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In January, Columbia University revealed that four patients at its Irving Medical Center in New York were suffering from an unusual version of the drug. E. coli , a common intestinal bacterium. Although the news has largely escaped the attention of the media, they have resounded among the world's experts in infectious diseases. E. coli is a relatively common and benign bacterium when it is in the gut, where it usually lives, but in the wrong places, like lettuce or ground beef, or our bloodstream, it can become deadly. When antibiotics have proven ineffective against a E. coli almost half of the patients who have the disease die within two weeks.
That's exactly why the Columbia E. coli was so disturbing. In the last two decades, E. coli has developed resistance to one antibiotic after the other. For some infected patients, their last hope is the antibiotic colistin, a toxic substance that can have adverse effects, including kidney and brain damage. Colombia E. coli had a mutation in a gene, MCR-1, which confers a terrifying attribute: imperviousness to colistin.
"We are looking for the next antibiotic and nothing is there," said Erica Shenoy, deputy chief of the infection control unit at Massachusetts General Hospital. "We are faced with the specter of patients with infections that we can not treat."
Since an experimental drug called penicillin, a miracle drug, was rushed to a Boston hospital in 1942 to save the lives of 13 victims of a nightclub fire, researchers said medicine have discovered more than 100 new antibiotics. We needed each of them – and they are not enough. This is not just E. coli . Drug-resistant strains of staphylococcus , Enterobacteriaceae and Clostridium difficile have consistently defeated antibiotics; a study found that the number of deaths from resistant infections had increased fivefold between 2007 and 2015. Recently, versions of the fungus resistant to treatment Candida auris have appeared in hospitals in New York and Chicago, killing half of the infected patients.
The US Centers for Disease Control and Prevention report that 2 million people a year are sick in the United States because of a bacterium or fungus resistant to major antibiotics and that 23,000 die from it. "It's probably a vast underestimate," says Karen Hoffman, who heads the Infection Prevention and Epidemiology Professionals Association. "We do not have a good reporting system for multidrug-resistant organisms, so we do not really know it." Studies suggest that the US health care system has a patient treatment cost of $ 3 billion a year.
This dark trend should accelerate. The World Health Organization predicts that the number of deaths from drug-resistant microbes in the world will rise from 700,000 per year to 10 million by 2050. At this stage, they will have overtaken cancer, diseases heart and diabetes to become the leading cause of death in Europe. human race. Before antibiotics, a small cut, tooth decay or routine operation could lead to a life-threatening bacterial infection. Penicillin, the "miracle drug" and other antibiotics have changed everything, saving countless lives over the years. But the age of the miracle drug seems to be ending.
Doctors are learning to identify and isolate already resistant insects in hopes of avoiding major epidemics. They are scrambling to strengthen the use of antibiotics to slow the development of resistant strains. It's too little, too late: the strategy will only save us time. At present, the oldest and weakest patients in hospitals are the most affected, but the risks are spreading. "We see healthy young people with urinary tract infections and skin that we do not have a pill on," says Helen Boucher, an infectious disease specialist at Tufts Medical Center in Boston. "And we may not be able to perform organ transplants, and even routine surgeries such as joint replacements. We should all be afraid. "
Medical experts base their hopes on entirely new strategies for treating infections. To find new ways to kill insects, they turn to exotic places – viruses and fish mud, even on other planets. They use the knowledge gained in genomics and other areas to develop new technologies to eliminate insects and prevent them from spreading. And they are reexamining practices in hospitals and other places of spread of bacteria, putting in place more comprehensive strategies for managing bacteria in our bodies as well as in our hospitals and doctor's offices.
The alternatives look promising, but they are far away. It is not obvious that we can invent new weapons before the super-insects, like an army of zombies at the doors, submerge our defenses.
"We need to invest heavily in other approaches," says Margaret Riley, a drug resistance researcher at the University of Massachusetts. "And we have to do it 15 years ago."
New bug hunters
Part of the problem with drug resistance is that microbes are evolving at an alarming rate to become new species. While a human needs 15 years or older to be mature enough to have offspring, microbes such as E. coli reproduce every 20 minutes. In a few years, they can go through an evolutionary change that would have taken humanity millions of years – a change that may include the acquisition of genetic attributes that allow them to resist drugs. A human under antibiotics is the ideal laboratory for developing resistant microbes. "Research shows that every time a new antibiotic comes into use, we start seeing the first resistant microbes about a year later," says Shenoy, of the mass general.
There is not much in the pharmaceutical pipeline to replace the antibiotics that the insects become resistant to. This is because developing a new antibiotic costs around $ 2 billion and takes about 10 years – with little hope of ending up with the type of star drug that justifies such an investment. "The purpose of a new antibiotic would be to use it as seldom as possible, as quickly as possible," says Jonathan Zenilman, head of the infectious diseases division at Johns Hopkins Bayview Medical Center in Baltimore. "Why would a pharmaceutical company want to develop a drug for a market like this?"
Medical researchers are now looking for other approaches. One is to recruit biologists with a flair for the theory of evolution in the war against insects. In the 1990s, Riley began Harvard and Yale to study how viruses kill bacteria and kill bacteria. In 2000, a colleague randomly asked him if the work could apply to human health. "I never thought of that," she says. "But everything suddenly clicked for me, and this question has consumed me."
For two decades, Riley has sought to apply the virus warfare strategy to the problem of resistant infections in humans. Viruses called "phages", which are essentially pieces of genetic material wrapped in a protective protein, will break through the cell wall of a bacterium and deflect its genetic mechanisms, turning the bacteria into a plant to produce more viruses. Riley is also studying how some bacteria sometimes kill other bacteria competing for food. A colony of bacteria sometimes eliminates a competitor by producing toxic proteins called "bacteriocins".
Riley's goal is not only to kill dangerous bacteria, but also to protect beneficial bacteria. Of the roughly 400 trillion bacteria that live in or on each of our bodies, the vast majority are helpful or benign – only 10 thousandths percent are potentially harmful, she says. The commonly used "broad spectrum" antibiotics such as penicillin, ciprofloxacin and tetracycline do not distinguish between good and bad bacteria – they all eliminate them. This not only contributes to the emergence of resistant bacteria, but also causes problems for patients.
"An antibiotic, it's like throwing an H bomb on an infection," says Riley. "You kill 50% or more of all the bacteria present in the body, and a deficiency of healthy bacteria is linked to obesity, depression, allergies and other problems." In contrast, phages and bacteriocins can be theoretically regulated to suppress a colony of bacteria causing infection in a patient, all without harming normal flora or creating a fertile breeding ground for insects. resistant.
ImmuCell, a biotechnology company based in Portland, Maine, has developed a bacteriocin that treats dairy cows for mastitis, a disease that costs the dairy industry $ 2 billion a year. According to Riley, laboratories like his can adapt phages and bacteriocins to virtually all types of microbial infection, with little risk of developing new resistance. "These are stable and robust killing mechanisms that evolved 2 billion years ago," she says.
Several clinical trials of phage therapy have already been successfully conducted in Poland, Georgia and Bangladesh. In the West, phage tests have been conducted against foot ulcers. No trials are underway for more serious infections, but successful phage treatment for an extremely multidrug-resistant patient in California in 2017 under the Emergency Rules of the Food and Drug Administration has more researchers in the United States seeking to develop phage treatments. According to Riley, one or more of them could be tested in the next few years, including one for multidrug-resistant tuberculosis and another for pulmonary infections in cystic fibrosis patients. . The bacteriocins are more late. The US government has promised to provide $ 2 billion to the development effort of these alternatives, "but it's far from enough," she says.
Cancer researchers are studying many drugs that can strengthen the immune system. These immunotherapies may help weakened patients fight against resistant insects that are trying to develop. Researchers produced human antibodies in cows and other animals that could be injected into patients. In an emergency effort, Harvard-affiliated Brigham and Women's Hospital in Boston announced that it had injected a combination of antibodies and antibiotics to rescue a patient with a drug-resistant infection, but the results have not been disclosed. Otherwise, little has been done to put in place a testing approach in infected patients. Researchers are also working on vaccines against resistant staphylococcal infections and other resistant bacteria, but these are only research efforts. "These non-antibiotic treatments are still in the early stages of the investigation," says David Banach, infection control manager at UConn Health Medical Center in Farmington, Connecticut. "But we have to keep thinking about new approaches."
Given the enormous urgency of the problem, why does it take so long to implement promising solutions towards testing and availability? Because there is little money in it, says Tufts's Boucher. The government is injecting billions of dollars into research, but private investment to turn this research into drugs and manufactured devices has not materialized. According to Boucher, pharmaceutical companies are unlikely to benefit from a drug that is unlikely to be taken by millions of people, or cost tens of thousands of dollars per dose. "The business model is broken," she says.
Manage bugs
Although antibiotics are really miracle drugs when they work, our current problems are due in part to the excessive dependence of medicine. Doctors prescribe them for ear infections, sore throats and urinary tract infections. Surgeons use them to prevent postoperative infections. Since bacteria can develop resistance, antibiotics are quite sensible as part of a holistic approach to managing the spread of bacteria and treating infections. As antibiotics begin to lose their usefulness, medical experts are increasingly emphasizing multi-pronged strategies for controlling insects.
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