Antibiotic resistance is not new – it existed long before people used drugs to kill bacteria



Antibiotic resistance can spread between microbes within hours.
Lightspring/Shutterstock.com

Ivan Erill, University of Maryland, Baltimore County

Imagine a world where your odds of surviving minor surgery were one to three. A world in which a visit to the dentist could spell disaster. This is the world into which your great-grandmother was born. And if humanity loses the fight against antibiotic resistance, this is a world your grandchildren may well end up revisiting.

Antibiotics changed the world in more ways than one. They made surgery routine and childbirth safer. Intensive farming was born. For decades, antibiotics have effectively killed or stopped the growth of disease-causing bacteria. Yet it was always clear that this would be a rough fight. Bacteria breed fast, and that means that they adapt rapidly. The emergence of antibiotic resistance was predicted by none other than Sir Alexander Fleming, the discoverer of penicillin, less than a year after the first batch of penicillin was mass produced.

Yet, contrary to popular belief, antibiotic resistance did not evolve recently, or in response to our use and misuse of antibiotics in humans and animals. Antibiotic resistance first evolved millions of years ago, and in the most mundane of places.

I am a bioinformatician, and my lab studies the evolution of bacterial genomes. With antibiotic resistance becoming a major threat, I’m trying to figure out how resistance to antibiotics emerges and spreads among bacterial populations.

A billion-years-old arms race

Most antibiotics are naturally produced by bacteria living in soil. They produce these deadly chemical compounds to fend off competing species. Yet, in the long game that is evolution, competing species are unlikely to sit idly by. Any mutant capable of tolerating a minimal quantity of the antibiotic will have a survival advantage and will be selected for – over generations this will produce organisms that are highly resistant.

So it’s a foregone conclusion that antibiotic resistance, for any antibiotic researchers might ever discover, is likely already out there. Yet people keep talking about the evolution of antibiotic resistance as a recent phenomenon. Why?

Resistance can and does evolve when bacteria are persistently exposed to a new antibiotic they have never encountered. Let’s call this the old-fashioned evolutionary road. Second, when bacteria are exposed to a novel antibiotic and are in contact with bacteria already resistant to this antibiotic, it is just a matter of time before they get cozy and trade genes. And, importantly, once genes have been packaged for trading, they become easier and easier to share. Bacteria then meet other bacteria, which meet more bacteria, until one of them eventually meets you.

Bacteria can evolve resistance to high levels of antibiotics in just days.

The rise and fall of sulfa drugs

For all their might, antibiotics are not the only substances capable of effectively killing bacteria (without killing us). A decade before the mass production of penicillin, sulfonamide drugs became the first commercial antibacterial agent. Sulfa drugs act by blocking an enzyme – called DHPS – that is essential for bacteria to grow and multiply.

Sulfa drugs are not antibiotics. No known organism produces them. They are chemotherapeutic agents synthesized by humans. No natural producer means no billion-year-old arms race and no pool of ancient resistance genes. We would expect bacteria to evolve resistance to sulfa drugs via the good old-fashioned way. And they did.

Just a few years after their commercial introduction, the first cases of resistance to sulfa drugs were reported. Mutations to the bacterial DHPS enzyme made sulfa drugs ineffective. Then penicillin and the antibiotic era came about. Sulfa drugs were relegated to a secondary role in medicine, but they gained popularity as cheap antimicrobials in animal husbandry. By the 1980s resistance to sulfa drugs was rampant and worldwide. What had happened?

At odds with resistance

To answer this question our research team took sequences of sulfa drug resistance genes from disease-causing bacteria and compared them to millions of “normal” versions of the DHPS enzyme in nonpathogenic bacteria.

The team identified two large groups of bacteria that had DHPS enzymes resistant to sulfa drugs. By studying their DNA sequences, we were able to show that these resistant DHPS enzymes had been present in these two groups of bacteria for at least 500 million years. Yet sulfa drugs were first synthesized in the 1910s. How could resistance be around 500 million years ago? And how did these resistance genes find their way into the disease-causing bacteria plaguing hospitals worldwide?

The clues left in gene sequences are too fuzzy to conclusively answer the latter, but we can certainly speculate. The bacteria we identified as harboring these ancient sulfa drug resistance genes are all soil and freshwater bacteria that thrive under the well-irrigated subsoil of farms. And farmers have been adding huge amounts of sulfa drugs to animal feed for the past 50 years.

The sublethal concentrations of sulfa drugs in the soil are the perfect setting for resistance genes to be transferred from these ancient resistant bacterial populations to other bacteria. All it takes is for one lucky bacterium to meet one of these ancient resistant ones in the subsoil. They trade some genes, one bacterium to the next, and resistance spreads until a newly minted resistant bacterium eventually makes it to the groundwater supply you drink from. You do the math.

Nothing new under the sun

As for why sulfa drug resistance genes would be around 500 million years ago, there are two plausible explanations. On the one hand, it could be that 500 million years ago there was a bacterium that synthesized sulfa drugs, which would explain the evolution of resistance. However, the lack of remnants from such a biosynthetic pathway makes this unlikely.

On the other hand, resistant bacteria may have been around just by chance. The argument here is that there are so many bacteria, and such diversity, that chances are that some of them are going to be resistant to anything scientists come up with. This is a sobering thought.

Then again, this is already the baseline for antibiotics. Like climate change, antibiotic resistance is one of those problems that always seem to be a couple decades away. And it may well be. A turning point for me in the climate change debate was a decade-old opinion piece in New Scientist. It stated that we should make every possible effort to prevent climate change, especially in the unlikely case that it was not caused by man, because that would mean that all we can do is palliate a natural phenomenon.

Our research points in the same direction. If resistance is already out there, drug development can offer only temporary relief. The challenge then is not to quell resistance, but to avoid its spread. It is a big challenge, but not an insurmountable one. Not feeding wonder drugs to pigs would do nicely, for starters.The Conversation

Ivan Erill, Associate Professor of Biological Sciences, University of Maryland, Baltimore County

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Legal highs: arguments for and against legalising cannabis in Australia



File 20180417 32339 16n0gjo.jpg?ixlib=rb 1.1
Many of the harms associated with cannabis use are to do with its illegality.
from http://www.shutterstock.com

Nicole Lee, Curtin University and Jarryd Bartle, RMIT University

Greens leader Richard Di Natale wants Australia to legalise cannabis for personal use, regulated by a federal agency. This proposal is for legalisation of recreational use for relaxation and pleasure, not to treat a medical condition (which is already legal in Australia for some conditions).

According to the proposal, the government agency would licence, monitor and regulate production and sale, and regularly review the regulations. The agency would be the sole wholesaler, buying from producers and selling to retailers it licences.

The proposed policy includes some safeguards that reflect lessons we’ve learned from alcohol and tobacco. These include a ban on advertising, age restrictions, requiring plain packaging, and strict licensing controls. Under the proposal, tax revenues would be used to improve funding to the prevention and treatment sector, which is underfunded compared to law enforcement.




Read more:
Greens want cannabis to be made legal


Cannabis legislation around the world

In Australia, cannabis possession and use is currently illegal. But in several states and territories (South Australia, ACT and Northern Territory) a small amount for personal use is decriminalised. That means it’s illegal, but not a criminal offence. In all others it’s subject to discretionary or mandatory diversion usually by police (referred to as “depenalisation”).

Several jurisdictions around the world have now legalised cannabis, including Uruguay, Catalonia and nine states in the United States. Canada is well underway to legalising cannabis, with legislation expected some time this year, and the New Zealand prime minister has flagged a referendum on the issue.

In a recent opinion poll, around 30% of Australians thought cannabis should be legal. Teenagers 14-17 years old were least likely to support legalistaion (21% of that age group) and 18-24 year olds were most likely to support it (36% of that age group).




Read more:
Australia’s recreational drug policies aren’t working, so what are the options for reform?


In the latest National Drug Strategy Household Survey, around a quarter of respondents supported cannabis legalisation and around 15% approved of regular use by adults for non-medical purposes.

What are the concerns about legalisation?

Opponents of legalisation are concerned it will increase use, increase crime, increase risk of car accidents, and reduce public health – including mental health. Many are concerned cannabis is a “gateway” drug.

The “gateway drug” hypothesis was discounted decades ago. Although cannabis usually comes before other illegal drug use, the majority of people who use cannabis do not go on to use other drugs. In addition, alcohol and tobacco usually precede cannabis use, which if the theory were correct would make those drugs the “gateway”.




Read more:
Could a regulated cannabis market help curb Australia’s drinking problem?


There is also no evidence legalisation increases use. But, studies have shown a number of health risks, including:

  • around 10% of adults and one in six teens who use regularly will become dependent

  • regular cannabis use doubles the risk of psychotic symptoms and schizophrenia

  • teen cannabis use is associated with poorer school outcomes but causation has not been established

  • driving under the influence of cannabis doubles the risk of a car crash

  • smoking while pregnant affects a baby’s birth weight.

What are the arguments for legalisation?

Reducing harms

Australia’s official drug strategy is based on a platform of harm minimisation, including supply reduction, demand reduction (prevention and treatment) and harm reduction. Arguably, policies should therefore have a net reduction in harm.

But some of the major harms from using illicit drugs are precisely because they are illegal. A significant harm is having a criminal record for possessing drugs that are for personal use. This can negatively impact a person’s future, including careers and travel. Decriminalisation of cannabis would also reduce these harms without requiring full legalisation.

Reducing crime and social costs

A large proportion of the work of the justice system (police, courts and prisons) is spent on drug-related offences. Yet, as Mick Palmer, former AFP Commissioner, notes “drug law enforcement has had little impact on the Australian drug market”.

Decriminalisation may reduce the burden on the justice system, but probably not as much as full legalisation because police and court resources would still be used for cautioning, issuing fines, or diversion to education or treatment. Decriminalisation and legalistaion both potentially reduce the involvement of the justice system and also of the black market growing and selling of cannabis.




Read more:
Assessing the costs and benefits of legalising cannabis


Raising tax revenue

Economic analysis of the impact of cannabis legalisation calculate the net social benefit of legalisation at A$727.5 million per year. This is significantly higher than the status quo at around A$295 million (for example from fines generating revenue, as well as perceived benefits of criminalisation deterring use). The Parliamentary Budget Office estimates tax revenue from cannabis legalisation at around A$259 million.

Civil liberties

Many see cannabis prohibition as an infringement on civil rights, citing the limited harms associated with cannabis use. This includes the relatively low rate of dependence and very low likelihood of overdosing on cannabis, as well as the low risk of harms to people using or others.

Many activities that are legal are potentially harmful: driving a car, drinking alcohol, bungee jumping. Rather than making them illegal, there are guidelines, laws and education to make them safer that creates a balance between civil liberties and safety.

What has happened in places where cannabis is legal?

Legalisation of cannabis is relatively recent in most jurisdictions so the long-term benefits or problems of legalisation are not yet known.

But one study found little effect of legalisation on drug use or other outcomes, providing support for neither opponents nor advocates of legalisation. Other studies have shown no increase in use, even among teens.

The ConversationThe research to date suggests there is no significant increase (or decrease) in use or other outcomes where cannabis legalisation has occurred. It’s possible the harm may shift, for example from legal harms to other types of harms. We don’t have data to support or dispel that possibility.

Nicole Lee, Professor at the National Drug Research Institute, Curtin University and Jarryd Bartle, Sessional Lecturer in Criminal Law, RMIT University

This article was originally published on The Conversation. Read the original article.

Prescribing generic drugs will reduce patient confusion and medication errors



File 20170509 20757 1w3h710
If doctors prescribe generic drugs rather than their brand name equivalents, most times patients benefit.
from www.shutterstock.com

Matthew Grant, Monash University

In last night’s federal budget, Treasurer Scott Morrison announced an anticipated range of measures to encourage doctors to prescribe generic medicines rather than their more expensive brand name equivalents. So unless specified by the doctor, patients will receive a prescription with the generic medication name on it. The Conversation

This is part of A$1.8 billion in measures announced to reduce the drugs bill over five years. But beyond saving costs, the push towards generics may also reduce confusion among patients and medication errors.


“Are you taking aspirin at the moment?” I ask Iris, a pensioner in her 80s.

“No dear, I haven’t taken that for years,” she says, as she empties a large brown paper bag filled with medication boxes, new, old and empty.

I see a new bottle of aspirin emerge from the bag and ask if she is taking them.

“Oh yes, I always take my Astrix tablets.”

It’s not just elderly people who can be confused about which medication they’re taking. Drug names are long, complex and there are usually multiple brands for the same product.

For any medication, there are likely to be up to 15 different brands available. People are likely to use these brand names to describe the drug, like Iris did with her Astrix tablets.

In Australia in 2010 only 19.5% of scripts issued by GPs used the generic term for a drug, compared with 83% in the United Kingdom.

Encouraging doctors to prescribe generics goes beyond economic value. It has the potential to lead to a simplification of the language around medications, less influence on our purchasing decision by pharmaceutical marketing, and fewer medication errors by both doctors and consumers.

When we visit the GP, unless a specific reason exists, we should receive a script written with the generic term.

What is a generic term for a medication?

The generic term for a medication is the name of the active ingredient it contains. This is the ingredient that actually does the work of controlling your asthma or reducing your risk of heart disease.

There is only one generic name for each medication. But several different brands may be available. The brand name is usually the largest writing on the packet. Nurofen, for instance, is the brand name for the generic medication ibuprofen.

Generic medications are available for older drugs, and are commonly offered by your pharmacist as a cheaper alternative to the original branded medication. These drugs are tested to contain exactly the same active ingredients, so they produce the same effects.

However, there are a few rare exceptions, such as in some epilepsy medications, where drug levels may differ slightly between brands. So in such cases, doctors can choose to prescribe the branded version for its specific clinical benefits.


Explainer: how to generic medicines compare with brand leaders?


Which medicine name your doctor writes on you prescription – brand name or generic – can often be a lottery.

If your doctor writes a prescription for a brand name, your pharmacist may offer to substitute this for an equivalent generic drug. So, people often leave the pharmacy with a medication name or package that bears no resemblance to the prescription.

Potentially confusing for patients

The main problem with all these multiple names is the potential for confusion, especially for those most likely to use multiple medications – the elderly.

As a result, patients are at risk of not understanding which medications they are taking or why they are taking them. This often leads to doubling-up of a certain drug (taking two brands of the same medication), or forgetting to take them because the name on the package doesn’t match the script.

This problem of some patients’ poor medication literacy significantly affects doctors, nurses and pharmacists, who need to know which medications people are using. While our own GP may have your list of medications, often we visit multiple doctors who won’t have access to these list (different GPs while on holidays, emergency departments or specialists). If patients doesn’t know their medications, neither will doctors.

Many elderly patients are confused about the names of their medications.
from shutterstock.com

An advisory group for Australian pharmaceuticals, well aware of the dangers this confusion can cause, and as far back as 2005, promoted the use of prescribing and labelling with generic terms. The US Institute for Safe Medication Practices estimates that 25% of medication errors result from name confusion.

Why do doctors use brand names when prescribing?

In a busy clinic running half an hour behind, the generic name of a medication is often the last thing on the doctor’s mind. There are thousands of medications and even the most diligent doctor can’t remember them all.

Pharmaceutical companies have marketed brand name medication to both doctors and (in some countries) consumers, so they are far more memorable and palatable – for instance Viagra, rather than the generic term sildenafil.

But when doctors rely on using brand names in conversation and prescribing, this can cause confusion. Doctors using branded prescribing can lead to serious medication errors. This may be due not knowing the active ingredients in those medications, or mixing up brand names, which are becoming increasingly difficult to recognise when written in doctor’s handwriting.

So, to avoid confusion, medication errors and allowing for patient control over purchasing decisions, we recommend doctors use generic terms when prescribing unless a specific reason exists.

How does this affect me?

Everyone uses medications. The key issue here is autonomy. A script that contains the generic term for a medication allows that person to decide exactly what type of medication they wish to purchase, rather than that be influenced by what brand the doctor writes on the script.

When language excludes (for instance, by being complex or relying on jargon) or confuses, it restricts our autonomy. At present, the language of medications may have two, three or ten words for each drug, and the words we use are often influenced by pharmaceutical marketing and what a doctor prescribes.

The greatest effect of this budget announcement may be the chance to simplify this language to a singular generic drug term, to reduce confusion and allow us to be more involved with our medication decisions.

Matthew Grant, Research Fellow, Palliative Medicine Physician, Monash University

This article was originally published on The Conversation. Read the original article.