How Scientists are Fighting Drug-Resistant Superbugs with Phages (cnn.com) 39
"It's ridiculous just how virulent some of these bacteria get over time," says Dwayne Roach, assistant professor of bacteriophages, infectious disease and immunology at San Diego State University.
But now CNN says doctors are fighting multi-drug-resistant superbugs with "nature's oldest predators — tiny tripod-looking viruses called phages designed to find, attack and gobble up bacteria." The microscopic creatures have saved the lives of patients dying from superbug infections and are being used in clinical trials as a potential solution to the growing problem of antibiotic resistance...
In labs around the country, phage scientists are taking research and discovery to the next level... [Yale scientists] are busy mapping which phages and antibiotics are most symbiotic in the fight against a pathogen. Roach's San Diego State lab is investigating the body's immune response to phages while developing new phage purification techniques to prepare samples for intravenous use in patients. Currently, clinical trials are underway to test the effectiveness of phages against intractable urinary tract infections, chronic constipation, joint infections, diabetic foot ulcers, tonsillitis and the persistent, reoccurring infections that occur in patients with cystic fibrosis. The chronic infections common in cystic fibrosis are typically due to various strains of drug-resistant Pseudomonas aeruginosa — the same pathogen responsible for Horton's ear infection and the artificial tears outbreak.
A number of labs are developing libraries of phages, stockpiled with strains found in nature that are known to be effective against a particular pathogen. In Texas, a new facility is taking that a step further — speeding up evolution by creating phages in the lab. "Rather than just sourcing new phages from the environment, we have a bioreactor that in real time creates billions upon billions of phages," said Anthony Maresso, associate professor at Baylor College of Medicine in Houston. "Most of those phages won't be active against the drug-resistant bacteria, but at some point there will be a rare variant that has been trained, so to speak, to attack the resistant bacteria, and we'll add that to our arsenal," Maresso said. "It's a next-generation approach on phage libraries." Maresso's lab published a study last year on the treatment of 12 patients with phages customized to each patient's unique bacterial profile. It was a qualified success: The antibiotic-resistant bacteria in five patients were eradicated, while several more patients showed improvements.
"There's a lot of approaches right now that are happening in parallel," Roach said. "Do we engineer phages? Do we make a phage cocktail, and then how big is the cocktail? Is it two phages or 12 phages? Should phages be inhaled, applied topically or injected intravenously? There's a lot of work underway on exactly how to best do this...." Genetically engineering phages would allow scientists to target each person's unique mix of antibiotic-resistant pathogens instead of searching sewage, bogs, ponds, the bilge of boats and other prime breeding grounds for bacteria to find just the right phage for the job.
Along with phage libraries, genetic engineering is also a key to churning out phages in mass, to distribute on a wider scale. In Russia and the country of Georgia, where phage therapy has been used for decades, patients can buy phage cocktails off the shelf in pharmacies.
But now CNN says doctors are fighting multi-drug-resistant superbugs with "nature's oldest predators — tiny tripod-looking viruses called phages designed to find, attack and gobble up bacteria." The microscopic creatures have saved the lives of patients dying from superbug infections and are being used in clinical trials as a potential solution to the growing problem of antibiotic resistance...
In labs around the country, phage scientists are taking research and discovery to the next level... [Yale scientists] are busy mapping which phages and antibiotics are most symbiotic in the fight against a pathogen. Roach's San Diego State lab is investigating the body's immune response to phages while developing new phage purification techniques to prepare samples for intravenous use in patients. Currently, clinical trials are underway to test the effectiveness of phages against intractable urinary tract infections, chronic constipation, joint infections, diabetic foot ulcers, tonsillitis and the persistent, reoccurring infections that occur in patients with cystic fibrosis. The chronic infections common in cystic fibrosis are typically due to various strains of drug-resistant Pseudomonas aeruginosa — the same pathogen responsible for Horton's ear infection and the artificial tears outbreak.
A number of labs are developing libraries of phages, stockpiled with strains found in nature that are known to be effective against a particular pathogen. In Texas, a new facility is taking that a step further — speeding up evolution by creating phages in the lab. "Rather than just sourcing new phages from the environment, we have a bioreactor that in real time creates billions upon billions of phages," said Anthony Maresso, associate professor at Baylor College of Medicine in Houston. "Most of those phages won't be active against the drug-resistant bacteria, but at some point there will be a rare variant that has been trained, so to speak, to attack the resistant bacteria, and we'll add that to our arsenal," Maresso said. "It's a next-generation approach on phage libraries." Maresso's lab published a study last year on the treatment of 12 patients with phages customized to each patient's unique bacterial profile. It was a qualified success: The antibiotic-resistant bacteria in five patients were eradicated, while several more patients showed improvements.
"There's a lot of approaches right now that are happening in parallel," Roach said. "Do we engineer phages? Do we make a phage cocktail, and then how big is the cocktail? Is it two phages or 12 phages? Should phages be inhaled, applied topically or injected intravenously? There's a lot of work underway on exactly how to best do this...." Genetically engineering phages would allow scientists to target each person's unique mix of antibiotic-resistant pathogens instead of searching sewage, bogs, ponds, the bilge of boats and other prime breeding grounds for bacteria to find just the right phage for the job.
Along with phage libraries, genetic engineering is also a key to churning out phages in mass, to distribute on a wider scale. In Russia and the country of Georgia, where phage therapy has been used for decades, patients can buy phage cocktails off the shelf in pharmacies.
All I can say is (Score:4, Funny)
It's pretty obvious these scientists never watched Star Trek: Voyager.
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I guess it makes sense (Score:2)
The issue with drug-resistant bacteria is that they evolve (pretty quickly) to resist drugs. If the thing we use to fight bacteria also evolves, I suppose that has a better chance of keeping up.
Providing, of course, that nothing goes wrong and we don't accidentally breed a phage that thinks human brain cells are simply yummy...
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Providing, of course, that nothing goes wrong and we don't accidentally breed a phage that thinks human brain cells are simply yummy...
Not to worry, nature already has that covered [clevelandclinic.org].
Re:I guess it makes sense (Score:4, Insightful)
If you use drug A then they evolve to survive A.
If you use a cocktail of drug A and drug B they evolve to survive A and B.
If you cease using drug A and only use drug B their evolution optimizes to survive B and may give up some protection against A since it is no longer present.
Repeat by rotating out drugs A, B, C, D, E, F, G, ... (and introducing new ones) and you can continually attack bacteria like the enterprise modulating their phasors.
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And in fact evolutionary biologists have documented this happening in nature - cycles of predator and prey adaptation and counter-adaptation repeating continually.
Once you've figured it out (or had it explained to you), it's obvious.
However, 'obvious' has only a small effect on human behaviour so we're going to continue to use everything all the time to maximize antibiotic resistance in the wild and minimize antibiotic effectiveness. And while I'd LOVE to blame doctors who prescribe antibiotics for viral i
Re:I guess it makes sense (Score:4, Insightful)
> I believe farmers are a much better primary target if we're going to try and stop the self-defeating stupidity.
It is the farmers. Once they learned otherwise healthy farm animals on antibiotics grew faster and larger it was game over. Proper regulation is required.
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Then they include antibiotics in most animal feed as standard. Apparently, it's difficult to find agricultural animal feed without antibiotics. Then they cram the animals into sheds in close proximity to each other, wallowing in their own filth. Some of the animals die & the corpse
Re: I guess it makes sense (Score:1)
Re:I guess it makes sense (Score:5, Informative)
Providing, of course, that nothing goes wrong and we don't accidentally breed a phage that thinks human brain cells are simply yummy...
That is not really how phages work. They are incredibly selective. Also they have been around forever and so far they have not attacked our brains. I mean, there are not any cases of bacteriophages somehow "evolving" to attach human cells. There may be viruses that attack brain cells but they evolved independently.
Phages were apparently discovered by inference. Biologists noticed that sometimes a "plaque" would form in the colony of bacteria they were trying to grow on a petri dish. Basically, a spot of dead bacteria that would spread out radially and kill the whole bacterial colony. They inferred something was "eating" the bacteria. A bacteria eater, or bacteriophage.
Incidentally, last time I looked into it, it seemed like the most advanced phage therapy was happening in the former Soviet state of Georgia. Not sure if that is still the case. I always said that if I ever got infected by anti-biotic resistant flesh eating bacteria, I would get on the first plane to Georgia.
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Indeed, the main problem is that they're too selective. So you have to have a massive archive of available phages to be able to target a specific infection, because minor differences between bacteria render them useless. Except that this runs up against a regulatory environment where each new treatment - including each new phage - requires trials and clinical approval. The combination of these two things has made it very difficult to bring phage treatments into practice.
But if the phages are well matched
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Incidentally, last time I looked into it, it seemed like the most advanced phage therapy was happening in the former Soviet state of Georgia. Not sure if that is still the case.
I remember having seen a BBC Horizon documentary on scientists in the republic of Georgia using bacteriaphages to fight drug resistant viral infections. Just tried to look it up. It seems that episode is on Youtube: Antibiotic Resistance - The Virus that Cures - BBC Horizon [youtu.be].
Amazed that documentary is already 27 years old.
Uh stupid (Score:2)
Bacteria can resist phages too. There’s a reason bacteria still exist. This phage war is just as ancient as the war bacteria have had against antibiotics. You realize that, right?
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Sure it's called evolution but it's an incredibly almost famously slow process whereas "we have a bioreactor that in real time creates billions upon billions of phages," is kinda turbo boosting the whole idea.
The doctors caused this problem (Score:5, Insightful)
How about this: Stop prescribing an antibiotic every time someone gets the sniffles? I know when a patient comes in the doctor knows the person is there to get a script. If the doctor doesn't give the patient a prescription, the patient is likely to go somewhere else and get one. The doctor will lose a recurring revenue stream.
Doctors need to grow some morals and ethics and stop this completely self inflicted problem.
Every time a doc gives me a prescription for antibiotics, I end up throwing it away (I've never filled one). The doc has never tested me for any specific bacteria, he just writes me a prescription. Doesn't seem to care if I have a virus. if I did develop a serious bacterial infection that started to get out of control, he doesn't have any idea whether or not the antibiotic he picked would be effective against it.
This truly is American medicine. Figure out a way to plug the symptom with another pill rather than fixing the root cause. However, I bet the treatments will be stupidly profitable for the medical community.
It's sad that the medical community created these horrible antibiotic resistant bugs, and now they are killing people. The medical community has no sense of remorse for the people they have killed or the damage they have done. We went from no antibiotics to this in how many years? My cause of death will most likely be cancer or a man made super bug. If one of these man made super bugs develops high airborne transmission, it might make Covid look like a joke.
(I know. Animal antibiotics, without a legitimate need, also need to stop.)
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Naa. That would be, I don't know, "smart and responsible"? That does not mesh with greed and not getting paid when you are sick.
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"The doc has never tested me for any specific bacteria", did you think there's a specific antibiotic for each strain of infectious bacteria? A broad spectrum antibiotic like amoxicillin generally works fine for many low-grade problems like ear infections, so that's where most people start. If it's a sore throat they can do a rapid antigen test for strep but guess what, amoxicillin is the typical treatment. If that doesn't work they will move farther along the list to antibiotics that have worse side effects
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Could also be preventative in itself. Yes, you may have a viral infection, but while your body is fighting that, your immune system is taxed. That makes it a lot easier for a bacterial infection to take hold - so your doctor "heads them off at the pass" by giving you antibiotics. Saves you from getting a secondary infection until your immune system has finished fighting off the virus.
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What typically happens in my experience is that if you see a doctor about a viral infection there's nothing he can do about it. Yes there are a handful of antivirals for flu and Covid but they only help if you take them very soon after infection. For everything else there is no remedy.
The doctor will tell you there's a lot of this going around, wait a couple of weeks and you will get over it, take some over-the-counter meds to alleviate the symptoms.
Re:The doctors caused this problem (Score:5, Insightful)
This truly is American medicine. Figure out a way to plug the symptom with another pill rather than fixing the root cause. However, I bet the treatments will be stupidly profitable for the medical community.
The systemic problem is the lack of positive motivation for doctors to look after their patients' wellness. Yes, they can possess an altruistic morality that looks after patient welfare, but that altruism has to fight against the real systemic motivations. Doctors lose a patient and revenue source if the patient dies, but that's relatively rare, so it doesn't really matter. Doctors lose revenue if they spend too much time with a patient. In fact, if the doctor's prescription and orders don't work, that perversely results in additional revenue with a follow-up visit. This means that doctors are incentivized to spend minimal time with a patient and prescribe a generic or even guessed-at remedy because this results in increased revenue and no penalty.
I don't even blame the doctors. The problem is with the system.
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In fact, if the doctor's prescription and orders don't work, that perversely results in additional revenue with a follow-up visit. This means that doctors are incentivized to spend minimal time with a patient and prescribe a generic or even guessed-at remedy because this results in increased revenue and no penalty.
I don't even blame the doctors. The problem is with the system.
Yes, the problem is with the system.
This is the same problem as using "number of closed tickets" as KPI, vs using customer satisfaction as KPI for your IT team. The former encourages spending as little time as possible for each ticket, the latter encourages spending more time to make sure the problem is fixed so the customer is happy and won't come back to give more work to you.
Nationalised health care encourages curing the patient in the least number of visits, as each extra visit brings more work (but no
Re:The doctors caused this problem (Score:5, Informative)
Antibiotic over-use by doctors is a problem, but it's dwarfed by the staggering amount of antibiotics fed to animals raised for meat. I'm not saying don't eat meat, since I do so myself, but I try (it's not always easy) to buy meat that is (ideally) locally-raised and at minimum "raised without antibiotics".
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Whoops. I Fnorded the last line of your post, sorry about that.
Re:The doctors caused this problem (Score:4, Interesting)
Where I was living in the Netherlands, way back when, an apothecary wouldn't sell you ibuprofen 200 or higher without a doctor's note. It was also quite often the case that if you went to the doctor, he/she would take your vitals, wrote those in your medical file, give you aspirin and the advice to come back next week if the aspirin didn't help.
By doing that, the doctors had more time left in the day to handle/manage patients with real/serious issues. Because, more often than not, symptoms would simply go away within a week. Then again, the doctor assigned to my family, was an old-school doctor, who didn't mind telling you that he should pull out his rifle to shoot you in the gut, in an effort to quickly get rid of the amounts of food you ate between doctor's visit.
That doctor was very much appreciated within the community, as the advice was honest in a clear manner and if you had a real issue, you could expect proper treatment with just enough medicine and (extra) care. Unfortunately, 10 years after I was born, het got his pension and died a few years later. His wife, also an very good house doctor and almost as "brutal" as he was, continued with the practice. She also got her pension some 10 years later.
In total I think I visited their practice some 10 times in total. 3 times because of a broken arm, 2 times because of a broken leg. All sporting accidents.
The "common-sense"-approach in healthcare made sure that the community was quite resilient. Access to quality food, water and air, plus playing outside for hours every day, cycling to everywhere did wonders for your general health. So there was hardly any need to see your doctor.
Although that location in the Netherlands has changed a lot over the years, it isn't as good a place anymore as it was way back when. Population almost tripled in 10 years time. And there are now several doctor's practices, filled with doctors who act more and more like doctors in the U.S. do...prescribing much more anti-biotics for everything.
Doctors in South-America, where I live now, already did that. Especially if they think you are person with money (read: gringo). And as you yourself stated in your post, if I see anti-biotics on the prescription, I simply don't take it if I think I can tough it out. In the almost 18 years that live here, I visited the hospital 3 times in total. 2 times because of accidents that weren't even my fault.
Unfortunately, I'm now in the age bracket where it is preferable if you visit the hospital once a year for a checkup/prostate exam. Still, I am convinced that my relative trouble-free life, health-wise, was purely because of the no nonsense approach to medicine, common at the time in the Netherlands.
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Not Freedom (Score:2)
You clearly misunderstand what "Freedom!!!" means.
Your freedom ends when the freedom of others begins.
In this concrete case, that means that doctors are not allowed to prescribe anything at will.
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I remember reading about this in the eighties ... (Score:2)
Universal healthcare would help hear (Score:4, Interesting)
One guy I knew who was super broke having dropped a couple of kids in a slightly above minimum wage job back before the last round of wage hikes would sometimes order antibiotics online for animals and take those.
It's a classic case of it being cheaper to be a good person.
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Only in US. Rest of the world mostly have public healthcare.
Read about this 10 yrs ago. (Score:5, Informative)
https://www.wired.com/2003/10/... [wired.com]
The discovery of phages is lost in murky rivalries and scientific disputes. What's certain is that in 1917 an eccentric French-Canadian scientist named Felix d'Herelle isolated them and named them bacteriophages - eaters of bacteria. Working independently, George Eliava discovered the minute creatures after collecting specimens from the Mtkvari River, which flows through the Georgian capital of Tbilisi. Eliava, head of the city's Central Bacteriology Laboratory, left a slide of river water containing cholera bacteria under a microscope for three days. When he returned, the germs were gone. Eliava surmised that something had destroyed them, and, like d'Herelle, he set about isolating the tiny bacteria killers. Eventually, the Georgian struck up a fruitful collaboration with his French colleague. They worked together at the Pasteur Institute in Paris and later at the Institute of Microbiology, founded in Tbilisi in 1923 and later renamed in Eliava's honor. It was there that a small band of scientists pioneered a new therapy, scrupulously assembling the world's only library of phages and developing cocktails of a dozen or more to treat a variety of bacterial disorders from stomach aches to pneumonia. Phages became part of the standard pharmacopoeia in the USSR, and they even enjoyed a brief heyday in the US, where Eli Lilly had an active phage-production program in the '30s. Soviet medics used the viruses on World War II battlefields, and soldiers with the German general Erwin Rommel carried phage treatments in disease-ridden North Africa.
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"the body's immune response to phages" (Score:2)
I'm curious to know how these phages are administered in such a way that they will cure internal infections. I can see how smearing a phage-infused paste over an external wound could help, but the immune system will attack them and possibly destroy anything that's injected or eaten.
Soviet medicine says "Hello!" (Score:3)
Re:Soviet medicine says "Hello!" (Score:4, Interesting)
Phages were avoided in the West because of NIH
This is broadly speaking, wrong.
Phages were also used a bit in the west, pre antibiotics, but were almost entirely displaced because broad spectrum antibiotics exist, but broad spectrum phages do not. It's hard to make phages work well. You have to identify the exact bacteria, and you have to have not only a different phage for each one, but a different phage engineered so the human's immune system won't immediately destroy it.
Compared to antibiotics, you need a lot of resources to make phage therapy work, not just a bunch of shelf-stable pills.
it's having something of a resurgence now because (a) antibiotics are getting tapped out so they are ceasing to be massively more effective and (b) biotech is a lot better now, and we're now at the stage where miniature, shelf stable test kits for some things can be made obviating the need for always having a good lab, and (c) logistics networks are vastly better, making rapid, widespread shipping of non shelf stable things much much better than in the 1940s.
Phages were widely used in USSR (Score:2)
Nothing new. Phages were fairly common in USSR and preferred over antibiotics for those very reasons.
Second time I have heard of these (Score:1)