The Need for New Antibiotics

07/03/2019

It is ironic that while the medical and veterinary professions are reducing their use of antibiotics, there is an urgent demand for new and more effective products.  These are especially required to treat drug resistant pathogens.  In 2017 the World Health Organization identified the need for antibiotics to counteract both critical and high-priority categories.  The critical category comprised effective drugs against carbapenem and cephalosporin-resistant pathogens including the genera Acinetobacter, Pseudomonas and Enterobacter.  Among the high priority category vancomycin and fluoroquiolone-resistant strains of the genera Camplyobacter, Salmonella and Enterococcus will require effective alternative drugs.  The WHO declared that the World is running out of functional antibiotics.  Accordingly, the Global Antibiotic Research and Development Partnership was established under the auspices of a “drugs for neglected diseases” program.  The Welcome Trust funded this collaboration comprising six EU nations and South Africa with a $70 million grant to establish new products.

 

The problem of antibiotic resistance is more pronounced in developing nations in part due to inappropriate and uncontrolled use in addition to the availability of local products with suboptimal concentration predisposing to emerging resistance.  Dr. Mya Nadimpalli conducting research at the Pasteur Institute determined that six percent of children presented to hospitals in Paris carried drug-resistant bacteria carrying genes coding for beta-lactamase.  In Cambodia where she conducted field studies, the prevalence rate of antibiotic resistance exceeded thirty percent Dr. Nadimpalli is now affiliated with the Tufts Center for Adaption Genetics and Drug Research, actively studying mechanisms of antibiotic resistance.

 

The Pew Charitable Trust issued a report in September 2018 emphasizing the dearth of candidate drugs in the antibiotic pipeline.  Of 42 prospects under development, major pharmaceutical companies were involved in only two of these compounds. Small start-up biotechnology companies are responsible for the majority of current antibiotic development, relying on venture capital and public sector funding. Achaogen a typical example, recently filed for bankruptcy.

 

The reasons for lack of development for new antibiotics relates to suboptimal financial return.  The cost of meeting regulatory requirements through a series of studies to demonstrate safety and efficacy are disproportionately high in relation to potential return.  New antibiotics have limited sales and a short market life compared to blockbuster drugs to treat cancer, cardiovascular disease and metabolic conditions.  It is estimated that only one in five candidate antibiotics is commercially successful even after considerable investment in development and testing.

 

Faced with the inevitability of emerging drug resistance and the need for new classes of antibiotics, alternative approaches to research and evaluation are required.  Lord O’Neill who chaired a UK parliamentary study on drug resistance suggested that development of new antibiotics should be undertaken by the public sector.  Antibiotics developed solely from government funding would be regarded as joint intellectual property and could be manufactured by generic drug companies. The price of these products would therefore not carry the costs of development now imposed on antibiotics of “last resort”.

 

Public-private consortia could be responsible for developing new products especially with a more realistic approach to evaluation.  The Global Antibiotic Research and Development Partnership participates in evaluating and promoting new antibiotics for pediatric infections.  Carb-X serves as a public-private partnership providing funding for basic antibiotic research especially directed to small companies that have developed basic concepts that require time and money to develop.

 

The livestock industry has been the beneficiary of human research with respect to antibiotics and antiparasitics since many pathogens are common to humans, livestock and companion animal species. Accordingly innovative models leading to the development of new drugs will ultimately benefit animals. Health professionals involved in livestock production should therefore encourage the development of new drugs as variations on novel classes for humans may have application in commercial production. Veterinarians in industrialized nations have reduced their use of antibiotics in responding to restrictions imposed by regulatory agencies in addition to ethical concerns. Practitioners in production medicine are relying more on vaccination, prebiotic, probiotic and botanical feed additives and are modifying ventilation, biosecurity, housing and management systems to reduce stress and promote an immune response. Notwithstanding these modalities, new antibacterial drugs are required against existing and emerging pathogens now and in the future.

 


















































































































































































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