Dr John Burke
Antimicrobials are key to protecting population health and well-being and, without them, even routine surgery will become hazardous. The World Health Organization (WHO) has listed antimicrobial resistance (AMR) as one of the urgent health challenges for the next decade.
Dr John Burke, medical director, Healthcare Management, Bupa Global and UK Insurance, explores the issue of AMR and offers some tips about discussing it with patients.
Antimicrobial resistance (AMR) describes pathogens that are resistant to drugs such as antibiotics, antivirals, anti-parasitics and antifungals.1
Antibiotics, such as amoxicillin and tetracycline, are a major type of antimicrobial used to treat bacterial infections and resistance occurs when bacteria change in response to the use of these medicines.
It is the bacteria, not humans or animals, which become antibiotic resistant. These bacteria may then infect humans and are harder to treat than non-resistant bacteria.2
AMR is a broad term, covering resistance to drugs that treat infections caused by other microbes as well as bacteria, such as:
Parasites – for example, malaria;
Viruses – for example, HIV;
Fungi – for example, Candida.
Resistance happens when micro-organisms change as they are exposed to antimicrobial drugs, which results in the medicines becoming ineffective. Infection then persists within the body and this increases the risk of the microorganisms spreading to others.3
Methicillin-resistant Staphylococcus aureus (MRSA) is a well-known example of a micro-organism that developed AMR and is resistant to several widely used antibiotics.4
The scale of the problem
Despite efforts, significant levels of resistance have been reported in countries of all income levels and almost every type of bacteria has become less responsive to antibiotic treatment.
Currently, at least 700,000 people die each year due to drug-resistant diseases, including 230,000 people who die from multidrug-resistant tuberculosis.5 If allowed to grow unchecked, it has been estimated that AMR will kill 10m people per year globally – more than cancer and diabetes combined – and cost society approximately $100-200 trillion by 2050.6
The escalating costs are associated with expensive and intensive treatments and an increase in resource utilisation. Treating patients with resistant infections by using a combination of regimens may be ineffective and, as a result, they may need longer hospital stays.
In addition, hospitals may also need more intensive care units (ICUs) and isolation beds to prevent the spread of infection.7 Outbreaks of healthcare associated infections with resistant pathogens may mean that hospital wings need to be closed and elective surgeries cancelled, costing hospitals money.
As well as these direct effects, AMR causes a burden on the health care system through secondary effects.8 These effects happen when procedures where antibiotics are used to decrease the risk of any infection after surgery are performed less often due to AMR increasing the risk of adverse events. It is clear, that AMR is a major concern for the healthcare industry.
It is therefore no surprise that the WHO has listed AMR as one of the urgent health challenges for the next decade, noting that ‘AMR threatens to send modern medicine back decades to the pre-antibiotic era’.9
Impact of Covid-19
The direct and indirect impacts of Covid-19 on AMR are becoming increasingly clear, but the net effect still remains to be seen.10
It could be argued that AMR will be reduced due to the efforts made to curb the spread of Covid-19, such as improved population hygiene measures or restriction of travel.
Extra vigilance around hygiene and additional sterilisation procedures in the clinical setting may contribute to reducing the spread of resistant infections locally and on a global scale.
Similarly, the increased use of antimicrobial soaps and disinfectants due to changes in infection prevention and control policy and individual habits may help to reduce the direct spread of AMR micro-organisms.
But the concentration of these products in the environment is important. If it is too high, although they would inhibit the spread of AMR, they could cause significant impacts in situations where bacteria perform a beneficial role. Too low and this could provide an opportunity for AMR to evolve.11
The use of antimicrobials to treat Covid-19 era infections may also increase the prevalence of AMR. As many as 70% of patients with Covid-19 receive antimicrobials and unnecessary use is likely to be high, potentially contributing to an increase in AMR.12
Patients may receive antimicrobial therapy because their Covid-19 symptoms can resemble bacterial pneumonia13 or they acquire secondary co-infections which require antimicrobial treatment.14
The presence of AMR will influence the choice of antimicrobials prescribed to those with Covid-19, and there is also concern that potential infection with resistant pathogens could lead to unnecessary prescribing of last resort antimicrobials to patients with Covid-19.14
Antimicrobial stewardship principles should guide the antibiotic management of patients with Covid-19. However, guidance on this differs. So we need clear and consistent guidance on which patients with Covid-19 would benefit most from empiric antibiotics, and in which patients the risks of antibacterial therapy exceed the benefits.12
It’s not easy to achieve a global consensus on any emerging disease and this demonstrates how the pandemic is impinging on pre-pandemic plans to tackle AMR.
Collecting data comparing the prevalence of AMR infections before and after the pandemic will help to realise the longer-term implications of additional sterilisation procedures in the clinical setting and changes to practice on the spread of AMR.
There is a significant lack of research on new antimicrobials, which heightens the problem of AMR for both developing and developed nations.15
Currently, the process is not commercially viable – reportedly taking 23 years before profit is achieved.16 This is because commercial return for any given new antibiotic is uncertain until resistance has emerged against the previous generation of drugs.
Also, the present focus on antibiotic stewardship to reduce AMR also presents an obstacle to antibiotics development. To safeguard the efficacy of new antibiotics, it is desirable to limit their use to those cases that cannot be successfully treated with existing products.
However, this makes for a poor business case for investors, since sale volumes for new antibiotics reaching the market remain minimal, at least initially, and the low expected return on investment leads to reduced interest.17
This is critical to reducing the wide-reaching impact of AMR, keeping authorities and clinicians aware of where and when resistance is present and evolving. However it presents many challenges owing to its multi-host, multi-pathogen, multi-drug nature.18
The WHO has developed the Global Antimicrobial Resistance and Use Surveillance System (GLASS). It is the first global system to incorporate official national data from surveillance of AMR in humans – monitoring of resistance and use of antimicrobial medicine – in the food chain and in the environment.
It provides a standardised approach for the collection, analysis, interpretation and dissemination of AMR data. So far, 109 countries worldwide have enrolled.
Currently, more attention is given to developing therapeutics rather than diagnostics, and most stakeholders agree that this is where the need is most critical.19 Both the therapeutics and the diagnostics ecosystems face similar market failures and lack of investment.
However, there is a growing demand for rapid antimicrobial susceptibility testing (AST) for bacterial infections to identify the antimicrobial treatment most likely to work.
Conventional diagnostic and AST technologies in clinical microbiology have long turnaround times – 18 to 36 hours – and, although new time-saving (two to four hours) automated AST technologies have been marketed, the conventional technologies are still being used and are usually expensive.20
4Artificial intelligence (AI)
This may be used to potentially help reduce the development time of new antimicrobial agents, improve diagnostic and therapeutic appropriateness.21
Recently an AI-based offline smartphone app for AST analysis demonstrated promising results. It uses the phone’s camera to capture images and guides the user throughout the analysis on the same device.
It showed that the automatic reading of antibiotic resistance testing could be feasible on a smartphone.22
The potential to predict bacteria’s resistance to antibiotics by determining the sequence of their genome has long been discussed.
As well as diagnostic applications, next-generation sequencing techniques have the potential to provide a link between AMR surveillance in the environment and in the other aspects of the One Health approach to AMR – in the healthcare setting, agriculture and food producing animals.
This may add value to the monitoring approaches currently established in each of these fields individually.23
Telehealth continues to grow due to strong uptake, favourable consumer perception and significant investment. There is concern that virtual consultations can correlate with lower guideline-directed antibiotic prescribing and increased antibiotics compared with other settings.24 Teleprescribing can also increase the speed of access to antibiotics which may lead to overuse.
However, currently available evidence in primary care is insufficient to confidently conclude that this is the case, with variable results reported for different conditions.25
As virtual consultations become more commonplace, clinicians need to make sure that appropriate governance is in place to inform safe and appropriate implementation of remote consulting across primary, secondary and tertiary care to minimise the impact on AMR.24
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