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An Introduction to Antimicrobial Resistance



Antibiotics are failing because bacteria are becoming increasingly resistant to them. The world is on the cusp of a "post-antibiotic era" as the alarming rate of bacterial resistant-strain emergence far outpaces our ability to develop the drugs that are urgently needed to combat them. In the past half-century, only two completely new classes of antibiotics have reached the market. The last of these was in 1987, and since then many strains have adapted to become almost, and in some cases completely, impervious to our dwindling supply of drugs.

If we fail to address this problem quickly and comprehensively then antimicrobial resistance (AMR) will make providing quality universal healthcare coverage much more difficult, if not impossible. This is because antibiotics underpin modern medicine in all its finery. Without them, the practice of medicine itself will become much more hazardous: routine medical procedures, such as minor surgeries, cancer treatments and even child birth will become life-threatening.

AMR is not only a threat to the future of medicine; it is already a significant global public health concern. Each year, drug- and multi-drug resistant infections cause more than 700,000 deaths, and this number is expected to rise dramatically over the coming years [ReAct, 2018]. Even more worryingly, pan-drug resistant bacteria have already emerged. For example, in a Nevada hospital in 2016, a patient infected with an imported pandrug-resistant superbug entered septic shock and died despite having received treatment comprising all 26 antibiotics in the United States' (US) medicine cabinet. Unfortunately, stories like this (which would have been almost unthinkable in the past) will become more common as antimicrobial resistance continues to develop at breakneck speed. Life expectancy in the United Kingdom (UK) has recently fallen for the first time because the Office for National Statistics (ONS) fears the "re-emergence of existing diseases and increases in antimicrobial resistance". This contrasts with the period between 1945 and 1972, when the introduction of antibiotics to treat infections that were previously considered life-threatening contributed to an eight-year increase in average life expectancy.

The UK's Chief Medical Officer, Professor Dame Sally Davies, has issued a stark warning:

"If we do not act now, any one of us could go into hospital for minor surgery in 20 years and die because of an ordinary infection that can't be treated by antibiotics".

She has also emphasized the importance of improving hygiene: "We need to address the growing problem of drug-resistant infections as the global medicine cabinet is becoming increasingly bare. Preventing infections in the first place is key".AMR Is a complex global problem which requires international cooperation. In 2015, the now former UN Secretary General, Ban Ki-moon, described antimicrobial resistance as a "fundamental threat to human health" at the first General Assembly meeting on drug-resistant bacteria. This was only the fourth time that the General Assembly has ever held a high-level meeting for a health issue, and all 193 Member States signed a declaration to combat the proliferation of antibiotic resistance. This Accord routes the global response to superbugs along a similar path to the one used to combat climate change; ensuring effective antimicrobial stewardship and improving hospital hygiene to prevent the spread of such infections to conserve existing antibiotics for when they are most acutely needed is one of its key objectives.

This is because many of the bacteria that are causing the biggest resistance concerns among the scientific and medical community are also responsible for increasingly difficult to treat hospital-acquired infections (HAIs). HAIs arise in healthcare facilities and are often transmitted within them due to failures in hygiene practices. The gathering storm that is forming from the combination of increasing incidence of HAIs and the rising prevalence of multi-drug resistant strains, has transformed a once commonly accepted need to improve hospital infection control programs into an urgent global healthcare priority. This places a great deal of responsibility upon the shoulders of the clinicians leading these programs. If they are adequately armed to rise to the challenge of AMR then the battle for the future of medicine can be won. In an age in which antibiotics are all-too-often rendered completely ineffective against drug-resistant superbugs, the old-adage "Prevention is better than cure" has seldom rung truer. 


What are Antibiotics and How Do They Work?



Antibiotics are a type of antimicrobial drug used to treat and prevent bacterial infections. Bacterial cells differ from our own, which has allowed us to take advantage of these differences and specifically interrupt the biological mechanisms in bacterial cells that are essential for their survival with antibiotics. Antibiotics are therefore able to prevent the growth of, or kill, bacterial cells while minimizing harm to our own bodies.

Bacterial species are immensely diverse but can be broadly categorised into two groups: gram-negative and gram-positive bacteria, based on their receptiveness to a technique called gram staining. Gram-negative bacteria have two cell membranes, separated by a thin layer of peptidoglycan (cell wall); Gram-positive bacteria do not have an outer cell membrane and instead have a thicker peptidoglycan cell wall that surrounds them.

Gram-negative pathogens such as Pseudomonas aeruginosa and Acinetobacter baumannii show intrinsic resistance to common antibiotics, due to their outer membrane, which effectively acts as an impermeable layer to antibiotics. This requires antibiotics to pass through membrane-spanning proteins called porins. Unlike gram-negative bacteria, the outer cell wall of gram-positive bacteria forms a coarse molecular mesh which permits the passage of some antibiotics. It is these fundamental variations in bacterial cells that account for the different levels of susceptibility and resistance to antibiotics between bacterial species.

Narrow-spectrum antibiotics only show activity against a small range of bacterial species; whereas broad-spectrum antibiotics act on both gram-negative and gram-positive bacteria - rendering them powerful and flexible drugs that can used to treat bacterial infections when the infecting bacterium has not yet been identified or remains unknown. Unfortunately, the same characteristics that make broad-spectrum antibiotics so clinically useful are also their Achilles heel: they attack both disease-causing bacteria as well as the normal flora of helpful bacteria that normally inhabit the human body. Because they act non-specifically on a wide range of bacteria they create selection pressures for the consequential development and transmission of antibiotic resistance.

In 1928, biologist Alexander Fleming was sorting through some petri dishes that were growing bacteria and noted an unusual colony of mold that had grown on one of the plates. The unexpected mold colony was somehow preventing bacteria from growing around it in a clear ring. Fleming identified the mold as a rare strain of Penicillium notatum and had in fact discovered the first antibiotic, penicillin.

Fleming's discovery of penicillin heralded the arrival of the golden age of antibiotic discovery. These miracle drugs significantly reduced mortality rates worldwide and contributed to a longer and better quality of life. Clinically relevant antibiotics in use today are effective against only five bacterial cell targets:  

table1

But Fleming foresaw the danger of resistance developing to these drugs:

"The time may come when penicillin can be bought by anyone in the shops. Then there is the danger that the ignorant man may easily underdose himself and by exposing his microbes to non-lethal quantities of the drug make them resistant." (December 11th, 1945).

Indeed, the global optimism surrounding antibiotic wonderdrugs didn't last. Infectious diseases are becoming ever-more difficult to treat and cure, and the last few decades have shown that we don't have to only contend with battling old diseases as new infections are constantly emerging.

Antibiotic resistance is silently spreading across the world
More than 78% of the populations in some areas carry multidrug-resistant bacteria in their normal bacterial flora [Monira et al, 2017] and as the world is becoming more globalized and interconnected, the spread of resistance is accelerating.

Antibiotic resistance kills
Estimates of failing to tackle AMR indicate that, by 2050, the world population will be up to 444 million persons lower than it would otherwise be in the absence of such resistance [Rand, 2018]. Every year, an estimated 214,000 newborns die from blood infections (sepsis) caused by resistant bacteria representing at least 30% of all sepsis deaths in all newborns alone [Sankar et al., 2016].

Antibiotic resistance is expensive
In the United States alone, antibiotic resistance adds $20 billion in excess direct health care costs, with additional costs to society for lost productivity as high as $35 billion a year. By 2050, global increases in healthcare costs from antimicrobial resistance are estimated to reach $1.2 trillion per year and cause average global decrease of 3.8% in annual GDP(World Bank). To put this into context, the economic impact will be much more devastating than the 2008/2009 financial crisis.


How Does Bacterial Resistance Occur?

Antimicrobial resistance is the ability of microorganisms (such as bacteria) to stop an antimicrobial agent (such as antibiotics) from working against them. AMR is a natural phenomenon, occurring as a product of bacteria's extraordinary evolutionary capacity to adapt and survive. As well as developing their own resistance, bacteria have the innate ability to transfer and receive a range of drug-resistant genes from other bacteria in their environment through what are known as mobile genetic elements (MGEs). MGEs comprise a range of genetic materials that are found in all organisms. This means that if a bacterial species develops resistance from, say antibiotics fed to livestock, the resistance genes can also easily spread to other bacterial species and subsequently render human antibiotic treatments useless.

Due to the fluid genetic makeup of bacteria, MGEs can quickly contribute to multi-drug resistance in single bacterial species. Recognizing the increasing severity of resistance, the terms extensively drug resistant and pandrug-resistant (resistant to all antibiotics) have been introduced and are documented with increasing frequency.

Carbapenems are some of the most powerful antibiotics in clinical use. They are used as a last resort for many bacterial infections, such as E. coli and Klebsiella pneumoniae carbapenemase (KPC). NDM-1 stands for New Delhi metallo--lactamase-1, and bacteria carrying the NDM-1 gene are able produce an enzyme that neutralizes these antibiotics. Bacteria carrying NDM-1 genes are some of the most dangerous superbugs in existence. First isolated in India in 2008, NDM-1 has now been found to be widespread in India, and by 2015, it had been detected in more than 70 countries worldwide. If NDM-1 is transmitted to other bacteria, secondary diseases will emerge, and as they spread around the world, it could lead to a health crisis in itself.

In 2012, scientists were studying the microbiome of Lechuguilla Cave in New Mexico. In particular, an area of the cave that had been isolated for over four million years was cultured for bacteria, and the results were stunning: While these microorganisms had been isolated from human contact for millennia, some of the newly-found strains were resistant to 14 different commercially available antibiotics. Resistance was detected to a wide range of structurally different antibiotics, including daptomycin, a last resort antibiotic used for life-threatening MDR bacterial infections.

But why is antibiotic resistance becoming such a huge health problem now? The world has changed dramatically since the 1920's in which antibiotics were discovered. Our world has become much more interconnected. Globalization means that we are now seamlessly exposing ourselves to previously hard-to-reach human, animal and bacterial populations, which has triggered an explosion in the global spread of infectious diseases and bacterial resistance.

Antibiotic resistance occurs when bacteria adapt to reduce the effectiveness of the antibiotics used against them. Bacteria use five main different defense mechanisms to achieve this:



1. Enzymatic Inhibition
This is the most common mechanism of resistance employed by bacteria. Enzymatic inhibition occurs when bacteria develop enzymes to chemically modify the structure of antibacterial compounds and render them ineffective. -lactamases are an enzyme family that pose a major problem in the treatment of gram-negative bacteria and can confer resistance against penicillin antibiotics.NDM-1 (New Delhi metallo-beta-lactamase 1) is an enzyme that makes bacteria resistant to a broad range of beta-lactam antibiotics, including the carbapenem family, which are a cornerstone for the treatment of antibiotic-resistant bacterial infections. The most common bacteria that make this enzyme are gram-negative such as Escherichia coli and Klebsiella pneumoniae, but the gene for NDM-1 can easily spread from one strain of bacteria to another.

2. Penicillin-Binding Protein Modifications
Penicillin-binding proteins (PBPs) are key proteins involved in the construction of bacterial cell walls. These proteins are essential to the assembly of peptidoglycan, the major constituent of cell walls. -lactam antibiotics mimic a part of peptidoglycan to fit into the active site of PBPs and form a tight complex that deactivates them. By mutation of the active site, bacteria are able to prevent -lactams from binding, or diminish their binding ability, and thus, develop resistance.The mecA gene is an example of a PBP that provides bacteria with resistance to antibiotics such as methicillin, penicillin and other penicillin-like antibiotics. The gene encodes a protein called Penicillin Binding Protein 2A that does not allow the ring-like structure of penicillin antibiotics to bind to the enzymes that help form the cell wall of bacteria, allowing the bacteria to replicate as normal.

3. Porin Mutations
The main constituent in the outer bilayer of gram negative bacteria is lipopolysaccharide, a highly hydrophobic (water-repelling) lipid that makes the passage of hydrophilic (water-attracting) compounds difficult. Porins are proteins that span the outer-membrane of gram negative bacteria to allow the allow the passage of compounds into and out of the cell. These porins can mutate to become selective against antibiotics or can be expressed in lower concentrations to reduce uptake to below minimum inhibitory concentration levels of antibiotics.ompF is a gene responsible for encoding the OmpF porin and confers general antibiotic resistance to a range of gram-negative bacteria by preventing the influx of antibiotics. The gene is widespread and is found in E. coli, Enterobacter and Salmonella, with the ability to prevent entry of -lactam, carbapenem and chloramphenicol antibiotics into bacterial cells.

4. Efflux Pumps
Bacteria use membrane-spanning proteins, known as efflux pumps, to actively eliminate substances from the cell. Efflux pumps can be used to eliminate specific antimicrobial compounds and higher levels of generic efflux pumps can be expressed to ensure antibiotics are below their minimum inhibitory concentration. There are a wide range of efflux pumps that can simultaneously confer multi-drug resistance to a variety of antibiotics.Tetracycline resistance is a classic example of efflux-mediated resistance, where tet genes encode efflux pumps that actively extrude tetracyclines from the cell. Currently, more than 20 different tet genes have been described, most of which are harbored in mobile genetic elements. The majority of these genes are found in gram-negatives bacteria, such as E. coli.

5. Target Mutations
Most antibiotics target the ribosome; the protein synthesis machinery of bacterial cells, necessary for replication. Antibiotics that target this machinery are potent inhibitors of bacterial growth. However, over decades of clinical use pathogens have developed resistance to inhibitors of protein synthesis. Bacteria often modify the amino acid sequences of antibiotic targets through point mutations that result in rapid and easy resistance, with minimized impact on the microbe's fitness.A well-characterized example of antibiotic resistance by these mechanisms are characterized in oxazolidinones (linezolid and tedizolid). These drugs are synthetic bacteriostatic antibiotics with broad gram-positive activity that exert their mechanism by interaction with bacterial ribosomes and blocking synthesis. The most commonly characterized mechanisms of linezolid resistance include mutations in genes encoding the ribosomal proteins L3 and L4 (rplC and rplD, respectively), which prevent linezolid and tedizolid from binding and disrupting protein synthesis.



Resistant Bacteria

The grave threat of spreading multidrug and pandrug-resistance has led the World Health Organization to develop a growing list of bacteria that are most concerning to global human health. These organisms are categorized by three categories of priority: 1 (critical), 2 (high), and 3 (medium) 

resistant bacteria table
To put the danger that these organisms pose to human health into perspective, 'Medium' priority organisms already cause severe bacterial infections worldwide. Haemophilus influenzae, for example, can cause a multitude of different infections in the human body, including meningitis, which kills 1 in 20 children it infects, and those survive may suffer long-term problems, such as hearing loss, seizures and learning disabilities.



Antibiotic Overuse in Healthcare and Agriculture

Humans are playing a crucial role in the development and spread of antibiotic resistant microorganisms.

Consistent antibiotic overuse and inappropriate prescriptions, coupled with high density and turnover of patients has made hospitals a key battleground in the fight against resistance. A 2016 CDC report estimates that one in every three antibiotic prescriptions are unnecessary [CDC, 2016], or 20,000 per day in the NHS by General Practitioners in the UK [GPOnline, 2018].

This is further exacerbated by the fact that when bacteria develop resistance to one drug, such as penicillin, the changes in the bacteria's biology often make it resistant to a range of other antibiotics too.

Human overconsumption of antibiotics is cause for serious concern; however, this pales in significance when compared with overuse in agriculture. In 2012, 26 EU Economic Area countries sold 3,400 tonnes of antimicrobials for human use, compared to 7,982 tonnes for livestock [Bowater, 2017]. In some countries, the figure reached 80% total consumption of medical antibiotics used in the animal sector.


Like humans, animals are susceptible to infectious diseases. To combat this, antibiotics are used therapeutically to treat individual animals with clinical diseases. However, antibiotics are often administered to livestock in feed to pre-emptively prevent infections and marginally improve growth. As a result of this, some animals receive a sub-therapeutic dose, creating the perfect conditions for the emergence of resistant bacteria, where susceptible bacteria are killed off, while allowing stronger resistant bacteria to survive.

Bacteria live in a plethora of environments where they are regularly exposed to sub-lethal doses of antibiotics, and resistant populations can emerge in a matter of hours. In a mixed culture of bacteria, there might thousands of bacteria that are susceptible to antibiotics, but if just one resistant bacterial cell has the competitive advantage of a resistance gene then it will rapidly proliferate.

What is so alarming about this approach to agriculture is that many of the antibiotics used to treat animals are identical to human medicines. Unsurprisingly, there is clear correlation between antibiotic resistance in humans and the widespread use of non-therapeutic antibiotics in animals [O'Neill, 2015]. Resistant bacteria are transmitted to humans through direct contact with animals, through to animal manure, consumption of undercooked meat, and through contact with uncooked meat or surfaces meat has touched.



Hospital Acquired Infections: Prevention is Better Than Cure

Many of the bacteria that are causing the biggest resistance concerns among the scientific and medical community are also responsible for hospital-acquired infections (HAIs), or nosocomial infections (infections that are contracted in hospital or healthcare facilities). HAIs are the most frequent adverse events in the delivery of care worldwide and are a leading cause of death in the developed world [WHO, n.d.]. It is estimated that in the US and UK alone, HAIs contribute to approximately 100,000 and 20,000 deaths each year, respectively.

The gathering storm that is forming from the combination of increasing incidence of HAIs and the rising prevalence of multi-drug resistant strains, has transformed a once commonly accepted need to improve hospital infection control programs into an urgent global healthcare priority. In an age in which antibiotics are all-too-often rendered completely ineffective against drug-resistant superbugs, the old-adage "Prevention is better than cure" has seldom rung truer.

Surfaces are rapidly contaminated with harmful microbes, and environmental contamination is often the root cause of infections spreading from person to person in the hospital environment. For example, up to 60% of surfaces in the patient care zone are contaminated with pathogens known to cause HAIs. These pathogens persist for months on surfaces; facilitating cross-contamination and subsequently infection transmission between healthcare professionals (HCPs) and patients.

Many HAIs are preventable and result from failures in healthcare that cause the needless suffering and waste scarce healthcare resources. Preventing the occurrence and spread of hospital acquired infections obviously saves lives. But, perhaps more importantly, reducing infection incidence also leads to fewer antibiotic treatments, which in turn decreases the likelihood of the development of antimicrobial resistant strains. Conserving antibiotics in this manner buys medicine time as it awaits the discovery of the new antibiotics that are urgently needed to replenish a presently diminishing drug arsenal.


Antimicrobial Stewardship

While the return to a 'post-antibiotic era' is seen as a worst-case scenario, it will be likely more devastating than this. Through globalization and the continued misuse of antibiotics, bacteria are able to much more rapidly spread and are much more aggressive than they were before the advent of antibiotics.

Infection control programs are fundamental in controlling the spread of resistance through hospital settings. Through training, conduct and strong implementation of good practice in hygiene and care, infection control programs have the power to significantly reduce antibiotic misuse and the subsequent emergence of highly-virulent, resistant bacterial strains.

Antimicrobial stewardship is a system-wide approach in healthcare facilities to promote and monitor the use of antimicrobials to preserve their effectiveness [NICE, 2015]. These coordinated programs act to promote the appropriate use of antimicrobials, improve patient outcomes, reduce antimicrobial resistance, and decrease the spread of infections caused by multidrug-resistant organisms. Antimicrobial stewardship programs are gaining global momentum as the issue of antibiotic resistance becomes a worldwide challenge. Effective antimicrobial stewardship programs improve the quality of patient care and have been shown to be significantly more cost effective, with reductions in antimicrobial use saving an average $200,000-900,000 per stewardship program, per year [Kon & Rai, 2016]

Antimicrobial stewardship programs may feature any of the following elements:  

hospital table

Ongoing education is a crucial element of antimicrobial stewardship programs, such as educational conferences, written guidelines and teaching seminars. Continued education by infection preventionist's is vital in keeping up-to-date with emergent pathogens, new guidelines and developing technologies. As antimicrobial stewardship programs move away from cost-cutting strategies and towards quality and patient safety, adoption of innovative technologies is becoming ever-more important in ensuring best practice.

The increasing levels of antibiotic resistance would not be such a threat if we have new antibiotics in the pipeline to replace those that are no longer effective. This is not the case. Since the 1950s, investment in pharmaceutical research has been driven by a profit model that depends on exclusive rights to new products, and the more products that a pharmaceutical company persuades doctors to buy and use, the better the financial returns. However, antimicrobial stewardship programs promote constraint by healthcare professionals in the use of antibiotics to prevent further propagating resistance. Antibiotics should therefore sit on the shelf until they are absolutely necessary for use. This results in an active reduction of antibiotic use, hurting pharma's current and potential profits, as they cannot make the money back spent on research and development of new compounds by widespread use of their product.

This has created an unwillingness for pharmaceutical companies invest in much-needed research and development of new antibiotic classes (who incidentally have the most power to do so). New reimbursement models are required to address the present market failures which threaten human health. Whilst some progress has been made in this regard, the pace of change needs to quicken substantially.



Due to this lack of efforts in developing new antibiotics, there hasn't been a new class developed for clinically-appropriate use in 30 years. Since then, many strains have gained large degrees of resistance to antibiotics, and in some cases completely.

Much of the potency of effective antibiotic treatments is due to the exclusivity of the bacterial mechanisms that they target. Targeting the membranes or distinct cellular machinery of bacteria ensures minimal damage to our own cells, but as resistance has developed and we have exhausted these exclusive targets over time, newer antibiotics are more harmful to our bodies and less effective at fighting bacteria. For example, the FDA is warning against fluoroquinolone antibiotics, which may cause sudden, serious, and potentially permanent nerve damage called peripheral neuropathy [FDA, 2016].

Today, antibiotics are one of the most common classes of drugs used in medicine and make possible many of the treatments and procedures that have become routine around the world. If we run out of effective antibiotics, medical advancement as we know it will be set back by several decades. Given the dire circumstances, there are two obvious outcomes for the future of antibiotics in our healthcare systems and daily lives:


A Future Without Antibiotics

The year is 2040 and little progress has been made in tackling AMR. Poor communication of this issue to healthcare professionals and the general public has resulted in crisis. Antibiotic consumption is rising inexorably. We have achieved no little-to-no control in non-therapeutic use of antibiotics in animal husbandry and antibiotic use in hospitals is still rife. Selection pressures have created widespread multidrug and pan-resistance in a variety of highly virulent bacteria. The pharmaceutical industry has continued to show little interest in the development of antibiotics, and as a result no genuinely novel antibiotic drugs have gained any traction, let alone reached the market.

The impact on human health has been devastating. Close to 10 million people are dying every year from untreatable antibiotic-resistant infections [WHO, 2016], surpassing mortality rates from cancer or diabetes. Invasive infections caused by carbapenem-resistant Klebsiella pneumoniae are now rife and spreading through Europe and elsewhere in the world, and we see the same trends with MRSA, VRE, C. difficile and others. The future of healthcare is bleak:

Surgery
Relatively minor surgeries, such as hip replacements or appendectomies will become life threatening. Antibiotics are often used before surgery to ensure that patients do not contract any infections from bacteria entering open cuts. Without this precaution, the risk of blood poisoning will become much higher, and many of the more complex surgeries doctors now perform may not be possible at all.

Cancer and Other Major Diseases
What is often mis-understood is the crucial role that antibiotics play in the treatment of non-infectious diseases, such as cancer or heart disease. Antibiotics underpin the effective treatment of many seemingly unrelated diseases by supporting the immune system and preventing opportunistic bacteria from infecting patients. Surgery remains one of the leading therapeutic interventions for treating tumors, and controlling infections during surgery can mean the difference between life and death. Techniques such as bone marrow transplantation would bring risk not only to cancer patients, but also to bone marrow donors. Even non-surgical cancer treatments like chemotherapy and radiotherapy weaken the immune system and leave patients vulnerable to infection. Procedures such as these will become life-threatening to the point where 6 months of terminal cancer gives better life expectancy than a surgery.

Sexually Transmitted Infections
Nowadays, STIs spread by bacteria often require a simple trip to the clinic and course of antibiotics. This is a far cry from the past were diseases like syphilis were incurable, slowly causing dreadful disfigurement before death. Gonorrhea is an STI that causes discharge and inflammation of the urethra, cervix, pharynx or rectum, and if left untreated can cause pelvic inflammatory disease and infertility in both men and women. The disease does not have a vaccination program and has developed extensive resistance. Currently, Gonorrhea needs to be treated with a two-drug cocktail to eradicate the infection, but treatment failures are continuing to emerge. A recent outbreak in England attracted worldwide media coverage when it was reported that a strain had resistance to both drugs in the two-cocktail treatment. Untreatable strains of gonorrhea will develop and leave sufferers infertile with serious debilitating symptoms.


A Future With Antibiotics

The year is 2030 and we've made tremendous progress in fighting AMR. Healthcare professionals around the world now accept the pressing need to control resistance through a 'prevention is better than cure' approach. Real progress has been made in reducing antibiotic consumption through widespread reduction in the use of antibiotics in human medicine and a global ban on non-therapeutic use of antibiotics in animal husbandry. Hospitals now place infection prevention and control programs at the heart of their care operations and significant progress has been made to implement and improve antimicrobial stewardship programs globally. While there have been no new antibiotic classes developed, a new model of discovery and development has mobilized the pharmaceutical industry, and a stream of new and improved antibiotics is beginning to reach the market.

We do not live in continual fear of death from cuts and scrapes, or the need to visit a hospital for a treatment or minor procedure. Our healthcare systems continue to uphold effective treatments for diseases such as cancer or heart disease, and infectious diseases remain a peripheral threat to most developed nations.


All in One Medical

As a society, the need to cooperatively fight the immense threat of AMR is evident. We face a collective struggle, and while the odds are now stacked against us, taking immediate measures to combat this threat may allow us to safeguard healthcare for future generations.

A global response to the chronic shortfall in antibiotic innovation is urgently needed to combat antimicrobial resistance. At All in One Medical, we are totally committed to combatting this global threat. Our mission is to ensure that our innovative antimicrobial technology is appropriately adopted in clinical practice, to protect patients throughout the world from contracting unnecessary HAIs and reduce the development of AMR.

We are advancing an expanding range of products which are highly effective at killing a broad spectrum of harmful pathogens. When integrated within hospital-wide infection control programs, our disruptive antimicrobial technology helps to prevent the transmission of HAIs which emanate from cross-contamination at high-frequency touchpoint surfaces.


References

Bowater: http://pubs.rsc.org/en/content/ebook/978-1-78262-167-6

CDC: https://www.cdc.gov/media/releases/2016/p0503-unnecessary-prescriptions.html

FDA: https://www.fda.gov/Drugs/DrugSafety/ucm500143.htm

GPOnline: https://www.gponline.com/gps-write-20000-unnecessary-antibiotic-prescriptions-per-day-officials-suggest

Kon & Rai: https://www.elsevier.com/books/antibiotic-resistance/kon/978-0-12-803642-6

Monira et al.: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5399343/

NICE: https://www.nice.org.uk/guidance/ng15

ONeill: https://amr-review.org/sites/default/files/Antimicrobials in agriculture

Rand: https://www.rand.org/randeurope/research/projects/antimicrobial-resistance-costs.html

ReAct: https://www.reactgroup.org/antibiotic-resistance/the-threat/

Sankar et al.: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4848744/

WHO (n.d.): http://www.who.int/gpsc/country_work/gpsc_ccisc_fact_sheet_en.pdf

WHO (2016): http://www.who.int/bulletin/volumes/94/9/16-020916.pdf