Combating AMR with phages

Afflictive bacteria have been the scourge of man but what is the bacterium's worst nightmare?

Effective antibiotics have been one of the pillars allowing us to live longer, live healthier, and benefit from modern medicine. Unless we take significant actions to improve efforts to prevent infections and also change how we produce, prescribe and use antibiotics, the world will lose more and more of these global public health goods. Based on current trends, the implications of AMR are bound to be devastating. Antimicrobial Resistance (AMR) which includes Antibiotic Resistance (AR), occurs when microorganisms (bacteria, fungi and parasites) adapt to the drug that is attempting to attack it and continue to multiply in its presence.

Since the discovery of the first antibiotic - penicillin - in 1928, subsequent antibiotic discoveries moved at a rapid pace, particularly from the 1940s to 1980s. Some notable discoveries include cephalosporins - a class of antibiotics structurally related to penicillin - in 1948, carbapenems in 1976 and fluoroquinolones - antibiotics used to treat urinary tract infections - in 1980. Athough antibiotics have transformed modern medicine and have saved millions of lives over the years, their overuse has been a main driver of antibiotic resistance. During the last 75 years, bacteria have shown the ability to become resistant to every antibiotic that has been developed. And the more antibiotics are used, the more quickly bacteria develop resistance.



The use of antibiotics at any time in any setting puts biological pressure on bacteria that promotes the development of resistance. When antibiotics are needed to prevent or treat disease, they should always be used. But research has shown that as much as 50% of the time, antibiotics are prescribed when they are not needed or they are misused (for example, a patient is given the wrong dose). This inappropriate use of antibiotics unnecessarily promotes Afflictive bacteria have been the scourge of man but what is the bacterium's worst nightmare? antibiotic resistance. One of many reasons why antibiotic use is so high is that there is a poor understanding of the differences between bacteria, viruses and other pathogens, and of the proper use and value of antibiotics. Antibiotics are very often prescribed for no useful purpose. Too many antibiotics are prescribed for viral infections such as colds, flu and diarrhea.



Surgery (elective and from trauma), cancer treatment (surgery and immunosuppressive therapy), intensive care, transplant surgery, even simple wound management would all become much riskier if we cannot use antibiotics to prevent infections, or treat infections if they occurred. Similarly, we now take it for granted that many infections are treatable with antibiotics, such as tonsillitis, gonorrhea and bacterial pneumonia. But some of these are now becoming untreatable. Excessive and incorrect use of antibiotics in foodproducing animals has also been a key player in drug resistance, since resistant bacteria can be transmitted to humans through the food we eat.

Antibiotics have saved countless lives throughout their long history in medicine but they are not without problems. Besides the looming terror of resistance, the use of antibiotics brings other concerns. For instance, although they destroy the bacteria that are causing disease, they also indiscriminately kill other species of bacteria. It is becoming ever clearer that our gut bacteria are an essential part of our health, and destroying them in huge numbers will have negative consequences. Antibiotics can also cause gastrointestinal distress - often because of the mass culling of bacteria. For these reasons, the hunt for alternatives to antibiotics is heating up.



Each year, drug-resistant infections kill around 7, 00,000 people worldwide, and by 2050, antibiotic resistant superbugs could end up killing around 10 million people, apart from increasing global healthcare costs by more than $1 trillion per year, according to recent research. A World Bank report analysing the economic threats of AMR also suggests a decline of 3.8% of world's annual GDP by 2050. In developing and tropical countries like India, Pakistan, Bangladesh, etc, the problem of antibiotic resistance is even more crucial as these countries bear a huge burden of infectious diseases as well. No wonder the World Health Organisation (WHO) describes the problem as one of the biggest threats to global health, food security, and development today.

The search for replacement antibiotics to combat multi-resistance has prompted researchers to explore new sources, including folk medicines - a field of study known as ethnopharmacology. A case in point is honey which has long been acknowledged for its antimicrobial properties. Traditional remedies containing honey were used in the topical treatment of wounds by diverse ancient civilisations. Manuka honey derived from nectar collected by honey bees foraging on the manuka tree in New Zealand is included in modern licensed wound-care products around the world. However, the antimicrobial properties of honey have not been fully exploited by modern medicine as its mechanisms of action are not yet known.

Microbiologists and pharmacologists are also focusing on environments where well-known antibiotic producers like Streptomyces can be found. And now preliminary trials have found that bacteriophages - viruses that infect bacteria - might be a viable replacement for antibiotics in the future. These ubiquitous viruses are found wherever bacteria exist and they are a bacterium's worst nightmare. It is estimated there are more than 1031 bacteriophages on the planet, more than every other organism on Earth, including bacteria, combined.

Although using a virus to fight off bacteria within our bodies might appear to be a risky idea, bacteriophages only attack bacteria, leaving human cells untouched. Also, they are highly specific to certain bacterial strains, meaning that there is no widespread cull of all species - neither good nor bad. Using viruses that infect only specific types of bacteria spares the many good bacteria in the gut, which are linked to numerous long-term beneficial health outcomes.

It has been shown in recent trials that bacteriophage treatment has no apparent side effects, at least with short-term use. Also, the potential uses for bacteriophage treatments go beyond gastrointestinal complaints. For instance, scientists are now exploring the use of bacteriophages in supplements to help restore balance in the microbiome of people with metabolic syndrome. These individuals typically have altered gut bacteria populations due to ongoing inflammation.

There may be a role for bacteriophages in developing countries where a significant number of people experience nutritional deficiencies due to chronic diarrhea. Interestingly, bacteriophages were used as antibacterial agents in the 1920s and '30s in the United States. One main reason that they fell out of favour was the advent of antibiotics, which were much easier to manufacture, store, and prescribe. But with the threat of antibiotic resistance rearing its head, a shift back toward bacteriophages might well be on the cards.