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Antimicrobial Resistance 101: The Clinical Burden of Resistant Microorganisms

Foreword


Antibiotics were a major breakthrough in science. Microorganisms such as viruses, bacteria, fungi, and more can be treated by antibiotics relatively simply. Upon the introduction of antibiotics, previously deadly illnesses could now be treated with incredible efficacy. However, the pathogens targeted by the first antibiotics soon started to become resistant.


Antimicrobial resistance is one of the biggest problems in modern medicine. There is evidence of bacterial infections evolving to become resistant to the complete arsenal of antibiotics. As a result, people are increasingly dying from simple infections that would not have been dangerous a few years ago. Because the situation is only going to get worse in the coming decades, it is time to think about alternatives.


The Antimicrobial Resistance 101 series will be mainly divided into the following chapters:





4. Antimicrobial Resistance 101: The Clinical Burden of Resistant Microorganisms


5. Antimicrobial Resistance 101: Solutions to Antimicrobial Resistance


6. Antimicrobial Resistance 101: Antimicrobial Resistance in the Future


Antimicrobial Resistance 101: The Clinical Burden of Resistant Microorganisms


The discovery of pencillin in 1928 revolutionised medicine (Sciencemuseum, 2021). Nowadays, bacterial infections are easily treated, and symptoms are typically not very severe. Sexually transmissible infections (STIs), acne, and even rare infections can be treated with simple drugs. This was not always the case, however. Before 1928 infections could seriously harm patients, sometimes leading to disfigurements or even death. Anything that could lead to a pathogen invading one’s body could be deadly; even papercuts, as they break the most formidable layer between your body and the outside world—the skin. Surgery too, was incredibly risky before penicillin, as surgeons have to cut patients, breaking the skin and exposing vital organs. Giving birth was also risky, mirrored in the likelihood of a mother dying during childbirth having decreased by about 50 times in Great Britain since the 1930s (Sealy, 2015). The use of antibiotics in a clinical setting only became common during World War II. The first researchers in England realised the potential of large-scale antibiotics, especially in the afterthought of World War II, during which more soldiers died of infection than of bombs and gunshots (Bernard, 2020). These researchers were not able to strike a deal with the British pharmaceutical industry, as these companies were preoccupied with the increased demand for medicine to treat wounded soldiers. They, therefore, struck deals with American pharmaceuticals, which had enough time, funds and interest to start mass-producing antibiotics. In the three years after these British scientists, Florey and Heatley, had arrived in New York, the production of penicillin had increased from 0 to 100 billion units per month, which was significantly more than the Nazis and their allies had at the time (Wainwright, 2004). Though perhaps its use did not lead the Allied Forces to victory, penicillin had a major influence on the war. An estimated 100,000 Allied Forces were treated with this antibiotic, making for a much healthier army (Conniff, 2017). Now, almost a century after the discovery of the first antibiotic, experts warn of a dystopian future, in which simple infection can no longer be treated, due to antimicrobial resistance (Sealey, 2015; Biba, 2017).


Humans have proved in recent centuries that our ingenuity, motivation and collaboration allow us to do things previously thought impossible. Human civilization has entered an era in which space flight is possible, biologists have come incredibly close to unravelling the code of biology—DNA, and the number of armed conflicts is low (Oneearthfuture, n.d.). Humans can, and have, tackled some major obstacles in the past. With increased funding and awareness of the problem of antimicrobial resistance, there is hope that the future of the healthcare system is bright. Enormous sums of money and time have been invested in developing new technologies to detect microorganisms’ resistance and eliminate resistant pathogens. The specifics of these techniques will be covered in the next article of this series.


Figure 1: When this picture was taken, and shared all over the globe in 1968, it became apparent that when scientists work together on a very complex problem, they can figure out practically anything (Neumann, 2019).

While there is reason for optimism, the current situation regarding global antimicrobial resistance, or AMR, is dire. A study from last year found that resistant infections are already among the top causes of death worldwide (Murray et al., 2022). The authors of the study concluded that 1.3 million people died as a direct result of resistant infections in the year 2019, which is significantly more than the death toll of Malaria or HIV (Thompson, 2022). Being a statistical analysis, the study is not conclusive. One thing is clear, however: AMR is not a future problem, it is a current problem. It is also worth noting that this study was performed on available data, and there are significant data gaps in developing countries. Data in developing countries can be scarce, as found by a study focused on describing the economic burden of HAIs in Australia (Wozniak et al., 2019). This shows that globally, and regionally, new pipelines for the analysis and monitoring of resistant infections are required.


A large portion of the patients suffering from resistant infections have become ill in hospitals, or other institutions or places affiliated with the healthcare system. These are termed healthcare-acquired infections, or HAIs for short. In places where sick people come together, and where many drugs are prescribed and used, such as hospitals, resistant pathogens are common. The majority of these HAIs are caused by the ESKAPE group. These are the six bacteria that are notoriously resistant and cause infections on a large scale. Thus, those at risk are mostly patients who stay in the hospital longer. An additional factor found to influence the occurrence of infections is immune status. Patients with a proper immune system will be able to deal with infections significantly better than patients taking immunosuppressors, drugs that, as the name suggests, suppress the immune system, and make patients less tolerant of infection. (Avershina et al., 2021).

Figure 2: Immunocomprimised patients have a weaker immune system, and have a larger risk of developing worse infections in comparison to people with a healthy immune system (Boehm, n.d.).

Internationally, healthcare systems are struggling more and more with the increasing number of resistant infections (Thompson, 2022). The outlook is grim, and healthcare systems should be prepared for an increasing number of infections globally. In the meantime, reports on healthcare personnel shortages are becoming more frequent. There are serious cases of understaffed healthcare facilities in Europe and the United States (World Health Organization, 2022; Duquesne University, 2023). It is likely, however, that healthcare facilities in developing countries will suffer the most (World Economic Forum, 2023). These problems are compounded by the increasing influx of patients suffering from infections that are becoming increasingly difficult to treat, due to antimicrobial resistance


If predictions become reality, and global policy is not adjusted to combat AMR, simple infections will become significantly deadlier than they have been for decades. This will have enormous consequences for public health, as more people will suffer from infections that grow increasingly difficult to treat. This will make the entire healthcare system less efficient, as more effort and time is dedicated to treating once-simple infections (Wozniak et al., 2019; Prestinaci et al., 2015). The Centers for Disease Control and Prevention (CDC) estimates that the United States alone is spending roughly 55 billion US Dollars on AMR annually. The World Bank has estimated that internationally, AMR could cost 100-210 trillion US Dollars annually, leading to a significant loss of GDP, specifically in developing countries (Dadgostar, 2019). There are numerous reasons why resistant infections are so incredibly expensive. Typically, these HAIs cause a significant increase in the length of stay of patients in healthcare facilities (Gidey et al., 2023). Additionally, patients often need an increased level of care. They may need to go to the intensive care unit (ICU), for example, which requires specialised personnel (Gidey et al., 2023). While the future is to some degree unpredictable, the outlook regarding AMR is clear: If nothing changes, the healthcare system as we know it today will be unaffordable.

Figure 3: (United Federation of Teachers, 2022).

While ARM is a concern for healthcare systems worldwide, there is still hope. Alarm bells have been going off all over the world in recent decades, resulting in stricter policies, mostly in developed nations. As AMR is becoming a more recognised danger all over the world, influential organizations are sharing action plans to combat it, such as the CDC, the European Centre for Disease Prevention and Control (ECDC), the African CDC and the Chinese government (Centers for Disease Control and Prevention, 2021; European Commission, n.d.; Africa Centres for Disease Control and Prevention, n.d.; Dall, 2022). All these agencies, and the relevant countries, are developing policies with the goal of slowing down the development of resistance, increasing the available therapeutic options and intensifying surveillance. The CDC and the ECDC specifically, wish to tackle AMR through a One Health approach, which has been extensively covered in this series. In short, a One Health approach considers how humans interact with the environment and with animals, and how all these interactions make for a network in which, for example, antimicrobial use in cattle can have serious consequences for human health (Centers for Disease Control and Prevention, 2021; European Commission, n.d.). Steps that have to be taken towards these goals are increased surveillance and filling in the data gaps on a global level (Abushaheen et al., 2020).


In the previous articles of this series, it was described how microbes may become resistant, and where resistant pathogens emerge in the world. Although the microbiology elements are certainly important to understand the problem that antimicrobial resistance poses, it is important to keep the bigger picture in mind too. Highly resistant infections have large consequences on healthcare as a whole, rather than simply on the patient.This is simply the case because an increasing occurrence of resistant pathogens will make the healthcare system as we know it today more expensive and less efficient. The next article, covering alternative therapies against resistant microbes, will offer another biological point of view of the problem, covering how these techniques work and why some therapies could be more successful than others. Finally, this series will be concluded with an article on the future perspective of the problem of antimicrobial resistance. As emphasised in this article, there is growing interest and awareness of the threat that antimicrobial resistance poses. Consequently, more governments, companies and academic researchers are focusing on this problem, leading to more fundamental research being done and more questions being answered. If history has shown us anything, it is that humans are ingenious and can tackle serious problems. It is still possible to tackle antimicrobial resistance and ensure a world in which simple infections can still be treated. It will require serious investment, but it is always better to prevent, than to cure.

Bibliographical References

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Africa Centres for Disease Control and Prevention. (n.d.). Africa CDC Framework for Antimicrobial Resistance. https://africacdc.org/download/africa-cdc-framework-for-antimicrobial-resistance/ Avershina, E., Shapovalova, V., & Shipulin, G. (2021). Fighting Antibiotic Resistance in Hospital- Acquired Infections: Current State and Emerging Technologies in Disease Prevention, Diagnostics and Therapy. Frontiers in Microbiology, 12. https://doi.org/10.3389/fmicb.2021.707330

Bernard, D. (2020). How a miracle drug changed the fight against infection during World War II. https://www.washingtonpost.com/history/2020/07/11/penicillin-coronavirus-florey-wwii- infection/

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Centers for Disease Control and Prevention. (2021). National Action Plan. https://www.cdc.gov/drugresistance/us-activities/national-action-plan.html

Conniff, R. (2017). Penicillin: Wonder drug of World War II. https://www.historynet.com/penicillin- wonder-drug-world-war-ii/

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Dall, C. (2022). China publishes new national action plan to combat antimicrobial resistance. https://www.cidrap.umn.edu/antimicrobial-stewardship/china-publishes-new-national-action- plan-combat-antimicrobial-resistance

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Gidey, K., Gidey, M. T., Hailu, B. Y., Gebreamlak, Z. B., & Niriayo, Y. L. (2023). Clinical and economic burden of healthcare-associated infections: A prospective cohort study. PLOS ONE, 18(2), e0282141. https://doi.org/10.1371/journal.pone.0282141

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Sealey, T. (2015). Life before antibiotics (and maybe life after an antibiotic apocalypse). https://www.bbc.com/news/newsbeat-34866829

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Wozniak, T. M., Bailey, E. J., & Graves, N. (2019). Health and economic burden of antimicrobial- resistant infections in Australian hospitals: a population-based model. Infection Control and Hospital Epidemiology, 40(3), 320–327. https://doi.org/10.1017/ice.2019.2

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