Tag Archives: Antibiotic resistance

Researchers Uncover How Bacteria is Able to Shut Its Doors to Antibiotics

Drug-resistant infections have been a growing concern across the medical and pharmaceutical industries. In the United States alone, approximately 23,000 people die each year from infections that are resistant to antibiotics. Now, researchers may know why this happens.
New findings from researchers at Imperial College London show that these bacterial infections are able to reject antibiotics by “closing tiny doors in their cell walls.”

By understanding how these cells are able to shut the doors, the researchers said this could provide new understandings for drugmakers to develop treatments that will “pick the locks” of the closed doors. The result of the research was published today in Nature Communications In the study, the Imperial College researchers, who are focused on antibiotic resistance, looked at the bacterium Klebsiella pneumoniae, which causes infections in the lungs, blood and wounds of people in hospitals. Patients that have compromised immune systems are especially vulnerable to this bacterium. The researchers said K. pneumoniae is becoming increasingly resistant to antibiotics, particularly a family of drugs called Carbapenems, which are used in hospitals when others have failed or are ineffective. Because of this resistance to the powerful antibiotics, the World Health Organization listed Carbapenem-resistant K. pneumoniae as a critical problem.


The researchers found that K. pneumoniae is able to resist Carbapenems by shutting down it surface pores, which is how the antibiotics typically attack the bacteria. The team compared the structures of K. pneumoniae bacteria that were resistant to Carbapenems to those that weren’t and found the resistant bacteria had modified or absent versions of a protein that creates pores in the cell wall. Resistant bacteria have much smaller pores, blocking the drug from entering, the researchers said in a statement.   Joshua Wong, from the Department of Life Sciences at Imperial and first author of the study, said with the growing threat of antibiotic-resistant bugs like K. pneumoniae, it’s important to understand how it happened in order to provide “vital insights that could allow new strategies and drugs to be designed.”

There is some good news though from this finding. The researchers said that the bacteria grow at a much slower rate when its doors are closed due to its inability to absorb nutrients while being attacked by the antibiotics.

Those closed doors will present a challenge to drug developers. Gad Frankel, head of the study team, said the ability of the bacteria to shut its doors to the antibiotics will also provide a mechanism to counteract many other drugs. He said that ability will be difficult to get around.
“However, we hope that it will be possible to design drugs that can pick the lock of the door, and our data provide information to help scientists and pharmaceutical companies make these new agents a reality,” Frankel said in a statement.

Over the past few years, there have been multiple stories about the rise of drug-resistant pathogens. Recently, a dangerous fungal infection known as  Candida auris reared its head in a New York hospital. The facility had to tear out part of the room a patient was housed in due to the spread of the fungal infection, which can be fatal. With growing concerns about the rise of drug-resistant bacteria, multiple companies are developing new forms of antimicrobials to take on serious health concerns, such as carbapenem-resistant enterobacteriaceae, Clostridium difficile, better known as C. diff, or Staphylococcus infections

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

https://www.biospace.com/article/researchers-discover-why-some-bacteria-has-become-resistant-to-antibiotics

United Nations Releases Critical Warning On Growing Concerns of Drug-Resistant Infections

With more and more common medications losing their ability to fight dangerous infections, and few new drugs in the pipeline, the world is facing an imminent crisis that could lead to millions of deaths, a surge in global poverty and an even wider gap between rich and poor countries, the United Nations warned in a report on April 29th – 2019.

Drug-resistant infections already claim 700,000 lives a year, including 230,000 deaths from drug-resistant tuberculosis, the report said. The rampant overuse of antibiotics and anti-fungal medicines in humans, livestock and agriculture is accelerating a crisis that is poorly understood by the public and largely ignored by world leaders. Without concerted action, a United Nations panel said, resistant infections could kill 10 million people annually by 2050 and trigger an economic slowdown to rival the global financial crisis of 2008.

The problem threatens people around the world. During the next 30 years, the United Nations experts said, 2.4 million people in Europe, North America and Australia could die from drug-resistant infections, making routine hospital procedures like knee-replacement surgery and childbirth far riskier than they are today.

“This is a silent tsunami,” said Dr. Haileyesus Getahun, director of the U.N. Interagency Coordination Group on Antimicrobial Resistance, which spent two years working on the report. “We are not seeing the political momentum we’ve seen in other public health emergencies, but if we don’t act now, antimicrobial resistance will have a disastrous impact within a generation.”

 

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

https://www.nytimes.com/2019/04/29/health/un-drug-resistance-antibiotics

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

 

 

 

Clifford McDonald, MD and Alison Laufer-Halpin, Ph.D., of the CDC Discuss the Human Microbiome on C. diff. Spores and More

C Diff Foundation’s “C. diff. Spores and More Global Broadcasting Network” is honored to announce Doctors McDonald and Laufer-Halpin as our guest speakers on

Tuesday, July 25, 2017 at 10 a.m. PT / 1 p.m. ET

(www.cdiffradio.com)

These two leading topic experts will be discussing significant ways to unlock the mysteries of the human microbiome; how it affects our health, the immune system, and why it is so important to protect it.

As part of the Centers for Disease Control and Prevention (CDC) efforts to protect patients and slow antibiotic-resistance, the CDC is investing in research to discover and develop new ways to prevent antibiotic-resistant infections.

To Listen To the Podcast – click on the following link:

https://www.voiceamerica.com/episode/100322/the-human-microbiome-how-it-works-how-it-affects-your-health-your-immune-system-and-why-it-is

 

Learn more about C Diff Radio at: http://www.cdiffradio.com/.

Two UK Researchers, Prof.Alistair Leanord and Dr. David Enoch, Present CDI Data At the 27th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID)

Repeated infection with the bacterium Clostridium difficile (C. difficile, C.diff.), which causes abdominal pain, fever, diarrhea is linked to higher death rates, as well as having a significant impact on health services in terms of cost and hospital beds occupied.

In the first of two presentations at the 27th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) (tomorrow (Saturday), Professor Alistair Leanord, from Glasgow University, UK, will say that in Scotland the extra impact on the health service from C. difficile infections amounted to 10,600 bed days a year. “This is the equivalent to a 30-bed hospital ward being fully occupied all year,” he will say.

He will tell the congress that the (median) average cost of a patient with C. difficile infection was £7,500 (€8,600 approximately) compared to £2,800 (€3,200 approx) for patients with other medical conditions. In Scotland over a one year period, from October 2015 to October 2016, there were 1,150 cases of C. difficile infection in patients aged 15 and over. This cost the National Health Service (NHS) in Scotland a total of £8,650,000. Out of this amount, the additional costs of treating C. difficile infection, over and above the basic cost of a hospital bed and normal medical care, was £1,955,000. The calculations were carried out at Strathclyde University, which is part of the Scottish Healthcare Associated Infection Prevention Institute (SHAIPI) research consortium.

Until now, little has been known about the impact on health service resources from C. difficile infections, and on patients in terms of recurrence of infection, readmission to hospital, length of stay and death rates.

Prof. Leanord and his colleagues in Scotland identified 3,304 patients with C. difficile in Scottish hospitals between 2010 and 2013 and matched them with 9,516 patients who did not have the infection (the control group). Approximately two-thirds of the C. difficile patients acquired the infection in hospital.

They found that patients with C. difficile infection had more than double the risk of dying from any cause within two months of being admitted to hospital; nearly a third of all C. difficile cases (29%) died within two months compared to 14% of patients in the control group. Patients with C. difficile stayed in hospital a (median) average 9.7 days longer than the patients without the infection. Of the 1,712 C. difficile patients who were discharged from hospital within 30 days of the first episode of infection, 59% were readmitted within six months; of the 626 cases discharged more than 30 days after the first episode 53% were readmitted within six months. Few of these re-admissions were directly related to C. difficile infection.

“However, nearly a sixth of patients (14%) who were cured of the initial infection recurred within three months, and nearly one third of them (29%) had a second recurrence within a year,” says Prof. Leanord.

Older people were more vulnerable to a recurrence. Among the patients with C. difficile infection, 22% were aged 85 or over, and patients aged 75 and over had approximately double the risk of a recurrence of the infection compared to those aged under 65. Patients aged between 65-74 had 1.5 times the risk of recurrence compared to younger patients.

Prof. Leanord will conclude: “Having a clear understanding of the nature of C. difficile infections in Scotland will allow the Scottish government to target resources at the most appropriate patients to try to reduce the overall burden of the disease on the health service. Our findings are very likely to be applicable to the rest of the UK and other countries as well.”

………………….

In a second presentation on Saturday, Dr David Enoch, a consultant microbiologist and infection control doctor at the National Infection Service, Public Health England, Cambridge (UK), will report the outcomes of 6,874 patients who had acquired C. difficile infection in hospital between 2002 and 2013 in England. Of these, 1,141 (16.6%) had recurrences of the infection.

“We found that 49% of hospital patients who suffer a recurrent episode of C. difficile infection die within a year, compared to 38% of those who suffer an initial infection only,” he will say. “In addition, 21% of patients with a recurrence suffered other complications as well, such as dehydration, malnourished and sometimes even perforation of the bowel, compared to 18% of patients who did not have a recurrence.”

Dr Enoch estimates that there are approximately 125,000 cases of C. difficile infection in Europe each year, and between 15-30% of these recur. “Cases in the UK have been coming down since 2008, which is most probably due to improvements in antibiotic prescribing and cleaning regimens in hospitals. This is encouraging but more still needs to be done.”

The average age of the patients was 77 and the average length of stay in hospital was 38 days.

“The main risk factor for developing C. difficile infection is prior antibiotic use. These patients are often already ill from some other underlying illness, which explains why they needed antibiotics in the first place. Older people are at greater risk of C. difficile infection as they are often sicker, have other illnesses or conditions, and so need more antibiotics,” he will say.

Dr Enoch continues: “Although much has been done, particularly in the UK, to try to prevent C. difficile infection, strict adherence to antibiotic guidelines by clinicians and thorough cleaning of the hospital environment are crucial in ensuring that patients don’t develop C. difficile infection in the first place. Treatment with a new drug called fidaxomicin has also been shown to reduce the risk of recurrence in patients who are unfortunate enough to develop an infection. However, we still have a lot to learn, particularly about how C. difficile infection occurs in the community, and how best to treat it.”

Treatments for recurrences of C. difficile infection  —–  include stopping the antibiotic that made the patient susceptible to the infection and starting a different antibiotic that is effective against C. difficile infection. These antibiotics include metronidazole, vancomycin and fidaxomicin. Supportive therapy, such as extra fluids, and surgery in serious or life-threatening cases may also be necessary. Faecal transplantation is emerging as a promising option; this is a process in which the good bacteria that the gut needs but which has been killed off by antibiotics is transplanted into the patient from a healthy donor.

(CDF:  Consider contacting an organization conducting Clinical Trials to Treat and Prevent.  Click on the following link for more information :  https://cdifffoundation.org/clinical-trials-2/

###

Abstract no: #1672, presented by Prof. Alistair Leanord in the “Clostridium difficile infections: epidemiology and outcome” oral session, 16.30-18.30 hrs, Saturday 22 April, Hall A.

Abstract no: #883, presented by Dr Enoch in the “Clostridium difficile: guts and glory” e-poster mini-oral session, 15.30-16.30 hrs, Saturday 22 April, ePoster Arena 4.

 

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

https://www.eurekalert.org/pub_releases/2017-04/esoc-cdi041917.php

Antibiotic Resistance IS A Serious Global Health Concern

C.diff. Treatments

A Nevada woman has died from an infection resistant to all available antibiotics in the United States, public health officials report.

According to the Centers for Disease Control and Prevention, the woman’s condition was deemed incurable after being tested against 26 different antibiotics.

Though this isn’t the first case of pan-resistant bacteria in the U.S., at this time it is still uncommon. Still, experts note that antibiotic resistance is a growing health concern globally and call the newly reported case “a wake up call.”

“This is the latest reminder that yes, antibiotic resistance is real,” Dr. James Johnson, a professor specializing in infectious diseases at the University of Minnesota Medical School, told CBS News. “This is not some future, fantasized armageddon threat that maybe will happen after our lifetime. This is now, it’s real, and it’s here.”

According to the report, the woman from Washoe County was in her 70s and had recently returned to America after an extended trip to India. She had been hospitalized there several times before being admitted to an acute care hospital in Nevada in mid-August.

Doctors discovered the woman was infected with carbapenem-resistant Enterobacteriaceae (CRE), which is a family of germs that CDC director Dr. Tom Frieden has called “nightmare bacteria” due to the danger it poses for spreading antibiotic resistance.

The woman had a specific type of CRE, called Klebsiella pneumoniae, which can lead to a number of illnesses, including pneumonia, blood stream infections, and meningitis. In early September, she developed septic shock and died.

The authors of the report say the case highlights the need for doctors and hospitals to ask incoming patients about recent travel and if they have been hospitalized elsewhere.

Other experts say it underscores the need for the medical community, the government and the public to take antibiotic resistance more seriously.

According to the CDC, at least two million people become infected with antibiotic resistant bacteria each year, and at least 23,000 die as a direct result of these infections.

The World Health Organization calls antibiotic resistance “one of the biggest threats to global health.”

A grim report released last year suggests that if bacteria keep evolving at the current rate, by 2050, superbugs will kill 10 million people a year.

While scientists are working to develop new antibiotics, that takes time, and experts encourage doctors and the public to focus on prevention efforts.

One of the most important ways to prevent antibiotic resistance is to only take antibiotics only when they’re necessary.

“Drug resistance like this [case] generally develops from too much exposure to antibiotics,” assistant professor of pediatrics at Johns Hopkins University School of Medicine and director of the Pediatric Antimicrobial Stewardship Program at The Johns Hopkins Hospital, told CBS News. “Every time you’re placed on an antibiotic it’s important to question if it’s absolutely necessary and what’s the shortest amount of time you can take this antibiotic for it to still be effective.”

Johnson notes that medical tourism – the practice of traveling to another country to obtain medical treatment, typically at lower cost – may no longer be worth the risk. “With this [antibiotic] resistance issue, the risk/benefit of this approach really changes and I think that people really need to be aware and seriously consider if it’s a good idea given the possibility of this kind of thing,” he said.

Frequent hand washing, particularly in healthcare settings, is also extremely important in preventing the spread of germs.

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

http://www.lasvegasnow.com/news/nevada-woman-died-from-superbug-resistant-to-all-available-antibiotics-in-us/640548775