Colistin (also known as polymyxin E) is an antibiotic belonging to the polymyxin family that was first used in clinical medicine in 1959. For many years it was used sparing due to the potential for it to cause kidney damage.  More recently, colistin has been reintroduced as a precious, last line treatment for infectious disease caused by bacterial that display resistance to multiple antimicrobial agents.

In 2015 a new gene, the mcr-1 gene, was identified on a plasmid (a mobile genetic element) in E. coli from humans and food animals in China. This report has prompted a worldwide effort to screen retrospective collections of clinical human and food animal bacterial isolates for the presence of the mcr-1 gene.

These studies show that the mcr-1 gene has now been detected in E. coli in over 17 countries from food sources in Malaysia (chickens, pigs, humans), Denmark (imported chicken meat),  Canada (lean beef), China (pigs), sub-Saharan Africa (poultry), France (cattle), Vietnam (poultry and pigs), Egypt (cow with mastitis) and in human clinical isolates in Canada, the Netherlands, France, Denmark, the UK, Italy, sub-Saharan Africa, Spain, Argentina, and Taiwan. Travellers returning from North Africa, China, Vietnam, Laos, Cambodia, Columbia, Algeria, Peru, Tunisia and Bolivia have been reported to be colonised by E. coli carrying the mcr-1 gene. It should also be emphasized that most E. coli strains that carry the mcr-1 gene also carry multiple resistance genes.

It is notable in one report that E. coli from children less than 27 months of age with no known history of contact with pets or farm animals was reported to harbour the mcr-1 gene.

Fortunately, colistin is used sparing in human medicine however, because polymyxin antibiotics are cheap to produce, colistin has been used widely as a growth promotant and to control infectious disease in food animals.

The spread of the mcr-1 gene does not appear to be associated with the spread of a successful clone. Rather, the mcr-1 gene is present in genetically diverse populations of E. coli and on multiple plasmid backbones. These data suggest that plasmid transfer is playing a major role in the spread of the mcr-1 gene. The mcr-1 gene has also been identified in Salmonella spp., and Klebsiella spp.

It is now established that E. coli isolates dating back as early as 2005 carry the mcr-1 gene indicating that this gene has been circulating globally for over 10 years. This observation highlights the importance of resourcing surveillance efforts for antibiotic resistance.

Antibiotic resistance is very real and is here, now. It is estimated that by the year 2050, multi-drug resistant bacteria will kill 10 million people a year, becoming the number one cause of death from disease. Now with the discovery of carbapenem-resistant enterobacteriaceae or CRE in the community also carrying resistant genes to colistin, we can see that future getting closer. This is very concerning as colistin, in spite of its toxicity, was a last line of defence against CREs, which are resistant to other antibiotics. It only took a few month after the announcement of uncovering colistin-resistant genes in pigs in China for us to find the same genes in a patient in the US. Every year, there are over 3 billion people that fly internationally meaning inter-continental transfer of resistant genes is inevitable. They might already be in Australia for all we know but before we see them, CRE bacteria carrying these genes must build enough numbers in a host to cause infection which does not always happen as our immune systems keep up the fight. This is more concerning for patients with a compromised immune system where they can't effectively kill bacteria. 

Antibiotic research and development is of paramount importance. Industry and research institution can become part of the solution by developing new antibiotics so we are always one step ahead of the bugs. At the clinic, it should become routine to always test for bacteria before prescribing an antibiotic and to also test for antibiotic resistance to find out which antibiotic the bacteria is sensitive to. Aside from the transfer of resistant genes between bacteria, selective pressures can also give rise to bacterial resistance from mutations. This can happen for instance when the wrong antibiotic is used or when the antibiotic dose is not high enough and so routine lab testing of patients suspected of having a bacterial infections can help reduce the incidence of emergence of drug resistant bacteria.

Antibiotics have saved countless numbers of lives, probably even yours. 

But because we have abused antibiotics, taking them when we don’t need to, and using them as growth promoters in animals, bacteria have developed resistance. They do so by collecting genes for resistance. The more genes they collect, the more resistant they are.

That’s why reports of spreading resistance to the antibiotic of last resort, colistin, are so worrying.

Resistance for colistin was first reported as being mobilised between bacteria in China, during November 2015.

Already this resistance gene has spread to other areas in Asia, Africa, Europe and South America. And now it’s been reported for the first time in the United States. Entry into Australia cannot be far off, if in fact it isn’t already here.

When multi-resistant bacteria acquire the colistin resistance gene, there will be no antibiotics left to treat infected people. Surgery will then become very dangerous, and people will commonly die of infectious disease. Estimates suggest that over 10 million people will be dying of antibiotic resistant infections every year by 2050, and that this death toll will be higher than deaths from cancer.

The identification of colistin-resistant bacteria is the US is further evidence of the real and present threat of antibiotic resistance to human health and social well-being.

Antibiotic resistance is a major global health threat, and the time for action is now. We must preserve the available antibiotics we have, manage our global use of antibiotics better while at the same time support efforts to discover and develop new antibiotics.

Critical to our efforts are four broad measures. First, we must reduce community and individual risk to these and other drug resistant bacteria. This can be achieved through infection control, implementing antimicrobial stewardship programs and supporting prudent use of antibiotics.

Secondly, we need to reduce cross‑transmission through integrated infection control management practices. Finally, we need enhanced laboratory screening and testing methods increase efforts to detect these and other organisms through screening of patients for colonisation or infection on admission to hospital.

Without these efforts, individuals and the community will be increasingly at risk of antibiotic resistance. Put simply, we will be unable to treat patients for infections which will result in significant pain, suffering and in some cases the death of patients. All citizens in all countries and settings must act and be part of the solution.

Dr Margaret Chan, the WHO Director-General, in her recent speech to the WHO Assembly highlighted antibiotic resistance as a major crisis facing the globe.

Potentially, ten million people will die every year by 2050 from antibiotic-resistant infections. This report from the US shows that the horse has bolted - the superbugs are already there. It is about colistin, which is the last resort for a type of superbug, if other antibiotics don't work.

The background to this story begins in late 2015 when in China, a colistin-resistance gene (mcr) was found. It was found in animals, meat products and in humans, demonstrating the link between animal and human bacteria. This makes sense because colistin is used far more in the animal industry than in humans in places like China and Europe.

Colistin resistance had been found before, but what was alarming was that this resistance gene came in a package called a plasmid. And plasmids can be transferred easily between bacteria; so, if a colistin-resistant bug made its way into our bowels, then it could easily pass that resistance on to other bacteria. Furthermore, in early 2016, it was discovered that this colistin gene wasn't limited to china - it was already in other regions such as Europe and Canada.

So it is a big deal that it has been found in the United States, especially in a patient who hasn't apparently been overseas for many months. It suggests that she has picked it up within the US, possibly from a food product, meaning that the colistin mcr-gene is already there. The nightmare scenario is if a subgroup of superbugs called CRE (Carbapenem-Resistant Enterobacteriaceae) picks up the colistin resistance from another bacterium, then there won't be any antibiotics with which to treat a sick patient - it will truly be like pre-antibiotic times, not even one hundred years ago.