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Antimicrobial Resistance: Forging A New Strategy Against an Old Threat

Antimicrobial resistance (AMR) is sadly not a new threat, and despite Alexander Fleming’s warnings about resistant bacteria rising up because of the frequent and misuse of antibiotics,1 only fairly recently have individuals truly started to pay attention. Not only is there a growing threat of resistant bacteria, but the development of new antibiotics has been woefully insufficient. A recent report found that “of the drugs in development, only 12 have the potential to address the most critical Gram-negative pathogens on the World Health Organization’s antibiotic-resistant priority pathogens list: carbapenem-resistant Enterobactericaeae, Pseudomonas aeruginosa, and Acinetobacter baumanii (see Table for the complete list.)

Furthermore, bacteria resistant to 1 antibiotic in a class are more likely to be resistant to others in that class and only approximately 1 in 4 antibiotics represent new drug classes or mechanisms of action to combat bacteria that are constantly evolving.”2

The challenges of drug research and development are startling in light of the predictions for AMR: 10 million deaths worldwide per year by 2050 and $100 trillion lost between now and then in terms of global production.3 Current data indicate that there are approximately 23,000 deaths in the United States already each year, and about $20 billion in excess direct health care costs (see Figure).

What is to be done? There are several initiatives, like the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator (CARB-X), that seek to infuse life into the research and development of new drugs. There is also a push on health care providers and agriculture to reduce the use of antimicrobials. But these are all long-term solutions that may take years or decades to implement. Although long-term plans are critical, if you were hospitalized today with a highly resistant infection, what would be the short-term plan of action your heath care providers would take?

One strategy that’s gathering momentum as an alternative to antibiotics is the use of bacteriophages (or phages), which are viruses that infect good bacteria and use them to produce more phages that continue the assault on the bacteria. Phages replicate quickly, and phage therapy is becoming a more viable approach because it has a narrow host range. This may not sound like a good thing, but the very specific bacterial targeting that certain phages have (and more phages exist than stars in the universe) means they can be used for a targeted approach. Not all bacteria are bad, and part of the problem so frequently seen with infections, like Clostridium difficile, is that antibiotics kill off a lot of good bacteria in the process of killing the bad. Phage therapy has the capacity to selectively kill specific bacteria within an ocean of bacteria. Harnessing phages that can attack certain bacteria with almost laser-like precision is exactly what is needed in when tackling resistant bacteria. Imagine a room full of people with 1 villain. Would you rather have a sniper capable of taking out just the villain or a shotgun that could potentially harm innocent bystanders? Phage therapy has a sniper-like selectivity that makes it extremely effective, but without the negative adverse effects so often seen with antibiotics.