The enemy of my enemy is my friend: bacteria and bacteriophages
If you were a clumsy kid like I was, you are probably very familiar with infections. I tripped on everything imaginable and scraped my knees more times than I could count. If that wasn’t bad enough, I loved picking on scabs, reopening the wounds, and inevitably getting an infection.
Invasion of bacteria into our body is one of the most common causes of disease in the world. When it comes to fighting infections, it helps to know the invading enemy well. What is the enemy’s weakness? What is different between our enemy and our own cells? Antibiotics are the products of this self vs. other concept – some drugs target bacterial-specific cell walls, ribosomes, and biosynthetic pathways. These drugs allow us to selectively injure the invading pathogen without harming our own cells. However, misuse and overuse of antibiotics have led to rise in pathogens that are now resistant to these drugs.
Searching for novel antibiotics can combat antibiotics-resistance, but we have another trick up our sleeves. Bacteria have a natural enemy – the bacteriophages (literally meaning “eaters of bacteria”) that have evolved to kill bacteria with exquisite specificity, which we can harness as a source of therapy. The concept of phage therapy is not new, but the safety and efficacy in humans, especially when given IV, are not well understood.
Researchers in the Westmead Bacteriophage Therapy Team in Australia sought to test the safety of bacteriophage therapy in a severe systemic blood infection called bacteremia. Bacteremia caused by the Staphylococcus aureusbacterium is associated with 30-day mortality of approximately 15%; this mortality rate is almost doubled when it infects the heart (infective endocarditis).
In a single-arm non-comparative clinical trial, researchers recruited 13 patients between the ages of 21 to 87 year with S. aureusbacteremia. 6 patients had confirmed infective endocarditis. AB-SA01, a cocktail of 3 highly concentrated phages, was intravenously administered twice a day for 14 days to all patients who were already on antibiotics. Signs of toxicity were monitored for 90 days. No new fevers, rashes, diarrhea, signs of kidney or liver damage were reported during the monitoring period, suggesting that AB-SA01 phage therapy is safe and well tolerated.
The treatment efficacy was hard to address in this study. 8 of 13 patients (62%) showed clinical improvement within 14 days and 5 (38%) died within 28 days. One died during a surgical procedure, three died after phage therapy was discontinued, and one died a few weeks after a surgical procedure. S. aureusobtained from blood throughout the treatment period show no sign of resistance to phage therapy. These are very complex cases with multiple interventions. The treatment efficacy was hard to interpret because of a large number of variables, lack of a comparison group, small cohort size, and the study was designed to evaluate safety rather than mortality. However, the safety and tolerability data presented in this study is exciting and provides a first step towards testing the efficacy in a larger clinical trial.
See primary article at: https://www.nature.com/articles/s41564-019-0634-z
By Than Kyaw