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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: CRITICALAcinetobacter baumannii, carbapenem-resistant, Pseudomonas aeruginosa, carbapenem resistant, Enterobacteriaceae, carbapenem-resistant, ESBL-producing. Priority 2: HIGHEnterococcus 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)

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.

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) BacteriophagesEssential 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"

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. 

The following article is interesting because it describes how microbes are high up in the sky riding air currents and winds to circle the earth, and eventually drop down somewhere. This is one way diseases can be spread from one part of the world to another. And the study looking at how antibiotic resistant bacteria are spread in the air from cattle feedlots has implications for how antibiotic resistance is spread. From Smithsonian:

Living Bacteria Are Riding Earth's Air Currents

Considering the prevailing winds, David J. Smith figured the air samples collected atop a dormant volcano in Oregon would be full of DNA signatures from dead microorganisms from Asia and the Pacific Ocean. He didn’t expect anything could survive the journey through the harsh upper atmosphere to the research station at the Mount Bachelor Observatory, at an elevation of 9,000 feet.

But when his team got to the lab with the samples, taken from two large dust plumes in the spring of 2011, they discovered a thriving bunch of hitchhikers. More than 27 percent of the bacterial samples and more than 47 percent of the fungal samples were still alive. Ultimately, the team detected about 2,100 species of microbes, including a type of Archea that had only previously been isolated off the coast of Japan. “In my mind, that was the smoking gun,“ Smith says. Asia, as he likes to say, had sneezed on North America.

 Microbes have been found in the skies since Darwin collected windswept dust aboard the H.M.S. Beagle 1,000 miles west of Africa in the 1830s. But technologies for DNA analysis, high-altitude collection and atmospheric modeling are giving scientists a new look at crowded life high above Earth. For instance, recent research suggests that microbes are hidden players in the atmosphere, making clouds, causing rain, spreading diseases between continents and maybe even changing climates.

"I regard the atmosphere as a highway, in the most literal sense of the term," Smith says. "It enables the exchange of microorganisms between ecosystems thousands of miles apart, and to me that’s a more profound ecological consequence we still have not fully wrapped our heads around."

Airborne microbes potentially have huge impacts on our planet. Some scientists attribute a 2001 foot-and-mouth outbreak in Britain to a giant storm in north Africa that carried dust and possibly spores of the animal disease thousands of miles north only a week before the first reported cases. Bluetongue virus, which infects domestic and wild animals, was once present only in Africa. But it's found now in Great Britain, likely the result of the prevailing winds.

In west Texas, researchers from Texas Tech University collected air samples upwind and downwind of ten cattle feedlots. Antibiotic resistant microbes were 4,000 percent more prevalent in the downwind samples. .... What's clear is there are far more viable microbes in far more inhospitable places than scientists expected.

New research found that one course of antibiotics (ciprofloxacin, clindamycin, amoxicillin or minocycline) had varying effects on the gut and saliva microbes, with ciprofloxacin having a negative and disruptive effect on gut microbiome diversity up to 12 months. While the microscopic communities living in the mouth rebound quickly, just one course of antibiotics can disrupt the gut microbiome for months - with amoxicillin the least and ciprofloxacin the most (up to a year).The researchers stressed that for these reasons "antibiotics should only be used when really, really necessary. Even a single antibiotic treatment in healthy individuals contributes to the risk of resistance development and leads to long-lasting detrimental shifts in the gut microbiome."

The scary part is that Americans typically take many courses of antibiotics throughout life. And people with conditions such as chronic sinusitis typically take many more than average. From Medical Xpress:

One course of antibiotics can affect diversity of microorganisms in the gut

A single course of antibiotics has enough strength to disrupt the normal makeup of microorganisms in the gut for as long as a year, potentially leading to antibiotic resistance, European researchers reported this week in mBio, an online open-access journal of the American Society for Microbiology. In a study of 66 healthy adults prescribed different antibiotics, the drugs were found to enrich genes associated with antibiotic resistance and to severely affect microbial diversity in the gut for months after exposure. By contrast, microorganisms in the saliva showed signs of recovery in as little as few weeks.

The microorganisms in study participants' feces were severely affected by most antibiotics for months, said lead study author Egija Zaura, PhD, an associate professor in oral microbial ecology at the Academic Centre for Dentistry in Amsterdam, the Netherlands. In particular, researchers saw a decline in the abundance of health-associated species that produce butyrate, a substance that inhibits inflammation, cancer formation and stress in the gut.

"My message would be that antibiotics should only be used when really, really necessary," Zaura said. "Even a single antibiotic treatment in healthy individuals contributes to the risk of resistance development and leads to long-lasting detrimental shifts in the gut microbiome."

It's not clear why the oral cavity returns to normal sooner than the gut, Zaura said, but it could be because the gut is exposed to a longer period of antibiotics. Another possibility, she said, is that the oral cavity is intrinsically more resilient toward stress because it is exposed to different stressors every day.

The investigators enrolled healthy adult volunteers from the United Kingdom and Sweden. Participants were randomly assigned to receive a full course of one of four antibiotics (ciprofloxacin, clindamycin, amoxicillin or minocycline) or a placebo. The researchers, who did not know which medication participants took, collected fecal and saliva samples from the participants at the start of the study; immediately after taking the study drugs; and one, two, four and 12 months after finishing the medications....

Researchers found that participants from the United Kingdom started the study with more antibiotic resistance than did the participants from Sweden, which could result from cultural differences. There has been a significant decline in antibiotic use in Sweden over the last two decades, Zaura said.

In addition, fecal microbiome diversity was significantly reduced for up to four months in participants taking clindamycin and up to 12 months in those taking ciprofloxacin, though those drugs only altered the oral cavity microbiome up to one week after drug exposure. Exposure to amoxicillin had no significant effect on microbiome diversity in either the gut or oral cavity but was associated with the greatest number of antibiotic-resistant genes.

Gut bacteria. Credit: Med. Mic. Sciences Cardiff Univ, Wellcome Images

The bottom line is to read the ingredients list on products, and avoid all products labeled "antimicrobial" or "antibacterial" (because those are the ones typically containing triclosan and triclorocarban). Over 2000 products contain antibacterial compounds. I've even seen them in pillows, pillow protectors, mattress pads, dish racks, toys, and blankets! As we know from the latest microbiology research, we need to cultivate a healthy microbiome, and not throw it out of whack by continuously trying to kill off all bacteria. From The Atlantic:

It's Probably Best to Avoid Antibacterial Soaps

Antimicrobial chemicals are so ubiquitous that a recent study found them in pregnant mothers' urine and newborns' cord blood. Research shows that their risks may outweigh their benefits.

Antimicrobial chemicals, intended to kill bacteria and other microorganisms, are commonly found in not just soaps, but all kinds of products—toothpaste, cosmetics, and plastics among them. There is evidence that the chemicals aren’t always effective, and may even be harmful, and their ubiquity means people are often continually exposed to them. One such chemical, triclosan, has previously been found in many human bodily fluids. New research found traces of triclosan, triclocarban, and butyl paraben in the urine of pregnant women, and the cord blood of newborn infants. 

The research looked at the same population of 180 expectant mothers living in Brooklyn, New York, most of Puerto Rican descent. In a study published last week in Environmental Science and Technology, researchers from Arizona State University and State University of New York’s Downstate School of Public Health found triclosan in 100 percent of the women’s urine samples, and triclocarban in 87 percent of the samples. Of the 33 cord blood samples they looked at, 46 percent contained triclosan and 23 percent contained triclocarban.

In another, still-unpublished study, the researchers found that all of the cord blood samples contained “at least one paraben,” according to Dr. Rolf Halden, director of ASU’s Center for Environmental Security. 

Triclosan and triclocarban are endocrine disruptors, Halden explains. The risk there is that the chemicals can mimic thyroid hormones, potentially disrupting the metabolism and causing weight gain or weight loss. Previous research has also shown a connection between higher levels of triclosan in urine, and allergy diagnoses in children.

In the study looking at butyl paraben, the researchers found an association between higher exposure to the chemical, and a smaller head circumference and length of babies after they were born. Butyl paraben is used as a preservative, so it’s found in a wider breadth of products, according to Halden.

From Science News: Pregnant women, fetuses exposed to antibacterial compounds face potential health risks 


As the Food and Drug Administration mulls over whether to rein in the use of common antibacterial compounds that are causing growing concern among environmental health experts, scientists are reporting that many pregnant women and their fetuses are being exposed to these substances. The compounds are used in more than 2,000 everyday products marketed as antimicrobial, including toothpastes, soaps, detergents, carpets, paints, school supplies and toys, the researchers say.

The problem with this, explains Pycke, a research scientist at Arizona State University (ASU), is that there is a growing body of evidence showing that the compounds can lead to developmental and reproductive problems in animals and potentially in humans. Also, some research suggests that the additives could contribute to antibiotic resistance, a growing public health problem.

Although the human body is efficient at flushing out triclosan and triclocarban, a person's exposure to them can potentially be constant. "If you cut off the source of exposure, eventually triclosan and triclocarban would quickly be diluted out, but the truth is that we have universal use of these chemicals, and therefore also universal exposure," says Rolf Halden, Ph.D., the lead investigator of the study at ASU.

Even though this study was done in a laboratory, it gives further support for the treatment of sinusitis with bacteria and other microbes. And it could help explain why repeated courses of antibiotics don't "cure"  many chronic infections - because biofilms filled with pathogenic bacteria are signs of microbial communities out-of-whack. Which is why my family's successful chronic sinusitis treatment with kimchi (juice) containing Lactobacillus sakei is all the more impressive. From Science Daily:

Link between antibiotics, bacterial biofilms and chronic infections found

The link between antibiotics and bacterial biofilm formation leading to chronic lung, sinus and ear infections has been found, researchers report. The study results illustrate how bacterial biofilms can actually thrive, rather than decrease, when given low doses of antibiotics. Results of this study may lead to new approach for chronic ear infections in children.

This research addresses the long standing issues surrounding chronic ear infections and why some children experience repeated ear infections even after antibiotic treatment," said Paul Webster, PhD, lead author, senior staff scientist at USC and senior faculty at the Oak Crest Institute of Science. "Once the biofilm forms, it becomes stronger with each treatment of antibiotics."

During the study, non-typeable Haemophilus influenzae (NTHi) bacteria a common pathogen of humans was exposed to non-lethal doses of ampicillin, a class of antibiotics commonly used to treat respiratory, sinus and ear infections, or other beta-lactam antibiotics. The dose of the antibiotic was not enough to kill the bacteria which allowed the bacteria to react to the antibiotic by producing glycogen, a complex sugar often used by bacteria as a food source, to produce stronger biofilms when grown in the laboratory.

Biofilms are highly structured communities of microorganisms that attach to one another and to surfaces. The microorganisms group together and form a slimy, polysaccharide cover. This layer is highly protective for the organisms within it, and when new bacteria are produced they stay within the slimy layer. With the introduction of antibiotic-produced glycogen, the biofilms have an almost endless food source that can be used once antibiotic exposure has ended.

There are currently no approved treatments for biofilm-related infections. Therefore, bacteria forced into forming stronger biofilms will become more difficult to treat and will cause more severe chronic infections. Adults will suffer protracted lung infections as the bacteria hunker down into their protective slime, and children will have repeated ear infections. What may appear to be antibiotic resistance when an infection does not clear up may actually be biofilms at work.

Webster believes modern medicine needs to find ways of detecting and treating biofilm infections before the bacteria are able to form these protective structures. The difficulties of treating biofilm infections, which can be up to 1,000 times more resistant to antibiotics,have prompted some physicians to propose a gradual move away from traditional antibiotic treatments and toward non-antibiotic therapies.

The bacteria called Haemophilus influenzae are a common cause of upper respiratory tract infection. By attaching to surfaces in the body the bacteria form a biofilm. When the bacteria encounter non-lethal amounts of specific antibiotics they are stimulated to form a biofilm, a structure that causes chronic infection and which can be highly resistant to antibiotics. Credit: Paul Webster, Ph.D