“Human resistance to antibiotics could bring ‘the end of modern medicine as we know it’,” according to The Daily Telegraph. The newspaper says that we are facing an antibiotic crisis that could make routine operations impossible and a scratched knee potentially fatal. Similarly, the Daily Mail’s headline stated that a sore throat could soon become fatal.
The alarming headlines follow a new report by the World Health Organization (WHO), which set out ways to fight the growing problem of antimicrobial resistance (AMR). AMR occurs when infectious organisms, such as bacteria and viruses, adapt to treatments and become resistant to them. The publication specifically addressed the long-known problem of antibiotic resistance, where increasing use of antibiotics can lead to the formation of “superbugs” that resist many of the antibiotic types we currently have. It outlined a variety of measures that are vital for ensuring we can still fight infections in the future and described how other major infectious diseases, such as tuberculosis, HIV, malaria and influenza, could one day become resistant to today’s treatment options.
However, despite the future danger posed by antimicrobial resistance, the situation is not irretrievable. As Dr Margaret Chan, director general of WHO, said: “much can be done. This includes prescribing antibiotics appropriately and only when needed, following treatment correctly, restricting the use of antibiotics in food production to therapeutic purposes and tackling the problem of substandard and counterfeit medicines.” The report also highlighted successful cases where antimicrobial resistance has been tackled, demonstrating that we can safeguard the effectiveness of important antimicrobial medicines with dedicated, rational efforts.
Where has the news come from?
WHO has just published a new report (“The evolving threat of antimicrobial resistance - Options for action”) that sets out a global strategy for fighting antibiotic resistance. It explores how over past decades, bacteria that cause common infections have gradually developed resistance to each new antibiotic developed, and how AMR has evolved to become a worldwide health threat. In particular, the report highlights that there is currently a lack of new antibiotics in development and outlines some of the measures needed to prevent a potential global crisis in healthcare.
This is not the first time WHO has set out such a strategy. In the 2001, WHO published its “Global strategy for containment of antimicrobial resistance”, which laid out a comprehensive list of recommendations for combating AMR. The current report looks at the experiences over the past decade of implementing some of these recommendations, the progress made, and what else should be done to tackle AMR.
What is antimicrobial resistance?
Antimicrobial resistance (AMR) occurs when microorganisms, such as bacteria, viruses, fungi or other microbes, develop resistance to the drug that is being used to treat them. This means that the treatment no longer effectively kills or inactivates the microorganism. The term “antimicrobial” is used to describe all drugs that treat infections caused by microorganisms. Antibiotics are effective against bacteria only, antivirals against viruses only, and antifungals against fungi.
The case of penicillin illustrates the AMR phenomenon well. When penicillin was first introduced in the 1940s, it revolutionised medicine and was effective against a wide range of staphylococcal and streptococcal bacteria. It was also able to treat infections that had previously been fatal for many people, including throat infections, pneumonia and wound infections. However, with increasing use of antibiotics over the decades, bacteria began to adapt and develop changes in their DNA that meant they were resistant to the actions of the once-powerful antibiotic. These bacteria would survive and proliferate, which meant their protective genes would then be passed on to other strains of bacteria. As a result, new and stronger antibiotics had to be created to combat the resistant bacteria.
AMR is driven by many factors, including overuse of antimicrobials for human and animal health and in food production, which can allow microbes to adapt to antimicrobials they are exposed to. Poor infection-control measures, which fail to prevent the spread of infections, also contribute. In particular, the WHO publication reports what it describes as the five most important areas for the control of AMR, as recognised in its 2001 strategy:
- surveillance of antimicrobial use
- rational use in humans
- rational use in animals
- infection prevention and control
- innovations in practice and new antimicrobials
How big is the problem?
As the report describes, AMR makes it difficult and more expensive to treat many common infections, causing delays in effective treatment or, in the worst cases, an inability to provide effective treatment at all. Many patients around the world suffer harm because infections from bacteria, viruses, fungi or other organisms can no longer be treated with the common medicines that would once have treated them effectively.
The report presents some startling facts on major infectious diseases worldwide:
- Malaria: malaria is caused by parasites that are transmitted into the blood stream by a bite from an infected mosquito. Resistance to antimalarial medicines has been documented for all classes of the drug, which presents a major threat to malaria control. The report describes that a change in national antimalarial treatment policy is recommended when the overall treatment failure rate exceeds 10%. Changes in policy have been necessary in many countries due to the emergence of chloroquine resistance. This means that alternative forms of combination therapy have to be used as first-line treatment.
- Tuberculosis: in 2010, an estimated 290,000 new multidrug-resistant tuberculosis (TB) cases were detected among the TB cases notified worldwide, and about one-third of these patients may die annually. Inaccuracies in diagnosis also impede appropriate treatment.
- HIV: resistance rates to anti-HIV drug regimens ranging from 10% to 20% have been reported in Europe and the USA. Second-line treatments are generally effective in patients when the first-line therapy has failed, but can only be started promptly if viral monitoring is routinely available.
- Common bacterial infections: various bacteria can cause infections within the chest, skin and urinary tract bloodstream, for example, and the inability to fight these infections appears to a growing problem in healthcare. Estimates from Europe are that there are 25,000 excess deaths each year due to resistant bacterial hospital infections, and approximately 2.5 million avoidable days in hospital caused by AMR. In addition, the economic burden from additional patient illness and death is estimated to be at least €1.5 billion each year in healthcare costs and productivity losses.
What can be done about AMR?
The five key areas that the report highlights could tackle the problem of AMR are as follows:
Surveillance of antimicrobial use
Tracking antimicrobial use (in particular antibiotic use) and looking at the emergence and spread of resistant strains of bacteria is a key tactic in the fight against AMR. This can provide information, insights and tools needed to guide policy and measure how successful changes in prescribing may be. This can happen both locally and globally.
AMR is a global problem but, at present, there appears to be wide variation in the way regions and countries approach AMR surveillance. This means there is a long way to go before it can be carried out worldwide.
Rational use in humans
Antimicrobials can obviously be important or even lifesaving in appropriate situations, but it is just as important to prevent unnecessary use of antimicrobials, which can lead to resistance. Putting this into practice worldwide is said to be difficult, but rationalising antimicrobial use has had a demonstrable impact on AMR in some cases.
Rational use in animals
Antibiotics are said to be used in greater quantities in food production than in the treatment of disease in human patients. Also, some of the same antibiotics or classes are used in animals and in human medicine. This carries the risk of the emergence and spread of resistant bacteria, including those capable of causing infections in both animals and people.
The problems associated with the use of antibiotics in animal husbandry, including in livestock, poultry and fish farming, are reportedly growing worldwide without clear evidence of the need for or benefit from it. There are said to be major differences in the amounts of antimicrobials used per kilogram of meat produced in high-income countries, and actions need to be taken by national and international authorities to control this.
Infection prevention and control in healthcare facilities
The hospital environment favours the emergence and spread of resistant bacteria. The report highlights the importance of infection-control measures to prevent the spread of microbes in general, regardless of whether they are resistant to antimicrobials. Many facilities and countries are reported to have progressed well since 2001, implementing many recommendations on infection control and prevention, although gaps and challenges still remain.
Lastly, the report describes how innovative strategies and technologies are needed to address the lack of new antimicrobials being produced. As the report says, while antimicrobials are the mainstay of treatment for infections, diagnostics and vaccines play important complementary roles by promoting rational use of such medicines and preventing infections that would require antimicrobial treatment. So far, new products coming on to the market have not kept pace with the increasing needs for improvements in antimicrobial treatment. However, current challenges to new research developments can be both scientific and financial.
Can these strategies really stop AMR?
While AMR poses a significant threat to health in the future, the situation does not appear to be irretrievable. The WHO report and an accompanying press release highlight some examples of success stories over the past years:
- In Thailand, the "Antibiotic Smart Use" programme is reported to have reduced both the prescribing of antibiotics by prescribers and the demand for them by patients. It demonstrated an 18–46% decrease in antibiotic use, while 97% of targeted patients were reported to have recovered or improved regardless of whether they had taken antibiotics.
- A pharmacy programme in Vietnam reportedly consisted of inspection of prescription-only drugs, education on pharmacy treatment guidelines and group meetings of pharmacy staff. These measures were reported to give significant reduction in antibiotic dispensing for acute respiratory infections.
- In Norway, the introduction of effective vaccines in farmed salmon and trout, together with improved fish health management, was reported to have reduced the annual use of antimicrobials in farmed fish by 98% between 1987 and 2004.
- In 2010, the University of Zambia School of Medicine was reported to have revised its undergraduate medical curriculum. AMR and rational use of medicines were made key new topics to ensure that graduates who enter clinical practice have the right skills and attitudes to be both effective practitioners and take a role in fighting AMR.
How can I do my part?
There are times when antibiotics are necessary or even vital. However, as patients and consumers, it is important to remember that antibiotics or other antimicrobials are not always needed to treat our illnesses, and we should not expect them in every situation.
For example, the common cold is caused by a virus, which means it does not respond to antibiotics. However, people may expect to be given antibiotics by their doctor when they are affected, even though they offer no direct benefit and could raise the risk of bacteria becoming resistant. Furthermore many common viral and bacterial infections such as coughs, throat and ear infections and stomach upsets, are “self-limiting” in healthy people, which means they will generally get better with no treatment at all.
If, on the other hand, you are prescribed an antimicrobial, it is important to take the full course as directed. Taking only a partial course of an antimicrobial may not kill the organism but may expose it to a low dose of a drug which can then contribute to resistance.