New ways to beating superbugs

As antibiotics become less effective, it’s time to invest in alternatives

Each month the Elsevier Atlas Award recognizes research that could significantly impact people's lives around the world.

March 2016 winner (free access)

Alternatives to antibiotics–a pipeline portfolio review

Lloyd Czaplewski, Richard Bax, Martha Clokie, Mike Dawson, Heather Fairhead, Vincent A Fischetti, Simon Foster, Brendan F Gilmore, Robert E W Hancock, David Harper, Ian R Henderson, Kai Hilpert, Brian V Jones, Aras Kadioglu, David Knowles, Sigríður Ólafsdóttir, David Payne, Steve Projan, Sunil Shaunak, Jared Silverman, Christopher M Thomas, Trevor J Trust, Peter Warn, John H Rex

The Lancet Infectious Diseases, Volume 16, Issue 2, February 2016, Pages 239-251.

Read the story about the award-winning research

There’s no question that antibiotics have and continue to save thousands of lives around the world each and every year. But, this staple of modern medicine is increasingly under threat by the rise of antibiotic resistant superbugs. Already, according to the World Health Organization, an estimated 25,000 people in the European Union alone die each year due to antibiotic-resistant infections acquired while in the hospital.

“As we often hear about in the news, we’re running out of effective antibiotics,” said Lloyd Czaplewski of Chemical Biology Ventures in the United Kingdom. “While we hope academics and industry will create new ones, it’s time to think about what the alternatives to traditional antibiotics might be.”

As a step in this direction, Czaplewski and his colleagues have conducted a review of the alternatives to antibiotics for treating serious, systemic infections, which was granted the Elsevier Atlas award of March 2016. As the review published in The Lancet Infectious Diseases shows, the quest for successful alternatives is limited primarily by funding, not a lack of options.

Traditional antibiotics are familiar drugs designed to target infectious bacteria. The most advanced alternatives include an array of approaches to prevent or treat infection by acting on the bacteria or its host, including vaccines, probiotics, and novel antibodies. Lesser known alternatives include viruses called bacteriophages that infect and kill bacteria or enzymes produced by bacteriophages that attack the bacterial cell wall.

The report shows that most of the research and development activity is focused on new methods to treat or prevent just a few serious and often life-threatening infections, including those caused by the bacteria Clostridium difficile, Pseudomonas aeruginosa, and Staphylococcus aureus. It’s also clear that, in the near term at least, alternatives to antibiotics are more likely to complement rather than replace traditional antibiotics.

The report commissioned by the Wellcome Trust and funded in part by the Department of Health, England, identified 19 current alternatives to antibiotics in all. Of those, the authors narrowed the list to 10 that appear most promising for immediate clinical or pre-clinical development.  While some of these approaches are on track to becoming available within the next five years, others will take longer.

Adequate testing to further explore which of the top 10 identified antibiotics alternatives are most likely to succeed will require a significant international investment, which the researchers estimate at £1.5 billion. They say that policy and funding must now be linked to address this pressing threat to global health.

“Without sufficient funding we can assume that new treatments to replace or supplement antibiotics will not be available, and the consequences of such a prolonged delay for global health-care systems needs to be considered now,” the authors write in their article. “Our analysis of just a subset of all activity that could contribute towards the fight against antimicrobial resistance suggests that funding is now the key limiting factor that is stalling a global response.”

A Conversation with Lloyd Czaplewski


In this podcast, we’re speaking with Atlas award-winner Lloyd Czaplewski of Chemical Biology Ventures in the U.K. about alternatives to antibiotics. The following has been edited for clarity and length.

Atlas: You point out that many of these alternatives to antibiotics aren’t all that new? Why hasn’t more progress been made?
Czaplewski: That’s a great question. Just because people think alternatives will work isn’t to say they will work in all or even any clinical setting. But I think it’s fair to say that we haven’t given them a proper chance. Few projects have gone to clinical studies. It can sometimes be quite a struggle to figure out how to use a new antibiotic. We have to invest more time, expertise, and resources to work out what the most useful alternatives might be and, once identified, how to use them.

Atlas: What needs to happen now?
Czaplewski: We use portfolio analysis to provide evidence for what we might expect to be delivered in the next ten to fifteen years. Only by having a good sense of what is likely, how much it will cost, and what it will take to see what impact (alternatives to antibiotics) might have in the immediate term can policymakers see if they think that’s an adequate impact or if we need to invest more to deliver more.

Atlas: How optimistic are you that timely progress can be made?
Czaplewski: We pulled a group together to look at alternatives used in challenging situations—not topical or superficial infections but life-threatening, systemic deep tissue infections where antibiotics transform outcomes. We recognize that alternatives will be used to treat wounds and ear infections and all uses will derive benefit and reduce the need for traditional antibiotics. What we’ve found in the case of life threatening infection is that alternatives most likely will be used initially as preventative measures or together with traditional antibiotics rather than as a replacement. It will take quite a bit longer to replace antibiotics.

Atlas: You note that the cost to adequately explore the alternatives will be somewhere between that of the Large Haldron Collider and the International Space Station. What led you to frame the cost in this way?
Czaplewski: We looked at the cost over the next decade to do a fair evaluation of the alternatives. It’s quite clear we’re talking about very substantial sums. This type of work will have to be done on an international basis. We will have to be coordinated to make it an efficient process rather than many people competing. Then we looked for examples where the international community has coordinated a successful effort. There are great examples of things like the International Space Station (which cost £96 billion) and the Large Haldron Collider (at £6 billion). So these things are doable. The question is one of framing the size, shape and duration of such an effort and then encouraging people to move in that direction.

About The Lancet Infectious Diseases

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WHO/Europe – Antimicrobial Resistance Data & Statistics (World Health Organization)

Review on Antimicrobial Resistance

Antibiotic Action

Chemical Biology Ventures

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