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Raising the alarm bells on antimicrobial resistance
Raising the alarm bells on antimicrobial resistance
Holly Forbes
Ulladulla High School
Abstract
Does exposure to and awareness of Antimicrobial Resistance reduce the misuse and overuse of antibacterial agents and subsequent antimicrobial resistance? If so, has there been a significant increase or decrease in the number of infections from antibiotic resistant strains? According to the WHO, the global spread of antimicrobial resistant bacteria is one of the major threats to human health in the twenty-first century. Misusing and overusing different antibacterial agents in the health care system and in the veterinary industry are considered the major reasons behind the emergence of Antimicrobial Resistance (AMR). This study examines how education strategies surrounding antimicrobial use, such as Antimicrobial Stewardship (AMS), can be effective in reducing the risks associated with AMR. The hypothesis, that if individuals are aware of antimicrobial resistance, then they will finish a course of antibiotics because they understand AMR, was accepted based on analysis tests such as a chi-square test. The conclusions drawn from this study come from local survey results from clinicians and the general public on antibiotic use and prescription strategies.
Literature review
Globally, infections caused by multidrugresistant (MDR) bacteria are on the rise. The increased use of antibiotics clinically is driving the rise in antimicrobial resistance (AMR).
According to the World Health Organization (WHO), AMR is responsible for the deaths of 700,000 people, while it’s estimated that by 2050 this figure will have risen to 20 million (Uddin, 2021). Antimicrobial stewardship (AMS) refers to programmes and interventions that aim to improve the use of antimicrobials. This review will focus on three major themes which arise from the literature reviewed. These themes are: the emergence of antibiotics and antimicrobial resistance, what issues arise in certain infections from AMR and how AMR can be controlled through AMS. The specific focus of this literature review is the misuse or overuse of antibiotics, and how this is driving the global health crisis.
The emergence of antibiotics and antimicrobial resistance
Antibiotics have been used to cure bacterial infections for more than 70 years. The first antibiotic in western civilisation, mycophenolic acid, was identified in 1893, by Bartolomeo Gosio (Tanvir Mahtab Uddin, 2021). In 1909, Paul Ehrlich and his collaborators discovered Salvarsan, the first synthetic antibiotic, which is effective against the causative pathogen of Syphilis. As salvarsan had elevated risk factors due to the presence of arsenic, it was overtaken by Prontosil, an antibacterial sulphonamide drug (Domagk, 1930).
Sulphonamides were eventually replaced by penicillin, as bacteria became resistant to Prontosil due to the occurrence of mutations in the DHPS enzyme. In 1928, Alexander Fleming discovered a fungus (Penicillium notatum) disrupted the development of the colonies of Staphylococcus aureus. He named it penicillin (Fleming, 1929). In 1939, Howard Florey and Ernst Chain were able to produce the antibiotic for the market. After penicillin was introduced in 1941, penicillin-resistant S. aureus emerged just a year later (Tanvir Mahtab Uddin, 2021). Methicillin, a penicillin related semi-synthetic antibiotic which was introduced to combat penicillin resistant S. aureus became resistant to methicillin (1960). AMR has been a major source of concern over the years, as it takes little time for an antibiotic to establish resistance, and with more than 70% of pathogenic bacteria having resistance to at least one antibiotic, it has now become one of the most serious challenges to sustainable healthcare (Uddin, 2021).
What issues arise in certain infections from AMR?
Antimicrobial resistance (AMR) occurs when a microorganism has one or more genetic mutations that allow them to resist therapeutics. Over time, these resistant strains can become dominant. A study conducted by Tien, Punjabi & Holubar (2019) investigated the increased rate in antibiotic resistant strains of sexually transmitted infections (STI). The study found that curable STIs, such as uncomplicated gonococcal infections, may be rendered uncurable as antimicrobial resistant strains become dominant.
Increased antibiotic use for infections like syphilis has created macrolide resistance globally. Sexually transmitted bacteria mycoplasma genitalium has developed a resistance to antimicrobials such as macrolides and fluoroquinolones. There are limited alternative therapeutic options for such bacteria (Tien et al, 2020). These findings were supported by a similar study which focused on the prescription of antibiotics to COVID-19 patients. Although COVID-19 is a viral illness, many patients admitted to hospital were prescribed antibiotics, based on concerns that COVID-19 patients may experience secondary bacterial infections, and the assumption that they may respond well to antibiotic therapy. This has led to an unnecessary increase in antibiotic use for some hospitalised patients at a time when accumulating antibiotic resistance is a major global threat to health (Euden, 2022).
How can AMR be controlled through AMS?
Considering the increase in superbugs globally, antimicrobial stewardship (AMS) education programs and studies have emerged to improve the situation. An investigation by AURA analyses the 2019 National Antimicrobial Prescribing Survey (NAPS) data to confirm issues identified in successive surveys since 2013. The appropriateness of antimicrobial use in Australian public and private hospital has not shown any consistent improvement, and compliance with national and local prescribing guidelines is frequently less than optimal (ACSQHC, 2021). These findings were supported by an investigation into the best methods of education and evaluation to improve antimicrobial use in a clinical setting (Bond, 2017). The study aimed to reduce the use of antibiotics by stopping the use of prophylactic gentamicin in orthopaedic surgery, due to concerns regarding gentamicin’s toxicity. The study found that effective AMS can result in the withdrawal of unnecessary antibiotic use perioperatively (Bond, 2017).
This review included relevant material to this study, however, was limited to the focus of clinical use of antibiotics on humans, rather than on animals due to there being a lack of available literature on the topic. The antimicrobials mentioned in this review are strictly antibiotics used to treat bacterial infections. Considering the evidence shown in these studies, it can be inferred that with the appropriate use of antimicrobials, and effective educational AMS strategies, we can reduce the spread of superbugs as a result of AMR.
Scientific research question
Does exposure to and awareness of Antimicrobial Resistance reduce the misuse and overuse of antibacterial agents and subsequent antimicrobial resistance? If so, has there been a significant increase or decrease in the number of infections from antibiotic resistant strains?
Variables
Independent - The exposure to and awareness of Antimicrobial Resistance.
Dependent - The behaviour surrounding antimicrobial use.
Scientific hypothesis
If individuals are aware of antimicrobial resistance, then they will finish a course of antibiotics because they understand the consequences of the misuse and overuse of antibacterial agents.
Null hypothesis: There is no correlation between awareness of AMR and the misuse and overuse of antibacterial agents.
Alternate: There is a correlation between awareness of AMR and the misuse and overuse of antibacterial agents.
Methodology
Aim
The aim of this investigation was to gather primary and secondary data to determine whether Antimicrobial Stewardship is an effective strategy at increasing awareness of the consequences of the misuse and overuse of antibacterial agents and reduce the misuse and overuse of antibacterial agents.
Secondary data was gathered from previous studies to provide examples of this study on a wider scale and support this study’s findings.
Primary data
Surveys were conducted to collect quantitative categorical data to establish what the public and professions know about AMS and AMR. This included asking how they use antibiotics themselves and with their pets, and how they perceive the threat of antimicrobial resistance. Two surveys were conducted, the first collected information about the general public and pet owners and the second was specific to clinicians (veterinarians and general practitioners).
• The survey was conducted primarily on people living and working in regional Milton/Ulladulla. The survey was sent to professionals at Vet Hospitals and Medical Centres in NSW and the ACT.
• Data was collected through March until June 2023.
• The results for the public survey were conducted from a group of 147 people anonymous.
• The results were analysed and compared in a spreadsheet.
Secondary data
Research was conducted on the “Evaluation of educational strategies for hospital antimicrobial stewardship: a multisite approach.”
The report aimed to determine if educational strategies on AMR in hospitals are effective. It also aimed to develop methods for AMS education and evaluate the role of technology and clinical decision support software. The report was a retrospective clinical study of gentamicin IDC prophylaxis around joint replacement surgery. Which focussed on measuring patient outcomes related to antimicrobial use.
• The report said that improvements in antimicrobial use were demonstrated. Those included discontinuation of perioperative use of gentamicin for prophylaxis in orthopaedic surgery, a reduction in recovery for communityacquired pneumonia, and a reduction in antimicrobial use across multiple hospitals sites following AMS implementation.
• The study also showed that technology and clinical decision support systems were successful, and the web-based E learning tool was successful for education.
• The report was chosen because it conducted primary research in regional hospitals on the surgical issues of overuse and misuse of antimicrobials. The report also recorded the effects of implementation of AMS strategies in hospital.
Research was conducted on a second investigation being carried out at a range of veterinary clinics across ACT. The program aimed to reduce the usage of antibiotics in vets through AMS strategies. The research was being conducted under the Australian Veterinary Association (AVA).
Results
The following analysis was developed from the surveys conducted in the Milton/Ulladulla districts, NSW, as well as from professionals at Kippax Veterinary Hospital, ACT.
The results in figure 1 show the awareness of antimicrobial resistance for the public was 10% and for the clinician’s 100%. A chi-square test showed a p-value of 0.00000000563 which is significantly less than the alpha significance level (0.05).
Therefore, we accept the alternate hypothesis, there is a significant difference between the percent of clinicians and the public aware of AMR.
The results in figure 2 show the awareness of antimicrobial stewardship for the public was 38% and awareness for the clinicians was 100%. The percentage of clinicians aware of AMS was significantly higher than the percentage of the aware public.
The results in figure 3 show that there is a higher percentage of people that complete their course of antibiotics when they are aware of AMR. 90% of people who are aware of AMR completed their course whereas 68% of people completed their course of antibiotics who are not aware of AMR. A chi square test showed the p-value was 0.0052, which is less than 0.05. Therefore, we accept the alternate hypothesis, there is an association between finishing a course of antibiotics and being aware of AMR.
The results in figure 4 show that there is no difference in the public’s awareness of AMS and the percentage of people that complete their course of antibiotics. 77% of people who were aware of AMS completed their antibiotics and 77% of people who were not aware of AMS completed their antibiotics.
The results in figure 5 show that there is more awareness of AMR than AMS. 10% of the public were aware of AMS whereas 38% were aware of AMR.
The results in figure 6 show that 63% of the public received antibiotics for a bacterial infection, 23% received antibiotics for a viral infection and 6% received antibiotics for a fungal infection.
The results in figure 7 show that 41% of pet owners have not received antibiotics for their pet and 59% of pet owners have received antibiotics for their pet.
The results in figure 8 show that the highest infection antibiotics were diagnosed for in pets was bacterial. 64% of pets received antibiotics for bacterial infections, 17% received antibiotics for fungal infections and 7% received antibiotics for viral infections.
The results in figure 9 show that 96% of pet owners that were aware of the impacts of the inappropriate use of antibiotics had a pet that finished a course of antibiotics.
The results in figure 10 show that 77% of the public are aware of the impact of inappropriate antibiotic use on humans whereas 93% of pet owners are aware of the impact inappropriate use of antibiotics has on animals.
The results in figure 11 show that 85% of clinicians with an AMS program in their workplace prescribe antibiotics for a bacterial infection “most of the time”. 0% prescribe antibiotics for a bacterial infection “always”.
The results in figure 12 show that 77% of clinicians without an AMS program implemented into their workplace prescribe antibiotics for a bacterial infection “most of the time”. 8% “always” prescribe antibiotics for a bacterial infection.
A chi-square test showed the p-value was 0.93038769, which was higher than the alpha significance value of 0.05. Therefore, the null hypothesis, there is no difference in prescription of antibiotics for bacterial infections based on whether there is an AMS program, is accepted.
The results in figure 13 show that 31% of clinicians that work with through an AMS program prescribe antibiotics for viral infections less than 40% of the time. 69% never prescribe antibiotics for a viral infection.
The results in figure 14 show that 54% of clinicians without an AMS program in their workplace prescribe antibiotics for a viral infection less than 40% of the time. 46% of clinicians “never” prescribe antibiotics for a viral infection.
The results in figure 15 show that 85% of clinicians without AMS programs in the workplace “never” prescribe antibiotics for fungal infections.
The results in figure 16 show that 62% of clinicians without an AMS program in the workplace “never” prescribe antibiotics for a fungal infection.
Statistical analysis:
Is there a difference in the awareness of antimicrobial resistance between clinicians and the public?
H0: There is no difference between the publics and the clinician’s awareness of AMR.
H1: There is a difference between the awareness of AMR of clinicians and the public.
Alpha significance = 0.05
A chi-square test of independence was chosen to determine if there was an association with the awareness of AMR between the public and the clinicians. This is a suitable test as there are more than two categories.
x² = 33.96
P-value = 0.00000000563
Is there an association between finishing a course of antibiotics and being aware of AMR?
H0: There is no association between finishing a course of antibiotics and being aware of AMR.
H1: There is an association between finishing a course of antibiotics and being aware of AMR.
Alpha significance = 0.05
x² = 7.806743743
P-value = 0.005205161
Is there a difference in the prescription of antibiotics for bacterial infections when an AMS program is present/not?
H0: There is no difference in prescription of antibiotics for bacterial infections based on whether there is an AMS program.
H1: There is a difference in prescription of antibiotics for bacterial infections based on whether there is an AMS program.
Alpha significance = 0.05
A chi-square test of independence was chosen as there are more than two categorical variables.
x² = 0.00763126
P-value = 0.93038769
Discussion
The aim of this study was to investigate the efficacy of Antimicrobial Stewardship (AMS) strategies and the impacts of awareness of Antimicrobial Resistance (AMR) on increased threat of resistance.
The key findings of the study that emerged from the data collected within the surveys were; (1) there is a lack of awareness of AMR in the general public; (2) there is a statistically significant association between awareness of AMR and completing a course of antibiotics; (3) there is an awareness of the impact misuse of antibiotics can have on animals; (4) there is a statistically significant difference between awareness of AMR of the public versus clinicians; (5) AMS programs can impact the methods of prescription of antibiotics.
The public survey collected data from 147 participants. Of this sample, 38% were aware of AMR and 10% were aware of AMS (Figure 5). The effectiveness of AMS strategies in a clinical workplace was supported in the clinician’s survey, which collected data from 26 participants, that 100% of clinicians were aware of both AMR and AMS (Figure 1 & 2). A chi-square test of independence was performed to determine if there was a statistically significant difference in the awareness of AMR between the public and clinicians. The p-value was significantly less than the alpha value = 0.05. The alternate hypothesis was accepted, as there was a significant difference in the awareness of AMR between the public and the clinicians. This suggests that further AMS strategies should be implemented to educate patients as well as professionals.
The study investigated the association between awareness of resistance and the effect this has on completing a course of antibiotics, the alternative hypothesis was that there is an association. A chi-square test of independence was used to determine whether the hypothesis was correct. The pvalue was 0.0052 which is significantly less than the alpha value. This indicates that there was a statistically significant association between awareness of AMR and completion of a course of antibiotics. As shown in the results, awareness of AMR equated to people being more likely to complete a course of antibiotics, and public awareness was significantly less than clinicians. Therefore, it would be advisable that clinicians use AMS strategies to ensure they educate their patients on awareness.
Studies have shown that the use of antibiotics prophylactically isn’t effective. In a study conducted on the use of gentamicin IDC prophylaxis for orthopaedic surgery, it was established that low infection rates occurred despite the presence of gentamicin or not (Bond S. 2017). The misuse of antibiotics is what creates superbugs and makes it much more difficult to treat infection. According to the WHO, the median rate of methicillinresistant Staphylococcus aureus (MRSA) occurring was 12.11%. Increases in MRSA could compromise the management and control of Staphylococcus aureus, like other current superbugs have for diseases such as gonorrhoea (WHO, 2021).
Further conclusions can be drawn from the survey on the pre-emptive use of antibiotics. Figure 8 shows what infection pets received antibiotics for Results showed that 2 pets received antibiotics for “injury”, and 1 pet received antibiotics for “after surgery”. Therefore, these could indicate a misuse of prescription of antibiotics as preventatives. The investigation collected data on the implementation of AMS programs in a workplace. Of the clinicians surveyed, 50% use AMS strategies when prescribing antibiotics. It was found that 85% of those clinicians with AMS strategies in place prescribe antibiotics for bacterial infections “Mostly”. Of the clinicians, 0% were found to prescribe antibiotics “Always” (Figure 11). For clinics without use of AMS strategies, 8% prescribed antibiotics for bacterial infections “Always” (Figure 12). In support of the investigation’s hypothesis, it can be problematic to prescribe antibiotics to a patient 100% of the time.
There is evidence suggesting that the COVID19 pandemic increased the risk of AMR due to a bacterial co- infection, associated with the disease, which increased the need for prescribing antibiotics (Joanne Euden, 2022). To prevent AMR, Procalcitonin testing was used to help identify patients for whom antibiotics should be prescribed. The Procalcitonin study supported this study’s findings on the importance of preventative methods when it comes to resistance (Joanne Euden, 2022). Further conclusions can be drawn from the implementation of AMS programs in clinical workplaces. A small sample of the vets surveyed for the investigation that have AMS strategies implemented in their workplace have been a part of an AMS awareness program in veterinary clinics that have reduced antibiotic usage by 18%, and specifically the most common antibiotic used by vets, fluoroquinolone by 47% (Bond A. 2019).
Other findings
The investigation hypothesised that there would be little awareness surrounding animal antibiotic use. Of pet owners, 93% were aware that inappropriate use of antibiotics can harm their pets (Figure 10). This result was significantly higher than the awareness on the harm of inappropriate antibiotic use in humans (77%). Therefore, the hypothesis that awareness of AMR in pets is less than in humans, can be refuted. However, this data also suggests that the public are not aware that AMR in animals can cause problems in resistance for humans (Bond A. 2019).
Is Antimicrobial Stewardship worth it?
The data shows that only 68% of people are finishing their course of antibiotics when not aware of AMR (Figure 3). It was also found that 70% of people rely on GPs for information on AMR. Only 50% of the clinicians sampled are implementing some sort of AMS strategy into their workplace. It can be concluded that the lack of awareness surrounding AMR is a result of the lack of AMS strategies that are implemented throughout professional workplaces.
Limitations
A third chi-square test (Table 9) was conducted to determine if there was a statistically significant difference in the prescription of antibiotics for a bacterial infection in the presence of AMS programs in a clinical workplace. The null hypothesis was accepted that there was no association between prescription of antibiotics and the implementation of an AMS program. This test refuted the hypothesis that lack of AMR awareness is related to misuse of antibiotics. Further research could involve developing a wider sample size for research surveys and forming more specific conclusions on the association between Antimicrobial Stewardship and the positive impacts on Antimicrobial Resistance.
Conclusion
The results from this experiment support the hypothesis that if individuals are aware of Antimicrobial Resistance, then they will finish a course of antibiotics because they understand the consequences of the misuse and overuse of antibacterial agents. As shown by chi-square tests of independence, there was a significant association between antibiotic misuse and awareness of AMR. Therefore, education strategies are important for the general public. Whilst the hypothesis was accepted, other trends in the results suggests that lack of awareness may not be the cause of resistance. There was no significant association between implementing an AMS program and the prescription of antibiotics. The hypothesis that it is less known that animal antibiotic resistance can occur as opposed to human antibiotic resistance was also refuted. In conclusion, AMS programs would be effective in reducing the risk of resistance if they are implemented nationwide in Veterinary clinics, General Practitioners, medical clinics, and hospitals. More information needs to be provided on the risks of antimicrobial resistance by promoting the impacts AMR can have on individuals.
Reference list
ACSQHC. (2021). Australian Commission on Safety and Quality in Health Care. Retrieved from “Antimicrobial prescribing practice in Australian hospitals.: https://www.safetyandquality.gov.au/sites/def ault/files/2021- 04/report__2019_hospital_naps.pdf
Antimicrobial resistance, Australian Government, Department of Health, department of Agriculture, water and the environment. (2019). Retrieved from “Australia’s National Antimicrobial Resistance Strategy – 2020 and Beyond.: https://www.amr.gov.au/sites/de fault/files/2022-11/australia-s- national-antimicrobial- resistance-strategy-2020-andbeyond_0.pdf
Bond, A. (2019). Vet, Kippax vet Hospital
Bond, S. (2017). Evaluation of educational strategies for hospital antimicrobial stewardship: a multisite approach. University of Wollongong
Joanne Euden, P. P.-H. (2022). MDPI. Retrieved from Procalcitonin Evaluation of Antibiotic Use in COVID-19 Hospitalised Patients (PEACH): Protocol for a Retrospective Observational Study: https://www.mdpi.com/2409- 9279/5/6/95
MDPI. (2022). Retrieved from “Procalcitonin Evaluation of Antibiotic Use in COVID-19 Hospitalised Patients (PEACH): Protocol for a Retrospective Observational Study: https://www.mdpi.com/2409- 9279/5/6/95
NCAS. (2020). National Centre for Antimicrobial Stewardship. Retrieved from https://www.ncas- australia.org/Education
Tanvir Mahtab Uddin, A. J. (2021). Antibiotic resistance in microbes: History, mechanisms, therapeutic strategies and future prospects. ScienceDirect. Retrieved from Journal of Infection and Public Health: Antibiotic resistance in microbes: History, mechanisms, therapeutic strategies and future prospects: https://www.sciencedirect.com/science/articl e/pii/S1876034121003403#:~:text=Resistance%20 was%20initially%20observed%20in,%2C%20i n%201942%20%5B3%5D
Tien, V. e. (2020). Journal of travel medicine. Retrieved from “Antimicrobial resistance in sexually transmitted infections.”: https://academic.oup.com/jtm/article/27/1/taz 101/5678669#198493512
Uddin, T. M. (2021). Journal of Infection and Public Health. Retrieved from Antibiotic resistance in microbes: History, mechanisms, therapeutic strategies and future prospects: https://www.sciencedirect.com/science/article/pii/S1876034121003403
Appendices
Appendix 6: Questions from public survey.
1. Have you heard of the term antimicrobial resistance (AMR)?
2. Have you heard of the term antimicrobial stewardship (AMS)?
3. What was the last infection you were diagnosed with?
4. Were you given antibiotics for the last infection?
5. The last time you were prescribed antibiotics, what was the type of infection?
6. If yes, did you finish your course of antibiotics?
7. Inappropriate use of antibiotics can cause future problems.
8. Not completing a course of antibiotics causes antibiotic resistance. How much of a problem do you perceive antimicrobial resistance to be?
9. If antibiotics are not used properly, and resistance occurs, what could happen?
10. Do you own a pet? If not, skip to last question.
11. If yes, what type of animal is your pet?
12. Has your pet ever been given antibiotics? If not, go to the end.
13. What infection were the antibiotics given for?
14. Did your pet finish their course of antibiotics?
15. The inappropriate use of antibiotics can harm your animals.
16. Where would you look to find more information on antibiotic use?
Appendix 7: Questions from clinician survey.
1. Are you a General Practitioner or a Veterinarian?
2. How many GP's/Veterinarians do you have in your workplace?
3. How long have you been practising?
4. Have you heard of the term Antimicrobial Resistance (AMR)?
5. Have you heard of the term Antimicrobial Stewardship (AMS)?
6. How much of a problem do you perceive Antimicrobial Resistance to be?
7. How likely are you to prescribe antibiotics for a bacterial infection?
8. How likely are you to prescribe antibiotics for a viral infection?
9. How likely are you to prescribe antibiotics for a fungal infection?
10. Do you want to comment on the prescription of antibiotics?
11. Has your practice implemented an AMS (Antimicrobial Stewardship) program into your workplace?
12. If not, are you implementing any strategies to patients specifically targeting education around the misuse of antibiotics?
