Counting the cost of CPE Mk II

Earlier this year, CMI published our article on the cost of a CPE outbreak in London, which cost 1.1m (Euros) over 10 months. EID have recently published a similar article, reporting a 0.6m (Euro) outbreak of CPE in the Netherlands.

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Dissecting the epidemiology of resistant Enterobacteriaceae and non-fermenters

chalk cheese

It was a great privilege to speak at the HIS / IPS Spring Meeting today. You can download my slides here. The meeting was entitled: “What’s that coming over the hill? Rising to the challenge of multi-resistant Gram-negative rods”. This, I think, is an (oblique) reference to the signature hit of a Welsh band ‘The Automatic’: “What’s that coming over the hill? Is it a monster?”. So, are multi-resistant Gram-negative rods monsters lurking underneath the bed? Dr Tom Frieden, CDC Director, has described CRE as “nightmare bacteria” and Dr Sally Davies, CMO, has painted a bleak post-antibiotic era picture in reference to the emergence of these bacteria. So, is it a monster? Yes, I think it probably is. But all monsters are not created equal…

My exploration of the differences in the epidemiology of resistant Enterobacteriaceae and non-fermenters (mainly A. baumannii) was designed to prompt anybody tempted to conflate these two related problems to think twice. Resistant Enterobacteriaceae and non-fermenters do share the same response to the Gram-stain and can be resistant to key antibiotics occasionally through shared mechanisms (principally the carbapenemases). But that’s about it. Otherwise they’re like chalk and cheese. (A. baumannii = chalk, which turns to dust; Enterobacteriaeae = a good cheese, which ultimately ends up in the gut.) (Table).

Table: Comparing the epidemiology of resistant Enterobacteriaceae and non-fermenters. 

Enterobacteriaceae (K. pneumoniae) Non-fermenters (A. baumannii)
At-risk population Primarily acute pts ICU, burns
Risk factors Travel Trauma, ICU stay
Epidemic potential High Low
Clinical UTI VAP
Mortality Stark increase (CPE) Minimal increase
Prevalence Emerging (rapidly) Patchy but stable
Sites of colonisation GI tract Skin, resp & GI
Colonization duration Months to >1 year Days to weeks
Transmission routes Hands ++, Env +/- Hands +, Env ++
Resistance Mainly acquired Intrinsic & acquired
Common clones KPC-producing ST258 Intl clones I-III

Probably the most important difference between the Enterobacteriaceae and the non-fermenters is their at-risk populations. A. baumannii is restricted mainly to high-risk patients in intensive care units. This is not so for the resistant Enterobacteriaceae, which have the potential to cause infection and colonization in a wide group of hospitalized patients and, perish the thought, the community. Related to this is their epidemic potential: resistant Enterobacteriaceae, including CRE, have already demonstrated the capacity to spread rapidly and broadly in hospital and to a lesser extent community populations. Rates of antibiotic resistance in A. baumannii can be high, but it does not possess the tools to spread outside of high-risk hospitalized patients.

Other differences between these two groups of resistant Gram-negative bacteria include the types of infection they cause and associated attributable mortality, their prevalence, their sites and duration of colonization, their transmission routes, their resistance mechanisms and their population structure and clonal dissemination patterns (Table).

One of the many acronyms in current circulation to describe resistant Gram-negatives is CRO (carbapenem-resistant organisms), which is used as a catch-all term to encompass both Enterobacteriaceae and non-fermenters. Given the fundamental differences in epidemiology, I don’t think it’s very helpful. After all, MRSA is a ‘CRO’ but we wouldn’t dream of lumping it together with K. pneumoniae or A. baumannii! So, we should expunge ’CRO’ from our collective vernacular and stick to CRE and CRAB.

I accept that there are limitations with my presentation. You could (and probably should) further dissect the epidemiology of K. pneumoniae vs. E. coli, A. baumannii vs. P. aeruginosa, and ESBL vs. carbapenemase producers. I suspect we will eventually have data to demonstrate different clinical manifestations associated with the various common carbapenemase genes.

That said, I think a separation of the resistant Enterobacteriaceae and non-fermenters is a useful distinction in terms of at-risk populations, epidemic potential, and effective control measures.

Finally, my preparation for the talk raised several challenging questions:

  • Which interventions work?
  • Are they different for Enterobacteriaceae and non-fermenters? (Probably, given their epidemiology.)
  • Has our focus on CPE taken our eye off CPNF, which are the ‘clear and present danger’ for many of us?
  • What is the prevalence of CPE in the UK?
  • How much do we believe a single negative screen?
  • Do we need rapid molecular diagnostics?
  • What is the duration of colonisation?
  • Are there decolonisation strategies other than “selective” decontamination using antibiotics?

Image credit: ‘Chalk and Cheese’ by Jackson Boyle.