Written by Seeking Science
Antimicrobial resistance has been declared among the top ten global public health threats by the World Health Organisation (WHO) [1], but what is it and how can we tackle it?
What is antimicrobial resistance?
You may be familiar with the term ‘antibiotic resistance’, which refers to the resistance that bacteria may develop to antibiotics [2]. Antimicrobial resistance encompasses all microbes including bacteria, viruses, fungi and even parasites, and their ability to evade drugs designed to kill them [2]. Antimicrobial resistance is currently responsible for 700,000 deaths each year, with estimates predicting that this could rise to 10 million annual deaths by 2050 [3].
How does antimicrobial resistance develop?
There are several ways in which a microbe may become resistant to pharmaceutical intervention, for example:
Drug overuse: Epidemiological studies have demonstrated the link between high levels of antibiotic consumption and the emergence of resistant bacteria strains. Sir Alexander Fleming, often credited as the father of antibiotic medicine, raised this concern back in 1945, stating that “the public will demand [the drug] … then will begin an era … of abuses.”
The overuse of antimicrobial drugs leads to resistance as microbes adapt to the selection pressure of a new drug and evolve ways to overcome it. This can also be achieved in several ways:
Horizontal gene transfer (HGT): If one bacterial cell develops a resistance gene, it can pass it on to surrounding bacterial cells via HGT, using a neatly packaged vessel known as a plasmid, containing all of the necessary genetic instructions. Interestingly, this can even occur between different species of bacteria.
Mutation: As an antimicrobial drug kills off most microbes in an infection, some will spontaneously develop modifications by sheer luck, which means the medicine doesn't kill them. These resistant microbes are left behind to consequently thrive and reproduce [4].
Inappropriate use of medication: Research indicates that treatment indication, choice of drugs, or duration of therapy is incorrect in 30–50% of cases. This means that the microbes intended to be killed by the medicine often survive, allowing them to evolve and reproduce along with their resistant genetic material [4].
A common misconception about antibiotics is that they can treat illnesses such as the common cold and flu. Viral infections cause these and as antibiotics are designed to kill bacteria, taking antibiotic medications won’t help to treat a cold or flu, but could help contribute to antibiotic resistance [5]. Furthermore, if you have been prescribed antibiotics for a bacterial infection, it’s essential to finish the entire course, even if you feel better, because failing to do so could leave remaining resistant bacteria that can reproduce and multiply [5].
Lack of novel antimicrobial drugs: The development of new antibiotic drugs has been declining steadily over the last 30 years. One of the reasons for this is that antibiotics are not as profitable as other drugs; hence pharmaceutical companies tend to invest less in their development [5]. It is also challenging to discover new antimicrobials, as many promising candidates often turn out to be too toxic for use or cannot be formulated into a drug [6].
What do substandard and falsified medicines have to do with antimicrobial resistance?
Several problems are associated with substandard and falsified (SF) medicines, including lack of efficacy and risk of adverse events [7]. One undesirable consequence of SF drug use that is less frequently spoken about is its contribution to antimicrobial resistance.
Sub-therapeutic doses of antimicrobial agents found in SF medicines will only kill susceptible microbes, leaving resistant strains free to reproduce and multiply [8]. The spread of substandard and falsified drugs is a global challenge, but its impact tends to be more concentrated in regions with [9]:
High levels of cross-border movement
Increased demand for cheaper drugs
Low stringency in national regulatory policies
The Mekong region which spans China, Myanmar, Lao PDR, Thailand, Cambodia and Vietnam has seen first-hand the devastating effects of antimicrobial resistance caused by falsified medicines. Artemisinin has declined in effectiveness over the last decade in this region and Plasmodium falciparum, the deadliest malaria parasite, is also becoming resistant to other antimalarials [10]. The WHO’s strategy to eliminate malaria from the area by 2030 includes tackling cross-border trafficking of falsified drugs before resistant strains are transmitted further [9].
What can be done to stop the spread of falsified medicines and antimicrobial resistance?
As we have learned, many factors contribute to the spread of antimicrobial resistance and the problem of SF medicines adds another complication to the mix. Antimicrobial resistance leads to a higher prevalence of infections and ineffective treatment of these infections; using SF medicines will inevitably lead to higher mortality rates. The threat of antimicrobial resistance on an individual, social, and economic level is already dangerously high [11].
Raising awareness of these issues is the first and probably easiest step we can take. In the long-term, tackling this problem will require stronger pharmacovigilance, an international collaboration between governments and pharmaceutical companies, and increased supply-chain security appears to be the best solution to ensure that medicines can do what they are intended to do: improve health, rather than threaten it.
References:
https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance (accessed November 2021).
https://www.medicalnewstoday.com/articles/283963#what-is-antimicrobial-resistance (accessed November 2021).
https://www.who.int/news/item/29-04-2019-new-report-calls-for-urgent-action-to-avert-antimicrobial-resistance-crisis (accessed November 2021)
Ventola, C., 2015. The antibiotic resistance crisis: part 1: causes and threats. Pharmacy and Therapeutics, [online] 40(4), pp.277–283. Available at: <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4378521/> [Accessed 8 November 2021].
https://www.verywellhealth.com/antibiotics-for-a-cold-or-flu-3860315 (accessed November 2021)
https://www.nature.com/articles/d41586-020-02886-1 (accessed November 2021).
Medicine, I., Health, B. and Committee on Understanding the Global Public Health Implications of Substandard, F., 2014. Countering the Problem of Falsified and Substandard Drugs. Washington: National Academies Press.
https://pharmaceutical-journal.com/article/research/substandard-and-falsified-medicines-global-and-local-efforts-to-address-a-growing-problem (accessed November 2021).
Sweileh, W., 2021. Substandard and falsified medical products: bibliometric analysis and mapping of scientific research. Globalization and Health, 17(1).
https://www.tropicalmedicine.ox.ac.uk/news/drug-resistance-triggers-war-to-wipe-out-malaria-in-the-mekong-region (accessed November 2021).
https://www.who.int/medicines/regulation/ssffc/publications/SE_Study_EN.pdf (accessed November 2021)