Antibiotic Resistance

Antibiotic resistance is a growing concern in the field of healthcare, posing a significant threat to global public health. As bacteria evolve and adapt, they develop mechanisms to survive the effects of antibiotics, rendering these medications less effective or completely ineffective. This phenomenon has far-reaching implications.

Pharmacists play a vital role in addressing antibiotic resistance by promoting appropriate antibiotic use and educating patients. In this interview, we will speak with a pharmacist to gain insights into antibiotic resistance and learn about the pharmacist’s perspective on this critical issue. Jerhne Chew Mei Cheng, the Director and Pharmacist of Smiles Pharmacy Sdn Bhd is here to share her insights on this topic.

1Twenty80: What is Antibiotic resistance and the story behind it?

Jerhne Chew: The first antibiotic in the world, ‘penicillin’, was discovered by Sir Alexander Fleming in 1928. In the 1940s, penicillin was first prescribed to treat serious infections. During World War II, penicillin saved the lives of many soldiers who were down with bacterial infections (Sengupta S et al., 2013). However, penicillin-resistant bacteria emerged in the 1950s, threatening the lives of many. This led to the crucial discovery of new beta-lactam antibiotics to overcome the problem of penicillin resistant bacteria (Spellberg B and Gilbert DN, 2014). Many antibiotics have later been developed and managed to save millions of lives.

Unfortunately, antibiotic resistance began to develop, affecting nearly all clinically used antibiotics and the lack of new drug discovery to solve the resistance issue has crippled the healthcare system (refer to figure 1) (C. Lee Ventola, 2015). In 2015, bacterial infections returned to become a serious threat to the healthcare industry.

“Survival of the fittest” is the phenomenon whereby the occurrence of genetic plasticity of bacterial pathogens leads to new acquisition of genetic material, bacterial mutational adaptations, and modification of gene expression, making these “superbugs” bacteria resistant to many antibiotics in clinical settings. In short, these “superbug” bacteria cannot be killed by antibiotics. In early 1945, Sir Alexander Fleming had pre-warned and foreseen the abuse of antibiotics use (Bartlett JG et.al., 2013). 

1Twenty80: Is Antibiotic resistance prevalent?

Jerhne: Multidrug-resistant organisms are rising not only in hospital settings but also in community environments. The World Health Organisation (WHO) has coined antibiotic resistance as one of the three most dominant public health threats of the 21st century [WHO,2014]. Some epidemiological studies have shown that the emergence and spreading of antimicrobialresistant strains are higher in areas where antibiotics are widely used (The antibiotic alarm, 2013). The worst bacteria-resistant infections are coming from gram-negative bacteria such as Enterobacteriaceae (commonly being the extended-spectrum-β-lactamase producing Klebsiella pneumoniae), Pseudomonas aeruginosa, Acinebacter, followed by Escherichia coli and Neisseria gonorrhoeae (Rossolini GM et.al., 2014).

1Twenty80: How does Antibiotic resistance happen?

Jerhne: Antibiotic resistance has been a normal phenomenon since the olden days. Many antimicrobials are naturally produced molecules that exist in our environment. Bacteria need to evolve in order to survive from these naturally occurring antimicrobials. This makes such bacteria intrinsically resistant to one or more antimicrobials. However, the main issue now is that many bacterias which are originally susceptible to certain antimicrobials are found to have developed resistance toward the same antimicrobials.

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Antibiotic resistance may arise from chromosomal gene mutations. The antibiotic-resistant genes can also be inherited from the bacteria’s relatives or transferred from non-relatives via mobile genetic elements like plasmids. Such horizontal gene transfer enables antibiotic resistance to be passed on to different species of bacteria. According to the law of natural selection, the resistant bacteria would be left behind to reproduce as the antibiotics have eliminated those which are susceptible to antimicrobials. Hence, the fittest “superbug” survived (Read AF and Woods RJ, 2014).

1Twenty80: What are the causes behind Antibiotic resistance?

Jerhne: Commercialised and routine use of antibiotics in modern medicine has led to the evolution of Multidrug-resistant organisms. The lack of antibiotics regulation in some countries has made antibiotics easily accessible over the counter without a prescription. Some patients can even buy them online in unlimited quantities, leading to the overuse of antibiotics (Michael CA et. al., 2014).

Wrongly prescribed antibiotics play a major role in promoting antibiotic resistance (Centers for Disease Control and Prevention, 2013). Often antibiotics were prescribed when they were not needed in the first place. Studies showed that in 30 to 50 percent of cases, the duration of antibiotic therapy was incorrect. Some antibiotic choices were inappropriate to treat a certain infection while some antibiotic doses given were suboptimal or subtherapeutic (Luyt CE et.al., 2014). All these not only cause antibiotic resistance, they unnecessarily expose patients to the side effects of antibiotic therapy (Lushniak BD, 2014).

Not many pharmaceutical industries are keen on developing new antimicrobial drugs due to the economic crisis-induced cut in funding and rigid regulatory requirements (Gould Im and Bal Am, 2013) (Piddock LJ, 2012). 15 out of 18 largest pharmaceutical companies have stopped producing antibiotics (Bartlett JG et.al., 2013). More funding is being channelled to make more profitable drugs that treat chronic diseases like diabetes, gastroesophageal reflux, psychiatric disorders, asthma, and chemotherapy drugs (Gould Im and Bal Am, 013). Moreover, due to the global rise in antibiotic resistance crisis, microbiologists and infectious disease, control experts are against antibiotic use, making it the“last resort” drug to treat serious illnesses. Thus, pharmaceutical companies will be expecting a very slow return on investment, making the development of new antibiotics seem unattractive (Piddock LJ, 2012). To make things worse, bacteria that are resistant to this new antibiotic would emerge very quickly, making the sales and profits of the new antibiotics very short-lived (Gould Im and Bal Am, 2013).

Moreover, the loss of patency on inventor drugs allows the shifting of sales to cheaper generic drugs (Wright GD, 2014), which makes the manufacturing of antibiotics even more unfavorable. In the last 20 years, U.S. FDA has made various changes to the clinical trial requirements, making the development of the antibiotic non-economical attractive (Piddock LJ, 2012). The extensive antibiotics use in agriculture further worsen the antibiotic resistance crisis. 80 percent of antibiotics sold in the US are being fed to livestock to promote growth, improve the quality of health and avoid infections (Gross M, 2013). The antibiotics kill or suppress susceptible bacteria in the livestock, leaving behind those antibiotic-resistant bacteria. When humans consume this livestock, the resistant bacteria will be passed on to humans, leading to infections and negative health complications (Bartlett JG et.al., 2013). The overuse of antibiotics on livestock may disrupt the environmental microbiome. Almost 90 percent of antibiotics fed to the livestock were found in their urine and stool which further contaminated the underground water and fertilizers (Bartlett JG et.al., 2013).

Antibiotics such as tetracycline and streptomycin are used as pesticides for fruit trees, this affects the environmental ecology by allowing the survival of more resistant bacteria over susceptible bacteria (Golkar Z et.al., 2014). Being too clean by over-sanitizing may prevent kids and adults from developing natural immunity to environmental antigens. This reduced immune system versatility may increase morbidity and mortality in future exposure to infections (Michael CA et. al., 2014).

1Twenty80: Are there any consequences of Antibiotic resistance?

Jerhne: MDR (multi-drug resistant)-organisms-induced infections bring a higher mortality rate compared to those by susceptible bacteria. Data analysis by the Centers for Disease Control and Prevention of the United States reported an estimated 23,000 deaths annually due to MDR infections. (Centers for Disease Control and Prevention, 2013).

Another review suggested that in 2050, the death rate may shoot up to 300 million, with a loss of close to $100 trillion to the world economy [The Review on Antimicrobial Resistance. 2014]. Things are only going to get worse if there is no more new and effective antimicrobial to combat these MDR organisms. Patients can only be left untreatable and ultimately die from infections.

The spike in antibiotic resistance increases the financial burden on the healthcare system, the patients, and their families. Patients who develop antibiotic-resistant infections tend to stay longer in hospitals (6.4 days vs 12.7 days), have higher doctor visits, are given more toxic (risk of kidney dysfunction) (Levin AS et.al., 1999) and expensive antibiotics, take longer to recover and at higher risk of long term disability (Golkar Z et.al., 2014).

The spike in antibiotic resistance increases the financial burden on the healthcare system, the patients, and their families.

Patients who are chronic users of antibiotics stand a higher chance of harboring antibiotic-resistant bacteria. The chronic use of antibiotics disrupts gut-protective microflora, leading to the development of leaky gut syndrome. When an individual has a leaky gut, the intestinal barrier is very permeable which allows toxic compounds to get in the blood, causing organ and system dysfunction. In the long run, leaky gut patients may develop auto-immunity, massive allergies, heart issues, cancer, recurrent infections, and many more (Ricardo SA et.al., 2023). Uncontrolled or prolonged use of antibiotics may also lead to gut dysbiosis whereby some good bacterial species are being removed or reduced by antibiotics, leading to systemic inflammation.

1Twenty80: Is Antibiotic resistance contagious?

Jerhne: Antibiotic resistance is not contagious. Some people hardly take antibiotics, their focus is solely on building strong inner immunity that helps them to fight most infections.

1Twenty80: Who is at risk of developing Antibiotic resistance?

Jerhne: Individuals who are chronic users of antibiotics will stand a higher chance of developing antibiotic resistance. When a person’s immunity is low, he or she will tend to fall sick easily. Often, antibiotics will be given to resolve an infection. The high frequency of falling sick and antibiotics consumption eventually lead to higher chances of getting antibiotic resistance.

1Twenty80: When are Antibiotics necessary?

Jerhne: Antibiotics are only needed when actual pathogens are identified via blood tests, urine, or feces cultures. Many times, antibiotics were prescribed as broad-spectrum treatment without confirming the existence of pathogens. This can be seen from a study done in the U.S. whereby pathogen was only found in 7.6 percent of 17435 patients hospitalized with community-acquired pneumonia (CAP) (Bartlett JG et.al., 2013).

1Twenty80: Are there ways to reduce or prevent Antibiotic resistance?

Jerhne: Firstly, cut down on the unnecessary use of antibiotics. The Infectious Diseases Society of America (IDSA) has proposed the rollout of “limited-population antibiotic drugs (LPAD)” whereby only small, cost-effective, and faster clinical trials will be needed to develop such antibiotics. Upon regulatory approval, LPAD will only be used on high-risk patients who will greatly benefit from the drug (Bartlett JG et.al., 2013). Proper diagnosis, blood tests, and patient history taking need to be done to render the need for antibiotics use.

Secondly, focus on strengthening the inner immunity to fight against infections. Repair leaky gut. A healthy gut will be able to defend against intruding bad microorganisms. This may lead to a better immunity against infections, minimizing the need to use antibiotics. The leaky gut syndrome can be repaired by taking a good diet that consists of low fats, and avoiding sugars, additives, and ultra-processed foods. Proper supplementation of probiotics/prebiotics, arginine, glutamine, polyphenols, vitamins, fibers, medical herbs, edible mushrooms, and fermentable oligosaccharides, disaccharides, monosaccharides, and polyols are found to repair leaky gut and increase intestinal immunity (Ricardo SA et.al., 2023). Taking a healthy, Mediterranean or plant-based diet helps to strengthen immunity against infections.

Focus on strengthening the inner immunity to fight against infections. Repair leaky gut. A healthy gut will be able to defend against intruding bad microorganisms. This may lead to a better immunity against infections, minimizing the need to use antibiotics.

Good and proper supplementation could help in boosting one’s immunity. Some nutraceuticals such as propolis, ionic silver, black seed, and garlic work very well as antibacterial and antiviral. Nutrients that help in reducing oxidative stress such as superfood extracts, and super antioxidants extract are powerful supplements that could speed up healing and tame cellular inflammation. Nevertheless, doing anaerobic and aerobic exercises at least 3 times a week, meditation, and breathing exercises work wonders in immune boosting too. Lastly, better new policies and research efforts should be implemented to encourage new antimicrobial drug development (Spellberg B and Gilbert DN, 2014).

Antibiotic resistance is a global crisis that will need combined efforts from the pharmaceutical research team, policymakers, healthcare system, and patients. More focus should be given to developing natural immunity, and strengthening our own immune system to make it more versatile against invading pathogens instead of relying solely on antibiotics. There are many effective and powerful antimicrobial compounds from nature, always ensuring your immunity is at its optimal and it will take care of any infections for you!

References: 

1. World Health Organization. 2014. Antimicrobial Resistance: Global Report on Surveillance 2014. WHO, Geneva Switzerland. 
2. The Review on Antimicrobial Resistance. 2014. Antimicrobial Resistance: Tackling a Crisis for the Future Health and Wealth of Nations. 
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