The TARGET Antibiotics Toolkit aims to help influence prescribers’ and patients’ personal attitudes, social norms and perceived barriers to optimal antibiotic prescribing. It includes a range of resources that can each be used to support prescribers’ and patients’ responsible antibiotic use, helping to fulfil CPD and revalidation requirements.
As well as providing all the energy and nutrients that infants need for the first months of life, breast milk protects against infectious diseases. Lactoferrin is a protein in milk which provides antimicrobial protection to infants, effectively killing bacteria, fungi and even viruses.
The antimicrobial activities of this protein are mainly due to a tiny fragment, less than a nanometre across, made up of six amino acids. Based on the metrology of antimicrobial mechanisms, the team predicted that copies of this fragment gather at the same time, and at the same point, to attack bacterial cells by targeting and disrupting microbial membranes.
Recognising the potential applications in the fight against antimicrobial resistance, the team of scientists from the National Physical Laboratory (NPL) and the University College London (UCL) re-engineered the fragment into a nanoscale building block which self-assembles into virus-like capsules, to effectively target bacteria. Not only can these capsules recognise and bind to bacteria, but they also rapidly convert into membrane-damaging holes at precise landing positions.
To monitor the activity of the capsules in real time we developed a high-speed measurement platform using atomic force microscopy. The challenge was not just to see the capsules, but to follow their attack on bacterial membranes. The result was striking: the capsules acted as projectiles porating the membranes with bullet speed and efficiency
explains Hasan Alkassem, a joint NPL/UCL EngD student who worked on the project.
Remarkably, however, these capsules do not affect surrounding human cells. Instead, they infected them like viruses do. When viruses are inside human cells they release their genes, which then use the body’s cellular machinery to multiply and produce more viruses. But if viral genes are replaced with drugs or therapeutic genes, viruses become effective tools in the pursuit of gene therapy to cure many diseases, from cancer to cystic fibrosis.
Structurally plastic peptide capsules for synthetic antimicrobial viruses, Chemical Science, 17th December 2015.
The research team explored this possibility and inserted model genes into the capsules. These genes were designed to switch off, or silence, a target process in human cells. The capsules harmlessly delivered the genes into the cells and effectively promoted the desired silencing. With therapeutic genes, this capability could be used to treat disorders resulting from a single mutated gene. Sickle-cell disease, cystic fibrosis or Duchenne muscular dystrophy are incurable at present, but can be cured by correcting corresponding mutated genes. The capsules therefore can serve as delivery vehicles for cures.
Antimicrobial resistance is an increasing public health threat which requires a strong and coordinated response. This work demonstrates the power of combining physics and engineering principles with innovative measurement methods to create new strategies for tackling the problem. It is exactly the sort of high priority problem that the National Physical Laboratory should be active in addressing in collaboration with others.
More than 80 pharmaceutical companies have called on governments to develop new ways of paying them to develop antibiotics
More than 80 leading international pharmaceutical, generics, diagnostics and biotechnology companies, as well as key industry bodies, have come together to call on governments and industry to work in parallel in taking comprehensive action against drug-resistant infections – socalled ‘superbugs’ – with a joint declaration launched today at the World Economic Forum in Davos, Switzerland. The statement sets out for the first time how governments and industry need to work together to support sustained investment in the new products needed to beat the challenges of rising drug resistance.
The Declaration by the Pharmaceutical, Biotechnology and Diagnostics Industries on Combating Antimicrobial Resistance – drafted and signed by 85 companies and nine industry associations across 18 countries – represents a major milestone in the global response to these challenges, with commercial drug and diagnostic developers for the first time agreeing on a common set of principles for global action to support antibiotic conservation and the development of new drugs, diagnostics, and vaccines. The industry is calling on governments around the world to now go beyond existing statements of intent and take concrete action, in collaboration with companies, to support investment in the development of antibiotics, diagnostics, vaccines, and other products vital for the prevention and treatment of drug-resistant infections.
In particular, the Declaration supports a continuation of efforts towards improved conservation of antibiotics, including a call for improved uptake of rapid point-of-care diagnostics to improve how antibiotics are prescribed, and changes to incentive structures within health systems that directly reward doctors, pharmacists and veterinarians for prescribing antibiotics in greater volumes.
In what the Review on Antimicrobial Resistance recognises to be a notable step for the industry, the signatory companies call on governments to work with them to develop new and alternative market structures that provide more dependable and sustainable market models for antibiotics, and to commit the funds needed to implement them. These mechanisms are needed to provide appropriate incentives (coupled with safeguards to support antibiotic conservation) for companies to invest in R&D to overcome the formidable technical and scientific challenges of antibiotic discovery and development. These include mechanisms to ensure that, where appropriate, the pricing of antibiotics more adequately reflects the benefits they bring; and novel payment models that reduce the link between the profitability of an antibiotic and the volume sold. An integral part of these models is a reduced need for promotional activity by companies.
As well as calling for continued progress by governments on these fronts, the Declaration sets out a commitment to further action on drug resistance by its signatories, which the Review warmly welcomes. These span across three broad areas:
Reducing the development of drug resistance The companies commit to encouraging better and more appropriate use of new and existing antibiotics, including through work that supports the antibiotic stewardship principles set out by the World Health Organization (WHO) Global Action Plan on antimicrobial resistance (AMR), and via improved education of clinicians. This support extends to promoting more judicious use of antibiotics in livestock, as part of a ‘one health’ approach.
Increasing investment in R&D that meets global public health needs Recognising the need to increase research into new antibiotics, diagnostics, vaccines and other alternative treatments, the companies commit to a continuation and extension of collaborative initiatives between industry, academia and public bodies to improve how R&D in the field is done and provide greater opportunities for the scientific barriers to antibiotic discovery to be overcome.
Improve access to high-quality antibiotics for all In light of the gaps that remain in global access to our existing antibiotics and vaccines, and the importance of ensuring that new generations of products are available to all those who need them, the signatories commit to supporting initiatives aimed at ensuring affordable access to antibiotics in all parts of the world, at all levels of income.
By bringing together such a wide range of companies in this unprecedented way, the Declaration provides a valuable roadmap to guide further collaborative efforts between industry, governments and NGOs in the global fightback against AMR. The Review will continue to work to drive progress towards a series of key international milestones in 2016 – including likely discussions on AMR at the UN General Assembly and as part of China’s G20 programme in the autumn – and in support of progress against the WHO Global Action Plan on AMR.
The Declaration will be updated every two years, to take account of the evolving global landscape of AMR and changing challenges and priorities. It remains open to accept new signatory companies and bodies at any time, with a complete list maintained on the Review on AMR’s website.
Joint Programming Initiative on Antimicrobial Resistance
The French National Research Agency, in partnership with 12 European countries (Belgium, Denmark, Germany, Italy, Latvia, Netherlands, Norway, Poland, Portugal, Spain, Sweden and UK), 3 associated countries (Israel, Turkey and Switzerland) and Canada, is set to launch a third joint call for proposals through the Joint Programming Initiative on Antimicrobial Resistance (JPIAMR).
The French National Research Agency Preannouncement An organism develops resistance to a drug either by a gene mutation or by the acquisition of genetic components from another strain (i.e. transmission of resistance). Resistant organisms can multiply in the presence of a drug (i.e. selection of resistance traits) but without transmission, resistance would remain an isolated problem. To understand the complex biological and environmental interactions that shape the spread of antibiotic resistance, we must identify and characterise the determinants that contribute to the spread of resistance in and between different reservoirs; including humans (sick and healthy people), animals (livestock, companion and wild animals) and the environment (indoor and outdoor).
Responding collectively through research Research in biology and epidemiology on resistance selection and transmission is therefore crucial for defining preventive measures to address this public threat. The existence and proliferation of antibiotic resistance in bacterial strains with a major impact on public health must be handled using risk analysis approaches based on bacterial pathogens’ genetic reservoirs and the environmental parameters which determine their community, veterinary, and clinical survival. In this context, the Joint Programming Initiative on Antimicrobial Resistance aims to coordinate research efforts on these issues at the international level.
A new call for proposals planned for January This third call for proposals will bring together the following funding organisations: FRS-FNRS and FWO (Belgium), CIHR (Canada), IFD (Denmark), BMBF/DLR (Germany), CSO-MOH (Israël), IT-MOH (Italy), VIAA (Latvia), ZonMw (Netherlands), RCN (Norway), NCN (Poland), FCT (Portugal), ICSIII and MINECO (Spain), SRC and Formas (Sweden), SNCF (Switzerland), Tubitak (Turkey) and MRC (UK). The initiative sets out to support research aimed at unravelling the dynamics of transmission and selection of antimicrobial resistance (AMR) at genetic, bacterial, animal, human, societal, and environmental levels, in order to design and evaluate preventive and intervening measures for controlling resistance. The primary aim of the call is to combine the resources, infrastructures, and research strengths of multiple countries in order to address transmission of antibiotic resistance following a ‘One Health Approach’.
Designed with multidisciplinary and transnational consortia in mind The goal is to foster multinational research collaborations to add value to and to build upon the research conducted independently at national level and to work together to improve the control of resistant bacterial infections of clinical and/or veterinary importance only. We expect that most collaborations to be multidisciplinary with expertise that could include, but are not limited to, bacteriologists (clinical, veterinary, and environmental), chemists, ecologists, mathematicians, informatics and computational modelers, medical practitioners (human and veterinary), etc., where appropriate. Consortia are encouraged to include participants from academia, medical and public health practitioners (both human and veterinary), policy makers, and industry, where appropriate (please note the national/regional regulations).
Livestock specific data would help us better understand how drug sales relate to antibiotic resistance on the farm that may in turn affect human health
U.S. FDA, For Industry, Animal Drug User Fee Act (ADUFA) 05/19/2015
In May 2015, the FDA issued a proposed rule to obtain more detailed information about antimicrobials sold or distributed for use in food-producing animals by including estimates of sales data by species. The additional data would improve understanding about the extent to which antimicrobials are sold or distributed for use in major food-producing species and help the FDA further target its efforts to ensure judicious use of medically important antimicrobials. It would also assist the agency in measuring the effectiveness of those efforts.
The U.S. Food and Drug Administration needs to hear from people like you
The proposed rule, if finalized, would require animal drug sponsors to submit species-specific estimates of antimicrobial sales for cattle, swine, chickens, and turkeys. The proposed rule also includes a provision to improve the timeliness of FDA’s annual summary report of these sales data by requiring the FDA to publish its annual summary report of antimicrobial sales and distribution information by December 31 of the following year.
Sources and more information
FDA proposes rule to collect antimicrobial sales and distribution data by animal species, Additional data to help Agency further target efforts to ensure judicious use of medically important antimicrobials, FDA News, May 19, 2015.
Bacteria Resistant to ALL Drugs Shows up in Denmark
Agricultural use of antibiotics is by far the greatest threat to us, promoting drug resistance on a grander scale than hospital use. We must get all countries to agree to eliminate colistin and carbapenem antibiotics, in particular, from animal use. They are our last ditch antibiotics at a time when there is little drug development. This, and limiting some types of food imports, will slow the tide of this latest superbug threatening us. Its arrival is inevitable though, given global travel and trade. We’ll just need to keep our finger in the dike for now while hoping that the government will restrict the importation of foods likely to be carriers of this gene, greatly reduce or bar the use of critical antibiotics in agriculture, and will allocate new resources to the development of treatments for these resistant organisms.
Continue reading New Superbug Resistant To All Antibiotics Linked To Imported Meat, forbes, DEC 10, 2015.
Statement by Antibiotic Resistance Action Center on spread of dangerous superbug gene from China to Denmark, publichealth, December 3, 2015.
Apocalypse Pig: The Last Antibiotic Begins to Fail
2015 Study abstract
Background Until now, polymyxin resistance has involved chromosomal mutations but has never been reported via horizontal gene transfer. During a routine surveillance project on antimicrobial resistance in commensal Escherichia coli from food animals in China, a major increase of colistin resistance was observed. When an E coli strain, SHP45, possessing colistin resistance that could be transferred to another strain, was isolated from a pig, we conducted further analysis of possible plasmid-mediated polymyxin resistance. Herein, we report the emergence of the first plasmid-mediated polymyxin resistance mechanism, MCR-1, in Enterobacteriaceae.
Methods The mcr-1 gene in E coli strain SHP45 was identified by whole plasmid sequencing and subcloning. MCR-1 mechanistic studies were done with sequence comparisons, homology modelling, and electrospray ionisation mass spectrometry. The prevalence of mcr-1 was investigated in E coli and Klebsiella pneumoniae strains collected from five provinces between April, 2011, and November, 2014. The ability of MCR-1 to confer polymyxin resistance in vivo was examined in a murine thigh model.
Findings Polymyxin resistance was shown to be singularly due to the plasmid-mediated mcr-1 gene. The plasmid carrying mcr-1 was mobilised to an E coli recipient at a frequency of 10−1 to 10−3 cells per recipient cell by conjugation, and maintained in K pneumoniae and Pseudomonas aeruginosa. In an in-vivo model, production of MCR-1 negated the efficacy of colistin. MCR-1 is a member of the phosphoethanolamine transferase enzyme family, with expression in E coli resulting in the addition of phosphoethanolamine to lipid A. We observed mcr-1 carriage in E coli isolates collected from 78 (15%) of 523 samples of raw meat and 166 (21%) of 804 animals during 2011–14, and 16 (1%) of 1322 samples from inpatients with infection.
Interpretation The emergence of MCR-1 heralds the breach of the last group of antibiotics, polymyxins, by plasmid-mediated resistance. Although currently confined to China, MCR-1 is likely to emulate other global resistance mechanisms such as NDM-1. Our findings emphasise the urgent need for coordinated global action in the fight against pan-drug-resistant Gram-negative bacteria.
This problem affects us all and we can all do something to help
More Antibiotic Resistance Concerns
Antibiotics are essential for treating many infections but they’re losing their effectiveness. Bacteria are fighting back by adapting and finding ways of surviving the effects of our medicines.
The bugs are smart – they can naturally become resistant to antibiotics over time but we’re making it worse because of overuse and misuse of our medications. This is already a risky situation and it will only get worse if we don’t take urgent action..
Cystitis superbugs! The commonest of infections could become untreatable It’s very common for women to suffer with cystitis but it’s usually more of a nuisance than a cause for serious concern. Mild cases will often get better by themselves within a few days. Right now though, urinary tract infections (UTIs) are becoming harder to treat as the bacteria are becoming resistant to antibiotics. Women are facing hospital stays or injected antibiotics for UTIs that would have once been cleared up by a packet of tablets.
Antibiotic-resistant bacteria could kill more people than cancer An influential study on antimicrobial resistance has warned that drug-resistant infections could kill an extra 10 million people across the world every year by 2050 if they are not tackled. That’s more deaths that are currently caused by cancer. But don’t forget this isn’t just a problem for the next generation as antimicrobial-resistant infections currently claim at least 50,000 lives each year across Europe and the US alone, with many hundreds of thousands more dying in other areas of the world.
Antibiotics kill good bacteria in your body Antibiotics are essential for some infections and they save lives, but taking them does have implications. When we take antibiotics, they kill healthy bacteria. They allow the bacteria that are resistant to the antibiotics you have just taken to become dominant. This means that further down the line when you DO need an antibiotic, it is less likely to work. Bacteria live in all of us and outnumber our human cells tenfold, and the majority of these bacteria are essential as they help us digest food, produce important vitamins and keep up our immunity. It’s vital to our wellbeing that we have these good bacteria, but each time we take antibiotics, we kill many of them. It can take a long time – from months up to years – for the good bacteria to recover.
Recent figures have outlined the mind-boggling economic cost of superbugs $100 Trillion! It sounds like too much money to even comprehend, but research has shown that by 2050 drug resistant infections could cost the world around $100 trillion in lost output: more than the size of the current world economy, and roughly equivalent to the world losing the output of the UK economy every year, for 35 years.
A course of tablets may not cut it anymore It’s easy to be complacent about bacterial infections and think a prescription and some pills will solve the problem. But antibiotic resistant bacteria present new and vastly different challenges for doctors and patients. When people are infected with drug-resistant bacteria the antibiotics doctors try often fail. Stronger and more expensive drugs may be tried for longer, and hospital stays become necessary. And already, sadly, some patients die. Previously trivial infections are now coming with a huge human and economic cost.
These TB stats are scary, and more relevant than many people will think In 2013 there were 480,000 recorded cases of multi drug-resistant TB (TB that can’t be treated by our usual medicines). TB is a bacterial infection that can spread through the lymph nodes and blood stream to any organ in your body. It commonly affects the lungs and while a lot of people might not consider it to be an issue in the UK, or think it couldn’t affect them, this isn’t true. 37 million lives worldwide have been saved by antibiotic treatment for TB since 2000. In some countries, it is becoming increasingly difficult to treat MDR-TB. Treatment options are limited, recommended medicines are not always available, and patients experience many adverse effects from the drugs.
“Last resort” antibiotics may not work Alongside cases of multi-drug resistant TB mentioned, gonorrhoea is also causing major problems – 10 countries across the world have reported treatment failures when using “last resort” medicines. There are worries that gonorrhoea may soon become untreatable as no vaccines or new drugs are in development. And resistance to the treatment of last resort for life-threatening infections caused by common intestinal bacteria has spread to all regions of the world.
What can we do about it?
This problem affects us all and we can all do something to help. Firstly, you can take a simple personal action by visiting our Antibiotic Guardian website and choosing one pledge that you will carry out to help save these vital medicines. There are pledges for the public, healthcare professionals and leaders.
There are plenty more things you can do too. Watch this video and learn more and talk to your family and friends about antibiotic resistance, and the fact that we don’t always need antibiotics when we’re ill. The Treat Yourself Better website will help you make good choices.