Bacteria

What You Need to Know About the Deadly ‘Superbug’ Infection Resistant to All FDA-Approved Antibiotics

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PHOTO: An illustration of a group of carbapenem-resistant Enterobacteriaceae bacteria. The image was based on scanning electron micrographic imagery.

The rise of drug-resistant bacterial “superbugs” have been a concern of public health officials for years, but the U.S. Centers for Disease Control and Prevention has reported a worse-case scenario — a woman with a bacterial infection that was resistant to all FDA-approved treatments.

A Nevada woman died in September after being infected with type of drug-resistant bacteria called Klebsiella pneumonaiae that was resistant to all antibiotics available in the U.S., the CDC reported on Friday.

The woman was in her 70’s when she arrived at hospital in August 2016 with signs of sepsis. She had been in India years before and had been treated for a broken leg and bone infection, according to the CDC. After doing tests, her doctors found the bacteria — which belonged to a class of drug-resistant bugs called carbapenem-resistant Enterobacteriaceae (CRE) — were resistant to all forms of FDA-approved antibiotics. The patient died in September after going into septic shock, according to the CDC.

The woman’s extremely rare infection has focused attention on the increasing problems surrounding these drug-resistant infections and the lack of antibiotics available to treat them.

Fewer New Antibiotics Being Developed

No matter how effective an antibiotic is at killing bacteria, new drugs will be needed as the bacteria mutate and grow more resistant to the existing drugs.

“Antibiotic resistance occurs as part of a natural evolution process, it can be significantly slowed but not stopped,” the CDC notes on its website. “New antibiotics will always be needed to keep up with resistant bacteria as well as new diagnostic tests to track the development of resistance.”

However, the number of drug applications for novel antibiotics being developed by pharmaceutical companies have been dropping steadily over the last three decades, according to the CDC.

From 1980 to 1984, there were nearly 20 FDA drug applications approved for new antibiotics, but from 2005 to 2009, there were fewer than five applications approved, according to the CDC.

In 2013, the CDC said developing new antibiotics and new diagnostic tests was one of its four core actions to stop antibiotic-resistant infections from increasing.

CRE Infections Are an ‘Urgent Threat’

In 2013, CDC characterized CRE infections as an “urgent” threat, meaning the bacteria is an “immediate public health threat that requires urgent and aggressive action.”

The bacteria cause 9,000 drug-resistant infections per year and 600 related deaths, according to the CDC.

While most drug-resistant CRE bacteria are still susceptible to one or more antibiotic, in the infection of the woman in her 70’s reported by the CDC, the bacteria was resistant to all FDA-approved antibiotics, an extremely rare event.

CRE include common bacteria such as E.coli and Klebsiella bacteria.

Doctors Can Attempt to Treat Even Drug-Resistant Infections

When a patient has a drug-resistant bacteria, doctors will sometimes have to use harsher antibiotics or high dosages in order to try and fight the infection.

If a patient has a drug-resistant infection, doctors will work with a lab to test different doses of various antibiotics in an effort to overwhelm and kill the bacteria, said Dr. William Schaffner, an infectious disease expert at Vanderbilt University Medical Center.

However, antibiotics can be taxing on the patient, especially if they are older and with underlying medical conditions.

“This is the kind of calculation you do with every patient,” Schaffner said. “Patients with underlying illnesses present a certain kind of challenge.”

The CDC authors reported that an intravenous version of an antibiotic called fosfomycin is available in other countries but not for use in the U.S. It’s unclear if the patient’s doctors attempted to get an FDA exemption to use the drug and treat the patient.

Long Exposure to Antibiotics and Long Hospital Stays Can Be Dangerous

While this recently reported case is frightening, it is also unusual. The patient had been in and out of hospitals in India for two years after fracturing the large femur bone in her leg and developing a bone infection.

Long hospitals stays, especially in India, and exposure to different antibiotics can increase the likelihood of eventually developing a drug-resistant bacterial infection. As travel around the globe is becoming easier, it’s increasingly important for doctors to find out where their patients may have acquired an infection, Schaffner said.

“India has a notorious reputation for this [type of bacteria,]” he noted. “Travel-related questions are becoming much more important … and just reinforce that we are a very small world.”

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Scientists are genetically engineering Salmonella to destroy brain tumours

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Salmonella is commonly linked to fevers and food poisoning, and generally speaking, it isn’t good news at all for your body. But scientists have come up with an exception: a genetically engineered form of Salmonella bacteria that can eat away at cancer tumours.

The modified bacteria target tumours in the brain rather than seeking out the human gut where Salmonella usually causes damage – and the technique could lead to  a highly targeted technique of fighting one of the worst types of cancer there is.

Researchers from Duke University gave the treatment to rats with the aggressive brain cancer glioblastoma, and saw significant increases in lifespans, with 20 percent of the rodents surviving an extra 100 days compared to control animals – the equivalent of 10 years in human terms.

“Since glioblastoma is so aggressive and difficult to treat, any change in the median survival rate is a big deal,” says one of the team, Johnathan Lyon.

“And since few survive a glioblastoma diagnosis indefinitely, a 20 percent effective cure rate is phenomenal and very encouraging.”

salmonella-close-lookBacteria (pink) take hold of cancer cells (blue). Credit: Duke University

It’s a promising direction of study, since survival rates of humans with this cancer are pretty bleak. Only about 30 percent of patients with glioblastoma live for more than two years after diagnosis.

Part of what makes it so hard to treat is that the tumours hide behind the blood-brain barrier, which separates the circulating blood from the brain’s own fluid.

Conventional drugs can’t easily reach through this membrane, so a more targeted approach is needed to stop glioblastoma from thriving.

To achieve this, the researchers used a genetically adjusted and detoxified form of Salmonella typhimurium, modified to be deficient in a crucial organic compound called purine.

Glioblastoma tumours are an abundant source of this enzyme, which induces the bacteria to seek out the cancer cells to get the purine that they need.

And when the bacteria get to the tumours, two more genetic tweaks kick into action.

Because cancerous cells multiply so quickly, oxygen is scarce inside and around tumours. Knowing this, the scientists coded their Salmonella to produce two proteins called Azurin and p53 in the presence of low levels of oxygen.

These compounds instruct the cancer cells to effectively self-destruct, so the end result is like a genetically-coded guided missile, seeking out the tumour and blitzing cancerous cells when it arrives.

The researchers say the technique is much more accurate than surgery, and because the bacteria are otherwise detoxified, there should be no damaging side effects for the patient.

Of course, having success with a group of rats is no guarantee that the treatment will translate to the human body, but the researchers are hopeful that the technique can be developed to treat cancer patients in the future.

The first step is to get that 20 percent success rate up. Based on initial tests, the 80 percent of cases where the treatment had no effect could be down to the tumour cells outpacing the bacteria, or inconsistencies in the Salmonella‘s penetration in the body.

“It might just be a case of needing to monitor the treatment’s progression and provide more doses at crucial points in the cancer’s development,” says Lyon.

“However, this was our first attempt at designing such a therapy, and there is some nuance to the specific model we used, thus more experiments are needed to know for sure.”

The research has been published in Molecular Therapy Oncolytics.

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Scientists have used bacteria to kill antibiotic-resistant superbugs

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I know you’ve already got a lot to worry about, what with the North Pole being 20 degrees hotter than it’s supposed to be, and the polar bear that went and crushed all our hearts this week, but don’t forget to feel concerned about the looming antibiotic resistance crisis sometimes.

If things keep going as they are, antibiotic-resistant superbugs are expected to kill 10 million people by 2050, and so far, we have no solution. But researchers have found that we could actually fight fire with fire – a predatory bacterium has been shown to kill antibiotic-resistant bugs.

The bacterium in question is called Bdellovibrio bacteriovorus, and it’s known as a predatory bacterium, because it seeks out and consumes its own kind.

A team from Imperial College London and the University of Nottingham in the UK decided to pit it against an antibiotic-resistant strain of the human pathogen Shigella flexneri – a common cause of food poisoning.

Shigella bacteria are responsible for making 160 million people sick each year (diarrhoea is its speciality), and more than 1 million people die each year from infection, mostly because of contaminated food.

There is currently no vaccine to prevent Shigella infection, and in many cases, antibiotics will not help – most patients are told to just wait it out until the infection resolves itself in five to seven days.

It’s a formidable foe – but not for Bdellovibrio, it seems.

When the researchers combined the two types of bacteria in the lab, Bdellovibrio caused the population of antibiotic-resistant Shigella to decline 4,000-fold.

Next they infected live zebrafish larvae with Shigella, and gave them a shot of Bdellovibrio. Rates of survival for the larvae were around 60 percent.

For the control group that didn’t get a shot of Bdellovibrio, only 25 percent of them lived long enough to reach the third day of infection.

The bacteria are so effective because they eat the Shigella bacteria from the inside out, growing large and swollen before bursting out of their dead host’s shell.

So far, the researchers have found no evidence of unwanted side effects from infecting the larvae with Bdellovibrio, and the same could be true for us, James Gallagher reports for the BBC, because previous research has found Bdellovibrio bacteria occurring naturally in healthy humans.

“This study really shows what a unique and interesting bacterium Bdellovibrio is, as it presents this amazing natural synergy with the immune system and persists just long enough to kill prey bacteria before being naturally cleared,” says one of the team, Serge Mostowy from Imperial College London.

While the introduced population of Bdellovibrio appeared to give the zebrafish larvae some level of protection even if they’d had their immune system compromised as part of the experiment, the researchers say the strongest response seems to come from the predatory bacteria working in tandem with the host’s own white blood cells.

“The predatory action of the Bdellovibrio breaks the Shigella-pathogen cells, and this stimulates the white blood cells; redoubling their ‘efforts’ against the pathogen and leading to increased survival of the zebrafish ‘patients’,” says one of the researchers, Liz Sockett from the University of Nottingham.

Of course, zebrafish aren’t humans, and humans aren’t zebrafish, so until similar results are demonstrated in humans, we can’t get too excited. But the researchers say this is a promising sign that the answer to the antibiotic resistance crisis could be the very thing we’re trying to fight.

“It may be unusual to use a bacterium to get rid of another, but in the light of the looming threat from drug resistant infections the potential of beneficial bacteria-animal interactions should not be overlooked,” Michael Chew from the Wellcome Trust in the UK, who wasn’t involved in the research, said in a press statement.

“We are increasingly relying on last line antibiotics, and this innovative study demonstrates how predatory bacteria could be an important additional tool to drugs in the fight against resistance.”

The research has been published in Cell Biology.

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New treatment based on ocean bacteria shown to stop the spread of prostate cancer

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Scientists just completed a trial of a new, non-surgical prostate cancer treatment that uses a tumour-killing drug based on ocean bacteria, and the procedure saw almost half the patients go into complete remission.

The treatment is known as vascular-targeted photodynamic therapy (VTP), and is made possible by a drug called WST11, which is derived from bacteria that live at the bottom of the ocean. These light-sensitive organisms convert photons into energy, and when the same trick is mimicked by WST11, the compound kills cancer cells.

In a broad clinical trial at 47 treatment sites across 10 different European countries, 49 percent of patients with early prostate cancer that were treated with VTP went into complete remission, compared with 13.5 percent in the control group.

“These results are excellent news for men with early localised prostate cancer, offering a treatment that can kill cancer without removing or destroying the prostate,” says lead researcher Mark Emberton from University College London.

“This is truly a huge leap forward for prostate cancer treatment, which has previously lagged decades behind other solid cancers such as breast cancer.”

Men diagnosed with early or low-risk prostate cancer are usually monitored via regular testing to make sure the cancer isn’t spreading.

But if it does begin to spread, patients face a dilemma, as traditional treatments such as surgery or radiation therapy can cause lifelong erectile problems and incontinence.

For these reasons, a non-surgical treatment that doesn’t come with such negative side effects has long been a goal of researchers, and VTP with WST11 could be it.

In the study, the procedure only caused short-term urinary and erectile problems, which had resolved within three months, and all other side effects disappeared within two years.

“This changes everything,” Emberton told James Gallagher at the BBC.

“Traditionally the decision to have treatment has always been a balance of benefits and harms. … To have a new treatment now that we can administer, to men who are eligible, that is virtually free of those side effects, is truly transformative.”

The treatment involves injecting WST11 into the bloodstream, and inserting optical fibres into the prostate gland.

When the optical fibres are turned on, light beams activate the drug in the patient’s blood, causing it to release high-energy free radicals that destroy tumour tissue while leaving surrounding tissue unharmed.

Of the individuals who took part in the trial, cancer progressed in 58 percent of men in the control group, who maintained regular monitoring during the study. But for the men who received VTP, only 28 percent saw tumours spread.

According to Emberton, these results would be even stronger today, as the researchers in the trial didn’t have access to the latest MRI technology when they began their study in 2011.

“We can now pinpoint prostate cancers using MRI scans and targeted biopsies, allowing a much more targeted approach to diagnosis and treatment,” Emberton said in a press release.

“This means we could accurately identify men who would benefit from VTP and deliver treatment more precisely to the tumour. With such an approach, we should be able to achieve a significantly higher remission rate than in the trial and send nearly all low-risk localised prostate cancers into remission.”

There’s also scope to extend the procedure to other cancers, including breast and liver cancer, but first the researchers need to continue monitoring the patients who took part in this trial and see if the remission rates hold up over time.

Meanwhile, the European Medicines Agency (EMA) is currently reviewing the treatment, but it could be years before it’s made available to patients in the broader population.

It’s important to note that there’s still a lot we don’t know about this treatment, and despite its early promise, it’s not necessarily more effective than surgery or radiation therapy at removing the danger of cancer.

That said, it also doesn’t seem to offer the same kinds of complications, so depending on how further research pans out, it could be a valid avenue of treatment in the future.

One man who hopes the wait isn’t too long is Gerald Capon, a 68-year-old from West Sussex in the UK, who took part in the study.

“[T]he trial changed my life. I’m now cancer-free with no side effects and don’t have to worry about needing surgery in future,” he says.

“I feel so lucky to be in this position… I hope that other patients will be able to benefit from this treatment in future.”

The findings are reported in The Lancet Oncology.

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