Bacteria lodged in Ella Balasa’s lungs were impervious to most antibiotics. At 26, gasping for breath, she sought out a dramatic experiment — inhaling a virus culled from sewage to attack her superbug.
“I’m really running out of options,” said Balasa, who traveled from Richmond, Va., to Yale University for the treatment.
Pitting one germ against another may sound radical. But increasingly people are dying of infections that once were easy to treat as many common bugs have evolved to withstand multiple antibiotics. Some are untreatable. Now scientists are racing to find alternatives to antibiotics, a hunt that is uncovering unusual ways to fight infection.
One possible treatment tricks bacteria out of a nutrient they need to survive. Others rev up the immune system. And viruses called bacteriophages — discovered a century ago but largely shelved in the West when easier-to-use antibiotics came along — are being tried in a handful of emergency cases.
“People’s frustration with antibiotic resistance boiled over,” said Yale biologist Benjamin Chan, who travels the world collecting phages. “We’re more appreciative of the fact that we need alternatives.”
Nature’s bacterial predator, each phage variety targets a different bacterial strain. It was originally used to treat dysentery in the early 20th century. Now Chan looks in ditches, ponds, and sewage treatment plants for types that attack human infections.
“The best places are often really dirty places, because we’re dirty animals,” he said.
At least 23,000 Americans die every year as a direct result of an antibiotic-resistant infection, and many more die from related complications, said a 2013 report from the Centers for Disease Control and Prevention. Other research has estimated the toll could be seven times higher.
And while there are no good counts in much of the world, one often-cited British report said unless solutions are found, by 2050 as many as 10 million people globally could be dying from drug-resistant infections, slightly more than die from cancer today.
Yet few new antibiotics make it to market, and many major drug companies have ended antibiotic research, seeing little profit in medicines that germs will soon outsmart. A recent report found just 11 traditional antibiotics are being studied to treat any of the World Health Organization’s list of worst bugs, with no guarantee they’ll work.
While some people are more at risk — those getting surgery or chemotherapy, for example — “antibiotic resistance is a problem essentially for everyone,” said Dr. Anthony Fauci, infectious diseases chief at the National Institutes of Health. “All indicators seem to point to the fact that this is going to get worse.”
Finding alternatives means “figuring out what the vulnerabilities of infecting bacteria are,” said Dr. Pradeep Singh.
Singh and fellow University of Washington lung specialist Dr. Christopher Goss zeroed in on iron, a nutrient vital for bacterial growth. It turns out that bugs can’t always tell the difference between iron and a chemically similar metal named gallium. Gallium doesn’t nourish and knocks other systems out of whack, Goss said.
For two small studies, researchers recruited cystic fibrosis patients who had antibiotic-resistant pseudomonas. The patients received a five-day infusion of a gallium-based drug. Over the next few weeks, their lung function improved, enough that next-step studies are being planned.
“It just seems like a proactive way of destroying bacteria,” said study participant Tre LaRosa, 24, of Cincinnati. “Antibiotic resistance I think is one of the least talked about and most significant concerns.”
Fauci envisions doctors one day vaccinating people before, say, a planned knee replacement to guard against catching a staph infection. Sixteen vaccines are in development to target various infections, according to a presentation to a presidential advisory council. Particularly promising, Fauci said, are lab-engineered “monoclonal antibodies” designed to home in on specific bugs.
In Virginia, Balasa had been keeping her infection in check with a daily dose of antibiotics. She has cystic fibrosis, which scars her lungs and traps bacteria, including superbug Pseudomonas aeruginosa. But then the drugs quit working. She learned of another CF patient helped by Yale’s phage experiments and asked to try, hoping to postpone the last option for CF, a lung transplant.
Phages work differently than traditional antibiotics. Like a parasite, the virus infiltrates bacterial cells and uses them to copy itself, killing the bug as those copies pop out and search for more bacteria. Once the infection is gone, the virus dies out. Because each phage only recognizes certain bacteria, it shouldn’t kill off “good bugs” in the digestive tract like antibiotics do.
Bacteria evolve to escape phages like they escape antibiotics, but they generally make trade-offs to do so — such as losing some of their antibiotic resistance, said Yale evolutionary biologist Paul Turner. “It’s reviving an arsenal of drugs that are no longer useful.”