Each day we prescribe antibiotics without knowing the specific cause of infection, yet. Some patients will have an infection caused by an ESBL-producing bug, and they would benefit from immediate treatment with a carbapenem or addition of an aminoglycoside. At the same time we don’t want to misuse carbapenems or hurt kidneys. Wouldn’t it be great if we could accurately predict who would need a carbapenem? Now you can. Continue reading
The analytical lab methods that we use to grow antibiotic-resistant bacteria make a big difference in terms of recovery. However, ‘pre-analytical’ factors are just as important in determining the sensitivity of prevalence studies. We are used to the idea of studies to work out the most sensitive anatomical site to sample for detecting colonisation with antibiotic-resistant bacteria. However, there are other ‘pre-analytical’ factors that may skew the findings of prevalence studies. A study from my old research group at KCL highlights how staff and patient choices, behaviours, and demographics can be pre-analytical factors that could skew prevalence studies.
Eurosurveillance have recently published a study from the TIMER group evaluating the impact of antimicrobial resistance on hospital mortality, excess length of stay (LOS), and cost of BSI in European hospitals. The study highlights the high cost of BSIs, especially when antimicrobial resistant.
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|
|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.