Tag Archives: antibiotics

Antibiotic resistance is at a crisis point – but new drugs could help defeat superbugs

Credit: Pxhere.

Antibiotic resistance poses one of the most important health challenges of the 21st century. And time has already run out to stop its dire consequences.

The rise of multidrug-resistant bacteria has already led to a significant increase in human disease and death. The U.S. Centers for Disease Control and Prevention estimates that approximately 2.8 million people worldwide are infected with antibiotic-resistant bacteria, accounting for 35,000 deaths each year in the U.S. and 700,000 deaths around the globe.

A 2019 joint report by the United Nations, World Health Organization and World Organization for Animal Health states that drug-resistant diseases could cause 10 million deaths each year by 2050 and force up to 24 million people into extreme poverty by 2030 if no action is taken. Superbugs are already able to evade all existing treatments – a 70-year-old woman from Nevada died in 2016 from a bacterial infection resistant to every available antibiotic in the U.S.

I am a biochemist and microbiologist who has been researching and teaching about antibiotic development and resistance over the past 20 years. I believe that solving this crisis requires more than just proper antibiotic use by doctors and patients. It also requires mutual investment and collaboration across industries and the government.

Antibiotics revolutionized modern medicine. But improper usage of antibiotics and lack of research funding have led to a growing crisis of antibiotic-resistant bacteria.

How do bacteria become resistant to drugs?

In order to survive, bacteria naturally evolve to become resistant to the drugs that kill them. They do this via two methods: genetic mutation and horizontal gene transfer.

Genetic mutation occurs when the bacteria’s DNA, or genetic material, randomly changes. If these changes let the bacteria evade an antibiotic that would have otherwise killed it, it will be able to survive and pass on this resistance when it reproduces. Over time, the proportion of resistant bacteria will increase as nonresistant bacteria are killed by the antibiotic. Eventually, the drug will no longer work on these bacteria because they all have the mutation for resistance.

The other method bacteria use is horizontal gene transfer. Here, one bacterium acquires resistance genes from another source, either through their environment or directly from another bacterium or bacterial virus.

Bacteria can gain resistance via infection from a virus (transduction), picking it up from the environment (transformation) or direct transfer from other bacteria (conjugation). 2013MMG320B/Wikimedia Commons

But the antibiotic resistance crisis is largely anthropogenic, or human-made. Factors include the overuse and abuse of antibiotics, as well as a lack of regulations and enforcement pertaining to proper use. For example, doctors prescribing antibiotics for nonbacterial infections and patients not completing their prescribed course of treatment give bacteria the chance to evolve resistance.

There are also no regulations on antibiotic use in animal agriculture, including controlling leakage into the surrounding environment. Only recently has there been a push for more antibiotic oversight in agriculture in the U.S. As an October 2021 report by the National Academies of Sciences, Engineering and Medicine noted, antibiotic resistance is an issue that connects human, environmental and animal health. Effectively addressing one facet requires addressing the others.

The antibiotic discovery void

One of the major reasons for the resistance crisis is the stalling of antibiotic development over the past 34 years. Scientists call this the antibiotic discovery void.

Researchers discovered the last class of highly effective antibiotics in 1987. Since then, no new antibiotics have made it out of the lab. This is partly because there was no financial incentive for the pharmaceutical industry to invest in further research and development. Antibiotics at the time were also effective at what they did. Unlike chronic diseases like hypertension and diabetes, bacterial infections don’t typically require ongoing treatment, and so have a lower return on investment.

Reversing this trend requires investment not just in drug development, but also in the basic research that allows scientists to understand how antibiotics and bacteria work in the first place.

Basic research focuses on advancing knowledge rather than developing interventions to solve a specific problem. It gives scientists the opportunity to ask new questions and think long-term about the natural world. A better understanding of the driving forces behind antibiotic resistance can lead to innovations in drug development and techniques to combat multidrug-resistant bacteria.

Basic science also provides opportunities to mentor the next generation of researchers tasked with solving problems like antibiotic resistance. By teaching students about the fundamental principles of science, basic scientists can train and inspire the future workforce with the passion, aptitude and competency to address problems that require scientific understanding to solve.

Collaboration by triangulation

Many scientists agree that addressing antibiotic resistance requires more than just responsible use by individuals. The federal government, academia and pharmaceutical companies need to partner together in order to effectively tackle this crisis – what I call collaboration by triangulation.

[The Conversation’s science, health and technology editors pick their favorite stories. Weekly on Wednesdays.]

Collaboration between basic scientists in academia and pharmaceutical companies is one pillar of this effort. While basic science research provides the knowledge foundation to discover new drugs, pharmaceutical companies have the infrastructure to produce them at a scale typically unavailable in academic settings.

The remaining two pillars involve financial and legislative support from the federal government. This includes enhancing research funding for academics and changing current policies and practices that impede, rather than offer, incentives for pharmaceutical company investment in antibiotic development.

To that end, a bipartisan bill proposed in June 2021, the Pioneering Antimicrobial Subscriptions to End Upsurging Resistance (PASTEUR) Act, aims to fill the discovery void. If passed into law, the bill would pay developers contractually agreed-upon amounts to research and develop antimicrobial drugs for a time period that ranges from five years up to the end of the patent.

I believe the passage of this act would be an important step in the right direction to address antibiotic resistance and the threat it poses to human health in the U.S. and around the globe. A monetary incentive to take up basic research around new ways to kill dangerous bacteria seems to me like the world’s best available option for emerging from the antibiotic resistance crisis.The Conversation

Andre Hudson, Professor and Head of the Thomas H. Gosnell School of Life Sciences, Rochester Institute of Technology

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Most appendicitis surgeries can be avoided with antibiotics, reports the largest trial yet on the subject

Antibiotics are an effective first-line treatment for most cases of appendicitis, according to the American College of Surgeons.

Image credits Steve Buissinne.

The decision is based on the results from the Comparing Outcomes of antibiotic Drugs and Appendectomy (CODA) trial, the largest randomized medical trial of appendicitis treatments ever performed. It included 25 hospitals across 14 states, totaling 1,552 patients with appendicitis. These participants were then randomized to undergo an appendectomy (surgery to remove the appendix) or follow an antibiotics course.

While both approaches had their advantages and downsides, the overall conclusion of the CODA trial is that both are safe to use and efficient in treating the condition.

Noninvasive is fine

“In the first three months after taking antibiotics for the condition, nearly 7 in 10 patients in the antibiotic group avoided an appendectomy. By four years, just under 50% had the surgery,” said Dr. David Flum, co-principal investigator and professor and associate chair of surgery at the University of Washington (UW) School of Medicine. “Other outcomes favored either antibiotics or surgery. Putting it all together, antibiotics look to be the right treatment for many, but probably not all, patients with appendicitis.”

“While there were advantages and disadvantages to each treatment, we found that both treatments are safe, and patients will likely value these outcomes differently based on their unique symptoms, concerns, and circumstances,” he adds.

The authors note that one of the most important factors regarding the efficacy of antibiotics for these patients was the presence of appendicoliths, calcified deposits found in about one-quarter of patients with acute appendicitis. Patients with appendicoliths had a higher chance of experiencing complications and a higher likelihood of needing an appendectomy during the first 30 days of treatment than their peers.

However, by the 90-day mark, this group of patients had no greater chance of needing an appendectomy than other appendicitis patients enrolled in the trial.

The percentage of patients in the antibiotics group who later underwent appendectomy was 40% at 1 year and 46% at the 2-year mark. This percentage was higher in patients with appendicoliths.

Overall, however, these findings are quite encouraging. Appendicitis is generally treated as an emergency, and the standard treatment approach is surgery, to have it removed. In most cases, even the suspicion that a patient might have appendicitis is cause enough for a doctor to send them into surgery, in a bid to avoid the possible complications caused by the rupturing of an inflamed appendix.

Needless to say, nobody likes undergoing surgery. The results of this trial show that antibiotics are an effective treatment option for a majority of cases. Patients and doctors should work together to discuss the best treatment approach. On the one hand, this would help improve the quality of life for appendicitis patients; on the other, it will free up medical resources which can be used on other essential surgeries.

“Given these results and new treatment guidelines, it is important for surgeons and patients to discuss the pros and cons of both surgery and antibiotics in deciding on the treatment that’s best for that person at that time,” said Dr. Giana Davidson, associate professor of surgery at UW and director of the CODA trial’s clinical coordinating center.

Towards that end, the CODA team put together an online decision-making tool for patients (http://www.appyornot.org) to help them better decide what option is right for them. The site includes videos in English and Spanish discussing the issue — other languages will be included in the future — to help inform them on the nuances of this choice.

“In the emergency setting, patients with appendicitis can make a treatment decision hurriedly,” Davidson said. “This online tool was built to help communicate the CODA results in laymen’s terms, and to spur a conversation between patients and surgeons about potential benefits and harms of each approach.”

The paper “Antibiotics versus Appendectomy for Acute Appendicitis — Longer-Term Outcomes” has been published in The New England Journal of Medicine.

Scientists Find New Technique to Defeat Antibiotic-Resistant Bacteria

Petri Dish Bacteria
Photo by Andrian Lange/Unsplash

Stress often causes bacteria to form biofilms. The stress can be in the form of a physical barrier, ultraviolet light, or a toxic substance such as antibiotics. These biofilms take from hours to days to form and can be of various shapes, sizes, colors, and textures depending on the species of bacteria involved.

Being in the state of a biofilm protects them from hazardous substances in their environment — biofilms have a unique outer wall, with different physical and chemical properties than their individual cells. They can coordinate metabolically, slow their growth, and even form an impenetrable barrier of wrinkles and folds.

This is one way they achieve high antibiotic resistance. Researchers from the United Kingdom recently studied the bacteria B. Sultilis transition from a free-moving swarm to a biofilm as a defense mechanism and published what they did to combat its antibiotic resistive properties in eLife.

Photo by Clemencedg/CC BY-SA 3.0/Wikimedia

To determine if their test strain behaves as others do, they recreated first performed stress tests on them. They tested the bacteria’s response to a physical barrier, ultraviolet light, and an antibiotic. The addition of a physical barrier led to a single-to-multi-layer transition of the bacteria, followed by an increase in cell density and the formation of multilayer islands near the barrier. Later, wrinkles developed on the islands near the barrier in the area the islands had started to appear initially.

When they applied ultraviolet light to the swarm, they again observed a drop in cell speed and an increase in density. And after the scientists added a large dose of the antibiotic kanamycin the bacterial cells formed a biofilm. The researchers then devised a strategy to tackle this bacteria biofilm.

They added kanamycin to the environment of a new batch of swarming bacterial cells and watched as a biofilm began to take shape. They then re-administered the antibiotic in a much larger dose than the first one, just before the completion of the biofilm’s formation. The breakdown of the partially formed biofilm and the death of the bacterial cells occurred as a result.

This shows that antibiotic-resistant bacteria lose their resistance to antibiotics when they undergo a phase transition, right before transitioning to a biofilm, where they would become much more resilient. So with proper timing of the administering of antibiotics, bacteria can be attacked in their most vulnerable state and eliminated. Researchersbelieve similar swarm-to-biofilm transitions occur in other bacterial species too.

Their research could pave the way to finding more effective ways of managing clinically relevant bacteria. Such as Salmonella enterica which spreads to the bloodstream and is transmitted by contaminated food. Or the multidrug-resistant Pseudomonas aeruginosa which causes infections in the blood, lungs (pneumonia), and other parts of the body after surgery and is spread in hospitals.

Scientists synthesize antibiotics to conquer resistant microbes

Credit: Pixabay.

The COVID-19 pandemic is on everyone’s mind right now. However, there’s another medical crisis looming that may be far more dangerous and consequential for decades to come. Scientists have been warning for years that microbes are becoming resistant to even the strongest antibiotics we throw at them. According to a new study, our silver lining might lie in the chemical synthesis of antibiotics that neutralize microbial adaptations.

Revisiting shelved antibiotics

After Alexander Fleming’s discovery of penicillin in 1928, the world entered the golden age of antibiotics. Within a remarkably small timeframe, the wide-scale adoption of antibiotics post-WWII changed the leading cause of death in the United States from communicable diseases to non-communicable diseases (cardiovascular disease, cancer, and stroke), and raised the average life expectancy at birth from 48 years to 78.8 years.

But microbes haven’t stayed idle. Some bacteria developed proteins or other molecules that allow them to multiply despite the presence of antibiotics. When such adaptations occur in a population, they quickly proliferate. This is why tens of thousands of preventable deaths occur each year due to drug-resistant strains of common bacteria like Staphylococcus aureus and Enterococcus faecium.

Until not too long ago, streptogramins, a class of antibiotics, used to be very effective against S. aureus infections. But then the bacteria started to produce proteins called virginiamycin acetyltransferases (Vats), which recognize streptogramins and will chemically deactivate these drugs before they can bind to the cell’s ribosome. This is why streptogramins are considered to be useless in many cases, especially for hospital-acquired bacterial infections.

But we shouldn’t cross out streptogramins just yet. Like most antibiotics, streptogramins are derived from naturally occurring compounds produced by other bacteria, which are later tweaked for optimized performance in the human body.

Assembling antibiotics like LEGO bricks

Researchers at the University of California San Francisco employed a different approach to antibiotic production, which enabled them to synthesize streptogramins that can overcome the resistance conferred by Vat enzymes.

However, the scientists didn’t create new antibiotics from scratch. That would be too time-consuming, expensive, and prone to failure. Instead, the team led by Ian Seiple, an assistant professor in the UCSF School of Pharmacy’s Department of Pharmaceutical Chemistry and the Cardiovascular Research Institute (CVRI), took a modular approach, redesigning existing streptogramins by altering and joining together precursor molecules like LEGO pieces. The resulting “rebuilds” of existing drugs blocked Vats from deactivating the antibiotics.

“The aim is to revive classes of drugs that haven’t been able to achieve their full potential, especially those already shown to be safe in humans,” said Seiple in a statement. “If we can do that, it eliminates the need to continually come up with new classes of drugs that can outdo resistant bacteria. Redesigning existing drugs could be a vital tool in this effort.”

“This system allows us to manipulate the building blocks in ways that wouldn’t be possible in nature,” added the researcher, who is the lead author of the new study published today in the journal Nature . “It gives us an efficient route to re-engineering these molecules from scratch, and we have a lot more latitude to be creative with how we modify the structures.”

In order to determine which LEGO bricks they would have to modify, the researchers employed cryo-electron microscopy and x-ray crystallography to create three-dimensional pictures of the drug at near-atomic resolution. They also modeled the bacterial ribosome and the Vat protein. This way, the researchers could isolate molecules that are essential to antibiotic function.

The team of researchers found that two of the seven building blocks for streptogramins were promising targets for chemical modification. After tweaking these regions, the researchers came up with a new promising candidate against streptogramin-resistant S. aureus. Experiments on mice showed that the antibiotic was over 10 times more effective than classical streptogramins.

According to Seiple, the same approach can be applied to other classes of antibiotics that have been shelved due to microbial resistance.

“We learned about mechanisms that other classes of antibiotics use to bind to the same target,” he said. “In addition, we established a workflow for using chemistry to overcome resistance to antibiotics that haven’t reached their potential.”

“It’s a never-ending arms race with bacteria,” said James Fraser, a professor in the School of Pharmacy’s Department of Bioengineering and Therapeutic Sciences in the UCSF School of Pharmacy. “But by studying the structures involved— before resistance arises—we can get an idea of what the potential resistance mechanisms will be. That insight will be a guide to making antibiotics that bacteria can’t resist.” 

Bangladesh’s waters are heavily contaminated with medicine, pesticides, and other chemicals

Researchers from the University at Buffalo (UB) and icddr,b, a leading global health research institute in Bangladesh, report that the waters in the city of Dhaka, the country’s capital, are awash with chemicals.

The city of Dhaka.
Image via Pixabay.

The research effort began in 2019 and it involved testing a lake, a canal, and a river in Dhaka, which is also the country’s largest city. The team also sampled water from ditches, ponds, and drinking wells in a rural area known as Matlab. All in all, the analysis revealed the existence of a mix of both pharmaceutical and non-pharmaceutical compounds including antibiotics, antifungals, anticonvulsants, anesthetics, antihypertensive drugs, pesticides, and flame retardants — among others.

Chemically-rich

“When we analyzed all these samples of water from Bangladesh, we found fungicides and a lot of antibiotics we weren’t looking for,” says Diana Aga, PhD, Henry M. Woodburn Professor of Environmental Chemistry in the UB College of Arts and Sciences and corresponding author of the study. “This kind of pollution is a problem because it can contribute to the development of bacteria and fungi that are resistant to the medicines we have for treating human infection.”

To conduct the study, members of the team traveled to Bangladesh to sample water and train scientists there on sample collection and preparation techniques. The samples were analyzed in the Buffalo laboratory using state-of-the-art analytical methods.

Dhaka’s canal and river contained several families of chemicals, with the team noting multiple antibiotics and antifungals at these two sites. Rural test sites generally showed lower levels of antimicrobials, but antifungal agents were commonly seen, as were some antibiotics.

While not all chemicals were identified at all test sites and sometimes present only in low amounts, the team says the ubiquity of contamination seen in Dhaka is very concerning. Carbendazim, an antifungal agent, alongside insect repellent DEET, and flame retardants, were found in each and every sample the team retrieved.

“The fact that we found so many different types of chemicals is really concerning,” Aga says. “I recently saw a paper, a lab study, that showed exposure to antidepressants put pressure on bacteria in a way that caused them to become resistant to multiple antibiotics. So it’s possible that even chemicals that are not antibiotics could increase antibacterial resistance.”

Finding antimicrobial compounds in the water around urban areas isn’t surprising, as such chemicals are often released through urine and eventually wind up in rivers. At rural sites, the presence of antibiotics and antifungals in water is most likely tied to local agriculture.

Furthermore, such contamination is not unique to Bangladesh, but “is expected in many countries throughout the world where antimicrobial use is poorly regulated in both human medicine and agriculture,” says study co-author Shamim Islam, MD, clinical associate professor of pediatrics in the Jacobs School of Medicine and Biomedical Sciences at UB.

“As undertaken in this study, we feel analyzing and characterizing such environmental antimicrobial contamination is a critically important component of global antimicrobial resistance surveillance and mitigation efforts,” Islam concludes.

The paper “Retrospective suspect screening reveals previously ignored antibiotics, antifungal compounds, and metabolites in Bangladesh surface waters” has been published in the journal Science of The Total Environment.

New, free app modifies antibiotics to work against drug-resistant infections

A new web tool could help us find novel antibiotics that work against Gram-negative bacteria (which tend to gain antibiotic resistance). The app works by offering instructions on converting drugs that kill other bacteria into compounds that work against Gram-negative strains.

Image credits Sheep purple / Flickr.

Gram-negative bacteria have an extra, outer membrane, that renders most antibiotics useless. It helps the bacteria to survive out in nature where many organisms (like fungi) naturally produce antibiotics. This would be fine except for the fact that some Gram-negative bacteria like to cause nasty infections in humans — which don’t respond to treatment and put patients at risk. In order to prove that their tool works, the team used it to modify a drug and successfully tested it against three different Gram-negative bacterial strains.

Computer, design a drug

“It’s really hard to find new antibiotics for Gram-negative pathogens, because these bacteria have an extra membrane, an outer membrane, that’s very good at keeping antibiotics out,” said University of Illinois chemistry professor Paul Hergenrother, who led the research.

Hergenrother explains that no new antibiotics against Gram-negative bacteria have been approved by the Food and Drug Administration in 50 years, leaving us virtually exposed to the pathogens. His team has been hard at work finding a solution for several years now. His team “discovered the molecular features that allowed an antibiotic compound to surpass this barrier” a few years ago, he said, adding that this tool is the implementation of those findings.

The team’s app/web tool is called eNTRyway, and evaluates the potential of known drug compounds to pierce the outer membrane of Gram-negative bacteria. It also estimates whether the drug can perform this at high enough levels to accumulate inside the bacterial cells in functional doses. Even better, this app can also point out how to modify existing drugs for the task of tackling Gram-negative pathogens.

The team used eNTRyway to identify a drug that’s currently in use against Gram-positive infections that, with a little bit of tweaking, could potentially hurt Gram-negative strains. The team then synthesized the drug (by adding an amine group to the original one) and tested it on Gram-negative infections in mice. It proved effective against several different strains, the team reports, successfully accumulating behind the outer membrane of these pathogens.

The whole process took only a few weeks, Hergenrother said. The team hopes that their app will greatly speed up the development of such drugs in the future.

“We can use this tool to rapidly identify compounds that accumulate in Gram-negative bacteria,” he said.

“Keep in mind that before this, over 100 derivatives of this same compound had been made. We found them in patents and papers,” he said. “And none of these other derivatives had notable Gram-negative activity.”

The team went on to identify over 60 antibiotics that could be converted to fight Gram-negative bacteria using a variety of chemical pathways. For example, one of their newly-developed drugs (christened Debio-1452-NH3) disturbs fatty acid synthesis in bacterial cells, but not in mammalian ones.

The paper “Implementation of permeation rules leads to a FabI inhibitor with activity against Gram-negative pathogens” has been published in the journal Nature Microbiology.

Bacteria’s social lives influence how they develop drug resistance

How bacteria live influences how they develop antibiotic resistance, a new study reports.

Independent and communal bacteria react differently to antibiotics and develop resistance to medicine in different ways, according to researchers at the University of Pittsburgh School of Medicine. The findings could help shape more efficient methods of infection control and antimicrobial therapies.

Together we stand

“What we’re simulating in the lab is happening in the wild, in the clinic, during the development of drug resistance,” said senior author Vaughn Cooper, Ph.D., director of the Center for Evolutionary Biology and Medicine at Pitt. “Our results show that biofilm growth shapes the way drug resistance evolves.”

According to study lead author Alfonso Santos-Lopez, Ph.D., the results could be used to find a chink in the armor of drug-resistant bacteria.

For the study, the team repeatedly exposed bacterial cultures to ciprofloxacin (a broad-spectrum antibiotic) to force them to develop resistance — and they did. However, the team was surprised to see that the ‘lifestyle’ of individual species led to them developing specific mechanisms for drug resistance.

The paper showcases the role “collateral sensitivity” can play in our fight against drug-resistant pathogens. In simple terms, when bacteria evolve to be more resistant to one drug or class of drugs, this can make them vulnerable to other antibiotics. If you know which drug that is, then you have an effective tool against the bugs.

In the team’s experiment, communal bacterias — which bunch together into biofilms — that developed resistance to ciprofloxacin also lost virtually all resistance to the cephalosporin class of antibiotics. In contrast, free-floating (individual) bacteria didn’t become susceptible to cephalosporins and developed, on average, 128 times the resistance to ciprofloxacin of the biofilm-grown bacteria.

“Biofilms are a more clinically relevant lifestyle,” said study coauthor Michelle Scribner, a doctoral student in Cooper’s lab. “They’re thought to be the primary mode of growth for bacteria living in the body. Most infections are caused by biofilms on surfaces.”

The paper “Evolutionary pathways to antibiotic resistance are dependent upon environmental structure and bacterial lifestyle” has been published in the journal eLife.

How one thumb injury led to one man getting drunk from eating carbs

A recent case study recounts the story of one man getting drunk from pizzas, sodas, and everything in between.

Perhaps the coolest sounding medical complication ever, auto-brewery syndrome (ABS) is a rarely-diagnosed condition where patients can get very drunk when eating carbohydrates (the much-bemoaned ‘carbs’). And, at least in the case of one 46-year-old patient, ABS can cause some social tensions when nobody believes you haven’t been drinking when a plate of pasta leaves you staggering.

Involuntarily inebriated

The case study looks at a patient that had completed a course of antibiotics for a thumb injury in 2011. One week after the treatment, he reported to the doctor’s office citing uncharacteristic personality changes such as depression, ‘brain fog’, aggressive behavior, and memory loss.

He was at one point referred to a psychiatrist and given antidepressants. However, the nature of his condition wasn’t fully understood until he was pulled over by police one morning in an apparent case of drunk driving. At the time, he refused to take a breathalyzer test, as he knew for a fact that he didn’t drink any alcohol. The officer had him hospitalized for a blood test. This showed the patient had a blood-alcohol level of 200 mg/dL, equivalent to having drunk approximately 10 pints of beer, and enough to cause confusion, disorientation, impaired balance, and slurred speech.

“The hospital personnel and police refused to believe him when he repeatedly denied alcohol ingestion,” researchers from Richmond University Medical Centre note in their case report.

Subsequent medical tests found Saccharomyces cerevisiae (brewer’s yeast) and a related fungus in the patient’s stool. S. cervisiae is used in brewing as it breaks down sugars in plants into alcohol. While he was successfully treated, later flare-ups of the same condition — with the most serious incident involving a fall while inebriated that caused intracranial bleeding — led to him being diagnosed with ABS.

The researchers note that while recovering in the hospital, the patient’s blood alcohol spiked as high as 400 mg/dL. Still, “medical staff refused to believe that he did not drink alcohol despite his persistent denials”. Ultimately, the patient received treatment conducted in collaboration with the Richmond University specialists; the team used a cocktail of anti-fungal therapies supported by probiotics to reset his gut microflora. With the exception of one relapse when the patient sneakily enjoyed some pizza and soda without telling his doctors, the fungal infection has been successfully treated, the team explains.

“Approximately 1.5 years later, he remains asymptomatic and has resumed his previous lifestyle, including eating a normal diet while still checking his breath alcohol levels sporadically,” the researchers explain.

It’s a happy ending for the patient, who looks to be finally free not only of his unasked-for drunkenness (and resultant health problems) but also of the cloud of disbelief it invited in those around him.

“For years, no one believed him,” says Fahad Malik, a chief medical resident at the University of Alabama at Birmingham and the lead author of the case study. “The police, doctors, nurses and even his family told him he wasn’t telling the truth, that he must be a closet-drinker.”

“We believe that our patient’s symptoms were triggered by exposure to antibiotics, which resulted in a change in his gastrointestinal microbiome allowing fungal overgrowth,” the authors explain, noting that we are only starting to recognise the complexity of this rare and probably under-diagnosed condition.

The paper “Case report and literature review of auto-brewery syndrome: probably an underdiagnosed medical condition” has been published in the journal BMJ Open Gastroenterology.

Dolphins are seeing a rise of antibiotic-resistant bacteria and it’s our fault

Antibiotic resistance is reaching dramatic levels in some wild ecosystems, reports a study on bottlenose dolphins living in Florida’s Indian River Lagoon.

Image credits Claudia Beer.

One of the scariest public health issues we’re contending with today is the rise of antibiotic resistance. Many common bacterial strains are evolving to resist the drugs we rely on to treat them, making even mundane infections potentially deadly — and antibiotic development isn’t keeping up.

Once primarily confined to health care settings, these resistant strains of bacteria are now commonly found in other places, especially marine environments, a new study reports.

No cure for the porpoise

“In 2009, we reported a high prevalence of antibiotic resistance in wild dolphins, which was unexpected,” said Adam M. Schaefer, MPH, lead author and an epidemiologist at Florida Atlantic University’s (FAU) Harbor Branch. “Since then, we have been tracking changes over time and have found a significant increase in antibiotic resistance in isolates from these animals.”

“This trend mirrors reports from human health care settings.”

The team from Florida Atlantic University’s Harbor Branch Oceanographic Institute, in collaboration with the Georgia Aquarium and the Medical University of South Carolina and Colorado State University, conducted a long-term study from 2003 to 2015 of antibiotic resistance among bacteria retrieved from dolphins (Tursiops truncatus) in Florida’s Indian River Lagoon. The site was picked because this lagoon has a large coastal human population with a pronounced environmental impact.

Using the Multiple Antibiotic Resistance (MAR) index, the researchers obtained a total of 733 pathogen isolates from 171 individual bottlenose dolphins. Several of these strains are important human pathogens, the team explains.

“Based on our findings, it is likely that these isolates from dolphins originated from a source where antibiotics are regularly used, potentially entering the marine environment through human activities or discharges from terrestrial sources,” Schaefer explains.

The overall prevalence of resistance to at least one antibiotic for the 733 isolates was 88.2%. The highest prevalence of resistance found by the team were to erythromycin (91.6% of isolates), ampicillin (77.3%) and cephalothin (61.7%), and resistance to cefotaxime, ceftazidime, and gentamicin increased significantly between sampling periods for all the isolates.

Resistance to ciprofloxacin among E. coli isolates more than doubled between sampling periods, the team reports, reflecting recent trends in human clinical infections. The MAR index increased significantly from 2003-2007 and 2010-2015 for Pseudomonas aeruginosa and Vibrio alginolyticus. P. aeruginosa causes respiratory system and urinary tract infections among others, while the latter is a common pathogenic strain of Vibrio found to cause serious seafood-poisoning.

“The nationwide human health impact of the pathogen Acinetobacter baumannii is of substantial concern as it is a significant nosocomial pathogen with increasing infection rates over the past 10 years,” said Peter McCarthy, Ph.D., co-author, a research professor and an associate director for education at FAU’s Harbor Branch.

“The high MAR index for this bacteria isolated from dolphins in the Indian River Lagoon represents a significant public health concern.”

The paper “Temporal Changes in Antibiotic Resistance Among Bacteria Isolated from Common Bottlenose Dolphins (Tursiops truncatus) in the Indian River Lagoon, Florida, 2003-2015” has been published in the journal Aquatic Mammals.

Hospital room.

Hospitals in Europe are contributing to the spread of extremely drug-resistant bacteria

New research from the Wellcome Sanger Institute is mapping the spread of extremely drug-resistant (XDR) strains of Klebsiella pneumoniae through hospitals in Europe.

Hospital room.

Image via Pixabay.

As far as antibiotics go, our last line of defense are carbapenem antibiotics; when all other antibiotics fail in dealing with a certain infection, these are sent in to finish the job. However, a Europe-wide survey of the Enterobacteriaceae family of bacteria found that antibiotic-resistant strains of Klebsiella pneumoniae, an opportunistic pathogen that can cause respiratory and bloodstream infections in humans, are spreading through hospitals in Europe. The findings are based on samples taken from patients in 244 hospitals in 32 countries.

Cureless

“In the case of carbapenem-resistant Klebsiella pneumoniae, our findings imply hospitals are the key facilitator of transmission — over half of the samples carrying a carbapenemase gene were closely related to others collected from the same hospital, suggesting that the bacteria are spreading from person-to-person primarily within hospitals,” says Dr. Sophia David, first author of the study.

It is estimated that carbapenem-resistant K. pneumoniae caused 341 deaths in Europe in 2007, a figure that grew to 2,094 by 2015 (a six-fold increase), the authors explain. This high number of deaths is owed to the fact that once carbapenems lose the ability to fight a population of antibiotic-resistant bacteria, doctors have very few options left. Infants, the elderly, and immuno-compromised individuals, whose bodies can’t take the strain of said options, are thus particularly at risk.

The survey, its authors write, is the largest of its kind and the first concrete step towards consistent surveillance of carbapenem-resistant bacteria in Europe. It was built from over 2,000 samples of K. pneumoniae collected from patients across 244 hospitals and sent to the Wellcome Sanger Institute, where the genomes of 1,700 of them were sequenced. The team identified a small cluster of genes that, when expressed, cause a strain to produce enzymes called carbapenemases that neutralizes the antibiotics.

The emergence of certain strains that carry one or more carbapenemase genes is of particular concern to public health, the authors explain, as these strains have spread relatively rapidly. Today’s heavy use of antibiotics in hospitals likely stacks the playing field in favor of these bacteria, the team adds, as they outcompete other strains that are more easily treatable with antibiotics. Samples used in the study were also more likely to be closely related to other samples in the same country rather than across countries, which suggests that national healthcare systems as a whole contribute to spread the strains around.

Not all is lost, however. The team explains that despite the deadliness of this carbapenem-resistant strains, infection control procedures in hospitals — ranging from consideration of how patients move between hospitals to hygiene interventions — still have an important impact.

“We are optimistic that with good hospital hygiene, which includes early identification and isolation of patients carrying these bacteria, we can not only delay the spread of these pathogens, but also successfully control them,” says Professor Hajo Grundmann, co-lead author and Head of the Institute for Infection Prevention and Hospital Hygiene at the Medical Centre, University of Freiburg.

“This research emphasises the importance of infection control and ongoing genomic surveillance of antibiotic-resistant bacteria to ensure we detect new resistant strains early and act to combat the spread of antibiotic resistance.”

The results were made available through MicroReact, a publicly-available web-based tool developed by the Centre for Genomic Pathogen Surveillance to help researchers and healthcare systems chart the spread of antibiotic resistance in pathogens like K. pneumoniae. A second survey is currently being planned.

“Genomic surveillance will be key to tackling the new breeds of antibiotic-resistant pathogen strains that this study has identified,” says Professor David Aanensen, co-lead author and Director of the Centre for Genomic Pathogen Surveillance.

“Currently, new strains are evolving almost as fast as we can sequence them. The goal to establish a robust network of genome sequencing hubs will allow healthcare systems to much more quickly track the spread of these bacteria and how they’re evolving.”

The paper “Epidemic of carbapenem-resistant Klebsiella pneumoniae in Europe is driven by nosocomial spread” has been published in the journal Nature Microbiology.

Hamburg river.

Many of the world’s waterways exceed safe levels of antibiotic substances — by a lot

Some of the world’s waterways exceed antibiotic concentrations considered ‘safe’ — by up to 300 times, the first global study on this subject reports.

Hamburg river.

Image via Pixabay

The researchers found meaningful concentrations of 14 common antibiotics across 65% of the sites they analyzed (the survey looked at rivers in 72 states across six continents). In many cases, these concentrations exceeded the values laid down in international safety guidelines.

By far the most concentrated offender was Metronidazole, which is used to treat bacterial infections including skin and oral infections. In one site in Bangladesh, it exceeded safe concentration values by a factor of more than 300.

Drugs, rivers, rock and roll

“The results are quite eye opening and worrying, demonstrating the widespread contamination of river systems around the world with antibiotic compounds,” Alistair Boxall, a scientist at the York environmental Sustainability Institute, said in a statement.

The research team compared drug concentrations retrieved from 711 locations around the world to ‘safe’ levels recently established by the AMR Industry Alliance. Depending on the antibiotic, these levels range from 20-32,000 nanograms per liter (ng/l). The AMR Industry Alliance is a grouping of more than 100 “biotech, diagnostics, generics and research-based pharmaceutical companies and associations” that aim to “provide sustainable solutions to curb antimicrobial resistance”, their website reads. The safety levels they set are meant to stop, or at least stifle, the development and spread of antibiotic resistance in pathogenic and non-pathogenic bacteria.

The team sent test kits to 92 partners across the world, who retrieved samples from local river systems. The samples were then frozen and shipped back to the University of York for testing. Some of the most iconic rivers in the world, including the Chao Phraya, Danube, Mekong, Seine, Thames, Tiber, and Tigris, were analyzed.

Which makes the team’s findings all the more worrying. On one hand, these antibiotics are very wide-spread in natural waterways. Safety limits were most frequently exceeded in Asia and Africa, but Europe and the Americas also have some waterways plagued by unsafe levels of antibiotics. The antibiotic seen most often was Trimethoprim, which was detected at 307 of the 711 sites tested. Trimethoprim is primarily prescribed for urinary tract infections. Ciprofloxacin, which is used to treat a number of bacterial infections, was the compound that most frequently exceeded safe levels, surpassing the threshold in 51 places.

On the other hand, the sheer concentrations the team found at some sites are nothing short of baffling. In the River Thames and one of its tributaries in London, the researchers detected a maximum total antibiotic concentration of 233 ng/l, which is over the safety limit, but not immensely so. At one site in Bangladesh, however, the concentration was 170 times higher.

Sites in Bangladesh, Kenya, Ghana, Pakistan, and Nigeria exceeded safety limits by the highest degree. In Europe, that ‘honor’ fell to one site in Austria, which boasted the highest antibiotic levels of all sites the team studied on the continent. High-risk areas tended to form around wastewater treatment systems, waste or sewage dumps, and in some areas of political turmoil, including the Israeli and Palestinian border.

Dr. John Wilkinson, from the Department of Environment and Geography, who coordinated the monitoring work, says that this study has a lot to teach us, because no other study on the subject had been done on this scale.

“Until now, the majority of environmental monitoring work for antibiotics has been done in Europe, N. America and China. Often on only a handful of antibiotics. We know very little about the scale of problem globally. Our study helps fill this key knowledge gap with data being generated for countries that had never been monitored before.”

“The results are quite eye opening and worrying,” adds Professor Alistair Boxall, Theme Leader of the York Environmental Sustainability Institute, “demonstrating the widespread contamination of river systems around the world with antibiotic compounds. Many scientists and policy makers now recognise the role of the natural environment in the antimicrobial resistance problem. Our data show that antibiotic contamination of rivers could be an important contributor.”

So can we solve the problem? The good news is that yes, yes we can. The bad news is that it’s going to be a very hard task, a “mammoth challenge” in Prof. Boxall’s words. We need tighter regulation, we need to develop and build better infrastructure for waste and wastewater treatment, and we’ll also have to clean the sites that are already contaminated.

The findings of this study were presented during two sessions at the annual meeting of the Society of Environmental Toxicology and Chemistry (SETAC) in Helsinki on 27 and 28 May.

Scanning electron micrograph of Mycobacterium tuberculosis bacteria, which cause TB. Credit: NIAID, Flickr.

New non-antibiotic treatment hijacks tuberculosis bacterium

Scanning electron micrograph of Mycobacterium tuberculosis bacteria, which cause TB. Credit: NIAID, Flickr.

Scanning electron micrograph of Mycobacterium tuberculosis bacteria, which cause TB. Credit: NIAID, Flickr.

Although the vaccine for tuberculosis (TB) was developed more than a century ago, infections are on the rise with 7.3 million diagnosed cases recorded worldwide in 2018 — this is up from 6.3 million two years prior. Once the first symptoms of the infectious disease set in, the patient needs to undergo a lengthy treatment with a powerful cocktail of antibiotics, which isn’t foolproof.

This is where a promising new treatment pathway identified by researchers at the University of Manchester may come in. The team found a way to treat TB in animals with a non-antibiotic drug.

The treatment works by targeting Mycobacterium tuberculosis’ defenses rather trying to destroy the bacteria itself.

Mycobacterium tuberculosis secretes molecules called Virulence Factors, which block the immune system’s response to the infection, making it extremely difficult to combat it. This is why people need strong antibiotics, often over 6 to 8 months. But even after the treatment is over, there’s a 20% risk that the infection will resurface.

Professor Lydia Tabernero, the project’s lead researcher, and colleagues targetted a specific Virulence Factor called MptpB, which, when blocked, allows white blood cells to destroy the bacteria more efficiently. In trials, monotherapy with an orally bioavailable MptpB inhibitor reduced infection burden in acute and chronic guinea pig models.

“The fact that the animal studies showed our compound, which doesn’t kill the bacteria directly, resulted in a significant reduction in the bacterial burden is remarkable,” Tabernero said in a statement.

Because MptpB isn’t found in humans, nor anything similar to it, the compounds used to block it are non-toxic to our cells.

What’s more, because the bacteria aren’t threatened directly, they are less likely to develop resistance against the treatment. Currently, the world is facing an antibiotic-resistance crisis that is threatening to undermine decades-worth of medical progress.

Scientists think that one in three people around the world is infected with TB, which kills 1.7 million annually. The disease is the most prevalent in Africa, India, China, but is on the rise in some western countries, particularly in the UK’s capital, London.

“TB is an amazingly difficult disease to treat so we feel this is a significant breakthrough,” said Tabernero.

”The next stage of our research is to optimise further the chemical compound, but we hope Clinical trials are up to four years away.”

The findings appeared in the Journal of Medicinal Chemistry.

Medicine.

The CDC warns that “chronic Lyme” is bogus and the treatments are horrifying and deadly

With summer upon us in earnest, ticks are popping up all over the place. Even so, a growing trend has physicians more preoccupied than the risk of contracting Lyme disease — last Friday, a report published by the CDC warns people about the slew of bogus treatments marketed for the condition.

Medicine.

Image credits Andrea Ajale.

It’s a dark day indeed when the CDC has to protect people from dishonest treatments rather than diseases — but that’s exactly what the center had to do last Friday. Writing in the CDC’s Morbidity and Mortality Weekly Report, a group of doctors from all over the country, including members from the University of Colorado, the CDC, Yale University, Stanford, and the University of California, San Francisco warn that alternative medical treatments for “chronic Lyme disease” are all unproven and very likely harmful — some even deadly.

These doctors recount the experience of five patients who, erroneously or intentionally diagnosed with what’s essentially a made-up condition with no scientific backing, suffered through and from such treatments which in some cases cost them their lives.

Fake Lymes

Now, Lyme disease is a real, well-documented, pretty nasty disease. It’s caused by an infection with Borrelia burgdorferi, a spirochete which uses blacklegged ticks as a vector. Initial symptoms include the appearance of a characteristic “bull’s eye” rash on the skin, fever, headache, and fatigue. If untreated, the infection spreads out through the body causing arthritis, heart inflammation, dysfunctionalities of the nervous system, even brain swelling.

Patients may develop an (actual and recognized) condition called Post-Treatment Lyme Disease Syndrome / PTLDS. Such patients will show lingering symptoms after being cured of Lyme’s, and, while it’s exact cause is unknown researchers suspect it comes down to lingering tissue damage and the way out immune system responds to them — not an infection, and not something which can be cured by antibiotics.

So it’s easy to see why nobody would be thrilled of contacting it. Luckily, its symptoms make Lyme disease pretty easy to spot and two to four weeks of antibiotic treatments usually flushes the spirochetes out of your system.

But capitalizing on that fear are people who advocate for chronic Lyme disease or, as I like to call it, male Bos taurus feces. It’s a wide-net grouping of vague, nondescript symptoms, ranging from fatigue and generalized pain to neurological disorders. Most times, the diagnostic is pinned without performing any FDA-approved lab testing, often without any lab testing at all, for that matter. In fact, it’s not uncommon for the patient to be told he’s suffering from chronic Lyme despite negative lab results for a B. burgdorferi infection. Because what’s a bit of evidence worth in the face of your pseudo-scientific conviction and/or willingness to con people out of money?

Take this pill daily — for years

Blacklegged Tick.

This is what a blacklegged (deer) tick looks like.
Image credits Fairfax County / Flickr.

Many patients, who are confused by their symptoms often fall for these treatments out of sheer desperation to find a cure to their suffering. Self-described “Lyme-literate” doctors, a term which isn’t indicative of any kind of training (if you hear your doctor say this it only means he’s particularly qualified to be replaced,) convince these patients they’re the victims of a chronic infection and put them on these “alternative” treatments.

What followed was exactly what you’d expect to happen when somebody treats you for something you don’t have in a way that doesn’t work — years of pointless suffering, avoidable infections, even death.

“Patients and their health care providers need to be aware of the risks associated with treatments for chronic Lyme disease,” the doctors declare.

Here’s a short recount of what the five patients mentioned by the authors went through.

[panel style=”panel-danger” title=”Fake Lyme, fake treatment, real pain.” footer=””]

One woman in her 30s showed fatigue and joint pain. She was given several rounds of oral antibiotics, and her condition got worse. She was then administered IV antibiotics for several weeks following which she developed a severe catheter-associated blood infection. She ultimately died of septic shock.

Another woman, in her 50s, who had been diagnosed with Lou Gehrig’s disease (amyotrophic lateral sclerosis, or ALS), also got a second diagnosis — chronic Lyme. She was prescribed a course of herbal remedies, and when these somehow, miraculously failed to cure the made-up disease, was put on IV antibiotics for seven months. This mammoth dose of drugs wrecked her intestinal flora and she developed C. difficile colitis, an intractable intestinal infection linked with antibiotic use. After two years battling the infection, she succumbed to ALS-associated complications.

One teenager suffering from headaches and back pain was diagnosed with chronic Lyme and put on a few months of oral antibiotics, followed by five months of IV antibiotics. She developed a severe blood infection as result of the treatment and suffered septic shock. She needed several weeks’ care in the ICU to recover.

A woman in her late 40s was put on several rounds of oral and IV antibiotics to treat her fatigue and cognitive difficulties two years after being treated for Lyme’s. She ultimately developed an infection which spread to her spine, destroying her 9th and 10th thoracic vertebrae.

The final patient, a woman in her 60s with an autoimmune disease, mixed connective tissue disease, and degenerative arthritis, was diagnosed with chronic Lyme and took more than 10 years of alternative therapies. During this time she overcame several catheter-associated blood infections, which eventually caused abscesses to form in her spine that required surgery.

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Regardless of whether you think you may suffer from PTLDS or “chronic Lyme”, you should avoid these alternative treatments at all costs, the CDC report reads. And there’s a lot of them out there. While the most widely-prescribed treatment are prolonged courses of antibiotics, in 2015 internet-listed therapies for Lyme disease and chronic Lyme ranged from simple herbal and vitamin supplements to $13,000 “photon” therapy, heat and magnet therapies, treatments to remove heavy metals such as mercury, bismuth treatments (potentially fatal), or infusions of hydrogen peroxide. That’s not all! The more exotic treatments included bee venom-based remedies, drinking a bleach solution, your own urine, or a coffee and herbal enema.

Delicious.

As you’ve seen earlier, antibiotics can cause a lot of harm. Their overuse destroys beneficial microbe communities in the body, power-level drug-resistant bugs in your body, and increase the chance of you getting a life-threatening, fully-resistant infection. But, since there’s such a bounty of these alternative treatments floating around, we can only imagine what the effects of some of them are — hint: definitely not good.

“These cases highlight the severity and scope of adverse effects that can be caused by the use of unproven treatments for chronic Lyme disease,” the authors conclude.

“In addition to the dangers associated with inappropriate antibiotic use, such as selection of antibiotic-resistant bacteria, these treatments can lead to injuries related to unnecessary procedures, bacteremia and resulting metastatic infection, venous thromboses, and missed opportunities to diagnose and treat the actual underlying cause of the patient’s symptoms.”

Credit: Wikipedia.

What is antibiotic resistance: everything you need to know

Antibiotics are medicines that combat infections caused by bacteria. However, due to misuse and overuse of antibiotics, many bacterial strains are developing antibiotic resistance.

antibiotic resistance art

Credit: Wikipedia.

Before Alexander Fleming discovered penicillin in 1928, there was no effective treatment for infections such as pneumonia, gonorrhea or rheumatic fever. Fleming’s discovery kicked off a golden age of antimicrobial research with many pharmaceutical companies developing new drugs that would save countless lives. Some doctors in the 1940s would famously prophesize that antibiotics would finally eradicate the infectious diseases that had plagued humankind throughout history. Almost a hundred years later since Fleming made his milestone discovery not only are bacterial infections still common, the misuse and overuse of antibiotics are threatening to undo all of this medical progress as bacterial strains become resistant. 

Antibiotic resistance: a modern problem that can be traced to ancient times.

Contrary to common belief, human exposure to antibiotics isn’t confined to the modern era. Traces of tetracycline, a broad-spectrum antibiotic, have been found in the skeleton remains from ancient Sudanese Nubia dating from 350-550 CE. Likewise, tetracycline has been found in remains dating from the late Roman period in the Dakhleh Oasis, Egypt. These people must have included tetracycline in their diet — and it was to their good fortune as the rate of infectious diseases documented in Sudanese Nubian populations was low. For thousands of years, Chinese herbalists have been using a variety of plants which contain antimicrobial active components for ancient traditional remedies.

Naturally, the selective pressure imposed by these ancient antimicrobial activities has led to the accumulation of antibiotic resistance genes. But that’s nothing like the scale and intensity of antibiotic resistance we’re seeing today.

What is antibiotic resistance

Antibiotic resistance occurs when an antibiotic is no longer effective at controlling or killing bacterial growth. Bacteria which are ‘resistant’ can multiply in the presence of various therapeutic levels of an antibiotic. Sometimes, increasing the dose of an antibiotic can help tackle a more severe infection but in some instances — and these are becoming more and more frequent — no dose seems to control the bacterial growth. Each year, 25,000 patients from the EU and 63,000 patients from the USA die because of hospital-acquired bacterial infections which are resistant to multidrug-action. The ECDC/EMA Joint Working Group estimated in 2009 that the cost due to multidrug-resistant bacterial infections amounts to EUR 1.5 million in the EU alone. According to a 2013 CDC report titled “Antibiotic Resistance Threats in the United States, antibiotic resistance is responsible for $20 billion in direct health-care costs in the United States.

Antimicrobial resistance threatens to undermine all the immense clinical and public health progress we’ve come to achieve so far. This is a very complex problem that requires concentrated and coordinated efforts of microbiologists, ecologists, health care specialists, educationalists, policy makers, legislative bodies, agricultural and pharmaceutical industry workers, and the public to deal with.

The main challenges in dealing with antibiotic resistance are, on one hand, genetically acquired immunity and, on the other hand, fewer and fewer novel drugs. Since the 1970s, the rate at which new antibiotic classes have been discovered has continued to drop. No novel drug classes have been developed in the last 20 years. Researchers nowadays agree that, at this current rate, humanity is destined to lose the arms race as sooner or later bacteria will acquire resistance to modified versions of currently available antibiotic classes.

How bacteria develop resistance to antibiotics

Schematic by MeMed.

Schematic by MeMed.

Every time a person takes antibiotics, sensitive bacteria are killed, but resistant germs may be left to grow and multiply. In time, these leftover populations can become so strong that antibiotics no longer are effective.

There are several mechanisms bacteria employ to become resistant. Some gain the ability to neutralize the drug before it gets the chance to attack the bacteria. Other bacteria can rapidly pump the antibiotic out or can even change the attack site so the function of the bacteria isn’t affected.

Whenever bacteria survives an antibiotic onslaught, it can acquire resistant through mutation of the genetic material or by ‘borrowing’ pieces of DNA that code for the resistance to antibiotics from other bacteria, like those from livestock. Moreover, the DNA that codes the resistance is grouped in an easily transferable package which enables the germs to become resistant to many antimicrobial agents.

The types of bacterial resistance

  • Intrinsic resistance. Some bacteria are intriguingly resistant to antibiotics, such as those that don’t build a cell wall (penicillin prevents cell-wall building).
  • Acquired resistance. Bacteria can acquire resistance through new genetic change or by transferring DNA from a bacterium that is already resistant. This is the issue we’re having today.

According to the CDC, the following bacterial strains have developed the most resistance such that they’ve been listed as urgent hazards:

  • Clostridium difficile. Causes severe diarrhea, especially in older people and those who have serious illnesses.
  • Enterobacteriaceae. These normally live in the digestive tract but can invade other parts of the body, like the urinary tract, and cause infections.
  • Neisseria gonorrhoeae. Causes gonorrhea, a sexually transmitted infection. In 2016, the WHO said gonorrhea might soon become untreatable. 

 

Why antibiotic resistance is growing

When antibiotics are introduced in a bacterial population, most of the population dies but some resistant bacteria may survive. These resistant bacteria will continue to proliferate despite the presence of the antibiotic. In time, their population will increase until it becomes comprised mainly of resistant bacteria. Credit: ReActGroup.

When antibiotics are introduced in a bacterial population, most of the population dies but some resistant bacteria may survive. These resistant bacteria will continue to proliferate despite the presence of the antibiotic. In time, their population will increase until it becomes comprised mainly of resistant bacteria. Credit: ReActGroup.

There are a number of factors that contribute to this growing health hazard. Among them we can mention:

  • self-medication;
  • hygienic habits such as the use of anti-bacterial soap which research suggests is useless but significantly contributes to the growing problem of antimicrobial resistance;
  • counterfeit drugs, particularly rampant in the developing world;
  • antibiotics for livestock;
  • infections acquired in hospitals and nursing homes, particularly in the developed world;

There’s no surprise in the fact that antibiotic resistance infections correlate with the level of antibiotic consumption. The more antibiotics a population consumes, the faster bacteria will adapt and become resistant. One huge problem is the mindless use of antibiotics. For instance, many patients request their doctors to prescribe antibiotics when there is no need for them, such as in the case of viral infections. Research shows that up to 15 million people in the United States go to the doctor for a sore throat every year. About 70 percent of these patients receive strep throat antibiotics but only 20 percent actually have strep throat, according to the IDSA.

Another problem is compliance with strict drug regimes. To be effective, antibiotics needs to be taken at least over several days and the scheduling needs to be respected on the clock yet many patients fail to follow these instructions.

Things are worse in some countries than others. For instance, in some countries, antibiotics are available without a prescription so the potential for self-medication abuse is huge especially if the patient is not educated about antibiotics. In the absence of a proper diagnosis, suitable antibiotic choice, correct usage, compliance, and treatment efficiency monitoring, self-medicating antibiotics can only exacerbate the mounting resistance problem.

Another issue lies with antibiotics for domestic animals, particularly livestock. Farmers widely use antibiotics to stave off infections but also for promoting growth. Approximately 80 percent of the antibiotics sold in the United States are used in meat and poultry production, and in the vast majority of cases, the antibiotics are used on healthy animals. This practice can lead to the evolution of ‘superbugs’ which can migrate into the environment as people consume meat.

In 2003, an Expert Workshop co-sponsored by the World Health Organization, Food and Agricultural Organization (FDA), and World Animal Health Organization (OIE) concluded “that there is clear evidence of adverse human health consequences due to resistant organisms resulting from non-human usage of antimicrobials.  These consequences include infections that would not have otherwise occurred, increased frequency of treatment failures (in some cases death) and increased severity of infections”

Most recently in 2012, the FDA stated “Misuse and overuse of antimicrobial drugs creates selective evolutionary pressure that enables antimicrobial resistant bacteria to increase in numbers more rapidly than antimicrobial susceptible bacteria and thus increases the opportunity for individuals to become infected by resistant bacteria.”

Solutions to antibiotic resistance

The sad reality today is that there’s not much we can do for patients who don’t respond to antibiotics, which is why mortality rates are so high.

“Antibiotic resistance is rising for many different pathogens that are threats to health,” said CDC Director Tom Frieden, M.D., in a statement. “If we don’t act now, our medicine cabinet will be empty and we won’t have the antibiotics we need to save lives.”

Some researchers have proposed alternatives to antibiotic treatment such as passive immunization or phage therapy but most efforts are directed towards the discovery of new and more efficient antibiotics. Like outlined earlier, however, most of our antibiotics have been isolated in the so-called ‘golden era’ of antibiotic discovery from a limited number of taxonomic groups, mainly from Actinomyces that live in the soil. Some research groups are exploring alternative ecological niches such as the marine environment. Other approaches involve borrowing antimicrobial peptides and compounds from animals and plants, as well as the natural lipopeptides of bacteria and fungi. There is also a potential to find new antibiotics by exploring the microbiota through the metagenomic approach. Finally, some groups are looking design new classes of antibiotics from scratch through complete synthesis.

Preventing antibiotic resistance

Finding new antibiotics, however, will likely not solve our growing antibiotic resistance problem. History has shown that after a new antibiotic therapy is introduced, sooner or later resistance will arise. This approach is destined to fail since bacteria will eventually respond to selective pressure by the emergence of resistance mechanisms.

What we can do, however, is to buy time until someone very clever figures a way to outsmart bacteria for good.

Scandinavian countries, for instance, banned the use of growth-promoting antibiotics in livestock since 2006 and other EU countries have been implementing similar measures. In 2012, the FDA ruled that certain extra-label uses of cephalosporin antimicrobial drugs should be banned from certain livestock.

It is estimated that in half of all cases, antibiotics are prescribed for conditions caused by viruses. Obviously, in such cases the antibiotics are useless and doctors and nurses ought to know better.

Governments have a critical role in combating antibiotic resistance. It’s imperative that robust action is taken both at a national and international level in order to regulate the appropriate use of quality medicines and education about the dangers of overuse. A lot of antibiotic resistance is building up in developing countries where there is little oversight. Governments need to work together to strengthen the health care quality in such places for the good of us all. Not least, the industry needs to move faster and more aggressively to research and develop new antibiotics.

What you can do

  • Don’t take antibiotics for a viral infection like a cold or the flu.
  • Do not save any antibiotics for the next time you get sick. Discard any leftover medication once you have completed your prescribed course of treatment
  • Always take antibiotics only after you’ve consulted with a health care professional. The FDA has a great campaign called “Get Smart: Know When Antibiotics Work”  that offers Web pages, brochures, fact sheets, and other information sources aimed at helping the public learn about preventing antibiotic-resistant infections.
  • Take an antibiotic exactly as the healthcare provider tells you. Do not skip doses.
  • Never pressure your provider to prescribe an antibiotic.
  • Never use antibacterial soap.
Tasmanian devil

Tasmanian devil milk might be the secret weapon against superbugs we’ve been waiting for

Tasmanian devil

Credit: Pixabay

Leading medical societies have warned time and time again that antibiotic resistance is looming and the effects could prove catastrophic. While some are working on synthesizing new classes of antibiotics in the lab, other groups are focusing on finding them in nature. After more than three years of research, Australian researchers think they found one of the most promising compounds against superbugs in the milk of an adorable, yet highly aggressive marsupial: the Tasmanian devil.

Momma’s milk

The discovery was made by a team at Sydney University who sequenced the devil’s genome. Devil mothers only need 21 days to gestate a pup, after which development continues in the pouch, as is the case with most marsupials. Given the short gestation and knowing a pouch is far from being the most sterile environment, the researchers presumed that the devil momma’s milk has to offer strong antimicrobial resistance.

Eventually, they found devil milk contains six varieties of peptides belonging to a class called cathelicidins, which act as natural antibiotics. Humans only have one, but most marsupials seem to have them in great abundance. Opossums have twelve and the tammar wallaby carries eight.

The peptides were replicated artificially then tested against a variety of germs, some of whom the most dangerous known to humans. The peptides proved effective against everything the researchers put out. Among the germs was Staphylococcus aureus, a bacteria that’s found in the nose and skin of 30 percent of people. While it’s harmless most of the time, the bacteria can prove fatal if it reaches the blood stream.

Another bacteria was enterococcus, which some strains are already resistant to vancomycin, one of the strongest antibiotics in our arsenal.

Emma Peel with a young Tasmanian devil.  Photo: Emma Peel

Emma Peel with a young Tasmanian devil. Photo: Emma Peel

Last year, an 18-month review into antimicrobial resistance found superbugs might kill 10 million people a year by 2050 or more than cancer.

“There are potential pathogens present in the devil microbiome, so the fact that the under-developed young in the pouch don’t get sick was a clue something interesting was going on,” said Emma Peel, one of the authors of the study published in Scientific Reports. “That’s what inspired our most recent study.”

It’s remarkable that a creature that’s on the brink of extinction might one day save millions of human lives. In only ten years, 80 percent of Tasmanian devil populations have collapsed at the hand of a nasty transmissible face cancer with an almost 100 percent fatality rate. Luckily, some individuals have developed resistance and it seems like the devils will survive. 

Next, the researchers plan on studying koalas as preliminary results suggest their milk also contains similar peptides.

Untreatable bacteria identified in the US

A strain of E. coli resistant to last-resort antibiotics has been identified on United States soil for the first time. Health officials say this could be “the end of the road for antibiotics,” leaving us virtually helpless in fighting future infections.

Last month, researchers identified a 49-year-old Pennsylvania woman as the carrier for a strain of E. coli resistant to the antibiotic Colistin. The woman visited a clinic in Pennsylvania, which forwarded a sample to Walter Reed National Military Medical Center. Walter Reed found the bacteria in her urine.

Think of this drug as our nuclear option — it’s employed for particularly dangerous pathogens, when every other drug fails. This includes the CRE family, a group of germs so resilient and deadly that health officials have dubbed it “nightmare bacteria”. Infection with these superbugs ends up killing up to 50 percent of patients in some instances, and the CDC lists them among the country’s most urgent public health threats.

Finding a bug that can shrug off even Colistin on home soil “heralds the emergence of a truly pan-drug resistant bacteria,” say the authors of the paper detailing the discovery.

“It basically shows us that the end of the road isn’t very far away for antibiotics — that we may be in a situation where we have patients in our intensive-care units, or patients getting urinary tract infections for which we do not have antibiotics,” CDC Director Tom Frieden said in an interview Thursday.

This is the first known carrier of a Colistin-resistant strain in the United States. Last November, a report by Chinese and British researchers who found the Colistin-proof strain in pigs, raw pork meat and several people in China was met with shock by public health officials worldwide. The deadly strain was later discovered in Europe and elsewhere.

Escherichia coli (E. coli) naturally occurs in your gut and most strains are harmless. Some, however, can cause food-borne diseases with fever, nausea and vomiting to bloody diarrhea. The infections are transmitted by eating or drinking contaminated food and water. E. coli resistance for a spectrum of drugs has been increasingly reported in cases of urinary tract infections, and the WHO warns that the most widely used oral treatment — fluoroquinolones — are rapidly becoming ineffective. Seeing strains develop virtual immunity to any of our antibiotics is very bad news, Frieden says.

“I’ve been there for TB patients. I’ve cared for patients for whom there are no drugs left. It is a feeling of such horror and helplessness,” he added. “This is not where we need to be.”

The CDC and the Pennsylvania State Health Department mobilized immediately to investigate the case and to trace the patient’s contacts to see if the bacteria had spread. The CDC also said it is looking for other potential cases in the healthcare facility the patient visited.

The full paper, titled “Colistin resistance in the USA” has been published online in the journal Antimicrobial Agents and Chemotherapy and can be read here.

Common antibiotics might cause mental confusion

Some antibiotics (including common ones) may cause serious brain disruption and other serious problems according to a new study.

Photo by Rob Brewer.

Photo by Rob Brewer.g

The study found a connection between the drugs and delirium (a disruption in brain functions that may be accompanied by hallucinations and agitation). Antibiotics are not the first drugs suspected of causing this but the fact that common ones may also be responsible brings up some big issues.

“People who have delirium are more likely to have other complications, go into a nursing home instead of going home after being in the hospital and are more likely to die than people who do not develop delirium,” said author Shamik Bhattacharyya, MD, of Harvard Medical School and Brigham and Women’s Hospital in Boston, Mass., and a member of the American Academy of Neurology. “Any efforts we can make to help identify the cause of delirium have the potential to be greatly beneficial.”

For the study, the team found reports from the past seven decades, and found almost 400 recorded cases of antibiotic-induced delirium. A total of 54 different antibiotics were involved, from 12 different classes of antibiotics, and the effects were quite severe. In 3 out of 4 cases, EEG results were abnormal. Half of them reported delusions or other types of hallucinations, 14 percent had seizures, 15 percent had involuntary muscle twitching and 5 percent had loss of control of body movements.

Of course, 400 people suffering from this across decades is not extremely worrying, but the odds are many other cases go unreported. Also, common antibiotics giving people delirium is not a matter that should be taken lightly. Researchers want to expand the study and better understand the patterns of toxicity caused by antibiotics.

“More research is needed, but these antibiotics should be considered as a possible cause of delirium,” said Bhattacharyya. “Recognition of different patterns of toxicity could lead to a quicker diagnosis and hopefully prevent of some of the negative consequences for people with delirium and other brain problems.”

The study has been published in “Views and Reviews” article published in the Feb. 17, 2016, online issue of Neurology®

UBC researchers Julian Davies and Shekooh Behroozian with their 'magic' clay.

Clay used by the First Nations people destroys fatal drug-resistant pathogens

A team at University of British Columbia claims that a type of clay found northwest of Vancouver is effective against a dangerous class of drug-resistant bacteria. These germs are called ESKAPE bacteria because they don’t seem to respond to any anti-microbial medication, escaping any agent we throw at them and causing extensive morbidity and mortality in infected patients. Once patients get infected with ESKAPE bacteria, there is no available treatment and most die, ironically in a hospital where the drug-resistant germs congregate. The clay investigated by the Canadian researchers destroyed the ESKAPE germs, in some instances in less than 5 hours. Furthermore, the clay is completely natural and no toxic side-effects have been reported thus far.

 UBC researchers Julian Davies and Shekooh Behroozian with their 'magic' clay.

UBC researchers Julian Davies and Shekooh Behroozian with their ‘magic’ clay.

“More than 50 years of misuse and overuse of antibiotics has led to a plague of antibiotic resistance that threatens to reduce the efficacy of antimicrobial agents available for the treatment of infections due to resistant organisms,” reads the paper.

“The main threat is nosocomial infections in which certain pathogens, notably the ESKAPE organisms, are essentially untreatable and contribute to increasing mortality and morbidity in surgical wards.”

The  Kisameet clay (KC), a natural clay mineral from British Columbia, has been widely known for its therapeutic qualities for many years. Anecdotal evidence suggests that it was used by the local First Nations (Heiltsuk) people for several centuries for a variety of ailments, including ulcerative colitis, duodenal ulcer, arthritis, neuritis, phlebitis, skin irritation, and burns. Such is the case with other clay minerals, not just KC, however no such therapy has  been approved by regulatory agencies in Canada.

What KC looks like. It's been used for medicinal purposes for thousands of years.

What KC looks like. It’s been used for medicinal purposes for hundreds of years.

The researchers at University of British Columbia are among the first to perform an extensive study of the therapeutic effects of KC.They collected 16 ESKAPE pathogen strains from a number of sources in Vancouver, including Vancouver General Hospital (VGH), St. Paul’s Hospital (SPH), and the University of British Columbia (UBC) wastewater treatment pilot plant (WWTP). Each strain was grown in-vivo in Luria-Bertani (LB) broth or on LB agar.

When all else fails, this clay shines

Tests were performed using a panel of 36 antibiotics. These showed that the pathogens were resistant to the antibiotics, though with variability in their resistance. The presence of KC dramatically reduced the viability of all strains tested, though.

“For example, after a 5-h exposure to KC, no viable cells of A. baumannii AB-1270, Enterobacter sp. strain MI1, or Enterobacter sp. strain MI16 could be recovered, indicating potent activity against these strains. S. aureus, K. pneumoniae, P. aeruginosa, A. baumannii AB-1264, and Enterobacter cloacae 1172 lost viability completely after 24 h, and the same killing took 48 h for E. faecium strains. In contrast, in water-only controls without KC, the decline in CFU during the same period of incubation was ≤1 log10 for all Gram-negative strains and ~1 to 3 log10 for E. faecium and S. aureus strains, respectively.”

The researchers were extremely surprised to find out the clay had killed at 16 strains! “They wanted microbial testing on clay, so I was a bit skeptical at first,” said UBC microbiologist Julian Davies. “Well, there are all sorts of claims out there, all kinds of folklore medicine and witchcraft.”

We’re beginning to run out of weapons against bacteria, which have caught on to our tricks. It may be only a matter of time until our anti-microbial arsenal is exhausted. Fatalities from ESKAPE pathogens will only increase in time, but there is progress. For one, there’s KC which definitely warrants more attention from the medical community (it works against fungal infections as well). Previously last week, I wrote about how nanoparticles activated by light selectively kill drug-resistant bacteria. The future isn’t as gloom as it seems, but such efforts require support, as Dr. Mark Blaskovich urged in a ZME Science guest post.

The clay is a complex mixture made up of about 24% by weight clay minerals, which are aluminum silicates, with various exchangeable metal ions and elemental sulfur. So, we don’t know for sure what makes KC so good at killing germs — even the toughest ones. “So far, we are sure that the mechanism of action is multifactorial,” says graduate student Shekooh Behroozian. “And we know the antimicrobial activity is pH-dependent, with the clay showing the best activity at acidic pH.”

“It’s a dream that there could be isolates [in the clay] that make new antibiotics,” says Davies. But the clay must be tested for toxicity and its activity defined well enough to satisfy drug regulators, he added.

Drug resistant Strep and the return of the scarlet fever

In a study published Monday in the journal Scientific Reports, researchers from the University of Queensland caution that the surge in scarlet fever cases may pose an unexpected threat.

Evolution is a wonderful thing — it brought us out of the primordial puddle and took us to the Moon, and will hopefully power us to even greater heights. It’s an awesome thing, and I’m a big fan of it. But evolution does tend to have one nasty habit — it never stops, not even for the bugs that are trying to kill us dead.

One of those bugs is group A Streptococcus; it’s the biological vector of scarlet fever, a condition that commonly affects children from 5 to 12. Most of those infected with this bacteria only develop strep throat, but in some cases it can escalate into a full-blown case of scarlet fever, thus named for the red, sandpaper-like rash it causes on the skin.

A scarlet fever rash.
Image via newsshopper

It used to be a deadly disease, but with the advent of modern antibiotics it’s just unpleasant — while there is no vaccine for it, medication can easily treat the condition.

But if the Streptococcus is easily kept in check with antibiotics, why the sudden increase in number of scarlet fever cases in the recent years? The answer is evolution — more to the point, evolution of drug-resisting bacteria.

“We now have a situation which may change the nature of the disease and make it resistant to broad-spectrum treatments normally prescribed for respiratory tract infections, such as in scarlet fever,” lead study author Nouri Ben Zakour said in a statement.

Ben Zakour’s team analyzed samples from 25 confirmed scarlet fever patients and 9 patients suffering from a number of group A strep infections from China and Hong Kong. They were able to confirm that a strain of group A strep that emerged in the 1980s was the common cause for all of the infections.

The usual treatment, penicillin, still works on this strain — other common antibiotics do not. The team found evidence of tetracycline, erythromycin and clindamycin resistance, raising immediate concerns for the patients who are allergic to penicillin. However, we’re all at risk here. Should a strain develop that also has resistance to penicillin, there will be few treatment options left for doctors.

The increase of antibiotic resistant bacteria should come as no surprise. As such substances become more and more common in the environment as consequence of human and agricultural use, more and more bacteria are exposed to them. Any that survive will multiply, and when they infect a human host they’ll be immune to one or more antibiotic substances. Antibiotic resistance causes an estimated 2 million illnesses and 23,000 deaths every year in the United States.

The findings, Ben Zakour said, suggest that monitoring the spread and evolution of this bacteria is of the utmost importance. The fact that penicillin still seems to work in most cases of scarlet fever means that it isn’t time to panic. But this is just the latest example of the ticking time bomb that is antibiotic resistance.

Photo: rodalenews.com

You may be using antibacterial soap incorrectly

Photo: rodalenews.com

Photo: rodalenews.com

Most people nowadays buy antibacterial soaps instead of normal ones, because they believe it keeps them safe and protects them for the oh-so dreaded bacterial infections. Apparently, there’s little evidence that antibacterial soaps provide any additional protection than the regular kind. The problem: most people don’t use them properly. For that matter, it may be wiser to ban antibacterial soaps and some other derived products altogether, to keep microbes from adapting.

The main active ingredients in antibacterial soaps are triclosan and triclocarban. These chemicals aren’t limited to soaps, though. The germ-free frenzy has caused the introduction of a myriad of related products that contain these anti-microbial agents from detergents, to clothing, to toothpastes and even pacifiers. In all, some 2,000 products on the US market alone contain triclosan or triclocarban. As such, some three-quarters of Americans have detectable traces of triclosan in their urine, according to Rolf Halden, director of the Center for Environmental Security at Arizona State University.

Useless soap chemicals

According to Halden, to ward off microbes people need to wash their hands with antibacterial products for 20 to 30 seconds, but studies show people use the soaps for just six seconds on average. You can imagine what a waste this is, but even more important is the potential bacterial disaster that the wide use of triclosan active products might cause.

Studies suggest microbes can adapt to these chemicals, and this adaptation may increase their resistance to the antibiotics that are used to treat infections, Halden said. Additionally, triclosan and triclocarban affect hormones in the body, according to studies conducted on animals. Late last year, the Food and Drug Administration said that antibacterial chemicals will need to be removed from personal care products unless the companies can prove that these chemicals are safe and effective.

“The FDA’s move is a prudent and important step toward preserving the efficacy of clinically important antibiotics, preventing unnecessary exposure of the general population to endocrine disrupting and potentially harmful chemicals, and throttling back the increasing release and accumulation of antimicrobials in the environment,” Halden said in a statement.

In fact, the danger posed by growing resistance to antibiotics should be ranked along with terrorism, the government’s chief medical officer for England has said. For instance, one of the easiest to treat STDs, gonorrhea, is making a come back for the worse, as more and more cases have been reported where antibiotics stop responding. If this trend continues, common antibiotics could stop responding , threatening the lives of millions across the world.

The breakdown? Triclosan poses enormous risk with no benefit. The U.S. Centers for Disease Control and Prevention and other non-industry-funded scientists have shown time and time again that washing with regular soap and water is just as effective than using antibacterial soaps.

The Arizona State researchers’ paper was published in the journal Environmental Science & Technology.