Opinion: 5 ways to save antibiotics

The world is linkurl:facing a crisis:;http://www.the-scientist.com/news/display/55951/ Bacteria have become linkurl:more and more resistant;http://www.the-scientist.com/news/display/53982/ to virtually all existing antibiotics, yet many companies are abandoning the field in favor of more lucrative medicines.

Ron Najafi
Image: NovaBay

People are proposing various solutions, such as offering financial incentives to the pharmaceutical industry to linkurl:spur the development of vitally needed antibiotics.;http://www.the-scientist.com/article/display/57352/ But along with creating new drugs, we can get more life from our existing antibiotics and maintain their utility. 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. In my opinion, there are five ways we can extend the functional life of our antibiotic arsenal.1. Do the obvious In a recent linkurl:New York Times;http://www.nytimes.com/2010/11/06/health/policy/06germ.html article, linkurl:Ramanan Laxminarayan,;http://www.rff.org/Researchers/Pages/ResearchersBio.aspx?ResearcherID=41 director of the linkurl:Extending the Cure;http://www.extendingthecure.org/ project on antibiotic resistance at the policy organization linkurl:Resources for the Future,;http://www.rff.org/Pages/default.aspx suggested that the government should 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.These are crucial steps, which should be taken immediately. First, we must 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. The U.S. Congress has already 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. A recent linkurl:CBS news report spotlighted microbiologist Stuart Levy;http://www.cbsnews.com/stories/2010/07/16/eveningnews/main6685734.shtml at Tufts University, the individual who identified tetracycline resistance in chickens more than 30 years ago. In his research, nearly all of the E. coli in the intestinal tracts of the chickens become tetracycline-resistant after one week of treatment.2. Assess the impact Sub-lethal quantities of antibiotics are known to create an environment for the development of resistance and multi-drug resistance mechanisms. We need to monitor the fate of all the mega-quantities of antibiotics sold as prescriptions and as over-the-counter medicine: 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?

NovaBay scientist at work
Image: NovaBay

3. Explore entirely different drugs We must look for antibiotics utilizing new mechanisms without the development of resistance. Simply adding new drugs to existing classes isn't cutting it. My company is developing a new class of agents with a novel mechanism of action that kills pathogens without the potential for resistance. These are fast acting, broad-spectrum, multi-targeting agents that do not persist in the environment.Confirmatory experiments in our labs are slated for publication in 2011. The preliminary experiments indicate that our linkurl:Aganocide compounds;http://www.novabaypharma.com/investors/release/Oct_25_2010_Impetigo_trial exert their activity against pathogens by the rapid and preferential inactivation of specific amino acid residues on essential membrane proteins, such as ATP machinery or ion channels which are located on the membrane of the bacteria. However, this machinery is protected inside of the mammalian cells. The consequence of this inactivation induces a change in the protein's tertiary structures and results in dysfunction, dysregulation or protein shedding from the membranes of pathogens. The end result is a fast-acting, broad-spectrum antimicrobial agent that is safe to mammalian cells within a therapeutics window. We continue to confirm these findings and integrate these observations into the elucidation of the mechanism of action as we develop this new class of antimicrobial agents. 4. Inactivate multiple essential targets When we attack bacteria with agents targeted against one particular cellular mechanism -- for example, fluoroquinolones target DNA gyrase -- the bugs simply select for a mutation to that mechanism that make them resistant, and the agent becomes ineffective. This will always be true of targeted agents, so we wind up with more of these agents every few years. We urgently need a parallel initiative in the development of multi-target agents, such as non-antibiotic agents that can inactivate essential protein targets that mutations cannot sidestep, and are not damaging to human tissues. As stated above, our company is currently pursuing multi-target agents. Subtle and selective multi-target agents to which bacteria cannot develop mutational resistance are the key to solving this huge problem. They are pivotal for our survival and should have fast-track consideration by all agencies. 5. Encourage and incentivize the industry 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. 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. Otherwise, the overall result will be fewer effective drugs to treat bad bugs. Ron Najafi, PhD is chairman and CEO of linkurl:NovaBay Pharmaceuticals, Inc (NBY).,;http://www.novabaypharma.com/company/profile an Emeryville, California-based biotechnology company developing anti-infective compounds for the treatment and prevention of antibiotic-resistant infections. He can be reached at rnajafi@novabaypharma.com.
**__Related stories:__***linkurl:MRSA: RIP?;http://www.the-scientist.com/news/display/53982/
[11th December 2007] *linkurl:Rising plague;http://www.the-scientist.com/news/display/55951/
[27th August 2009] *linkurl:Garden of antimicrobial delights;http://www.the-scientist.com/article/display/57352/
[May 2010]

Opinion: 5 ways to save antibiotics

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