Combining Antibiotics Changes How Effective They Are

The implications from this should be studied more in light of the major antibiotic resistance problem this century. Among other things, the research found that the compound vanillin (which gives vanilla its taste) combined with an antibiotic that has mostly stopped being used (spectinomycin) increased the effectiveness of the antibiotic.

The effectiveness of antibiotics can be altered by combining them with each other, non-antibiotic drugs or even with food additives. Depending on the bacterial species, some combinations stop antibiotics from working to their full potential whilst others begin to defeat antibiotic resistance, report EMBL researchers and collaborators in Nature on July 4.

In the first large-scale screening of its kind, scientists profiled almost 3000 drug combinations on three different disease-causing bacteria. The research was led by EMBL group leader Nassos Typas.

Overcoming antibiotic resistance

Overuse and misuse of antibiotics has led to widespread antibiotic resistance. Specific combinations of drugs can help in fighting multi-drug resistant bacterial infections, but they are largely unexplored and rarely used in clinics. That is why in the current paper, the team systematically studied the effect of antibiotics paired with each other, as well as with other drugs and food additives in different species.

Whilst many of the investigated drug combinations lessened the antibiotics’ effect, there were over 500 drug combinations which improved antibiotic outcome. A selection of these positive pairings was also tested in multi-drug resistant bacteria, isolated from infected hospital patients, and were found to improve antibiotic effects.

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According to Nassos Typas, combinations of drugs that decrease the effect of antibiotics could also be beneficial to human health. “Antibiotics can lead to collateral damage and side effects because they target healthy bacteria as well. But the effects of these drug combinations are highly selective, and often only affect a few bacterial species. In the future, we could use drug combinations to selectively prevent the harmful effects of antibiotics on healthy bacteria. This would also decrease antibiotic resistance development, as healthy bacteria would not be put under pressure to evolve antibiotic resistance, which can later be transferred to dangerous bacteria.”

General principles

This research is the first large-scale screening of drug combinations across different bacterial species in the lab. The compounds used have already been approved for safe use in humans, but investigations in mice and clinical studies are still required to test the effectiveness of particular drug combinations in humans. In addition to identifying novel drug combinations, the size of this investigation allowed the scientists to understand some of the general principles behind drug-drug interactions. This will allow more rational selection of drug pairs in the future and may be broadly applicable to other therapeutic areas.

Latest Synthetic Antibiotic is Capable of Eliminating Some Antibiotic-Resistant Superbugs

An important discovery for sure.

A “game changing” new antibiotic which is capable of killing superbugs has been successfully synthesised and used to treat an infection for the first time — and could lead to the first new class of antibiotic drug in 30 years.

The breakthrough is another major step forward on the journey to develop a commercially viable drug version based on teixobactin — a natural antibiotic discovered by US scientists in soil samples in 2015 which has been heralded as a “gamechanger” in the battle against antibiotic resistant pathogens such as MRSA and VRE.

Scientists from the University of Lincoln, UK, have now successfully created a simplified, synthesised form of teixobactin which has been used to treat a bacterial infection in mice, demonstrating the first proof that such simplified versions of its real form could be used to treat real bacterial infection as the basis of a new drug.

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As well as clearing the infection, the synthesised teixobactin also minimised the infection’s severity, which was not the case for the clinically-used antibiotic, moxifloxacin, used as a control study. The findings are published in the Journal of Medicinal Chemistry.

It has been predicted that by 2050 an additional 10 million people will succumb to drug resistant infections each year. The development of new antibiotics which can be used as a last resort when other drugs are ineffective is therefore a crucial area of study for healthcare researchers around the world.

Dr Ishwar Singh, a specialist in novel drug design and development from the University of Lincoln’s School of Pharmacy, said: “Translating our success with these simplified synthetic versions from test tubes to real cases is a quantum jump in the development of new antibiotics, and brings us closer to realising the therapeutic potential of simplified teixobactins.

“When teixobactin was discovered it was groundbreaking in itself as a new antibiotic which kills bacteria without detectable resistance including superbugs such as MRSA, but natural teixobactin was not created for human use.

“A significant amount of work remains in the development of teixobactin as a therapeutic antibiotic for human use — we are probably around six to ten years off a drug that doctors can prescribe to patients — but this is a real step in the right direction and now opens the door for improving our in vivo analogues.”

Dr Lakshminarayanan Rajamani from SERI added: “We need sophisticated armour to combat antibiotic-resistant pathogens. Drugs that target the fundamental mechanism of bacterial survival, and also reduce the host’s inflammatory responses are the need of the hour. Our preliminary studies suggest that the modified peptide decreases the bacterial burden as well as disease severity, thus potentially enhancing the therapeutic utility.”

Powerful New Type of Antibiotics Found in Dirt

The antibiotic type has the potential to kill MRSA. In an age where antimicrobial resistance is already at dangerous levels, valuable new approaches — such as what’s described in the article — are needed.

The modern medical era began when an absent-minded British scientist named Alexander Fleming returned from vacation to find that one of the petri dishes he forgot to put away was covered in a bacteria-killing mould. He had discovered penicillin, the world’s first antibiotic.

Ninety years later, the world faces an antibiotic crisis.

Superbugs have evolved resistance to dozens of drugs in doctors’ arsenals, leading to infections that are increasingly difficult to treat. Global deaths from antibiotic-resistant infections are predicted to hit 10 million a year by 2050.

So in labs around the world, scientists are racing against time tocultivatenew microbe-destroying molecules – but most of the low-hanging fruit has already been picked.

With due respect to Fleming, microbiologist Sean Brady thinks it’s time to shift tactics. Instead of growing antibiotics in a petri dish, he hopes to find them in the ground.

“Every place you step, there’s 10,000 bacteria, most of which we’ve never seen,” said Brady, an associate professor at Rockefeller University in New York.

Many of these bacteria behave in ways that aren’t yet understood and produce molecules that we haven’t been seen before.

That idea is beginning to pay off: in a study published Monday in the journal Nature Microbiology, he and his colleagues report the discovery of a new class of antibiotic extracted from unknown microorganisms living in the soil.

This class, which they call malacidins, kills several superbugs – including the dreaded methicillin-resistant Staphylococcus aureus (MRSA) – without engendering resistance.

You won’t find this antibiotic at your pharmacy next week, Brady cautioned. It takes years for a novel molecule to be developed, tested and approved for distribution.

But its discovery is proof of a powerful principle, he said: a world of potentially useful untapped biodiversity is still waiting to be discovered.

Though antibiotics are prized for their ability to combat the microbes that make humans sick, most of the drugs come from bacteria.

For example, streptomycin, which has been used to treat tuberculosis and plague, is produced by the bacterium Streptomyces griseus. (This microbe was originally found in the dirt of a New Jersey farm field, though the antibiotic research was conducted using cell cultures.)

Bacteria have been fighting one another for billions of years – far, far longer than humans have been around – so it’s hardly surprising that they have evolved all the best weapons.

Yet the vast majority of these microbes don’t grow well under controlled laboratory conditions, making them difficult to study.

“Maybe, using that simple culture-based approach, we’ve missed most of the chemistry that are produced by bacteria,” Brady said.

It would be better to derive interesting molecules directly from the environment. And with the advent of metagenomics, techniques that allow all the genetic material in a sample to be sequenced en masse, researchers can do just that.

Indian Farm Chickens Dosed with the World’s Strongest Antibiotics, Worsening Antibiotic Resistance

This news is a big cause for concern due to the sheer amount of last-resort antibiotics being used on these animals. Farm antibiotic use needs to be restricted before antibiotic resistance becomes a severe problem.

Chickens raised in India for food have been dosed with some of the strongest antibiotics known to medicine, in practices that could have repercussions throughout the world.

Hundreds of tonnes of an “antibiotic of last resort” – only used in the most extreme cases of sickness – are shipped to India each year to be used, without medical supervision, on animals that may not require the drugs but are being dosed with them nevertheless to promote the growth of healthy animals.

Routine use of some of the strongest antibiotics, which doctors have said should be preserved for the most extreme cases lest resistance to them should increase and prevent their use for the diseases for which they are intended, is now a common practice in farming in the developing world. The consequences will be felt throughout the world because resistance to strong antibiotics is spread among organisms.

Germs with qualities that can make them dangerous to humans will, if untreated or poorly treated, mutate into more powerful pathogens that are resistant to treatment. Poor or inadequate public heath treatments assists this process, potentially spreading pathogens around the world.

A study by the Bureau of Investigative Journalism has found that hundreds of tonnes of colistin, described as an antibiotic of last resort, have been shipped to India for the routine treatment of animals, chiefly chickens, on farms.

The finding is concerning because the use of such powerful drugs can lead to an increasing resistance among farm animals around the world. Colistin is regarded as one of the last lines of defence against serious diseases, including pneumonia, which cannot be treated by other medicines. Without these drugs, diseases that were commonly treatable in the last century will become deadly once again.

There is nothing to prevent Indian farmers, which include some of the world’s biggest food producers, from exporting their chickens and other related products overseas. There are currently no regulations that would prevent such export to the UK on hygiene terms, except for those agreed under the EU. Any regulations to be negotiated after Brexit might not take account of these regulations.

Supercharged Antibiotics Could Fight Antibiotic-Resistant Superbugs

Now the question here becomes one of how many older antibiotics can be revitalized.

An old drug supercharged by University of Queensland researchers has emerged as a new antibiotic that could destroy some of the world’s most dangerous superbugs.

The supercharge technique, led by Dr Mark Blaskovich and Professor Matt Cooper from UQ’s Institute for Molecular Bioscience (IMB), potentially could revitalise other antibiotics.

Antibiotic-resistant bacteria — superbugs — cause 700,000 deaths worldwide each year, and a UK government review has predicted this could rise to 10 million by 2050.

Dr Blaskovich said the old drug, vancomycin, was still widely used to treat extremely dangerous bacterial infections, but bacteria were becoming increasingly resistant to it.

“The rise of vancomycin-resistant bacteria, and the number of patients dying from resistant infections that cannot be successfully treated, stimulated our team to look at ways to revitalise old antibiotics,” Dr Blaskovich said.

“We did this by modifying vancomycin’s membrane-binding properties to selectively bind to bacterial membranes rather than those of human cells, creating a series of supercharged vancomycin derivatives called vancapticins.”

The rebooted vancomycin has the potential to treat methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE).

Professor Cooper said pharmaceutical companies had departed the antibiotic discovery field because new antibiotics were difficult to find and were not as lucrative as cholesterol-lowering medications or cancer treatments.

“Hence many scientists are re-engineering existing drugs to overcome bacterial resistance, rather than searching for new drugs,” he said.

“Drug development is normally focused on improving binding to a biological target, and rarely focuses on assessing membrane-binding properties.

“This approach worked with the vancapticins, and the question now is whether it can be used to revitalise other antibiotics that have lost effectiveness against resistant bacteria.

“Given the alarming rise of multi-drug resistant bacteria and the length of time it takes to develop a new antibiotic, we need to look at any solution that could fix the antibiotic drug discovery pipeline now,” Professor Cooper said.

The research, published in the journal Nature Communications, was supported by the Wellcome Trust, the world’s largest biomedical charity, and Australia’s National Health and Medical Research Council.