The emergence of CPE (and carbapenem-resistance in other Gram-negative bacteria) has forced us to reach to the dusty old antibiotic shelf to revive the clinical use of older agents with activity against Gram-negative bacteria, principally colistin. Colistin isn’t perfect by any means – it has poor tissue penetration compared with the carbapenems, and is associated with nephrotoxicity (although the high levels of nephrotoxicity in the older medical literature has not been reported due to better management of the drug). Furthermore, resistance has already been reported. To date – this has been mutational resistance, which does not have the capacity to spread horizontally. It was only a matter of time before a colistin resistance gene mobilised.
And so to the faeces of a Chinese pig, from which a plasmid-mediated colistin resistance gene was detected and published in the Lancet ID last week (no swine poo, I mean flu, jokes please). The gene, mcr-1, was detected after a notable increase in colistin resistance during routine surveillance of antibiotic resistant E. coli from animals in China. Lab experiments then confirmed that mcr-1 was plasmid-mediated and could be transferred to other Enterobacteriaceae (including K. pneumoniae) and non-fermenters. To make matters worse, the transfer rate of the plasmid is higher than usual, and the colistin resistance seems to be stable – even in the absence of colisin exposure.
One of the most chilling findings of the study is that mcr-1 is already firmly established in the food chain in China. 21% of 804 pigs in slaughter houses carried the gene, with a year-on-year increase from 2012-2014. Perhaps even more concerning was that 15% of 523 retail meat samples carried the gene. So it’s no surprise that mcr-1 is beginning to show up in human infections. E. coli infections from 1.4% of 902 human infections (and K. pneumoniae from 0.7% of 420 human infections) were found to produce mcr-1.
We can do our best to slow the development of colistin resistance by clamping down on its extensive use in agriculture, and indiscriminate use as a component of (non) selective digestive decontamination. But there’s a certain inevitability about all of this. Plasmid-mediated colistin resistance was bound to emerge. And now that it has, it is bound to spread.
Image: Christopher Cozier.