Biology: Antibiotic Resistance - The Most Pressing Challenge Facing Medicine

Note: The following essay was written by Zuhair Bilal L6C (20bilalz@students.watfordboys.org)

Introduction 

The first true antibiotic drug, penicillin, was discovered by Sir Alexander Fleming in 1928 and became widely available after the Second World War (Adedeji, 2016). Antimicrobial resistance (AMR) has been defined by Morier (2017) as the “loss of susceptibility of bacteria to the killing or growth-inhibiting properties of an antibiotic agent”. According to Uddin et al. (2021), bacterial resistance to specific antibiotic drugs emerged in the early stages of the antibiotic era, but was not initially a problem due to the abundance of alternative antibiotics. However, the discovery of new classes of antibiotics had largely halted by 1987. AMR poses a growing threat to modern medicine, which relies heavily on antibiotics to treat or cure bacterial infections. AMR has led to a higher risk of treatment failure, increased mortality, and longer treatment durations (Iván Oterino-Moreira et al., 2025). Understanding the mechanisms, scale, and drivers of AMR is therefore essential in order to contribute towards addressing this global medical challenge. 

Biological mechanisms 

Being aware of how the world’s “superbugs”, i.e. multi-drug resistant bacterial strains, are resistant to antibiotics offers insight into how to combat their resistance, for example with the use of classes of antibiotics the strain in question may be susceptible to, or the use of alternative therapies to antibiotics. Therefore, the main mechanisms by which bacteria develop resistance to antibiotics are noteworthy. The bacterial species Acinetobacter baumannii, is considered by the World Health Organization (2024) to be one of the most dangerous drug-resistant pathogenic bacteria. It is highly resistant to several antibiotic classes (Kebriaee et al., 2025). 

These are the primary resistance mechanisms exhibited by A. baumannii: 

1. Antibiotic-modifying enzymes - A. baumannii possesses β-lactamases, which are able to deactivate β-lactam antibiotics by changing their structure. Aminoglycosides are also deactivated using Aminoglycoside-modifying enzymes (Marino et al., 2024; Kebriaee et al., 2025).

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2. Target modification - A. baumannii alters antibiotic binding sites such that antibiotic molecules can no longer attach: this primarily affects β-lactams, aminoglycosides and colistin (Marino et al., 2024) 

3. Reduced permeability - Through the alteration of transport proteins and glycolipids in the cell-surface membrane, as well as the production of a capsule around the cell, A. baumannii is able to reduce the frequency of antibiotic diffusion into the cell. As well as this, the formation of biofilms (clumps of bacterial cells and large molecules) increase the diffusion distance for antibiotics, further reducing diffusion frequency (Marino et al., 2024). 

4. Efflux pumps - Transport proteins in A. baumannii’s membrane called Efflux pumps allow the excretion of harmful chemicals, including antibiotics, from the cell. Affected antibiotics include: fluoroquinolones, tetracyclines, and chloramphenicol (Marino et al., 2024). 

Below: Diagram of AMR in A. baumannii

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While the process by which bacteria develop resistance is natural, it is vital that we examine the human drivers and systemic accelerators behind the emergence of multidrug-resistant pathogens such as A. baumannii. 

Drivers of AMR 

When an antibiotic eradicates the majority of a bacterial population, a small number may survive due to pre-existing random mutations that confer resistance. These survivors now have a significant selective advantage, as the antibiotic has eliminated susceptible competitors, allowing the resistant bacteria to proliferate. This phenomenon was described by microbiologist Stuart Levy as the ‘antibiotic paradox’ (Levy, 2002). In his 1945 Nobel Prize speech, Sir Alexander Fleming, the discoverer of penicillin, warned that microbes could become resistant to penicillin if the drug was used inappropriately. In spite of this prescient warning, antibiotic use has increased dramatically in the last few decades (Irfan, Almotiri and AlZeyadi, 2022). Historically, the prescription of antibiotics to treat viral infections was also common, notwithstanding their ineffectiveness against viruses. In a 1997 study involving 787 patients, 77% requested antibiotics to treat their respiratory infections, despite the fact that viruses cause many such infections (Macfarlane et al., 1997). 581 of the patients were prescribed an antibiotic. However, the study found that only one fifth should “definitely” have received them, while around 150 should “definitely not” have been prescribed antibiotics. Most of the 76 doctors in the study said that they went against their own clinical judgement because of pressure from patients. This study sheds light on one of the main causes of the spread of antibiotic resistance: inappropriate use. The World Health Organization (2020) identifies the principal drivers of AMR as the overuse and misuse of antibiotics (in both animals and humans), alongside inadequate access to clean water, sanitation and hygiene. The cumulative effect of these drivers is not only the accelerated emergence of AMR, but also its widespread dissemination, with profound consequences for modern medicine worldwide.

Scale and consequences 

AMR has profound consequences for both individual patients and healthcare systems. Iván Oterino-Moreira et al. (2025) found that AMR was associated with a 37-40% increase in mortality risk and prolonged average hospital stays from 8 days to 14 days. A study published in The Lancet (Naghavi et al., 2024) found that in 2019, there were 4.95 million deaths associated with AMR, of which 1.27 million were directly attributable, excluding COVID-19-related deaths. The rate of deaths associated with AMR in 2019 was estimated to be 15.5 per 100,000, falling to 14.5 per 100,000 in 2021, compared to 19.8 per 100,000 in 1990. The authors further reported that in 1990, the majority of deaths attributable to AMR were concentrated in Africa and some regions in Asia, whereas they were more evenly distributed in 2021. Projections suggest that by 2050, annual deaths attributable to AMR could reach 1.91 million, and 8.29 million associated deaths. This corresponds to an approximate rate of 20.4 deaths per 100,000 attributable to AMR, representing a significant increase from 2021. 39.1 million deaths attributable to AMR are predicted to occur between 2025 and 2050, and 169 million associated deaths. Notably, the 2014 Review on Antimicrobial Resistance (O’Neill, 2014) estimated an even higher death count attributable to AMR by 2050: 10 million per year. These findings underscore that AMR is an urgent global problem that threatens modern medicine, demanding action from doctors to mitigate its spread. 

How I would contribute as a doctor 

Clinicians worldwide have a responsibility to contribute to slowing the spread of AMR in several ways. Firstly, prescribing antibiotics appropriately is something I would strive to do as a doctor; antibiotic stewardship is one of the primary ways modern healthcare systems combat the progression of AMR. It is crucial that doctors choose the correct drug, dose and duration when treating a bacterial infection. It is also vital that doctors avoid using antibiotics for viral infections, against which they are ineffective. Secondly, I would emphasise the general prevention of infections through hygiene - it is important that healthcare workers regularly wash hands and adhere to hospital hygiene protocols, thereby reducing the transmission of bacteria and therefore antibiotic-resistant bacterial strains. Thirdly, I would engage in research into potential alternative treatments for bacterial infections - while we can slow the spread of AMR through stewardship and hygiene, this does not eliminate the need for alternative therapies. It is therefore essential that research is undertaken into possible alternate methods of dealing with bacterial infections.

One of the most promising of these is bacteriophage therapy. Bacteriophages, meaning “bacteria eaters”, are viruses that target specific strains of bacteria, and were discovered independently by Frederick Twort and Felix d’Herelle in 1915 and 1917, respectively (Ling et al., 2022; Häusler, 2006). Phage therapy has been used to treat thousands of patients over the decades; these were often patients with infections against which antibiotics were futile. Due to the rise of antibiotics in the 1940s and onwards, the West largely abandoned phage therapy, remaining more prevalent in the USSR. However, since the dissolution of the USSR, phage therapy has been largely confined to the Eliava Institute in Georgia. Phages have been shown to successfully treat infections that multiple last-resort antibiotics combined could not cure, as demonstrated by the case of Alfred Gertler in 2001 (Häusler, 2006). Global interest in phage therapy has increased in recent years, and research is ongoing. I would contribute to this research in order to help develop novel therapies for bacterial infections using bacteriophages as an alternative to or in conjunction with antibiotics. 

Conclusion 

In conclusion, Antimicrobial resistance can be considered the largest challenge facing modern medicine, threatening not only healthcare systems, but tens of millions of lives. While it develops naturally in bacteria due to mutations and natural selection, its spread has been accelerated by the inappropriate use of antibiotics over decades. I would take various steps in order to combat the progression of this global health problem, including educating the masses about how to responsibly use antibiotics, organising stewardship programmes to ensure the appropriate use of antibiotics in healthcare settings, and research into alternative therapies such as bacteriophage-based therapeutics.

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