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.

Metallodrug Effective in “Taming” Antibiotic Resistant Superbugs

Metallodrugs are pharmaceuticals that use metal as an active ingredient, and according to the research, this one is able to substantially reduce the dangerous advancement of antibiotic resistance. More hospitals and medical researchers should therefore know about this.

Antimicrobial resistance posed by “superbugs” has been a major public health issue of global concern. Drug-resistant infections kill around 700,000 people worldwide each year. The figure could increase up to ten million by 2050, exceeding the number of deaths caused by cancers, according to figures of the World Health Organization (WHO).

Current clinical options for treating antibiotic resistant infections include increasing the prescribed antibiotic dose or using a combination therapy of two or more antibiotics. This might potentially lead to overuse of antibiotics, producing superbugs more resistant to antibiotics. Nevertheless, the development of antibiotic resistance far outruns the approvals of new antibacterial agents. While it may take a decade and cost an unusual high investment of USD 1 billion in average to bring a new drug to market, generating resistance to a new drug only requires a short couple of years by bacteria. Scientists and clinicians are in desperate need to discover an economic, effective, safe alternative strategy to meet the global public health challenge of antimicrobial resistance.

A research team led by Professor Sun Hongzhe of the Department of Chemistry, Faculty of Science and Dr Richard Kao Yi-Tsun of the Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong (HKU) discovered an alternative strategy by repositioning colloidal bismuth subcitrate (CBS), an antimicrobial drug against Helicobacter pylori (H. pylori) -related ulcer.

They found the bismuth-based metallodrug to effectively paralyze multi-resistant superbugs, e.g. Carbapenem-resistant Enterobacteriaceae (CRE) and Carbapenem-resistant Klebsiella pneumoniae (CRKP) and significantly suppress the development of antibiotic resistance, allowing the lifespan of currently-used antibiotic to be largely extended. CRE and CRKP can cause deadly infections such as bacteremia, pneumonia, and wound infections.

The team is the first globally to link the “resistance-proof” ability of metallo-drug to the treatment of superbugs. This bismuth drug-based therapy looks set to become the last-line strategy against superbugs infections apart from development of new antibiotics. Since CBS is a US Food and Drug Administration (FDA)-approved drug, it will hopefully be rapidly ready for human clinical trials.

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More importantly, the brand-new therapy allows the dose of antibiotics to be reduced by 90% to attain the same level of effectiveness, and the development of NDM-1 resistance to be significantly slowed down, which will largely extend the life cycle of currently used antibiotics.

In the mouse model of NDM-1 bacterial infection, combination therapy comprising CBS and Carbapenem significantly prolonged the life expectancy and raised the eventual survival rate of infected mice by more than 25 percentage points compared to Carbapenem monotherapy. The research team now concentrates on using CBS-based therapy in other animal infection models, e.g. urinary tract infection (UTI), hoping to offer a more extensive approach to combat with antibiotic resistant superbugs.

Dr Ho found the results very encouraging, he said: “There is currently no effective approach to overcome the NDM superbug. Bismuth has been used clinically for decades. Knowing that it can tame the NDM is like “a good rain after a long drought” for the scientific community.”

CDC Warning About Resistant “Nightmare Bacteria” Appearing in the U.S.

Antimicrobial resistance is among the most important issues facing society today, and it’s somewhat unnerving that there’s such a lack of focus on it. There needs to be a massive new funding effort to develop new ways to fight this threat.

You’ve probably read about antibiotic resistance at some point, but sometimes it’s hard to stress just how important this issue is, especially when it feels like a far off problem.

So how about this – each year, over 23,000 Americans die because of bacteria that is resistant to antibiotics.

According to a new study from the Centers for Disease Control and Prevention (CDC), last year, nationwide tests discovered 221 instances of ‘unusual’ germs – bugs resistant to all, or most antibiotics tested on it.

This is no longer a far-off problem – it’s something hospitals are fighting right now.

“Unusual resistance germs, which are resistant to all or most antibiotics tested and are uncommon or carry special resistance genes, are constantly developing and spreading,” the CDC team writes for their in-house journal, Vital Signs.

“Lab tests uncovered unusual resistance more than 200 times in 2017 in “nightmare bacteria” alone.”

Nightmare bacteria are bacteria that are either nearly, or fully untreatable.

The study found that one in four samples sent into the lab for testing had bacteria with special genes that allowed them to spread resistance to other bacteria.

Not only that, but in facilities that had these bacteria with unusual genes, about 1 in 10 symptomless people who were screened had at least one resistant bug.

These people can pass on the resistant bacteria, effectively becoming a silent carrier of an illness.

“CDC’s study found several dangerous pathogens, hiding in plain sight, that can cause infections that are difficult or impossible to treat,” said CDC Principal Deputy Director Anne Schuchat.

So, what can we do? Many researchers are working on developing more antibiotics, or ways of stopping bacteria without antibiotics, but the CDC is urging hospitals and healthcare providers to stay on top of the problem as well.

“As fast as we have run to slow [antibiotic] resistance, some germs have outpaced us,” Schuchat said to Kaiser Health News.

“We need to do more and we need to do it faster and earlier.”

The paper recommends rapid identification of bacteria to check for resistance, completing infection control assessments, and testing those without symptoms who may also carry and spread the germs.

This is on top of the advice already provided by the CDC to do with correct use to antibiotics, both in prescribing, and taking them – for example, not using antibiotics when you have a viral infection like the common cold or the flu.

But there is some good news as well – the CDC lab network “is working at an absolutely high level of effectiveness,” said William Schaffner, from the Vanderbilt University School of Medicine to Kaiser Health News.

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.”

Platypus Milk Could Help Fight Antibiotic Resistance

An important finding through studying animals reveals itself again, and the fight against antibiotic resistance is among the most serious issues of the 21st century.

Researchers previously discovered that platypus milk confers antimicrobial protection to the species’ young, and now a new study led by scientists at Australia’s CSIRO has figured out what it is about platypus milk that’s so effective against bacteria.

“Platypus are such weird animals that it would make sense for them to have weird biochemistry,” says one of the team, molecular biologist Janet Newman.

“By taking a closer look at their milk, we’ve characterised a new protein that has unique antibacterial properties with the potential to save lives.”

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It’s possible, the team thinks, the platypus evolved to produce its antimicrobial Shirley Temple curls, as a defence against bacteria attracted to this exposed milk, ensuring the pups got fed, not bugs in the environment.

That’s just a hypothesis at the moment, but now that we know about the molecular structure of this natural antimicrobial structure, the team says we might be able to replicate the protein for antibiotic medications – providing us with a new means of fighting the growing scourge of antibiotic resistance.

It’s not the first time this unusual animal has come to our aid. In 2016, researchers discovered a hormone contained in platypus venom could actually help us develop new kinds of diabetes treatments.

Not bad for a wacky hybrid of stitched-together animal parts that’s probably just a joke somebody’s playing on us. Not bad at all.

“There’s a quote from [Louis] Pasteur which is ‘Chance favours the prepared mind’,” Newman told Radio NZ.

“You can find discoveries in all sorts of places.”

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.