|Five Important Steps for Extending the Life of the World’s Arsenal of Antibiotics|
|By Ron Najafi, PhD|
|Wednesday, 24 November 2010 08:12|
On November 5th, The New York Times ran an article by Andrew Pollack titled “Antibiotics Research Subsidies Weighed by U.S.” It reported that government officials are considering offering financial incentives to the pharmaceutical industry to spur the development of vitally needed antibiotics.Such proposals, Pollack writes, “have taken on more urgency as bacteria steadily become resistant to virtually all existing drugs at the same time that a considerable number of pharmaceutical giants have abandoned this field in search of more lucrative medicines.”
One of the most interesting opinions in the article came from Ramanan Laxminarayan, director of the Extending the Cure project on antibiotic resistance at the policy organization Resources for the Future. He notes that the government could focus on conserving the effectiveness of existing antibiotics by preventing their unnecessary use in people and farm animals and by requiring better infection control measures in hospitals.
As the head of a company focused on the development of compounds to treat and prevent a wide range of infections without causing bacterial resistance, this is an issue I find both fascinating and vitally important. Based on my experience in the field, five steps must be followed in order to extend the functional life of our antibiotic arsenal.
First, we must immediately stop and assess the use of antibiotics as additives to the feed of our farm animals, and specifically prevent the unnecessary use of antibiotics in animals that are not sick. This is an important part of making the public more aware of the excessive use of antibiotics and the associated potential health risks. In a CBS News report that aired on July 16, Katie Couric highlighted the overuse of antibiotics in farm animals. Congress has urged farmers to stop the overuse of antibiotics in animals because it is creating new, drug-resistant strains of bacteria that can spread to humans. The CBS report spotlighted Dr. Stuart Levy, the individual who identified tetracycline resistance in chickens more than 30 years ago. In that case, nearly all of the E. coli in the intestinal tracts of the chickens became tetracycline-resistant after one week of treatment.
Next, we should immediately assess and monitor the impact of antibiotics entering our public and farm waste-management systems. Research must be undertaken now regarding the ultimate impact of antibiotics in the environment. Sub-lethal quantities of antibiotics are known to create an environment for the development of resistance and multi-drug resistance mechanisms. The fast replication cycles of bacteria coupled with the mistakes made during replication give these pathogens a Darwinian advantage in responding to and overcoming antibiotic drug pressures. We need to monitor the fate of all the mega-quantities of polysporin, Neosporin and Bacitracin that are consumed off the store shelves: Do they end up in our wastewater systems and landfills and become a breeding ground for new superbugs? What happens to the groundwater runoff from farms, sewage systems and landfills? We need to understand the fate and ramifications of antibiotics in our wastewater and runoff systems.
Third, we must undertake more research to provide us with safe and effective antibiotics utilizing new mechanisms without the development of resistance. My company is developing a new class of agents with a novel mechanism of action that kills pathogens without showing resistance. Unfortunately, developing additional antibiotics in existing classes of compounds that are showing drug resistance may not help. This is because bugs that have developed a resistance to a member of a specific class of drug—e.g. the fluoroquinolone class of antibiotics, like Cipro—can apply the same resistance mechanism to the rest of that class. Resistance mechanisms can also be transferred to other bacteria, making the resistance issue a larger problem. A recent example of the latter is the case of the New Delhi metallo-beta-lactamase (NDM-1) resistance.
Fourth, when we attack bacteria with agents targeted against one particular cellular mechanism—for example, the way that the fluoroquinolones target DNA gyrase—the bugs simply mutate that mechanism to make it resistant, and then pass the mutation around until all bugs are resistant and the agent is useless. This will always be true of targeted agents, so we need more of these agents every few years, and limiting their use in agriculture (including aquaculture) is a great idea. We urgently need a parallel initiative in the development of multi-target agents that attack so many targets that the bugs cannot sidestep them. All bacteria are susceptible to phenol and chlorhexidine, even though these compounds have been used since Florence Nightingale. The trick, with multi-target agents, is to make sure that the human host is not one of the targets. Consequently, we need subtle agents that attack multiple bacterial targets, while being non-damaging to human tissues. Subtle and selective multi-target agents are the key to solving this huge problem. Bacteria cannot develop mutational resistance to them, and we understand the biofilm problems that confer non-mutational resistance to them. As a result, they are pivotal for our survival and should have fast-track treatment by all agencies.
Finally, we should encourage and incentivize the pharmaceutical and biotech industry to develop safe and effective non-antibiotic anti-infectives that could replace all topical antibiotics for eyes, skin, ear, over-the-counter antibiotics, etc. Once a topical antibiotic develops resistance, that resistant gene will find its way into all sorts of pathogenic bacteria. Bacteria love to share survival mechanisms.
Overall, we need to understand the sources of antibiotic resistance—whether it originates in farms, sewers, landfills, or other locations—and find ways to save our precious few antibiotics for systemic blood-borne infections. We also must aim for appropriate use of antibiotics in humans and in our farm animals, have a better understanding and guidelines for infection control, and strongly encourage antibiotic stewardship. Otherwise, the overall result will be fewer effective drugs to treat bad bugs.
About the Author
Ron Najafi, PhD is chairman and CEO of NovaBay Pharmaceuticals, Inc (Amex:NBY)., an Emeryville, CA-based biotechnology company developing anti-infective compounds for the treatment and prevention of antibiotic-resistant infections. He can be reached at [email protected]