Bacteriophages, or bacteria eaters, exist abundantly on land – in water and within any form of life harbouring bacteria. There are believed to be ten million trillion trillion more bacteriophages than any other organism on earth, including bacteria, and each is evolved to infect only one or a few types of bacteria.

By taking over the reproductive machinery of the bacteria, they replicate themselves and destroy the bacterial cell, splitting it open and allowing the new viral cells to continue the process.

Phage therapy was actually discovered in the 1900s. Nonetheless, the results were inconsistent and lacked scientific validation. Following the emergence of antibiotics, it was quickly abandoned everywhere, except in Eastern Europe and the Soviet Union.

Now, however, the ever-pressing need for a successful alternative to antibiotics means it is being revived. Just in September, the World Health Organisation (WHO) warned that the world is running out of antibiotics.

“There is an urgent need for more investment in research and development… otherwise we will be forced back to a time when people feared common infections and risked their lives from minor surgery,” expressed WHO Director-General Dr Tedros Adhanom Ghebreyesus.

Phage therapy needed in two dire cases

Bacteriophages (green) attacking a bacterium (orange). Photo credit: Graham Beards/UC San Diego Health
Bacteriophages (green) attacking a bacterium (orange). Photo credit: Graham Beards/UC San Diego Health

The first is Tom Patterson, a 69-year-old professor of Psychiatry at the University of California San Diego School of Medicine. Patterson became infected with a multidrug-resistant strain of Acinetobacter baumannii, in November 2015.

Whilst he initially began to recover, it was on the last day before his discharge that an internal drain designed to localise his infection – and keep it at bay – slipped, spilling bacteria into his abdomen and bloodstream. Immediately experiencing septic shock, Patterson went into coma for two months.

Remembering a colleague who had a friend who underwent Phage therapy – and was “miraculously cured” – his wife, Steffanie Strathdee, chief of the Division of Global Public Health at the University of California, enlisted the help of colleague Chip Schooley, and together they found centres with phages, that had the potential to cure Patterson.

Following purification of the phage samples and obtaining of emergency approval from the US Food and Drug Administration (FDA), the phages were introduced through catheters into Patterson’s abdominal cavity and intravenously to address a broader, systemic infection.

No-one knew what to expect.

Three days later, Patterson awoke and while some of the bacteria developed resistance in what Schooley called “the recurring Darwinian dance”, the team compensated by continually tweaking treatment with new phage strains. A year later, Patterson was allowed to go home.

“As a treating doctor, it was a challenge,” remarked Schooley. “Usually, you know what the dosage should be, how often to treat. Improving vital signs is a good way to know that you’re progressing. But, when you’re doing it for the first time, you don’t have anything to compare it to.”

The second patient is only 25

Having suffered from cystic fibrosis her whole life, Mallory Smith had a lung transplant but Burkholderia cepacia bacteria from her old lungs were still clinging to the crevices of her upper airways.

About a month later they had migrated to her chest, giving her pneumonia and significantly reducing her chances of survival. Hearing the story of Patterson, Smith’s father contacted Strathdee, who agreed to help.

Pulling together a team with great difficulty, Strathdee and Smith are now trying to find the right phage and get the treatment approved legally. “The length of time that the idea [of phage therapy] has been around, and the fact that we don’t have it yet, tells us that it’s really tough to do,” highlighted Dr John LiPuma, a professor of paediatrics at the University of Michigan, who directs a lab and repository dedicated to Burkholderia cepacia.

Diane Shader Smith, Mallory’s mother says, “I want this to save my daughter’s life – but if it doesn’t, I sure as hell want to figure this all out, so it can save others.”

The far-reaching potential in Phage treatment

Researchers from Spain and Portugal have found that bacteriophage can be used in fish farming. The targeted method kills the problem bacteria, but leaves those in the fish’s intestinal tract. In addition, there was almost no impact on bacterial ecology or human health. It also significantly reduced the environmental impact of fish farms, whilst increasing their profitability since it reduced the mortality of the fish.

Although, there are currently phase one studies happening in Australia, they are not planning for phase two trials until the second half of 2018. Therefore, despite the promise of phage therapy, it is important to remember that the WHO predicts that by 2050, at least 50 million people will be killed every year by the growing threat of antibacterial resistance. Therefore, doctors should remain vigilant and cautious in their prescription of antibiotics. MIMS

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