Alternatives to antibiotics not a short-term solution to drug-resistant infections

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A handful of alternatives to antibiotics – such as treatments and preventative measures based on live microorganisms or ‘probiotics’ – have the potential to combat bacterial infections in the next decade, but they are unlikely to replace traditional antibiotics.

A new report assesses whether alternatives to antibiotics could contribute to controlling the rise of drug-resistant infections, one of the greatest global public health threats of our time.

The findings strongly suggest that alternatives will not be a solution to the problem of drug-resistant infections in the immediate future. Traditional antibiotics continue to be the best way of fighting bacterial infection, and we must do all we can to preserve the effectiveness of existing antibiotics and invent new ones.

Probiotics are the only alternative treatment likely to receive product approval in the next decade, although they will only be able to treat very specific infections. Unlike popular probiotics regularly taken by healthy people, these would be probiotic treatments specifically tailored for people with defined conditions and available only with medical oversight.

Other possible alternative therapeutics are progressing more slowly. Along with vaccines, probiotics are also expected to have a role in the prevention of infections.

The authors of the independent report, commissioned by the Wellcome Trust and co-funded by the Department of Health, consulted a wide range of experts who identified novel non-antibiotic approaches that will most likely deliver new options for the treatment and prevention of infections within the next 10 years.

The report makes a conservative estimate that £1.5 billion is needed over the next 10 years to develop the key alternatives to antibiotics and demonstrate their clinical efficacy. The cost of alternatives is a small part of a much bigger effort that is needed from international governments and funders to tackle drug-resistant infections, which includes developing new diagnostics, refreshing the pipeline for traditional antibiotics and international policy changes.

The report focusses on substitutes to antibiotic compounds that target either the bacteria themselves or the host organism. The authors reviewed agents that could be taken orally, by inhalation or by injection to treat invasive bacterial infections.

Nineteen alternatives to antibiotics were identified that are actively being progressed, several in Phase II or Phase III trials. The most advanced novel therapies are probiotic-based treatments for Clostridium difficile, a common cause of diarrhoea, for which the report estimates there will be product approval within the next decade. This treatment uses live bacteria that benefit the digestive system to tackle the C. difficile infection.

The most advanced preventative alternatives include probiotics for prevention of C. difficile infection and novel antibodies for prevention of bacterial infections caused by the bacteria Staphylococcus aureus and Pseudomonas aeruginosa.

Other potential alternatives to antibiotics, either treatments or prevention strategies, are progressing more slowly and include bacteriophages (viruses that infect and kill bacteria) and lysins (enzymes produced by bacteriophages that digest the cell wall of bacteria). While both have potential to replace the use of some antibiotics, the therapies may be limited to targeting only one bacterial species at a time.

Antibiotic ‘enhancers’, which use alternative therapies in combination with antibiotics, could also be useful to improve treatment, but insufficient research makes development less likely in the near term.

Dr Lloyd Czaplewski, Director of Abgentis Limited and co-author of the report said, “We are at the end of a 70-year era of life-saving antibiotics being readily available, and we are now faced with a generational challenge. The search for new antibiotics and alternatives to antibiotics needs to be on the same scale as other international endeavours in science, like CERN and the Francis Crick Institute. It is vitally important that the global community commits to developing new therapies in the next decade and beyond.”

Dr Mike Turner, Head of Infection and Immunobiology at the Wellcome Trust said, “Drug-resistant infections are one of the greatest threats to our health, and with limited antibiotics available we must find effective solutions rapidly. Some alternative therapies look promising and may contribute to addressing the problem in the longer term. This report clearly shows however, that conventional antibiotics will still be necessary. Our current cost estimates may be conservative given the scale of the problem, and levels of funding are likely to have a significant impact on global response.”

The report, Alternatives to antibiotics: a pipeline portfolio review, is published in The Lancet Infectious Diseases.