Tag Archives: antibiotics

Image result for pills wikipedia Hah!  A study that builds on what is already known by many women - that the non-prescription product D-mannose works for urinary tract infections (UTIs). D-mannose is amazingly effective for urinary tract infections caused by E. coli bacteria (up to 90% of UTIs), even infections that  keep recurring (30 to 50% of infections), and which don't respond to numerous antibiotics. D-mannose is effective because it attaches to E. coli bacteria, and prevents them from attaching to the walls of the urinary tract. But as women know, there are many (all effective) D-mannose products on the market - so the big pharmaceutical companies can't claim it as their own (with patents) for the big bucks $$$. So...this study is basically chemically reformulating the mannose sugar (which is in D-mannose) for a new product (mannosides) - one that they can claim as their own. Maybe it'll be a little better than ordinary D-mannose, and maybe not. Human studies are needed.

By the way, this study may be big news to physicians because most don't seem to know about D-mannose as a treatment for UTIs - they all seem to focus just on antibiotics and perhaps cranberry juice in treating UTIs. This may be because D-mannose is considered as an "alternative treatment". And I could find only one study that compares antibiotics and D-mannose for recurrent UTIs - and guess which one did a little better?  Yup...D-mannose (see post). From Medical Xpress:

New treatment reduces E. coli, may offer alternative to antibiotics

Urinary tract infections (UTIs) are among the most common infections, and they tend to come back again and again, even when treated. Most UTIs are caused by E. coli that live in the gut and spread to the urinary tractA new study from Washington University School of Medicine in St. Louis has found that a molecular decoy can target and reduce these UTI-causing bacteria in the gut. With a smaller pool of disease-causing bacteria in the gut, according to the researchers, the risk of having a UTI goes down...."This compound may provide a way to treat UTIs without the use of antibiotics."

Close to 100 million people worldwide acquire UTIs each year, and despite antibiotic treatment, about a quarter develop another such infection within six months. UTIs cause painful, burning urination and the frequent urge to urinate. In serious cases, the infection can spread to the kidneys and then the bloodstream, where it can become life-threatening. Most UTIs are caused by E. coli that live harmlessly in the gut. However, when shed in the feces, the bacteria can spread to the opening of the urinary tract and up to the bladder, where they can cause problems. Conventional wisdom holds that UTIs recur frequently because bacterial populations from the gut are continually re-seeding the urinary tract with disease-causing bacteria.

Hultgren, graduate student Caitlin Spaulding, and colleagues reasoned that if they could reduce the number of dangerous E. coli in the gut, they could reduce the likelihood of developing a UTI and possibly prevent some recurrent infections. First, the researchers identified genes that E. coli need to survive in the gut. One set of genes coded for a kind of pilus, a hairlike appendage on the surface of E. coli that allows the bacteria to stick to tissues, like molecular velcro. Without this pilus, the bacteria fail to thrive in the gut. Earlier studies found that the identified pilus attaches to a sugar called mannose that is found on the surface of the bladder. Grabbing hold of mannose receptors on the bladder with the pilus allows the bacteria to avoid being swept away when a person urinates. Bacteria that lack this pilus are unable to cause UTIs in mice.

Previously, Hultgren and co-author, James W. Janetka, PhD, an associate professor of biochemistry and molecular biophysics at Washington University, chemically modified mannose to create a group of molecules, called mannosides, that are similar to mannose but changed in a way that the bacteria latch onto them more tightly with their pili. Unlike mannose receptors, though, these mannosides are not attached to the bladder wall, so bacteria that take hold of mannosides instead of mannose receptors are flushed out with urine.

Since the researchers found that this same pilus also allows the bacteria to bind in the gut, they reasoned that mannoside treatment could reduce the number of E. coli in the gut and perhaps prevent the spread of the bacteria to the bladder. To test this idea, they introduced a disease-causing strain of E. coli into the bladders and guts of mice to mirror the pattern seen in people. In women with UTIs, the same bacteria that cause problems in the bladder usually also are found living in the gut.

The researchers gave the mice three oral doses of mannoside, and then measured the numbers of bacteria in the bladders and guts of the mice after the last dose of mannoside. They found that the disease-causing bacteria had been almost entirely eliminated from the bladder and reduced a hundredfold in the gut, from 100 million per sample to 1 million. .... researchers measured the composition of the gut microbiome after mannoside treatment. They found that mannoside treatment had minimal effect on intestinal bacteria other than the ones that cause most UTIs. This is in stark contrast to the massive changes in the abundance of many microbial species seen after treatment with antibiotics. Furthermore, since mannoside is not an antibiotic, it potentially could be used to treat UTIs caused by antibiotic-resistant strains of bacteria, a growing problem. 

Image result for bdellovibrio bacteriovorus 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.

Kallen estimates that there have been fewer than 10 cases of completely resistant bacterial infections in the United States. Such absolute resistance to all available drugs, though incredibly rare, was a “nightmare scenario,” says Daniel Kadouri, a micro-biologist at Rutgers School of Dental Medicine in Newark, N.J. Antibiotic-resistant bacteria infect more than 2 million people in the United States every year, and at least 23,000 die, according to 2013 data, the most recent available from the CDC.

It’s time to flip the nightmare scenario and send a killer after the killer bacteria, say a handful of scientists with a new approach for fighting infection. The strategy, referred to as a “living antibiotic,” would pit one group of bacteria — given as a drug and dubbed “the predators” — against the bacteria that are wreaking havoc among humans.

The notion of predatory bacteria sounds a bit scary, especially when Kadouri likens the most thoroughly studied of the predators, Bdellovibrio bacteriovorus, to the vicious space creatures in the Alien movies. B. bacteriovorus, called gram-negative because of how they are stained for microscope viewing, dine on other gram-negative bacteria. All gram-negative bacteria have an inner membrane and outer cell wall. The predators don’t go after the other main type of bacteria, gram-positives, which have just one membrane.

“It’s a very efficient killing machine,” Kadouri says. That’s good news because many of the most dangerous pathogens that are resistant to antibiotics are gram-negative (SN: 6/10/17, p. 8), according to a list released by the WHO in February. It’s the predator’s hunger for the bad-guy bacteria, the ones that current drugs have become useless against, that Kadouri and other researchers hope to harness.  Pitting predatory against pathogenic bacteria sounds risky. But, from what researchers can tell, these killer bacteria appear safe. “We know that [B. bacteriovorus] doesn’t target mammalian cells,” Kadouri says.

Predatory bacteria can efficiently eat other gram-negative bacteria, munch through biofilms and even save zebrafish from the jaws of an infectious death. But are they safe? Kadouri and the other researchers have done many studies, though none in humans yet, to try to answer that question.... Other studies looking for potential toxic effects of B. bacteriovorus have so far found none. Both Mitchell and Kadouri tested B. bacteriovoruson human cells and found that the predatory bacteria didn’t harm the cells or prompt an immune response. The researchers separately reported their findings in late 2016 in Scientific Reports and PLOS ONE.

Image result for bdellovibrio bacteriovorus Bdellovibrio bacteriovorus  Credit: BBC

Bdellovibrio bacteriaBACTERIAL COMBATANTS Bdellovibrio bacteria (yellow) attack larger bacteria (blue), using the prey’s remains to replicate. Bdellovibrio microbes are a kind of living antibiotic (predator bacteria). Credit: Science News

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.

Image result for pills wikipedia Sometimes there is a need to take antibiotics during pregnancy. A recent study of 182,369 pregnant women found that the use of certain antibiotics during early pregnancy was linked with a higher rate of miscarriage before 20 weeks. These antibiotics included quinolones (Avelox, Cipro, Levaquin, Tequin), tetracyclines, sulfonamides (Septra, Bactrim), metronidazole (Flagyl), and macrolides (such as azithromycin, clarithromycin, but not erythromycin).

Certain antibiotics were not associated with spontaneous abortions. These antibiotics were penicillins, cephalosporinsnitrofurantoin, and erythromycin. The researchers pointed out that nitrofurantoin is a good antibiotic option for urinary tract infections - which is one of the most common infections in pregnancy. From Medscape:

Antibiotics During Pregnancy May Increase Miscarriage Risk

Use of certain antibiotics early in pregnancy is associated with an increased risk for spontaneous abortion, the authors of a new study report. Macrolides (except erythromycin), quinolones, tetracyclines, sulfonamides, and metronidazole all were associated with a greater risk, compared with penicillins, cephalosporins, or no antibiotic exposure at all, Flory T. Muanda, MD, and colleagues write in an article published in the May 1 issue of CMAJ. 

To assess the potential effect of antibiotics on miscarriage risk, Dr Muanda, from the Faculty of Pharmacy, Université de Montréal, Quebec, Canada, and colleagues analyzed data from the Quebec Pregnancy Cohort on pregnancies that occurred between January 1998 and December 2009....Women who experienced a clinically detected spontaneous abortion before gestational week 20 were considered cases, with the calendar date of the spontaneous abortion designated the index date.  Antibiotic exposure was defined as "having filled at least 1 prescription for any type of antibiotic either between the first day of gestation and the index date, or before pregnancy but with a duration that overlapped the first day of gestation," the authors explain. 

Antibiotic exposure occurred in 12,446 (13%) of those pregnancies, including 1428 that ended in spontaneous abortion (16.4% of all pregnancies ending in spontaneous abortion). Among the control patients, 11,018 (12.6% of all controls) were exposed to antibiotics.

In some instances, these findings support data from other studies, the authors point out. The class effect observed of tetracyclines and quinolones "supports current guidelines used in obstetrics that do not recommend use of these drugs in early pregnancy." Their finding that metronidazole was associated with a 70% increase in the risk for spontaneous abortion is similar to that of a study among Medicaid patients showing a 67% increased risk.... No increased risk was associated with nitrofurantoin, erythromycin, penicillins, or cephalosporins.

Mediterranean Diet is Healthy Eating – A Good Option for Seniors An article was just published in a research journal to discuss the fact that humans - in part due to lifestyles which include less dietary fiber (due to eating fewer varieties and amounts of plants) and due to medical practices (such as frequent use of antibiotics) has resulted in gut "bacterial extinctions". In other words, humans (especially those living an urban industrialized Western lifestyle) have fewer gut bacterial species than those living a more traditional lifestyle, and this loss of bacterial species is linked to various diseases. Humans can increase the number of certain bacterial species, but the loss of some bacterial species is forever. 

The researchers discuss that humans have the "lowest level of gut bacterial diversity"  of any hominid and primate. They stated that the shrinking of the variety of microbial species in the human gut (the gut microbiome) began early in human evolution (as humans started eating more meat), but that it has accelerated dramatically within industrialized societies. And that evidence is accumulating that this gut bacterial "depauperation" - the loss of a variety of bacterial species - may predispose humans to a range of diseases.  Some of it is due to evolution (as humans ate more meat), and some to lifestyle changes. A term is used throughout this paper: depauperate - which means lacking in numbers or variety of species in the gut microbiome (the microbial community or ecosystem).

Other research has also shown that eating a highly processed Western diet results in gut microbial changes that are linked to various diseases (here, here, here) - that is, the microbes being fed are those associated with diseases. Also, certain diets encourage certain microbial species to flourish (here, here).  Bottom line: studies find health benefits from higher levels of dietary fiber - from fruits, vegetables, seeds, nuts, whole grains, and legumes (beans). From Current Opinion In Microbiology:

The shrinking human gut microbiome

Highlights: Humans harbor the lowest levels of gut bacterial diversity of any hominid. Humans in industrialized nations harbor fewer gut bacterial taxa than any primate. Medical practices and lack of dietary fiber may drive gut bacterial extinctions. Depauperate microbiotas may predispose entire human populations to certain diseases.

Mammals harbor complex assemblages of gut bacteria that are deeply integrated with their hosts’ digestive, immune, and neuroendocrine systems. Recent work has revealed that there has been a substantial loss of gut bacterial diversity from humans since the divergence of humans and chimpanzees. This bacterial depauperation began in humanity’s ancient evolutionary past and has accelerated in recent years with the advent of modern lifestyles. Today, humans living in industrialized societies harbor the lowest levels of gut bacterial diversity of any primate for which metagenomic data are available, a condition that may increase risk of infections, autoimmune disorders, and metabolic syndrome. Some missing gut bacteria may remain within under-sampled human populations, whereas others may be globally extinct and unrecoverable.

A typical human harbors on the order of 1013 bacterial cells in the large intestine. This gut microbiota, which can contain over a thousand species, is deeply integrated with virtually every tissue and organ system in the body. Gut bacteria process difficult to digest components of the diet, promote angiogenesis in the intestine, train the immune system, regulate metabolism, and even influence moods and behaviors.

In contrast to hunter–gatherer to agricultural transitions, adoptions of industrial and post-industrial lifestyles have led to massive reductions in bacterial richness within human gut microbiotas. Individuals living in urban centers in the United States harbor fewer gut bacterial species on average than do individuals living more traditional lifestyles in Malawi , Venezuela, Peru, and Papua New Guinea.....Industrialized and traditional lifestyles differ in many respects, confounding the identification of the specific practices that have led to decreases in gut bacterial diversity within industrialized societies. One potential cause is the rise of food processing and the corresponding reductions in the intake of dietary fiber in favor of simple sugars. Recently, studies in model systems have indicated that long-term reductions in dietary fiber can lead to the extirpation of gut bacterial taxa from host lineages. 

Other potential causes of reduced gut bacterial diversity within industrialized human populations include certain modern medical practices. For example, longitudinal studies in humans have shown that levels of gut bacterial diversity decrease drastically after antibiotic use. Although bacterial richness may recover after treatment is completed, the timeline and extent of the restoration is highly subject-dependent. The consequences of antibiotic use on gut bacterial diversity may be most severe when treatment is administered during the early years of life, before the adult microbiota has fully formed .

  It's now 4 years being free of chronic sinusitis and off all antibiotics! Four amazing years since I (and then the rest of my family) started using easy do-it-yourself sinusitis treatments containing the probiotic (beneficial bacteria) Lactobacillus sakei. My sinuses feel great! And yes, it still feels miraculous.

After reading the original ground-breaking research on sinusitis done by Abreu et al (2012), it led to finding and trying L. sakei as a sinusitis treatment. Of course, there is an entire community of microbes (bacteria, fungi, viruses) that live in healthy sinuses - the sinus microbiome - but L. sakei seems to be a key one for sinus health.

I just updated the post The One Probiotic That Treats Sinusitis (originally posted January 2015) using my family's experiences (lots of self-experimentation!) and all the information that people have sent me. The post has a list of brands and products with L. sakei, treatment results, as well as information about some other promising probiotics (beneficial bacteria). Thank you so much!

Thank you all who have written to me  - whether publicly or privately. Please keep writing and tell me what has worked or hasn't worked for you as a sinusitis treatment. If you find another bacteria or microbe or product that works for you - please let me know. It all adds to the sinusitis treatment knowledge base. I will keep posting updates. 

(NOTE: I wrote our background story - Sinusitis Treatment Story back in December 2013, and there is also a  Sinusitis Treatment Summary page with the various treatment methods quickly discussed. One can also click on SINUSITIS under CATEGORIES to see more posts about what is going on in the world of sinusitis research.)

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 new study has summarized what we know about fungi that live in and on babies - and yes, we all have fungi both on and within us. It's called the mycobiome. In healthy individuals all the microbes (bacteria, viruses, fungi, etc) live in balanced microbial communities, but the communities can become "out of whack" (dysbiosis) for various reasons, and microbes that formerly co-existed peacefully can multiply and become problematic. Or other pathogenic microbes can enter the community, and the person becomes ill.

In healthy adults, approximately 0.1% of the microbes in the adult intestine are fungi, from approximately 60 unique species. Most species live peacefully in the body, and some fungi even have health benefits (e.g., Saccharomyces boulardii prevents gastrointestinal disease). Some fungi that many view as no good and involved with diseases (e.g., Candida and Aspergillus) are also found normally in healthy people. Studies show that normally infants also have fungi. Some fungi that live in the baby's gut (thus detected in fecal samples) are Candida (including C. albicans), Saccharomyces, and Cladosporium. The researchers (from the Univ. of Minnesota) point out that the study of fungi in babies has been neglected and much more research needs to be done.

Whether an infant is born vaginally or through cesarean delivery (C-section) affects the composition of the baby's bacterial communities over the first 6 months of life. And similarly, it looks like when the baby passes through the birth canal, the baby is exposed to the mother's mycobiota (fungi), and then these colonize in the infant's gut. Babies born by C-section have some differences in their fungi, such as being colonized by the mother's skin fungi (such as Malassezia fungi). After birth, a parent kissing and touching the baby (skin to skin contact) also transmits microbes, including fungi, to the baby.

Whether a baby drinks breast milk or formula strongly affects the infant's bacteria within the GI tract. For example, breast-fed infants have more Bifidobacteria and Labctobacilli in their gut compared to formula-fed infants. One study found about 700 species of bacteria in breast milk. Thus, scientists think that human breast milk also influences the infant gut mycobiota (fungi), although this research still needs to be done.

Whether a baby is born prematurely or at term (gestational age) is important. For infants born prematurely, intestinal fungi can cause big problems, such as an overgrowth in the gut. For example, 10% of premature babies get invasive, systemic Candidiasis, and about 20% die. Some factors leading to this are: a naïve immune system, bacterial communities out of whack (dysbiosis) due to antibiotic exposure, and use of parenteral nutrition (because this doesn't contain all the microbes from the mother that are in breast milk). In premature infants, beneficial fungi such as S. boulardii, may help to regulate the growth of opportunistic fungal colonizers such as Candida.

it is clear that whether the baby received antibiotics is important. The bacterial community of infants is altered by exposure to antibiotics in both term and preterm infants. For example, in a lengthy study over the first 3 years of life, infants receiving multiple courses of antibiotics had bacterial community changes following antibiotics and their gut bacterial microbiome became less diverse (fewer species). Although most commonly used antibiotics do not directly act on fungi, anti-bacterial antibiotic exposure is associated with alterations to the mycobiota (fungi) -  such as increased rates of fungal colonization, fungal overgrowth, and changes in the fungal community. For ex., premature infants exposed to cephalosporin antibiotics have an increased risk for invasive Candidiasis (a fungal overgrowth).

Out of whack (dysbiotic) microbial communities, incuding fungi, are found in IBD (intestinal bowel diseases) in children. They have more of some fungi (e.g. Pichia jadinii and Candida parapsilosis) and less of Cladosporium cladosporiodes, and an overall decrease in fungal diversity in the gut, as compared to healthy children.

From BMC Medicine: Infant fungal communities: current knowledge and research opportunities

The microbes colonizing the infant gastrointestinal tract have been implicated in later-life disease states such as allergies and obesity. Recently, the medical research community has begun to realize that very early colonization events may be most impactful on future health, with the presence of key taxa required for proper immune and metabolic development. However, most studies to date have focused on bacterial colonization events and have left out fungi, a clinically important sub-population of the microbiota. A number of recent findings indicate the importance of host-associated fungi (the mycobiota) in adult and infant disease states, including acute infections, allergies, and metabolism, making characterization of early human mycobiota an important frontier of medical research. This review summarizes the current state of knowledge with a focus on factors influencing infant mycobiota development and associations between early fungal exposures and health outcomes. We also propose next steps for infant fungal mycobiome research....

 What things in our environment have an effect on the microbes living within us? We now know that gut microbes are important for our health in many ways, and that thousands of species of bacteria, as well as viruses, fungi, and other microbes normally live in a healthy person's gut. We refer to these microbes as the human microbiota or human microbiome. When the community of gut microbes is thrown out of whack (dysbiosis) there can be a number of negative health effects, including diseases. Researchers are just learning about all the microbes within us and their importance in health and disease. [See all posts on the human microbiome.]

Past posts have discussed such things as antibiotics, emulsifiers, different foods and diets, heartburn drugs, etc. having an effect on the human microbiome, but what else? A recent study from China reviewed some environmental pollutants and their effects on gut microbiota - as shown in both human and animal studies. They reviewed studies on antibiotics, heavy metals (arsenic, cadmium, lead), persistant organic pollutants or POPs (organochlorine pesticides, polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers, and polycyclic aromatic hydrocarbons or PAHs), pesticides (permethrin, chlorpyrifos, pentachlorophenol, epoxiconazole and carbendazim, imazalil), emulsifiers, nanoparticles (e.g., silver nanoparticles), and artificial sweeteners. They found that all these environmental pollutants had effects on gut microbes - with some effects lasting for years. Their conclusion: gut microbes are very sensitive to drugs, diet, and environmental pollutants. By the way, notice that popular food ingredients such as emulsifiers and artificial sweeteners were considered "environmental pollutants" by the researchers.

Excerpts from Environmental Pollution: Effects of environmental pollutants on gut microbiota

Environmental pollutants have become an increasingly common health hazard in the last several decades. Recently, a number of studies have demonstrated the profound relationship between gut microbiota and our health. Gut microbiota are very sensitive to drugs, diet, and even environmental pollutants. In this review, we discuss the possible effects of environmental pollutants including antibiotics, heavy metals, persistent organic pollutants, pesticides, nanomaterials, and food additives on gut microbiota and their subsequent effects on health. We emphasize that gut microbiota are also essential for the toxicity evaluation of environmental pollution. In the future, more studies should focus on the relationship between environmental pollution, gut microbiota, and human health.

Thousands of species are found in the gut microbiome, and the majority of these species belong to six bacterial phyla: Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, Fusobacteria, and Verrucomicrobia (Eckburg et al., 2005). Gut microbiota are highly dynamic and have substantial interindividual and intraindividual variation....The gut microbiota are very essential for host health. They participate in the regulation of many physiological functions. The gut microbiota reside in our intestinal mucus layer and even participate in shaping the mucus layer (Jakobsson et al., 2015). They help us to digest food (such as fiber); synthesize vitamins and amino acids (Spanogiannopoulos et al., 2016); play very important roles in energy metabolism and storage, immune system modulation, growth, and neurodevelopment; and can even regulate our behavior.... The occurrence of many diseases is correlated with altered gut microbiome composition (Lange et al., 2016). Gut microbiota dysbiosis is considered to be a potential cause of obesity (Cani et al., 2007; Fei and Zhao, 2013). However, gut microbiota are very sensitive to drugs, diet, and environmental pollutants.

Although most environmental pollutants do not directly target gut microbiota, some pollutants can enter the body and interact with the gut microbiota through different pathways. A number of previous studies have shown that exposure to environmental pollutants can alter the composition of the gut microbiome, leading to disorders of energy metabolism, nutrient absorption, and immune system function or the production of other toxic symptoms (Jin et al., 2015c; Zhang et al., 2015b). In the present review, we conclude that different kinds of environmental pollutants can induce gut microbiota dysbiosis and have multiple potential adverse effects on animal health

Heavy metals in the environment have become a severe health risk in recent years (Liu et al., 2016a). As a common form of environmental pollution, heavy metals are associated with a wide range of toxic effects, including carcinogenesis, oxidative stress, and DNA damage, and effects on the immune system..... Recently, several studies have stated that heavy metal exposure could also lead to gut microbiota dysbiosis, indicating that study of gut microbiota provides a new approach to analyze the mechanisms of heavy metal toxicity

Immune system function is tightly coupled to our gut microbiome. Gut microbiota and their metabolites can interact with both the innate immune system and the adaptive immune system (Honda and Littman, 2016; Thaiss et al., 2016).... Alterations in the gut microbiome can disrupt the balance between the host immune system and gut microbiota, induce immune responses, and even trigger some immunological diseases. Furthermore, immune system imbalance may influence the microbiota metabolites. For example, trimethylamine, which is absorbed from food by gut microbiota, can induce atherosclerosis (Chistiakov et al., 2015).

Image result for Klebsiella pneumoniae bacteria 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 woman was isolated so that her superbug would not infect other patients in the hospital. And subsequent samples from other patients near her in the hospital have not turned it up. If this superbug is somehow gone from the hospital and gone from the U.S., that would be great news. But even if so, other pan-resistant superbugs are likely to emerge.

Here’s why: The most worrisome kind of colistin resistance is caused by a single gene called mcr-1....What makes mcr-1 special is that sits on a loop of free-floating DNA called a plasmid, which bacteria of different species can pass back and forth. And there are many plasmids out there with genes that confer resistance to this or that class of antibiotics. Where might bacteria go to hang out and swap plasmids? Well your gut is a big bag of bacteria. One day, you might pick up some bacteria with a plasmid carrying resistance to colistin. Years later, you might pick up some bacteria with a plasmid carrying resistance to carbapenems. And so. They start swapping plasmids. All this time you are healthy, and these bacteria just lurk in your gut, not causing much trouble. Then you get sick, your immune system is down, and you take antibiotics for an infection. The antibiotics kill everything but the resistant bacteria, which have by now collected all the resistance genes and no competition. That’s how you get a pan-resistant infection.