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Tag: bacterial infections

  • No antibiotics worked, so this woman turned to a natural enemy of bacteria to save her husband's life | CNN

    No antibiotics worked, so this woman turned to a natural enemy of bacteria to save her husband's life | CNN

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    CNN
     — 

    In February 2016, infectious disease epidemiologist Steffanie Strathdee was holding her dying husband’s hand, watching him lose an exhausting fight against a deadly superbug infection.

    After months of ups and downs, doctors had just told her that her husband, Tom Patterson, was too racked with bacteria to live.

    “I told him, ‘Honey, we’re running out of time. I need to know if you want to live. I don’t even know if you can hear me, but if you can hear me and you want to live, please squeeze my hand.’

    “All of a sudden, he squeezed really hard. And I thought, ‘Oh, great!’ And then I’m thinking, ‘Oh, crap! What am I going to do?’”

    What she accomplished next could easily be called miraculous. First, Strathdee found an obscure treatment that offered a glimmer of hope — fighting superbugs with phages, viruses created by nature to eat bacteria.

    Then she convinced phage scientists around the country to hunt and peck through molecular haystacks of sewage, bogs, ponds, the bilge of boats and other prime breeding grounds for bacteria and their viral opponents. The impossible goal: quickly find the few, exquisitely unique phages capable of fighting a specific strain of antibiotic-resistant bacteria literally eating her husband alive.

    Next, the US Food and Drug Administration had to greenlight this unproven cocktail of hope, and scientists had to purify the mixture so that it wouldn’t be deadly.

    Yet just three weeks later, Strathdee watched doctors intravenously inject the mixture into her husband’s body — and save his life.

    Their story is one of unrelenting perseverance and unbelievable good fortune. It’s a glowing tribute to the immense kindness of strangers. And it’s a story that just might save countless lives from the growing threat of antibiotic-resistant superbugs — maybe even your own.

    “It’s estimated that by 2050, 10 million people per year — that’s one person every three seconds — is going to be dying from a superbug infection,” Strathdee told an audience at Life Itself, a 2022 health and wellness event presented in partnership with CNN.

    “I’m here to tell you that the enemy of my enemy can be my friend. Viruses can be medicine.”

    sanjay pkg vpx

    How this ‘perfect predator’ saved his life after nine months in the hospital

    During a Thanksgiving cruise on the Nile in 2015, Patterson was suddenly felled by severe stomach cramps. When a clinic in Egypt failed to help his worsening symptoms, Patterson was flown to Germany, where doctors discovered a grapefruit-size abdominal abscess filled with Acinetobacter baumannii, a virulent bacterium resistant to nearly all antibiotics.

    Found in the sands of the Middle East, the bacteria were blown into the wounds of American troops hit by roadside bombs during the Iraq War, earning the pathogen the nickname “Iraqibacter.”

    “Veterans would get shrapnel in their legs and bodies from IED explosions and were medevaced home to convalesce,” Strathdee told CNN, referring to improvised explosive devices. “Unfortunately, they brought their superbug with them. Sadly, many of them survived the bomb blasts but died from this deadly bacterium.”

    Today, Acinetobacter baumannii tops the World Health Organization’s list of dangerous pathogens for which new antibiotics are critically needed.

    “It’s something of a bacterial kleptomaniac. It’s really good at stealing antimicrobial resistance genes from other bacteria,” Strathdee said. “I started to realize that my husband was a lot sicker than I thought and that modern medicine had run out of antibiotics to treat him.”

    With the bacteria growing unchecked inside him, Patterson was soon medevaced to the couple’s hometown of San Diego, where he was a professor of psychiatry and Strathdee was the associate dean of global health sciences at the University of California, San Diego.

    “Tom was on a roller coaster — he’d get better for a few days, and then there would be a deterioration, and he would be very ill,” said Dr. Robert “Chip” Schooley, a leading infectious disease specialist at UC San Diego who was a longtime friend and colleague. As weeks turned into months, “Tom began developing multi-organ failure. He was sick enough that we could lose him any day.”

    Patterson's body was systemically infected with a virulent drug-resistant bacteria that also infected troops in the Iraq War, earning the pathogen the nickname

    After that reassuring hand squeeze from her husband, Strathdee sprang into action. Scouring the internet, she had already stumbled across a study by a Tbilisi, Georgia, researcher on the use of phages for treatment of drug-resistant bacteria.

    A phone call later, Strathdee discovered phage treatment was well established in former Soviet bloc countries but had been discounted long ago as “fringe science” in the West.

    “Phages are everywhere. There’s 10 million trillion trillion — that’s 10 to the power of 31 — phages that are thought to be on the planet,” Strathdee said. “They’re in soil, they’re in water, in our oceans and in our bodies, where they are the gatekeepers that keep our bacterial numbers in check. But you have to find the right phage to kill the bacterium that is causing the trouble.”

    Buoyed by her newfound knowledge, Strathdee began reaching out to scientists who worked with phages: “I wrote cold emails to total strangers, begging them for help,” she said at Life Itself.

    One stranger who quickly answered was Texas A&M University biochemist Ryland Young. He’d been working with phages for over 45 years.

    “You know the word persuasive? There’s nobody as persuasive as Steffanie,” said Young, a professor of biochemistry and biophysics who runs the lab at the university’s Center for Phage Technology. “We just dropped everything. No exaggeration, people were literally working 24/7, screening 100 different environmental samples to find just a couple of new phages.”

    While the Texas lab burned the midnight oil, Schooley tried to obtain FDA approval for the injection of the phage cocktail into Patterson. Because phage therapy has not undergone clinical trials in the United States, each case of “compassionate use” required a good deal of documentation. It’s a process that can consume precious time.

    But the woman who answered the phone at the FDA said, “‘No problem. This is what you need, and we can arrange that,’” Schooley recalled. “And then she tells me she has friends in the Navy that might be able to find some phages for us as well.”

    In fact, the US Naval Medical Research Center had banks of phages gathered from seaports around the world. Scientists there began to hunt for a match, “and it wasn’t long before they found a few phages that appeared to be active against the bacterium,” Strathdee said.

    Dr. Robert

    Back in Texas, Young and his team had also gotten lucky. They found four promising phages that ravaged Patterson’s antibiotic-resistant bacteria in a test tube. Now the hard part began — figuring out how to separate the victorious phages from the soup of bacterial toxins left behind.

    “You put one virus particle into a culture, you go home for lunch, and if you’re lucky, you come back to a big shaking, liquid mess of dead bacteria parts among billions and billions of the virus,” Young said. “You want to inject those virus particles into the human bloodstream, but you’re starting with bacterial goo that’s just horrible. You would not want that injected into your body.”

    Purifying phage to be given intravenously was a process that no one had yet perfected in the US, Schooley said, “but both the Navy and Texas A&M got busy, and using different approaches figured out how to clean the phages to the point they could be given safely.”

    More hurdles: Legal staff at Texas A&M expressed concern about future lawsuits. “I remember the lawyer saying to me, ‘Let me see if I get this straight. You want to send unapproved viruses from this lab to be injected into a person who will probably die.’ And I said, “Yeah, that’s about it,’” Young said.

    “But Stephanie literally had speed dial numbers for the chancellor and all the people involved in human experimentation at UC San Diego. After she calls them, they basically called their counterparts at A&M, and suddenly they all began to work together,” Young added.

    “It was like the parting of the Red Sea — all the paperwork and hesitation disappeared.”

    The purified cocktail from Young’s lab was the first to arrive in San Diego. Strathdee watched as doctors injected the Texas phages into the pus-filled abscesses in Patterson’s abdomen before settling down for the agonizing wait.

    “We started with the abscesses because we didn’t know what would happen, and we didn’t want to kill him,” Schooley said. “We didn’t see any negative side effects; in fact, Tom seemed to be stabilizing a bit, so we continued the therapy every two hours.”

    Two days later, the Navy cocktail arrived. Those phages were injected into Patterson’s bloodstream to tackle the bacteria that had spread to the rest of his body.

    “We believe Tom was the first person to receive intravenous phage therapy to treat a systemic superbug infection in the US,” Strathdee told CNN.

    “And three days later, Tom lifted his head off the pillow out of a deep coma and kissed his daughter’s hand. It was just miraculous.”

    Patterson awoke from a coma after receiving an intravenous dose of phages tailored to his bacteria.

    Today, nearly eight years later, Patterson is happily retired, walking 3 miles a day and gardening. But the long illness took its toll: He was diagnosed with diabetes and is now insulin dependent, with mild heart damage and gastrointestinal issues that affect his diet.

    “He isn’t back surfing again, because he can’t feel the bottoms of his feet, and he did get Covid-19 in April that landed him in the hospital because the bottoms of his lungs are essentially dead,” Strathdee said.

    “As soon as the infection hit his lungs he couldn’t breathe and I had to rush him to the hospital, so that was scary,” she said. “He remains high risk for Covid but we’re not letting that hold us hostage at home. He says, ‘I want to go back to having as normal life as fast as possible.’”

    To prove it, the couple are again traveling the world — they recently returned from a 12-day trip to Argentina.

    “We traveled with a friend who is an infectious disease doctor, which gave me peace of mind to know that if anything went sideways, we’d have an expert at hand,” Strathdee said.

    “I guess I’m a bit of a helicopter wife in that sense. Still, we’ve traveled to Costa Rica a couple of times, we’ve been to Africa, and we’re planning to go to Chile in January.”

    Patterson’s case was published in the journal Antimicrobial Agents and Chemotherapy in 2017, jump-starting new scientific interest in phage therapy.

    “There’s been an explosion of clinical trials that are going on now in phage (science) around the world and there’s phage programs in Canada, the UK, Australia, Belgium, Sweden, Switzerland, India and China has a new one, so it’s really catching on,” Strathdee told CNN.

    Some of the work is focused on the interplay between phages and antibiotics — as bacteria battle phages they often shed their outer shell to keep the enemy from docking and gaining access for the kill. When that happens, the bacteria may be suddenly vulnerable to antibiotics again.

    “We don’t think phages are ever going to entirely replace antibiotics, but they will be a good adjunct to antibiotics. And in fact, they can even make antibiotics work better,” Strathdee said.

    In San Diego, Strathdee and Schooley opened the Center for Innovative Phage Applications and Therapeutics, or IPATH, in 2018, where they treat or counsel patients suffering from multidrug-resistant infections. The center’s success rate is high, with 82% of patients undergoing phage therapy experiencing a clinically successful outcome, according to its website.

    Schooley is running a clinical trial using phages to treat patients with cystic fibrosis who constantly battle Pseudomonas aeruginosa, a drug-resistant bacteria that was also responsible for the recent illness and deaths connected to contaminated eye drops manufactured in India.

    And a memoir the couple published in 2019 — “The Perfect Predator: A Scientist’s Race to Save Her Husband From a Deadly Superbug” — is also spreading the word about these “perfect predators” to what may soon be the next generation of phage hunters.

    VS Phages Sanjay Steffanie

    How naturally occurring viruses could help treat superbug infections

    “I am getting increasingly contacted by students, some as young as 12,” Strathdee said. “There’s a girl in San Francisco who begged her mother to read this book and now she’s doing a science project on phage-antibiotic synergy, and she’s in eighth grade. That thrills me.”

    Strathdee is quick to acknowledge the many people who helped save her husband’s life. But those who were along for the ride told CNN that she and Patterson made the difference.

    “I think it was a historical accident that could have only happened to Steffanie and Tom,” Young said. “They were at UC San Diego, which is one of the premier universities in the country. They worked with a brilliant infectious disease doctor who said, ‘Yes,’ to phage therapy when most physicians would’ve said, ‘Hell, no, I won’t do that.’

    “And then there is Steffanie’s passion and energy — it’s hard to explain until she’s focused it on you. It was like a spiderweb; she was in the middle and pulled on strings,” Young added. “It was just meant to be because of her, I think.”

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  • Someday, You Might Be Able to Eat Your Way Out of a Cold

    Someday, You Might Be Able to Eat Your Way Out of a Cold

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    When it comes to treating disease with food, the quackery stretches back far. Through the centuries, raw garlic has been touted as a home treatment for everything from chlamydia to the common cold; Renaissance remedies for the plague included figs soaked in hyssop oil. During the 1918 flu pandemic, Americans wolfed down onions or chugged “fluid beef” gravy to keep the deadly virus at bay.

    Even in modern times, the internet abounds with dubious culinary cure-alls: apple-cider vinegar for gonorrhea; orange juice for malaria; mint, milk, and pineapple for tuberculosis. It all has a way of making real science sound like garbage. Research on nutrition and immunity “has been ruined a bit by all the writing out there on Eat this to cure cancer,” Lydia Lynch, an immunologist and a cancer biologist at Harvard, told me.

    In recent years, though, plenty of legit studies have confirmed that our diets really can affect our ability to fight off invaders—down to the fine-scale functioning of individual immune cells. Those studies belong to a new subfield of immunology sometimes referred to as immunometabolism. Researchers are still a long way off from being able to confidently recommend specific foods or dietary supplements for colds, flus, STIs, and other infectious illnesses. But someday, knowledge of how nutrients fuel the fight against disease could influence the way that infections are treated in hospitals, in clinics, and maybe at home—not just with antimicrobials and steroids but with dietary supplements, metabolic drugs, or whole foods.

    Although major breakthroughs in immunometabolism are just now arriving, the concepts that underlie them have been around for at least as long as the quackery. People have known for millennia that in the hours after we fall ill, our appetite dwindles; our body feels heavy and sluggish; we lose our thirst drive. In the 1980s, the veterinarian Benjamin Hart argued that those changes were a package deal—just some of many sickness behaviors, as he called them, that are evolutionarily hardwired into all sorts of creatures. The goal, Hart told me recently, is to “help the animal stay in one place and conserve energy”—especially as the body devotes a large proportion of its limited resources to igniting microbe-fighting fevers.

    The notion of illness-induced anorexia (not to be confused with the eating disorder anorexia nervosa) might seem, at first, like “a bit of a paradox,” says Zuri Sullivan, an immunologist at Harvard. Fighting pathogenic microbes is energetically costly—which makes eating less a very counterintuitive choice. But researchers have long posited that cutting down on calories could serve a strategic purpose: to deprive certain pathogens of essential nutrients. (Because viruses do not eat to acquire energy, this notion is limited to cell-based organisms such as bacteria, fungi, and parasites.) A team led by Miguel Soares, an immunologist at the Instituto Gulbenkian de Ciência, in Portugal, recently showed that this exact scenario might be playing out with malaria. As the parasites burst out of the red blood cells where they replicate, the resulting spray of heme (an oxygen-transporting molecule) prompts the liver to stop making glucose. The halt seems to deprive the parasites of nutrition, weakening them and tempering the infection’s worst effects.

    Cutting down on sugar can be a dangerous race to the bottom: Animals that forgo food while they’re sick are trying to starve out an invader before they themselves run out of energy. Let the glucose boycott stretch on too long, and the dieter might develop dangerously low blood sugar —a common complication of severe malaria—which can turn deadly if untreated. At the same time, though, a paucity of glucose might have beneficial effects on individual tissues and cells during certain immune fights. For example, low-carbohydrate, high-fat ketogenic diets seem to enhance the protective powers of certain types of immune cells in mice, making it tougher for particular pathogens to infiltrate airway tissue.

    Those findings are still far from potential human applications. But Andrew Wang, an immunologist and a rheumatologist at Yale, hopes that this sort of research could someday yield better clinical treatments for sepsis, an often fatal condition in which an infection spreads throughout the body, infiltrating the blood. “It’s still not understood exactly what you’re supposed to feed folks with sepsis,” Wang told me. He and his former mentor at Yale, Ruslan Medzhitov, are now running a clinical trial to see whether shifting the balance of carbohydrates and lipids in their diet speeds recovery for people ill with sepsis. If the team is able to suss out clear patterns, doctors might eventually be able to flip the body’s metabolic switches with carefully timed doses of drugs, giving immune cells a bigger edge against their enemies.

    But the rules of these food-illness interactions, to the extent that anyone understands them, are devilishly complex. Sepsis can be caused by a whole slew of different pathogens. And context really, really matters. In 2016, Wang, Medzhitov, and their colleagues discovered that feeding mice glucose during infections created starkly different effects depending on the nature of the pathogen driving disease. When the mice were pumped full of glucose while infected with the bacterium Listeria, all of them died—whereas about half of the rodents that were allowed to give in to their infection-induced anorexia lived. Meanwhile, the same sugary menu increased survival rates for mice with the flu.

    In this case, the difference doesn’t seem to boil down to what the microbe was eating. Instead, the mice’s diet changed the nature of the immune response they were able to marshal—and how much collateral damage that response was able to inflict on the body, as James Hamblin wrote for The Atlantic at the time. The type of inflammation that mice ignited against Listeria, the team found, could imperil fragile brain cells when the rodents were well fed. But when the mice went off sugar, their starved livers started producing an alternate fuel source called ketone bodies—the same compounds people make when on a ketogenic diet—that helped steel their neurons. Even as the mice fought off their bacterial infections, their brain stayed resilient to the inflammatory burn. The opposite played out when the researchers subbed in influenza, a virus that sparks a different type of inflammation: Glucose pushed brain cells into better shielding themselves against the immune system’s fiery response.

    There’s not yet one unifying principle to explain these differences. But they are a reminder of an underappreciated aspect of immunity. Surviving disease, after all, isn’t just about purging a pathogen from the body; our tissues also have to guard themselves from shrapnel as immune cells and microbes wage all-out war. It’s now becoming clear, Soares told me, that “metabolic reprogramming is a big component of that protection.” The tactics that thwart a bacterium like Listeria might not also shield us from a virus, a parasite, or a fungus; they may not be ideal during peacetime. Which means our bodies must constantly toggle between metabolic states.

    In the same way that the types of infections likely matter, so do the specific types of nutrients: animal fats, plant fats, starches, simple sugars, proteins. Like glucose, fats can be boons in some contexts but detrimental in others, as Lynch has found. In people with obesity or other metabolic conditions, immune cells appear to reconfigure themselves to rely more heavily on fats as they perform their day-to-day functions. They can also be more sluggish when they attack. That’s the case for a class of cells called natural killers: “They still recognize cancer or a virally infected cell and go to it as something that needs to be killed,” Lynch told me. “But they lack the energy to actually kill it.” Timing, too, almost certainly has an effect. The immune defenses that help someone expunge a virus in the first few days of an infection might not be the ones that are ideal later on in the course of disease.

    Even starving out bacterial enemies isn’t a surefire strategy. A few years ago, Janelle Ayres, an immunologist at the Salk Institute for Biological Studies, and her colleagues found that when they infected mice with Salmonella and didn’t allow the rodents to eat, the hungry microbes in their guts began to spread outside of the intestines, likely in search of food. The migration ended up killing tons of their tiny mammal hosts. Mice that ate normally, meanwhile, fared far better—though the Salmonella inside of them also had an easier time transmitting to new hosts. The microbes, too, were responding to the metabolic milieu, and trying to adapt. “It would be great if it was as simple as ‘If you have a bacterial infection, reduce glucose,’” Ayres said. “But I think we just don’t know.”

    All of this leaves immunometabolism in a somewhat chaotic state. “We don’t have simple recommendations” on how to eat your way to better immunity, Medzhitov told me. And any that eventually emerge will likely have to be tempered by caveats: Factors such as age, sex, infection and vaccination history, underlying medical conditions, and more can all alter people’s immunometabolic needs. After Medzhitov’s 2016 study on glucose and viral infections was published, he recalls being dismayed by a piece from a foreign outlet circulating online claiming that “a scientist from the USA says that during flu, you should eat candy,” he told me with a sigh. “That was bad.”

    But considering how chaotic, individualistic, and messy nutrition is for humans, it shouldn’t be a surprise that the dietary principles governing our individual cells can get pretty complicated too. For now, Medzhitov said, we may be able to follow our instincts. Our bodies, after all, have been navigating this mess for millennia, and have probably picked up some sense of what they need along the way. It may not be a coincidence that during viral infections, “something sweet like honey and tea can really feel good,” Medzhitov said. There may even be some immunological value in downing the sick-day classic, chicken soup: It’s chock-full of fluid and salts, helpful things to ingest when the body’s electrolyte balance has been thrown out of whack by disease.

    The science around sickness cravings is far from settled. Still, Sullivan, who trained with Medzhitov, jokes that she now feels better about indulging in Talenti mango sorbet when she’s feeling under the weather with something viral, thanks to her colleagues’ 2016 finds. Maybe the sugar helps her body battle the virus without harming itself; then again, maybe not. For now, she figures it can’t hurt to dig in.

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    Katherine J. Wu

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  • Bacterial Infections to Blame for 1 in Every 8 Deaths Worldwide

    Bacterial Infections to Blame for 1 in Every 8 Deaths Worldwide

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    By Dennis Thompson 

    HealthDay Reporter

    TUESDAY, Nov. 22, 2022 (HealthDay News) — Bacterial infections are to blame for 1 in 8 deaths and are second only to heart disease as the world’s leading cause of death, a new report reveals.

    About 7.7 million people died in 2019 from infection with one of 33 common types of bacteria, according to the report published Nov. 21 in The Lancet. That’s nearly 14% of deaths for that year.

    More than 75% of bacteria-related deaths came from one of three illnesses – lower respiratory infections, bloodstream infections and abdominal infections, the study authors said.

    And five specific and generally well-known germs — Staphylococcus aureus, Escherichia coli, Streptococcus pneumoniae, Klebsiella pneumoniae, and Pseudomonas aeruginosa — were responsible for more than half the deaths from bacterial infection.

    The pathogen associated with the most deaths globally was S. aureus, with 1.1 million deaths. This bacteria causes “staph” infections that can lead to pneumonia and sepsis.

    The four other bacteria were each associated with more than a half-million deaths: E. coli (950,000 deaths); S. pneumoniae (829,000); K. pneumoniae (790,000); and P. aeruginosa (559,000), the researchers reported.

    More deaths were linked to S. aureus and E. coli each than HIV/AIDS in 2019, which killed 864,000 people.

    Despite this, the investigators noted that HIV research received $42 billion in funding compared to $800 million for E. coli research.

    “These new data for the first time reveal the full extent of the global public health challenge posed by bacterial infections,” said co-researcher Dr. Christopher Murray, director of the Institute for Health Metrics and Evaluation at the University of Washington School of Medicine, in Seattle.

    “It is of utmost importance to put these results on the radar of global health initiatives so that a deeper dive into these deadly pathogens can be conducted and proper investments are made to slash the number of deaths and infections,” Murray said in a journal news release.

    The bacterial infection death rate varied by location. Sub-Saharan Africa had the highest, with 230 deaths for every 100,000 people. By comparison, Western Europe, North America and Australasia had a combined rate of 52 deaths per 100,000.

    The germs associated with the most deaths also differed by age.

    S. aureus caused the most deaths in people 15 or older, while Salmonella enterica serovar Typhi killed the most 5- to 14-year-olds. Meanwhile, pneumonia bacteria killed the most children under 4 years of age.

    More information

    Harvard Medical School has more on how to prevent infections.

     

    SOURCE: The Lancet, news release, Nov. 21, 2022

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