Background 3986 views last update:Dec 21, 2015

New colistin resistance gene found in China

Resistance to colistin, an antibiotic commonly used in some countries for the control of E. coli infections, especially in pigs, has been found in China (Liu and others, 2015). The difference is that the gene is found in a plasmid, which can be transmitted between bacteria.

The report of a new resistance gene (mcr-1) against polymixins (colistin) found in Escherichia coli from pigs in China, which can be potentially plasmid transferred between bacterial species and 'potentially' to man via meat, is indeed disturbing and disappointing. Formerly, colistin resistance both in man and animals was thought to be chromosomally related and therefore unlikely to be transferred between bugs, although resistant clones could develop.

It is noted that most of the genetic work was carried out on a plasmid basis and not on the resistance gene itself, so the final link between pigs, pork, man and human disease has not been completely established, epidemiologically. However, it was found in E. coli in 20.9% of pigs surveyed at slaughter, 22.3% of raw pork products, 28% of chicken products and in 13/902 (1.4%) of patients being treated for E. coli infections and 3/420 (0.7%) with Klebsiella pneumoniae infections. Recent work looking at attribution of extended-spectrum beta lactamase (ESBL) resistance in E. coli from food to man has shown that man to man is the major contributor (99.73%: 0.27%) (Weblog - Are we being hoodwinked again) due to hospital and care facility spread of bacteria carrying the resistance genes. As a result, further genetic work is required to confirm the direct linkage between food and E. coli and K. pneumoniae infections in man with the mcr-1 gene.

So saying, it must be remembered that China has the largest pig production in the World over twice that of Europe's, they are major producers of generic antimicrobial drugs and their use in animals is not normally under veterinary control. Fortunately, the supply of live pigs and pork is in the direction from Europe to China and due to the nature of the endemic diseases in China, such as Foot and Mouth Disease, it is unlikely that this will be reversed. The possibility of transfer by man, however, is a more likely risk with increased trade and tourism between the two regions of the World.  This is a good example of the complexity and global nature of antibiotic resistance and the need for countries to work together to address this One Health issue.

In the response to the European Commission by the European Medicines Agency (2013) regarding the use of old classes of antibiotics, like colistin, which have been re-introduced to treat multi-resistant bacteria in humans they recommended: "Despite the abundant use of colistin in veterinary medicine for over 50 years, from the available information colistin resistance transmission via horizontal gene transfer or sustained clonal expansion has not been observed for the target Gram-negative organisms. However the rapid emergence of resistance in humans after oral use in the Intensive Care Unit (ICU) for selective digestive tract decontamination shows that resistance in Enterobacteriaceae can emerge following oral use. The lack of emergence of resistance should be addressed with caution since in depth epidemiological surveys in veterinary medicine are scarce. Large studies combining consumption and resistance are limited, because colistin susceptibility tests are not fully reliable.

There is a need to implement robust systems for surveillance of antimicrobial resistance to detect any potential increase of colistin resistance in animal bacteria in the future that could lead to a review of the current advice."

In Europe, 80% of polymixin (mainly colistin) sales are made in only 3/26 Member States i.e. Spain Germany and Italy (ESVAC, 2015) (see Figure 1) and it would be of great value to review the surveillance data from these countries to see if the situation has changed dramatically in recent years, before any radical decisions over restrictions of use in veterinary medicine are made here.  Colistin is commonly used in some Member States for post-weaning diarrhoea as an alternative to Zinc Oxide. The health and welfare of the animals treated responsibly with this medication also needs to be weighed up against any possible over-reaction before a full review has taken place.

EMA (2013) European Medicines Agency - Answer to the first request from the European Commission for scientific advice on the impact on public health and animal health of the use of antibiotics in animals. EMA/363834/2013.
ESVAC (2015) European Medicines Agency – Fifth ESVAC report – Sales of veterinary antimicrobial agents in 26 EU/EAA countries in 2013.
Liu, Y-Y, and others (2015) Emergence of plasmid-mediated MCR-1 in animals and human beings in China: a microbiological and molecular biological study. www.thelancet.com

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