Mcr-1 and the end of the world

If you read this, you may well be concerned about antibiotic resistance and consider reducing the burden of disease caused by AMR as one of your professional goals. Broad attention helps us to fight the problem: it creates awareness and funds for research. So, how do we cope with data that may jeopardize these ambitions (raising awareness fort he problem AMR)? Here is the eaxmple of mcr-1.

 

The discovery of plasmid-borne resistance to colistin, a gene called mcr-1, in November 2015 was received as the onset of Armageddon. Although we had, at that time (and now) little evidence of the effectiveness of colistin in treating critically ill patients, the upheaval caused by mcr-1 promoted colistin to a wonder-drug on which the world seemed to float. Within a few weeks mcr-1 was reported from 5 continents, which was interpreted as “rapid global spread” (although the genes might have been there for ages…). And the first E. coli with mcr-1 in the USA was announced in a CDC press conference (in which they forgot to tell that the bug was susceptible to most other antibiotics).

The reality checks (or alternative facts) are now coming in: Two surveillance studies from China in Lancet ID (study 2) demonstrating the following: among 1,495 E. coli and 571 K. pneumoniae bloodstream infections from 28 hospitals between Sept 2013 and Nov 2014 there were 21 isolates (20 E. coli) with mcr-1 (0,05%) , but only 1 E. coli was also resistant to carbapenems (<0.05%). And among 21,621 non-duplicate clinical Enterobacteraicaea, Acinetobacter and P. aeruginosa isolates collected between 2007 and April 2015, 91 had mcr-1 (0,005%), 75 being E. coli, of which 1 isolate was also resistant to mero-/imipenem (<0.005%). Among 4,123 isolates from colonization studies, 45 had mcr-1, all but 1 E. coli, of which 1 E. coli was resistant to mero-/imipenem (0,02%). Both isolates harbored NDM-1. So, the risk of an invasive infection with a carbapenem+colistin resistant bacterium seems not to differ fundamentally between China and the Netherlands. Moreover, both studies failed to demonstrate evidence of nosocomial clonal spread of mcr-1 containing bacteria, at least not based on clinical culture results.

So, this doesn’t fit in all the bad news (thruth and fake) coming to the civilized world since January 20. It may, in fact, be very reassuring. Mcr-1 has had the opportunity to spread all over the world, without being noticed (as it was not yet discovered) assisted by selective pressure provided by unlimited colistin use in agricultural industry. It did spread, but it did not unite with carbapenem resistance in the human reservoir. It failed, total disaster!

With the well-deserved attention for reducing antibiotic use in animals (that I support) the likelihood that mcr-1 will become a problem for humans will further reduce. So, if you were dreaming of a career build on mcr-1, it might be the right time to consider a change. Unless you read this amazing study, that appeared last night on the prepint server bioRxiv: an impressive analysis demonstrating increased prevalence of carriage with mcr-1 and mcr-1+cefotaxim-resistant Gram-negatives in Chinese (hospitalized) subjects between April 2011 and March 2016. That pictures the opposite of reassurance…..

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