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NEW HAVEN, Conn. (AP) – Bacteria buried deep in Ella Balasa's lungs were impervious to most antibiotics. At 26, out of breath, she looked for a dramatic experience: deliberately inhaling a virus taken from wastewater to attack her superbug.
"I'm really out of options," said Balasa, a native of Richmond, Va., Where Yale University is located for the treatment of last resort. "I know it might not have an effect. But I am very optimistic. "
Pricking one seed against another may seem radical, but it's a sign of a growing global crisis. More and more people are dying of infections that were once easy to treat because many common insects have now evolved to resist many antibiotics. Some, called "nightmarish bacteria", are incurable. Today, scientists are working to find new alternatives to traditional antibiotics, a hunt that reveals unusual ways to fight infection in unusual places.
A possible treatment removes bacteria from a nutrient they need to survive. Others strengthen the immune system to better fight germs.
And viruses called bacteriophages – discovered a century ago, but largely unresolved in the West with the arrival of antibiotics easier to use – are being tested in a handful of cases. ;emergency.
"People's frustration with antibiotic resistance has come down," said Benjamin Chan, a biologist at Yale, who travels the world collecting phages and is receiving calls from desperate patients asking to try them. "We are more aware of the fact that we need alternatives."
As a bacterial predator of nature, each variety of phage targets a different bacterial strain. Originally used to treat dysentery in the early 20th century, Chan now seeks out places such as ditches, ponds and, yes, in sewage treatment plants for types that attack a variety of human infections.
"The best places are often really dirty places because we are dirty animals," he said.
Chan hoped that Balasa was in a laboratory bowl covered with brownish bacterial mud.
Balasa has a genetic disease called cystic fibrosis that heals the lungs and traps bacteria, including a superbug called Pseudomonas aeruginosa. A daily dose of inhaled antibiotics helped control the infection until last fall, when the drugs stopped working. An antibiotic of last resort IV did not help much either.
Chan developed a sample of Balasa bacteria from his phlegm. Then came the key test: he flushed several phages targeting pseudomonas into the dirty dish – and clear circles appeared as the viruses consumed the insects around them.
But what worked in the lab would really help Balasa's lungs?
BUGS OUTPUT PRODUCTS
According to a 2013 report by the Centers for Disease Control and Prevention, at least 23,000 Americans die each year from an antibiotic-resistant infection and many others die from related complications. The CDC anticipates an updated count, but other research has estimated that the toll could be seven times higher.
And while there are no good numbers in most of the world, a British report often quoted said that if solutions were not found, by 2050, 10 million people Worldwide could die of drug-resistant infections, a little more than cancer today.
However, few new antibiotics are coming to the market and many large pharmaceutical companies have ended antibiotic research, saying that the drugs that sprouts would not make profitable would soon be more advantageous than others. A recent report found that only 11 traditional antibiotics were being studied to treat one of the worst bacteria in the World Health Organization, with no guarantee of their effectiveness.
And while some people are at higher risk – those who undergo cancer surgery or chemotherapy, for example, "antibiotic resistance is a problem for everyone," said Dr. Anthony Fauci, head of infectious diseases at the National Institutes of Health.
"Over the next few years, all the indicators seem to indicate that the situation will get worse," he added.
LOOKING FOR LOW POINTS OF BUGS
Finding alternatives means "determining what are the vulnerabilities of an infecting bacteria. What do they need to cause an infection? Said Dr. Pradeep Singh of the University of Washington.
Singh and his lung specialist, Dr. Christopher Goss, have targeted iron, a nutrient essential for bacterial growth. It turns out that insects can not always tell the difference between iron and a chemically similar metal called gallium. Gallium does not feed and knock out other systems, says Goss.
For two small studies, the researchers recruited patients with cystic fibrosis whose lungs had an antibiotic-resistant pseudomonas, but were not overtly sick. Patients received a five-day infusion of a gallium-based drug. Over the next few weeks, their lung function has improved, enough for next-stage studies to be planned.
"It just seems to be a proactive way to kill the bacteria," said Tre LaRosa, a 24-year-old participant in the Cincinnati study. His sister died of cystic fibrosis and, although his own CF are under control, he fears that one day a resistant infection will occur. "I can not do anything to prevent that. I think antibiotic resistance is one of the least serious and important concerns. "
DYNAMIZING THE IMMUNE SYSTEM
Fauci envisions that doctors vaccinate a day a few weeks before, for example, a planned replacement of the knee to guard against staph infection in the hospital.
Sixteen experimental vaccines are under development to target various infections, according to a recent presentation to a Presidential Advisory Council on resistant germs.
According to Fauci, "monoclonal antibodies" designed in the laboratory are particularly promising and designed to fight against specific insects. In a series of studies, researchers have administered experimental antibodies to ventilated patients who have an accumulation of bacteria that could trigger pneumonia.
SHOOTING VIRUSES FOR GOOD ATTACK
In Virginia, Balasa learned that another cystic fibrosis patient, assisted by Yale's experiments on a phage, had asked to try, in hopes of postponing the last option for cystic fibrosis, a lung transplant.
Phage work very differently from traditional antibiotics. Like a parasite, the virus infiltrates into bacterial cells and uses them to copy itself, which kills the virus when these copies come out and look for other bacteria. Once the infection is gone, the virus turns off. Each phage recognizes only certain bacteria, it must not kill the "good insects" of the digestive tract, unlike antibiotics.
Bacteria evolve to escape both phages and antibiotics, but they usually make compromises, for example by losing some of their antibiotic resistance, said Yale's evolution biologist, Paul Turner.
For example, some phages recognize bacteria through a pump on their surface that deflects antibiotics. While phages kill these insects, bacteria evolve rapidly to get rid of this pump on the surface – meaning that survivors should again be sensitive to antibiotics.
"It's about restoring an arsenal of drugs that are no longer useful," Turner said.
The first case of Yale's test was an 82-year-old man about to die of a heart implant full of incurable pseudomonas. Mr. Chan purified a phage from a Connecticut lake that he compared to the patient's germs. With the urgent permission of the Food and Drug Administration, doctors injected him into the wound. The infection of the man has disappeared.
Then, doctors at the University of California at San Diego rescued a colleague who was in a coma for several months using an intravenous mixture of several phages that targets a superbacterium called Acinetobacter baumannii.
Doctors and families began calling both centers for emergency care, even though official studies were underway to try to prove the value of phages.
"There is an incredible opportunity here," said Yale's pulmonologist Dr. Jon Koff. "But with that, you must have the proper skepticism," with careful testing to find out when it might help.
Last month, Balasa became Yale's eighth patient, inhaling billions of phages in seven days.
Almost immediately, she spat fewer bacteria. It took her a few weeks to feel better, and during that time she briefly used antibiotics she had already abandoned. Without a formal study, it is difficult to know, but Chan's tests suggest that phages have killed much of its predominant pseudomonas strain and made survivors sensitive again to taking these antibiotics.
Balasa called it "very successful for me" and managed to stop his antibiotics. She did not notice any further improvement after a second set of phages targeting different strains.
"The real test," said Balasa, "is the time during which I can continue to use antibiotics again."
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The Associated Press Health and Science Department receives support from the Howard Hughes Medical Institute's Department of Science Education. The AP is solely responsible for all content.
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