On November 5th, 2010, 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.”
Although the article focused on action to be initiated at the federal level, individual businesses can and must play a part as well. It is clear that a set of steps should be followed in order to extend the functional life of our antibiotic arsenal.
First, Big Agriculture must immediately stop and assess the use of antibiotics as additives to the feed of 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 last 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.
Next, waste-management businesses 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, pharmaceutical businesses must undertake more research to provide us with safe and effective antibiotics utilizing new mechanisms without the development of 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 pharmaceutical manufacturers decide to 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, the pharmaceutical and biotech industries must be encouraged 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 bugs. Bugs love to share survival mechanisms.
Overall, businesses 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. Businesses 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.
Ron Najafi, PhD is chairman and CEO of NovaBay Pharmaceuticals, Inc., an Emeryville, CA-based biotechnology company developing anti-infective compounds for the treatment and prevention of antibiotic-resistant infections. He can be reached at rnajafi@novabaypharma.com.
