Thursday, May 5, 2016

Antibiotic Resistance and the Last Line of Defense

Last December in an article published in the Lancet it was reported that E. coli bacteria worldwide are sharing a gene that confers resistance to an antibiotic called colistin one of the rarely used so called last resort antibiotics in the polymyxin family. Until now antibiotic resistance had developed as a result of chromosome mutation, not gene transfer. Now, antibiotic resistance was observed and documented as a result of a gene transfer. This was discovered during a routine surveillance project on antimicrobial resistance in E. coli bacteria from food animals in China where a major increase of colistin resistance had been observed. They found that an E coli strain that had colistin resistance could be transferred to another strain. Though viruses had been known to transfer properties this way, it had not been observed in bacteria.

The researchers believe that their finding of a colistin resistance that is transmissible among bacteria will result in rapid transmission of the resistance and the progression of extensive drug resistance to pan-drug resistance- meaning there is no effective treatment available. This is a frightening prospect of potential global significance. The consequences of this resistant gene spreading will result in increased deaths.

Although in modern, well-funded healthcare systems, obtaining access to second and third-line treatments may not be an issue, mortality rates for patients with infections caused by resistant bacteria are significantly higher, as are their costs of treatment. And we are seeing in parts of Europe and the United States an increasing number of patients in intensive care units, haematology units and transplant units who have pan-resistant infections. The death toll from resistant bacteria in the United States, Great Britain and Europe is estimated at 50,000 per year, but is for cast to grow by a power of 10 by 2050.

Antibiotics were discovered in the early part of the 20th century and went on to revolutionize healthcare, becoming the bedrock of many of the greatest medical advances of the 20th century. Common yet frequently deadly illnesses such as pneumonia and tuberculosis (TB) could be treated effectively. A small cut no longer had the potential to be fatal if it became infected, and the dangers of routine surgery and childbirth were vastly reduced. But bacteria and other pathogens have always evolved so that they can resist the new drugs that medicine has used to combat them. Resistance has increasingly become a problem in recent years because the pace at which we are discovering novel antibiotics has slowed drastically, while antibiotic use is rising. Massive amounts of antibiotics are routinely used prophylactically in agriculture, and to increase weight gain in farm animals.

Colistin was developed in the 1950s, one of a class of compounds called polymyxins. It is known as a last resort drug — physicians avoid using it when possible — because it tends to damage patients’ kidneys. As a consequence, bacteria have been slow to develop resistance to colistin, compared to other antibiotics, and it has become in many cases of resistant bacteria the last line of defense. In the China study polymyxin resistance was shown to be entirely due to the plasmid-mediated MCR-1 gene.

In December it was believed that MCR-1 was confined to China, but now a new study published on April 28th 2016 found that MCR-1 is present in South America where colistin resistance was investigated in 4,620 Enterobacteriaceae isolated from human, animal, food and environmental samples collected from 2000 to 2016. Enterobacteriaceae are a large family of bacteria that includes such pathogens as Salmonella, E. coli, Yersinia petis, Klebsiella and Shigella and others. They found that MCR-1-positive Enterobacteriacae have been emerging in South America since at least 2012. This finding supports a previous report on the possible acquisition of MCR-1-harbouring E. coli by European travelers visiting Latin American countries.

The rapid pace that other mechanisms of drug resistance spread indicates that, with the transmissible colistin resistant gene, progression of Enterobacteriaceae from extensive drug resistance to pan-drug resistance is inevitable and will ultimately become global. The discovery of the emergence of transmissible resistance in the form of MCR-1 is a finding of global significance. Wash your hands, keep outdoor shoes, clothing and backpacks in the mudroom and away from the rest of the house.

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