Category Archives: Antibitoc Resistance

Running Out of Options; Bacteriophages to Treat Antibiotic Resistance Infections

Ella Balasa, a 26-year-old from Richmond, Virginia, recently made the news when she was apparently successfully treated for a lung infection using a kind of virus called a bacteriophage. The word “apparently” is important in terms of determining exactly how effective the treatment was, in a clinical sense.

A bacteriophage is a virus that infects bacteria. They aren’t typically used to treat bacterial infections, but in desperate cases, they have been used to treat particularly antibiotic-resistant infections. Such as the one that Balasa was battling.

“I’m really running out of options,” Balasa told AP. “I know it might not have an effect. But I am very hopeful.”

Balasa has cystic fibrosis, which is a disease that affects the lungs, scarring lung tissue, which can trap bacteria. She had picked up an antibiotic-resistant strain of Pseudomonas aeruginosa. At first, inhaled antibiotics controlled the infection, but then they stopped working. She was placed on intravenous antibiotics, but Balasa didn’t respond to those either.

Balasa took part in a procedure at Yale University that used bacteriophages that attack and kill P. aeruginosa. It was a last-ditch effort to avoid a high-risk lung transplant. She was the eighth patient to try the approach.

The first test case at Yale was an 82-year-old man who was close to death from a heart implant and untreatable pseudomonas infection. Benjamin Chan, a Yale biologist who focuses on phages, purified a phage found in a Connecticut lake that he matched to the patient’s strain of bacteria. With emergency permission from the U.S. Food and Drug Administration (FDA), physicians tried the purified phage on the man’s infection—successfully. The infection cleared up.

“People’s frustration with antibiotic resistance boiled over,” Chan told. “We’re more appreciative of the fact that we need alternatives.”

Bacteriophages were discovered independently by Frederick Twort in 1915 and Felix d’Herelle in 1917—a full decade before the discovery of penicillin. At that time, they were used to treat dysentery and cholera. But timing is important, and not much was known about viruses and phages at the time—it would be another 25 years, in 1940, before an image of a phage was made using an electron microscope.

And unlike broad-screen antibiotics, strains of phage are specific to strains of bacteria. A broad-screen antibiotic can be used to treat a range of bacterial infections, but phages need to be chosen and purified specific to the infecting bacteria.

On the other hand, as antibiotic-resistance becomes a bigger issue and development of new antibiotics is slow, attention is turning toward the possibilities of phages to treat antibiotic-resistant bacteria. A 2017 article by Veerasak Srisuknimit on the Harvard University blog, wrote, “Now that more and more bacteria have developed resistance to antibiotics, scientists around the world have a renewed interest in phages. The European Union invested 5 million euros in Phagoburn, a project that studies the use of phages to prevent skin infections in burn victims. In the USA, the FDA approved ListShield, a food addictive containing phages, that kills Listeria monocytogenes, one of the most virulent foodborne pathogens and one cause of meningitis. Currently, many clinical trials using phage to treat or prevent bacterial infections such as tuberculosis and MRSA are undergoing.”

And Balasa? She inhaled billions of phages over seven days. It appeared to have an almost immediate effect, although it took several weeks for her to feel better. And during that period she began retaking some antibiotics she had abandoned. As AP notes, without a formal study it’s hard to say just how successful the approach was, but the tests “suggest phages killed much of her predominant pseudomonas strain and made the survivors sensitive again to a course of those antibiotics.”

She was able to quit the antibiotics, but a second round of a different strain of phages did not seem to show more improvement. “The true test,” Balasa told AP, “is how long I can go without using any antibiotics again.”

By Mark Terry

 

To read this article in its entirety please click on the following link to be redirected. Thank you.

https://www.pharmalive.com/bacteriophages-to-the-rescue-a-possible-approach-to-antibiotic-resistance/

Breakout Labs Has Invested in SciBac, a Company Targeting the Growing Problem of Antibiotic Resistance

It’s not surprising that Breakout Labs, the Thiel Foundation‘s seed-stage fund that aims to propel radical science to improve human health, has invested in SciBac, a company targeting the growing problem of antibiotic resistance. Among health risks that threaten mankind, the one that may prove most deadly is the rise of superbugs — drug-resistant bacteria that can make simple surgeries and medical treatments like chemotherapy impossible.

Why Peter Thiel is backing a tiny start-up waging war against the global superbug crisis

  • 700,000 people worldwide die each year from antibiotic-resistant infections, and numbers are increasing.
  • Antimicrobial resistance is projected to kill more people than cancer by 2050, according to the World Health Organization.
  • Many big pharmaceutical companies are exiting the antibiotic drug development field due to low margins.
  • Start-ups like SciBac, which made the 2018 CNBC Upstart 100 list, are developing alternative solutions.

Over the years ever more powerful strains have spread around the world. It’s a crisis that has even garnered the attention of world leaders at the United Nations. That’s because the urgency is clear: 700,000 people die each year worldwide from antibiotic-resistant infections, and that number is increasing by the day. In the United States alone at least 2 million people become infected with antibiotic-resistant bacteria each year, according to the Centers for Disease Control and Prevention, and 23,000 die each year as a result of those infections.

The future trend is alarming. According to the World Health Organization, Hemai Parthasarathyis projected to kill more people than cancer by 2050, which would reduce global economic output by between 2 percent and 3.5 percent — a staggering $100 trillion cut in GDP globally — and severely cripple modern medical and surgical advances.

A $40 billion superbug market Big Pharma is neglecting

It’s no wonder many scientists call antimicrobial resistance “a slow-motion tsunami.” Yet lack of drug development and discovery by Big Pharma has exacerbated the problem. “Within the last two years, five large pharmaceutical and many biotech companies have exited the field due to the scientific, regulatory and economic challenges posed by antibiotic discovery and development,” said Thomas Cueni, chairman of the AMR Industry Alliance, a coalition of 100 companies and pharmaceutical associations set up to curb antimicrobial resistance. Among the pharmaceutical giants to exit this research field: Novartis, AstraZeneca, Sanofi and Allergan.

The void has spurred many nimble biotech start-ups to look for solutions in this new $40 billion superbug market. One is SciBac, a biotherapeutics company named to the 2018 CNBC Upstart 100 list. The Silicon Valley start-up shifts the paradigm on how to tackle superbugs. It is developing a microbe pill to boost the body’s microbiome in the gut, lungs and skin to kill bacteria that cause antibiotic-resistant disease. Its first product treats and prevents Clostridium difficile infection (CDI), commonly known as deadly diarrhea and our nation’s top antibiotic-resistant threat. It is also working on developing a drug to treat and prevent chronic Pseudomonas infections in the lungs of cystic fibrosis patients.

“Our patented platform technology has applications to treat other infections,” said SciBac CEO Jeanette Mucha. “It allows us to mate different species of microbes into a single hybrid that can target specific diseases through multiple modes of action that kill the bacteria and toxins in the body. At the same time, the technology bolsters the microbiome for fast recovery.”

SciBac CEO, Jeanette Mucha is on a quest to develop an antibiotic alternative.

According to Hemai Parthasarathy, Ph.D., scientific director of the Thiel Foundation’s Breakout Labs, “It’s clear we are running out of an arsenal to attack the superbug crisis, and the world needs new approaches.”

To help SciBac’s team move their technology out of the lab, Breakout has taken a board role to help with business strategy and will help introduce the founders to venture capitalists and potential business partners in the months ahead.

To date, the three-year-old upstart has raised $1.45 million in equity financing and a $3.7 million grant from CARB-X, a nonprofit public-private partnership funded by the U.S. government, Wellcome Trust, the NIH, Bill and Melinda Gates Foundation and the U.K government, that invests in antibacterial research worldwide. Its goal: to fast-track the development of a pipeline of new antibiotics, vaccines and other products to fight the war on superbugs.

“SciBac is essentially creating a new drug that is an antibiotic alternative,” said Kevin Outterson, executive director of CARB-X. “The microbiome is providing exciting new approaches to the prevention and treatment of life-threatening infections of all kinds. It’s a promising new scientific approach.”

SciBac’s answer to the superbug threat has caught the attention of investors.

As Outterson explains, most of the innovation in this field is coming from tiny pre-clinical trial companies like SciBac. That’s because many Big Pharma companies feel the margins aren’t worth the high R&D costs, which can run into the billions of dollars. “As soon as you make an antibiotic, it is already dying because bacteria are evolving in response to the drug. Eventually, random mutations will make antibiotic resistance come.”

For this reason, drug companies feel antibiotics are undervalued in the marketplace.

To help boost the start-up’s odds of success, CARB-X will provide SciBac with consultants and experts in R&D, toxicity and regulation that can help them navigate how to get their science from the lab to clinical trials for FDA approval. It has set milestones for the company that it must meet to get financing.

Like many entrepreneurs pursuing breakthrough science, Mucha seems energized by her formidable challenge of kickstarting the development of a new drug.

Mucha said she and co-founders Anthony Cann, a chemical engineer, and Derik Twomey, a cell biologist, stumbled on the idea. They had experience working with a species of bacteria known as clostridium while developing a biofuel for Cobalt Technologies. After that company closed shop, Mucha set up a lab in her garage to experiment with probiotics and see if she could induce gene transfer in bacteria. It worked. Then the entrepreneurs moved into an incubator, Molecular Sciences Institute in Milpitas, California, to set up a lab. Ten months later they applied to Breakout Labs for $350,000 of seed financing, which gave them matching funds to help secure the CARB-X grant. Now the company is in the midst of getting bridge financing to fund clinical trials and manufacturing.

“This drug development will take time,” Mucha said. “It won’t be ready for FDA drug approval until 2025. But we’re seeing a lot of investor interest in this alternative technology.”

 

To review article in its entirety please click on the following link to be redirected:

https://www.cnbc.com/2018/10/09/peter-thiel-backs-a-start-up-fighting-the-global-superbug-crisis.html

 

 

 

C. diff. Infections Related to Dental Care and the Unnecessary Use of Antibiotics

During the annual ID Week2017— an annual meeting of the Infectious Diseases Society of America (IDSA), the Society for Healthcare Epidemiology of America (SHEA), the HIV Medicine Association (HIVMA) and the Pediatric Infectious Diseases Society (PIDS)— researchers presented findings that suggest that the prevalence of Clostridium difficile is likely caused by the unnecessary prescription of antibiotics by dentists.

“Dentists have been overlooked as a source of antibiotic prescribing, which can potentially delay treatment when doctors are trying to determine what is causing a patient’s illness,” Stacy Holzbauer, DVM, MPH, lead author of the study and career epidemiology field officer for the CDC and MDH, said in a statement. “It’s important to educate dentists about the potential complications of antibiotic prescribing, including C. diff.

To read the article in its entirety please click on the following link:

https://www.rdmag.com/article/2017/10/dentists-overprescribing-antibiotics-overlooked-cause-superbug-infection

“Dentists write more than 24.5 million prescriptions for antibiotics a year,” she added. “It is essential that they be included in efforts to improve antibiotic prescribing.”

C. diff is a deadly bacterial infection that causes severe and possibly fatal diarrhea. Taking antibiotics can put patients at an increased risk for developing the infection.

“Research has shown that reducing outpatient antibiotic prescribing by 10 percent could decrease C. diff rates outside of hospitals by 17 percent,” Holzbauer said. “Limiting the use of inappropriate antibiotics in dentistry could also have a profound impact.”

For the study, the Minnesota Department of Health tracked community-associated C. diff infections—patients who did not have an overnight stay in a hospital or nursing home—in five Minnesota counties.

For the study, the researchers interviewed 1,626 people with community-associated C. diff between 2009 and 2015, 57 percent of which reported they had been prescribed antibiotics.  The researchers also found that patients that were prescribed antibiotics for tended procedures tended to be older and likely received the medication ….   clindamycin.

The six-year study shows that 15 percent of those with the infection had taken antibiotics prescribed to them from dental procedures, one-third of which had a medical chart that did not list dental procedure-related antibiotics, highlighting the apparent disconnect between dental care and medical care.

Another study conducted by the MDH found that 36 percent of dentists prescribed antibiotics in situations that were generally not recommended by the American Dental Association.

“It is possible some dentists aren’t aware of the updated recommendations or are being asked by other healthcare providers to continue preventive antibiotics despite the change,” Holzbauer said.

Study Show 9% Fewer Antibiotics Prescribed

The use of antibiotics among Americans with commercial health insurance has decreased during the past several years, according to a new analysis that nevertheless
shows lingering variations for different ages and in different parts of the country.

The study released provides the latest evidence of how doctors and patients have begun to heed warnings that excessive antibiotic use breeds dangerous drug resistance and “superbug” bacteria.

The analysis is based on 173 million insurance claims from people under age 65 with Blue Cross Blue Shield coverage
who filled prescriptions
between 2010 and 2016.

 

It is a sequel of sorts to research by the federal Centers for Disease Control and Prevention, which found a smaller decline and comparable age and geographic variations.

The CDC reported a 5 percent decrease overall between 2011 and 2014 in antibiotic prescriptions written in outpatient settings such as doctors’ offices, clinics and hospital emergency rooms.

The study by the Blue Cross Blue Shield Association found that 9 percent fewer antibiotics prescribed in outpatient settings were filled in 2016, compared with 2010.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

The Blue Cross Blue Shield Study:

https://www.bcbs.com/the-health-of-america/reports/antibiotic-prescription-rates-declining-in-the-US?utm_source=social&utm_medium=linkedin&utm_content=&utm_campaign=hoa-antibiotics

 

To read more of this article please click on the link provided below:

https://www.washingtonpost.com/news/to-your-health/wp/2017/08/24/fewer-antibiotic-prescriptions-are-being-filled-a-new-analysis-finds/?utm_term=.d30b61b8fae7

Researchers Long Efforts Find Super-Antibiotics May Combat Vancomycin-Resistant Bacteria

Vancomycin, long considered a “drug of last resort,” kills by preventing bacteria from building cell walls. It binds to wall-building protein fragments called peptides, in particular those that end with two copies of the amino acid D-alanine (D-ala). But bacteria have evolved. Many now replace one D-ala with D-lactic acid (D-lac), sharply reducing vancomycin’s ability to bind to its target.

The world’s last line of defense against disease-causing bacteria just got a new warrior: vancomycin 3.0. Its predecessor—vancomycin 1.0—has been used since 1958 to combat dangerous infections like methicillin-resistant Staphylococcus aureus.

But as the rise of resistant bacteria has blunted its effectiveness, scientists have engineered more potent versions of the drug—vancomycin 2.0.

Now, version 3.0 has a unique three-pronged approach to killing bacteria that could give doctors a powerful new weapon against drug-resistant bacteria and help researchers engineer more durable antibiotics.

“This is pretty special,” says Scott Miller, a chemist at Yale University who was not involved in the new work. “It’s really the culmination of a decades-long effort.”

Vancomycin, long considered a “drug of last resort,” kills by preventing bacteria from building cell walls. It binds to wall-building protein fragments called peptides, in particular those that end with two copies of the amino acid D-alanine (D-ala). But bacteria have evolved. Many now replace one D-ala with D-lactic acid (D-lac), sharply reducing vancomycin’s ability to bind to its target.

Today, that resistance has spread so that dangerous infections like vancomycin-resistant enterococci (VRE) and vancomycin-resistant Staphylococcus aureus (VRSA) are becoming more common. According to the U.S. Centers for Disease Control and Prevention, about 23,000 Americans die from 17 antibiotic-resistant infections each year (although it’s difficult to parse out how much is due to vancomycin resistance).

To solve the D-lac problem, researchers led by Dale Boger, a chemist at the Scripps Research Institute in San Diego, California, began synthesizing new versions of vancomycin that bind to peptides ending in D-ala and D-lac.

They succeeded in 2011. Meanwhile, other groups developed new ways of killing bacteria with vancomycin: One alteration found a novel way to halt cell wall construction, whereas another caused the outer wall membrane to leak, leading to cell death.

TO READ ARTICLE IN ITS ENTIRETY:  

http://www.sciencemag.org/news/2017/05/superantibiotic-25000-times-more-potent-its-predecessor

Now, Boger and his colleagues have assembled all three weapons into one single vancomycin analog.

The new antibiotic is at least 25,000 times more potent against microbes such as VRE and VRSA, they report this week in the Proceedings of the National Academy of Sciences.

Moreover, when Boger’s team tested vancomycin-resistant bacteria against the new three-part analog, the microbes were unable to evolve resistance even after 50 rounds.

Many antibiotics begin to fail after just a few rounds.

This suggests the new compound may be far more durable than current antibiotics, Boger says.

“Organisms just can’t simultaneously work to find a way around three independent mechanisms of action,” he says. “Even if they found a solution to one of those, the organisms would still be killed by the other two.”

Miller adds that antibiotics are often found by trial and error when researchers test a new compound to see whether it stops bacterial growth. By contrast, this work shows the power of rationally designing novel antibiotics to hit microbes where they are weak. “Getting something to do two things by design is hard. Getting something to do three things by design is even harder.”

Still, Boger cautions that the new compound isn’t yet ready for human trials. Next up, he and his colleagues plan to cut down on the 30 chemical steps it takes to make the new compound, in the hopes of producing it more cheaply.

Then they’ll test their drug in animals, and finally humans. If it passes this gauntlet, humanity’s last line of defense against dangerous infections will become considerably stronger.

WHO’s World Hand Hygiene Day In Conjunction With Fight Antibiotic Resistance – It’s In Your Hands

SAVE LIVES: Clean Your Hands

WHO’s global annual call to action for health workers


SAVE LIVES: Clean Your Hands 5 May 2017 – Fight antibiotic resistance – it’s in your hands

The WHO’s calls to action are:

  • Health workers: “Clean your hands at the right times and stop the spread of antibiotic resistance.”
  • Hospital Chief Executive Officers and Administrators: “Lead a year-round infection prevention and control programme to protect your patients from resistant infections.”
  • Policy makers: “Stop antibiotic resistance spread by making infection prevention and hand hygiene a national policy priority.”
  • IPC leaders: “Implement WHO’s Core Components for infection prevention, including hand hygiene, to combat antibiotic resistance.”

Every 5 May, WHO urges all health workers and leaders to maintain the profile of hand hygiene action to save patient lives. Being part of the WHO SAVE LIVES: Clean Your Hands campaign means that people can access important information to help in their practice. This year Pr Pittet and three leading surgeons explain why hand hygiene at the right times in surgical care is life saving.

 

 

Le 5 mai de chaque année, l’OMS exhorte tous les travailleurs et responsables de santé à maintenir haut le profil de la promotion des bonnes pratiques d’hygiène des mains afin de sauver la vie de patients. Faire partie de la campagne Pour Sauver des Vies: l’Hygiène des Mains signifie que soignants et collaborateurs de santé peuvent accéder à des informations importantes pour améliorer leurs pratiques. Cette année, le Pr Pittet et trois chirurgiens de renommée internationale expliquent pourquoi l’hygiène des mains au bon moment au cours des soins chirurgicaux sauve des vies.

 

5 Moments for Hand Hygiene

The My 5 Moments for Hand Hygiene approach defines the key moments when health-care workers should perform hand hygiene.

This evidence-based, field-tested, user-centred approach is designed to be easy to learn, logical and applicable in a wide range of settings.

This approach recommends health-care workers to clean their hands

  • before touching a patient,
  • before clean/aseptic procedures,
  • after body fluid exposure/risk,
  • after touching a patient, and
  • after touching patient surroundings.

 

 

 

 

 

 

For further Information on WHO My 5 Moments for Hand
Hygiene visit:
To download hand hygiene reminder tools for the workplace visit:
To access WHO hand hygiene improvement tools and resources for use
all year round visit:
To see the latest number of hospitals and health care facilities which
have signed up to support the campaign visit:

 

The World Health Organization (WHO) Ranks Worlds Most Deadliest “Superbugs” In the World

 

the WHO has ranked world’s most deadly “Superbugs” in the world:

Three bacteria were listed as critical:

  • Acinetobacter baumannii bacteria that are resistant to important antibiotics called carbapenems. These are highly drug resistant bacteria that can cause a range of infections for hospitalized patients, including pneumonia, wound, or blood infections.
  • Pseudomonas aeruginosa, which are resistant to carbapenems. These bacteria can cause skin rashes and ear infectious in healthy people but also severe blood infections and pneumonia when contracted by sick people in the hospital.
  • Enterobacteriaceae that are resistant to both carbepenems and another class of antibiotics, cephalosporins. This family of bacteria live in the human gut and includes bugs such as E. coli and Salmonella.

The list, which was released February 27th, 2017 and enumerates 12 bacterial threats, grouping them into three categories: critical, high, and medium.

“Antibiotic resistance is growing and we are running out of treatment options. If we leave it to market forces alone, the new antibiotics we most urgently need are not going to be developed in time,” said Dr. Marie-Paule Kieny, the WHO’s assistant director-general for health systems and innovation.

The international team of experts who drew up the new list urged researchers and pharmaceutical companies to focus their efforts on a type of bacteria known as Gram negatives.

(The terminology relates to how the bacteria respond to a stain — developed by Hans Christian Gram — used to make them easier to see under a microscope.)

Dr. Nicola Magrini, a scientist with the WHO’s department of innovation, access and use of essential medicines, said pharmaceutical companies have recently spent more efforts trying to find antibiotics for Gram positive bacteria, perhaps because they are easier and less costly to develop.

Gram negative bacteria typically live in the human gut, which means when they cause illness it can be serious bloodstream infections or urinary tract infections.

Gram positive bacteria are generally found outside the body, on the skin or in the nostrils.

Kieny said the 12 bacteria featured on the priority list were chosen based on the level of drug resistance that already exists for each, the numbers of deaths they cause, the frequency with which people become infected with them outside of hospitals, and the burden these infections place on health care systems.

Paradoxically, though, she and colleagues from the WHO could not provide an estimate of the annual number of deaths attributable to antibiotic-resistant infections. The international disease code system does not currently include a code for antibiotic-resistant infections; it is being amended to include one.

Six (6) others were listed as high priority for new antibiotics. That grouping represents bacteria that cause a large number of infections in otherwise healthy people. Included there is the bacteria that causes gonorrhea, for which there are almost no remaining effective treatments.

Three (3)  other bacteria were listed as being of medium priority, because they are becoming increasingly resistant to available drugs. This group includes Streptococcus pneumoniae that is not susceptible to penicillin. This bacterium causes pneumonia, ear and sinus infections, as well as meningitis and blood infections.

The creation of the list was applauded by others working to combat the rise of antibiotic resistance.

“This priority pathogens list, developed with input from across our community, is important to steer research in the race against drug resistant infection — one of the greatest threats to modern health,” said Tim Jinks, head of drug-resistant infections for the British medical charity Wellcome Trust.

“Within a generation, without new antibiotics, deaths from drug-resistant infection could reach 10 million a year. Without new medicines to treat deadly infection, lifesaving treatments like chemotherapy and organ transplant, and routine operations like caesareans and hip replacements, will be potentially fatal.”

FULL LIST:

Priority 1: Critical
1. Acinetobacter baumannii, carbapenem-resistant
2. Pseudomonas aeruginosa, carbapenem-resistant
3. Enterobacteriaceae, carbapenem-resistant, ESBL-producing

Priority 2: High
4. Enterococcus faecium, vancomycin-resistant
5. Staphylococcus aureus, methicillin-resistant, vancomycin-intermediate and resistant
6. Helicobacter pylori, clarithromycin-resistant
7. Campylobacter spp., fluoroquinolone-resistant
8. Salmonellae, fluoroquinolone-resistant
9. Neisseria gonorrhoeae, cephalosporin-resistant, fluoroquinolone-resistant

Priority 3: Medium
10. Streptococcus pneumoniae, penicillin-non-susceptible
11. Haemophilus influenzae, ampicillin-resistant
12. Shigella spp., fluoroquinolone-resistant

 

to read the article in its entirety click on the link below to be redirected:

http://www.businessinsider.com/the-who-has-ranked-the-deadliest-superbugs-in-the-world-2017-2