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Published on Leave a comment on Using Bacteria To Tolerate Infections

The following article is about Dr. Janelle Ayres, a researcher in California, working on "beneficial bacteria" to help the body tolerate infections. This is different than the usual medical approach of fighting infections - where antibiotics are used to kill microbes.  Reading the article, my first thought was "Well, duh....of course this approach works." This is what we've been doing in using Lactobacillus sakei, a beneficial bacteria, in successfully treating sinusitis since early 2013! ..... The good news in reading this article is that using bacteria to treat infections or diseases seems to finally be going mainstream.

Ayres, and some of her colleagues, are interested in why some people can deal with infections, or can repair damaged tissue even during bouts of serious disease, while other people succumb to the disease. She believes she can develop drugs that will boost those qualities in patients who lack them, and help keep people alive through battles with sepsis, malaria, cholera, and a host of other diseases. Their approach looks at "tolerance" — which is a body’s ability to minimize damage while infected, and she calls it the “tolerance defense system.”

She is focusing on this approach because she feels that drugs that target bacteria (such as antibiotics) become useless because the bacteria evolve to resist those drugs. Instead, she thinks we can harness bacteria (even ones normally classified as pathogens) to make new drugs. Her approach to treating an infection could be summarized as: Don't fight it. Help the body tolerate it. Excerpts from STAT News:

She’s got a radical approach for the age of superbugs: Don’t fight infections. Learn to live with them

As her father lay dying of sepsis, Janelle Ayres spent nine agonizing days at his bedside. When he didn’t beat the virulent bloodstream infection, she grieved. And then she got frustrated. She knew there had to be a better way to help patients like her dad. In fact, she was working on one in her lab. Ayres, a hard-charging physiologist who has unapologetically decorated her lab with bright touches of hot pink, is intent on upending our most fundamental understanding of how the human body fights disease.

Scientists have focused for decades on the how the immune system battles pathogens. Ayres believes other elements of our physiology are at least as important — so she’s hunting for the beneficial bacteria that seem to help some patients maintain a healthy appetite and repair damaged tissue even during bouts of serious disease. If she can find them — and she’s already begun to do so — she believes she can develop drugs that will boost those qualities in patients who lack them and help keep people alive through battles with sepsis, malaria, cholera, and a host of other diseases. Her approach, in a nutshell: Stop worrying so much about fighting infections. Instead, help the body tolerate them.

An associate professor at the Salk Institute in the heart of San Diego’s booming biotech beach, Ayres is harnessing all manner of high-tech tools from the fields of microbiomics, genetics, and immunology — and looking to a menagerie of animals — to sort out why some individuals tolerate infection so much better than others. It’s work that’s desperately needed, Ayres said, as it becomes ever more clear that our standard approach to fighting infection using antibiotics and antivirals is hopelessly inadequate. The drugs don’t work for all diseases, they kill off good bacteria along with bad — and their wanton use is contributing to the rise of antibiotic resistant bacteria, or “superbugs,” which terrify disease experts because there are few ways to stop them.

....They went on to propose that the immune response to pathogens wasn’t the whole story, and that tolerance — a body’s ability to minimize damage while infected — may play a key role as well. Ayres has since gone on to call what she studies the “tolerance defense system.”

Society needs drugs that don’t target bacteria, which can so quickly evolve to evade our best medicines, she argues. Instead, she thinks we can harness those bacteria — even the ones normally classified as pathogens — to make new drugs that save lives by targeting an infected person’s tissues and organs. That would be an entirely new class of therapeutics, which could lessen our dependence on antibiotics and help save lives in cases, like her father’s, where antibiotics fail.

She’s been working furiously in her own lab, rolling out a series of studies that have found critical targets for new drugs. Her main focus: the trillions of bacteria — known collectively as the microbiome — that reside in our bodies but do not sicken us. Ayres suspects they might play a key role in the tolerance defense system. But if bacteria do help increase tolerance to disease, what strains are involved and what exactly are they doing?

Published on Leave a comment on Will We Use Predator Bacteria To Destroy Superbugs In the Future?

Great idea and one that this blog has been pushing for a long time - the use of beneficial bacteria to get rid of other harmful bacteria. Some researchers refer to the bacteria acting as "living antibiotics" when they overpower harmful bacteria.

Researchers such as Daniel Kadouri, a micro-biologist at Rutgers School of Dental Medicine in Newark, are studying bacteria that aggressively attack harmful  bacteria, and calling them "predator bacteria". They are focusing on one specific bacteria - Bdellovibrio bacteriovorus, a gram-negative bacteria that dines on other gram-negative bacteria. They hope to eventually be able to give this bacteria as a medicine to humans , and then this predator bacteria would overpower and destroy "superbugs" (pathogenic bacteria that are resistant to many antibiotics). A great idea, but unfortunately the researchers think that it'll take about 10 more years of testing and development before it's ready for use in humans. From Science News:

Live antibiotics use bacteria to kill bacteria

The woman in her 70s was in trouble. What started as a broken leg led to an infection in her hip that hung on for two years and several hospital stays. At a Nevada hospital, doctors gave the woman seven different antibiotics, one after the other. The drugs did little to help her. Lab results showed that none of the 14 antibiotics available at the hospital could fight the infection, caused by the bacterium Klebsiella pneumoniae.... The CDC’s final report revealed startling news: The bacteria raging in the woman’s body were resistant to all 26 antibiotics available in the United States. She died from septic shock; the infection shut down her organs.  ...continue reading "Will We Use Predator Bacteria To Destroy Superbugs In the Future?"

Published on Leave a comment on Big Pharma’s Pollution Leading To Superbugs

Image result for pills wikipedia Nowadays there is tremendous concern about the spread of antibiotic resistant bacteria  or "superbugs" throughout the world. Articles frequently mention India being at the epicenter of this crisis - that is, the source of many antibiotic resistant strains (both in and out of hospitals), which then travel throughout the world due to global travel. The massive overuse and misuse of antibiotics (whether in humans, animals, and even crops) is usually given as the major reason for the development of antibiotic resistant strains of bacteria (here, here, and here).

Thus the following article about unchecked pollution from pharmaceutical companies in India fueling the creation of deadly superbugs was shocking to read - and it may explain why the problem is so severe there. Note that the Indian companies supply just about all the world's major drug companies with antibiotics and anti-fungals. It appears that the companies are ignoring local laws (which have been called "toothless") which would cut down on the pollution. What is stressed in the article is that one of the world’s biggest drug production hubs (the Indian city of Hyderabad) is producing dangerous levels of pharmaceutical pollution, and the international agencies that ensure drug safety are basically ignoring this problem (and doing little to address it).

Thousands of tons of pharmaceutical waste is produced each day by the many pharmaceutical companies in Hyderabad, India, which is then contaminating the water sources in the area. With the result that water samples (from rivers, lakes, groundwater, drinking water, surface water, treated sewage water) in  that area contain bacteria and fungi resistant to multiple drugs (superbugs), and these superbugs then get spread to humans throughout India and eventually globally.   This article is definitely worth reading in its entirety. Excerpts from The Bureau of Investigative Journalism:

Big Pharma's Pollution Is Creating Deadly Superbugs While The World Looks The Other Way

Industrial pollution from Indian pharmaceutical companies making medicines for nearly all the world’s major drug companies is fueling the creation of deadly superbugs, suggests new research. Global health authorities have no regulations in place to stop this happening. A major study published today in the prestigious scientific journal Infection found “excessively high” levels of antibiotic and antifungal drug residue in water sources in and around a major drug production hub in the Indian city of Hyderabad, as well as high levels of bacteria and fungi resistant to those drugs. Scientists told the Bureau the quantities found meant they believe the drug residues must have originated from pharmaceutical factories.

The presence of drug residues in the natural environment allows the microbes living there to build up resistance to the ingredients in the medicines that are supposed to kill them, turning them into what we call superbugs. The resistant microbes travel easily and have multiplied in huge numbers all over the world, creating a grave public health emergency that is already thought to kill hundreds of thousands of people a year.

When antimicrobial drugs stop working common infections can become fatal, and scientists and public health leaders say the worsening problem of antibiotic resistance (also known as AMR) could reverse half a century of medical progress if the world does not act fast. Yet while policies are being put into place to counter the overuse and misuse of drugs which has propelled the crisis, international regulators are allowing dirty drug production methods to continue unchecked. Global authorities like the Food and Drug Administration and the European Medicines Agency strictly regulate drug supply chains in terms of drug safety - but environmental standards do not feature in their rulebook. Drug producers must adhere to Good Manufacturing Practices (GMP) guidelines - but those guidelines do not cover pollution.

The international bodies say the governments of the countries where the drugs are made are the ones responsible for stopping pollution - but domestic legislation is having little impact on the ground, say the study's authors. The lack of international regulation must be addressed, they argue, highlighting the grave public health threat faced by antibiotic resistance as well as the rampant global spread of superbugs from India, which has become an epicentre of the crisis.

A group of scientists based at the University of Leipzig worked with German journalists to take an in-depth look at pharmaceutical pollution in Hyderabad, where 50% of India’s drug exports are produced. A fifth of the world’s generic drugs are produced in India, with factories based in Hyderabad supplying Big Pharma and public health authorities like World Health Organisation with millions of tons of antibiotics and antifungals each year.

The researchers tested 28 water samples in and around the Patancheru-Bollaram Industrial zone on the outskirts of the city, where more than than 30 drug manufacturing companies supplying nearly all the world’s major drug companies are based. Thousands of tons of pharmaceutical waste are produced by the factories each day, the paper says. Almost all the samples contained bacteria and fungi resistant to multiple drugs (known as MDR pathogens, the technical name for superbugs). Researchers then tested 16 of the samples for drug residues and found 13 of them were contaminated with antibiotics and antifungals. Previous studies have shown how exposure to antibiotics and antifungals in the environment causes bacteria and fungi to develop immunity to those drugs.

Environmental pollution and poor management of wastewater in Hyderabad is causing “unprecedented antimicrobial drug contamination” of surrounding water sources, conclude the researchers - contamination which appears to be driving the creation and spread of dangerous superbugs which have spread across the world. Combined with the mass misuse of antibiotics and poor sanitation, superbugs are already having severe consequences in India - an estimated 56,000 newborn babies die from resistant infections there each year.

The companies in question strongly deny that their factories pollute the environment, and the sheer number of factories operating in Hyderabad means it is impossible to identify exactly which companies are responsible for the contamination found in the samples tested. What is clear is one of the world’s biggest drug production hubs is producing dangerous levels of pharmaceutical pollution, and the international bodies tasked with ensuring drug safety are doing little to address it.

Around 170 companies making bulk drugs like antibiotics operate in and around Hyderabad, the majority clustered in sprawling industrial estates along the banks of the Musi river. Companies in Europe and the US, as well as health authorities like WHO and the UK’s NHS are reliant on drugs being produced in these factories.

The area has long been criticised for its pollution, which has continued unabated despite decades of campaigning by Indian NGOs, say the report authors. In 2009 the Patancheru-Bollaram zone was classified as “critically polluted” in India’s national pollution index and construction in the area was banned. But the government relaxed the rules in 2014 and building was allowed to begin again. Last year India’s Supreme Court ordered the country’s pharmaceutical companies to operate a zero liquid waste policy, but “massive violations” have reportedly occurred, says the Infection report....India has become the epicentre of the global drug resistance crisis, with 56,000 newborn Indian babies estimated to die each year from drug-resistant blood infections, and 70 to 90% of people who travel to India returning home with multi-drug-resistant bacteria in their gut, according to the study.

Researchers took water samples from rivers, lakes, groundwater, drinking water and surface water from rural and urban areas in and around the industrial estate, as well as pools near factories and water sources contaminated by sewage treatment plants. Four were taken from taps, one from a borehole, and the remaining 23 were classed as environmental samples. The samples were tested for bacteria resistant to multiple drugs (known as MDR pathogens, the technical name for superbugs). The researchers then tested 16 of the samples for the antibiotics and antifungals used to treat infections. All samples apart from one taken from tap water at a four star hotel were found to contain drug-resistant bacteria. All 23 environmental samples contained carbapenemase-producing bacteria - a group of bugs dubbed the “nightmare bacteria” because they are virtually untreatable and kill 40-50% of people whose blood gets infected with them.

Of the 16 samples then tested for drug residue, 13 were found to be contaminated with antibiotics and antifungals, some in disturbingly high levels. The researchers compared the levels of residue to limits recommended by leading microbiologists; once levels exceed those limits it is likely that superbugs will develop. The amounts of antimicrobials found in the new tests were “eye-wateringly high”, said Dr Mark Holmes, a microbiologist at the University of Cambridge. “The quantities involved mean the amount in the water is almost the same as a therapeutic dose,” he said, calling on the Indian authorities to investigate immediately by testing each factory’s effluent. 

There are reams of regulations and stipulations that manufacturers have to adhere to in order to export their products to the US and Europe – known as the Good Manufacturing Practices (GMP) framework. These focus on making sure drugs are safe, pure, and effective. Stringent inspections by the FDA, WHO and European authorities check that these rules are being followed. However these regulations do not address environmental concerns. Inspectors have no mandate to sanction a factory for polluting, failing to treat its waste or other environmental problems – this falls within the remit of local governments.

Published on Leave a comment on New Antibiotics Are Needed For Twelve Scary Superbugs

Image result for Acinetobacter baumannii Many posts on this blog are about beneficial microbes, and the many species of microbes (bacteria, fungi, viruses) living within and on us. But there are also bacteria in the world that pose a serious threat to human health, and the list of these are growing due to antibiotic resistance. This week the World Health Organization (WHO) officials came out with a list of a dozen antibiotic-resistant "priority pathogens" that pose the greatest threats to human health. These are bacteria resistant to multiple antibiotics - thus superbugs.

Antibiotic resistance is increasing due to misuse of antibiotics (or antimicrobials), and this is occurring throughout the world (post with video of how superbugs evolve). This is because bacteria are constantly evolving against the antibiotics they're exposed to. We may reach a point where simple cuts or infections could lead to death because no antibiotics will work. The World Health Organization said in a 2014 report that: "The problem is so serious that it threatens the achievements of modern medicine. A post-antibiotic era—in which common infections and minor injuries can kill—far from being an apocalyptic fantasy, is instead a very real possibility for the twenty-first century."

Part of the problem is that farmers are still giving antibiotics (antimicrobials) to farm animals unnecessarily, typically as "growth promoters" or to try to prevent disease. Currently about 80% of all antibiotics used in the US are given to livestock animals (of which nearly 70 percent of those used are considered “medically important” for humans).

New antibiotic development is not keeping pace with the emergence of new antibiotic resistant bacteria. According to the CDC: "Each year in the United States, at least 2 million people become infected with bacteria that are resistant to antibiotics and at least 23,000 people die each year as a direct result of these infections."

According to WHO officials "The bacteria on the list are responsible for severe infections and high mortality rates mostly in hospitalized patients, transplant recipients, those receiving chemotherapy or patients in intensive care units." They have also been seen in our hospitalized and returning military service people. The WHO list is meant to steer public and private research dollars toward developing new antibiotics for these particular families of bacteria. Pharmaceutical companies currently lack financial incentives to develop new drugs aimed at these superbugs. Currently too few new antibiotics are under development. From World Health Organization:

WHO publishes list of bacteria for which new antibiotics are urgently needed

WHO today published its first ever list of antibiotic-resistant "priority pathogens" – a catalogue of 12 families of bacteria that pose the greatest threat to human health. The list was drawn up in a bid to guide and promote research and development (R&D) of new antibiotics, as part of WHO’s efforts to address growing global resistance to antimicrobial medicines. The list highlights in particular the threat of gram-negative bacteria that are resistant to multiple antibiotics. These bacteria have built-in abilities to find new ways to resist treatment and can pass along genetic material that allows other bacteria to become drug-resistant as well.....The WHO list is divided into three categories according to the urgency of need for new antibiotics: critical, high and medium priority.

The most critical group of all includes multidrug resistant bacteria that pose a particular threat in hospitals, nursing homes, and among patients whose care requires devices such as ventilators and blood catheters. They include Acinetobacter, Pseudomonas and various Enterobacteriaceae (including Klebsiella, E. coli, Serratia, and Proteus). They can cause severe and often deadly infections such as bloodstream infections and pneumonia. These bacteria have become resistant to a large number of antibiotics, including carbapenems and third generation cephalosporins – the best available antibiotics for treating multi-drug resistant bacteria. The second and third tiers in the list – the high and medium priority categories – contain other increasingly drug-resistant bacteria that cause more common diseases such as gonorrhoea and food poisoning caused by salmonella.

WHO priority pathogens list for R&D of new antibiotics: Priority 1: CRITICAL - Acinetobacter baumannii, carbapenem-resistant, Pseudomonas aeruginosa, carbapenem resistant, Enterobacteriaceae, carbapenem-resistant, ESBL-producing. Priority 2: HIGH - Enterococcus faecium, vancomycin-resistant, Staphylococcus aureus, methicillin-resistant, vancomycin-intermediate and resistant, Helicobacter pylori, clarithromycin-resistant, Campylobacter spp., fluoroquinolone-resistant, Salmonellae, fluoroquinolone-resistant, Neisseria gonorrhoeae, cephalosporin-resistant, fluoroquinolone-resistant. Priority 3: MEDIUM - Streptococcus pneumoniae, penicillin-non-susceptible, Haemophilus influenzae, ampicillin-resistant, Shigella spp., fluoroquinolone-resistant.

Image result for Acinetobacter baumannii Acinetobacter baumannii  Credit: Centers for Disease Control and Prevention (CDC)

Published on Leave a comment on Woman Dies From Superbug Resistant To 26 Antibiotics

A few days ago the CDC (Centers for Disease Control and Prevention) released a report about a Nevada woman who died in August 2016 of a bacterial infection that was resistant to all 26 antibiotics available in the US, including the antibiotic of last resort - colistin. Apparently she had picked up the bacterial infection in India, where she been staying for an extended visit and where she had been hospitalized (a fractured leg, which led to a hip infection). Because of the antibiotic resistance, the infection spread, and she went into septic shock and died.

India has soaring rates of antibiotic resistance due to misuse of antibiotics (or antimicrobials). But this is not just a problem with infections acquired in India, but throughout the world. Antibiotic resistance is increasing everywhere (post with video of how superbugs evolve). This is because bacteria are constantly evolving against the antibiotics they're exposed to. We may reach a point where simple cuts or infections could lead to death because no antibiotics will work. The World Health Organization said in a 2014 report that: "The problem is so serious that it threatens the achievements of modern medicine. A post-antibiotic era—in which common infections and minor injuries can kill—far from being an apocalyptic fantasy, is instead a very real possibility for the twenty-first century."

New antibiotic development is not keeping pace with the emergence of new antibiotic resistant bacteria. According to the CDC: "Each year in the United States, at least 2 million people become infected with bacteria that are resistant to antibiotics and at least 23,000 people die each year as a direct result of these infections." On top of that, too few antibiotics are under development, and those antibiotics tend to be developed by small companies, not the big pharmaceutical companies. Farmers are still giving antibiotics (antimicrobials) to farm animals unnecessarily, typically as "growth promoters" or to try to prevent disease. The sale of antibiotics routinely fed to animals has been increasing in recent years, and currently about 80% of all antibiotics used in the US are given to livestock animals (of which nearly 70 percent of those used are considered “medically important” for humans).

Excerpts from The Atlantic: A Woman Was Killed by a Superbug Resistant to All 26 American Antibiotics

Yesterday morning, I published a story about the silent spread of resistance against the antibiotic of last resort, colistin—a major step toward the emergence of a superbug resistant to all antibiotics. While reporting this story, I interviewed Alex Kallen, an epidemiologist at the CDC, and I asked if anyone had found such a superbug yet. “Funny you should ask,” he said.

Funny—by which we all mean scary—because yesterday afternoon, the CDC also released a report about a Nevada woman who died after an infection resistant to 26 antibiotics, which is to say all available antibiotics in the U.S. The woman, who was in her 70s, had been previously hospitalized in India after fracturing her leg, eventually which led to an infection in her hip. There was nothing to treat her infection—not colistin, not other last-line antibiotics. Scientists later tested the bacteria that killed her, and found it was somewhat susceptible to fosfomycin, but that antibiotic is not approved in the U.S. to treat her type of infection.

Published on Leave a comment on Botanical Remedies May Be In Our Future

The big scary question: What will happen after antibiotics cease to work? And people start dying by the millions from infections that used to be easily treated? We are fast approaching that point of total antibiotic resistance, with superbugs that resist all antibiotics. More and more disease-causing bacteria are rapidly evolving immunity to every existing antibiotic (see short video). Soon routine surgeries and minor wounds or even scratches could kill a person. About 70% of antibiotics are currently being used (much of it unnecessary) in farm animals - why aren't governments putting a stop to that? Resistant bacteria already result in the deaths of about 700,000 people globally, but experts predict that by 2050 they will kill 10 million people annually.

What is to be done? New antibiotics? Big pharma generally isn't interested - not enough profit. Using good bacteria and other microbes to dominate over pathogenic microbes? (For example, using  L. sakei to treat chronic sinusitis) Bacteriophages? Essential oils? The following is a wonderful article about another possibility: ethnobotany - the use of medicinal plants. Cassandra Quave is the ethnobotanist based at Emory University discussed in the article. From the New York Times:

Could Ancient Remedies Hold the Answer to the Looming Antibiotics Crisis?

Ethnobotany is a historically small and obscure offshoot of the social sciences, focused on the myriad ways that indigenous peoples use plants for food, shelter, clothing, art and medicine. Within this already-tiny field, a few groups of researchers are now trying to use this knowledge to derive new medicines, and Quave has become a leader among them. Equally adept with a pipette and a trowel, she unites the collective insights of traditional plant-based healing with the rigor of modern laboratory experiments. Over the past five years, Quave has gathered hundreds of therapeutic shrubs, weeds and herbs and taken them back to Emory for a thorough chemical analysis.  ...continue reading "Botanical Remedies May Be In Our Future"

Published on Leave a comment on The Development of Antibiotic Resistant Bacteria

Here is an amazing short video for those interested in seeing how bacteria mutate and grow when exposed to antibiotics - and evolving to become superbugs. Researchers filmed an experiment that created bacteria a thousand times more drug-resistant than their ancestors. In the time-lapse video, a white bacterial colony (E.coli bacteria) creeps across an enormous black petri dish plated with vertical bands of successively higher doses of antibacterial drugs (antibiotics).

How they did it: The researchers imaged the E. coli bacteria every 10 minutes for 10 days as the microbes expanded across the plate. You can see that the bacteria paused briefly at the boundaries of increasingly stronger antibiotic concentrations until a mutant bacteria struck out into the stronger antibiotic territory. By challenging the bacteria with differing doses of antibiotic, the team demonstrated that E. coli evolve higher resistance more quickly if they first encounter an intermediate, rather than a high, concentration of antibiotic. It's a beautiful, yet horrifying video. NOTE: the bacteria grows on agar, which is a thick, clear substance that comes from seaweed and is used for growing bacteria in scientific research. From Harvard Medical School, on YOUTUBE:

From NPR:  WATCH: Bacteria Invade Antibiotics And Transform Into Superbugs

In the time-lapse video, a white bacterial colony creeps across an enormous black petri dish plated with vertical bands of successively higher doses of antibiotic. The colony pauses when it hits the first band of antibiotic, creating a stark border between the white colony and the black petri dish. Then the bacteria start to edge their way into the toxic soup. More dots appear and they start growing, racing to the next, stronger band of antibiotic. The bacteria are evolving. After almost two weeks of real time have passed, they've become resistant to the strongest completely taken over the kitchen-table-sized petri dish.

We know dangerous bacteria are getting stronger all the time and that it's our fault because of our excessive and indiscriminate use of antibiotics. Each year, 23,000 people in the U.S. die as a result of superbug infections. But we typically don't get to see superbugs created.... Their video and report were published Thursday in the journal Science.