Unblocking the antibiotics pipeline

From ABC Science, 2 May 2014:

The time has come for a major rethink on antibiotics believes Monash University researcher Professor Jian Li.

“People think you can throw antibiotics in the system or in the patient and it will kill the bacterial cells, but actually there are two major factors we have to consider,” says Li, senior research fellow with the Australian National Health and Medical Research Council.

“The first one is, we need to understand how the antibiotic kills bacterial cells and how bacterial cells can develop resistance, and another important factor is we have to make sure that antibiotics reach the infection site at the right time and with the right concentrations.”

Li and many others researchers like him are taking a much closer look at how antibiotics work, how bacteria develop resistance to them, and how we can be smarter in using the antibiotics that already exist.

To that end, Li and colleagues are investigating an early type of antibiotic called polymixin, that was abandoned in the 1970s because of its kidney toxicity.

Their research, funded by the US National Institutes of Health, explores how polymixins work in the body and how bacteria respond to them, with the goal of making polymixins not only safer, but also more effective.

But their quest to resurrect a last-line drug such as polymixin is a sign of how dire the fight against antibiotic resistance has become.

Antibiotic resistance in bacteria is nothing new. Bacteria have been evolving mechanisms to deal with chemical attack since long before humans even existed, and resistance genes similar to those found today have been discovered in 30,000-year old preserved mammoths.

But, according to the World Health Organization, antibiotic resistance now poses a major threat to global health.

Our overuse and misuse of antibiotics have created a perfect storm of natural selection, driving a type of bacteria known as gram-negative bacteria to adapt furiously.

This means that for some diseases, in particular tuberculosis, bacteria are becoming resistant to multiple antibiotics, leaving doctors with dwindling choices for treating infections.

In some worst-case scenarios, which are mainly occurring in parts of the world where medical infrastructure is not as robust such as south-east Asia, India and Eastern Bloc countries, individuals are dying from total treatment failure because their infection is resistant to every antibiotic that is thrown at it.

Australia has escaped the worst of antibiotic resistance, although Associate Professor Tom Gottlieb says we are not immune.

“Every hospital and every infectious diseases specialist sees one or two people coming in with different varieties of resistant organisms,” says Gottlieb, a specialist in infectious diseases and microbiology at Sydney’s Concord Hospital, and president of Australian Society for Antimicrobials.

“Some are locally acquired in the community, some are patients in nursing homes which have a higher percentage of these, and some — particularly the more resistant strains — are coming from people who’ve travelled overseas.”

But resistance is just one part of the problem. Read more.

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