘crapsules’ become a ‘new statin’: “a crapsule a day keeps the bad bugs away”?

Article citationYoungster I, Russell GH, Pindar C, Ziv-Baran T, Sauk J, Hohmann EL. Oral, Capsulized, Frozen Fecal Microbiota Transplantation for Relapsing Clostridium difficile Infection. JAMA 2014; in press.

What’s trending in the infection prevention and control literature? HIS 2012 -> HIS 2014

I was privileged to speak at the Healthcare Infection Society meeting in France today on ‘What’s trending in the infection prevention and control literature? HIS 2012 -> HIS 2014’. You can download my slides here, and view the recording below:

I have always enjoyed attending these light-hearted summary sessions at other conferences, so I hope I struck the right tone. In order to track some of the trends in the infection prevention and control literature since the last HIS conference (in late 2012), I plugged some search terms into Google trends (Figure).

Figure: Google Trends for all search terms (excluding viruses) (2004 to present). Logos and arrows represent the time of the HIS 2012 and HIS 2014 conferences. Search terms: hospital cleaning; carbapenem resistant Enterobacteriaceae, whole genome sequencing, fecal microbiota transplantation. [Note, I had to spell it ‘wrong’ (fecal v faecal) to detect a trend. Blasted Americans.]what's trending google trends

Based on my search terms, there was one infection control trend that trumped all others: Ebola. If I include in with the other Google search terms, it eclipses all others! Whilst trends in Google searches may not necessarily correlate with trends in the infection prevention and control literature, in this case, it is true that the outbreak of Ebola in West Africa has prompted a lot of publications in the literature – and consumed an awful lot of professional time for all who are connected with hospital infection prevention and control! Aside from Ebola, other trends in the infection prevention and control literature that I covered include MERS-CoV, universal vs. targeted interventions, faecal microbiota transplantation, whole genome sequencing, carbapenem-resistant Enterobacteriaceae (CRE), and some aspects of environmental science. Finally, I looked into my crystal ball and predict some of the trends in the infection prevention and control literature by the time HIS 2016 comes around.