1. Background
Microorganisms have existed on Earth for more than 3.5 billion years and play a significant role in maintaining the balance of various ecosystems including human species 1. Most microbes are harmless or even beneficial, very few of them are pathogenic which are responsible for diseases 2. To combat these pathogens, antimicrobial agents have been developed. They include antibiotics, fungicides, antiviral agents, and parasiticides. Additionally certain heavy metals, disinfectants, antiseptics, and natural products may also possess antimicrobial properties 3,4. Antimicrobials found useful in healthcare systems. Bring significant benefits to humans, animals, and agriculture by reducing the burden of infectious diseases for many years. However, the effectiveness of antimicrobial treatments is currently threatened by the emergence of antimicrobial resistance 5,6. AMR refers to the phenomenon where microorganisms such as bacteria, viruses, parasites, or fungi develop resistance to the effects of drugs. Consequently, numerous treatments that were once effective against infections are now becoming less potent 5–7. AMR has been listed as one of the top 10 global health and development threats to humanity by the World Health Organization (WHO). Up to 10 million deaths per year are projected by 2050, impacting economies and pushing more people into poverty 8,9. AMR can also have a substantial impact on agricultural production, further impacting economies and food security. Most of this burden is anticipated to fall on low-income and lower middle-income nations 9,10. The majority of global attention regarding AMR has focused on human health and agriculture sectors, but there is emerging evidence highlighting the critical involvement of the environment in the evolution, transmission, and spread of AMR 11. Effective handling of AMR can be accomplished by adopting the 'One Health' strategy, acknowledging the interconnectedness of human well-being, animal welfare, plant health, and the environment 11–14.
2. Causes of Antimicrobial Resistance
The inappropriate use of antimicrobial drugs in humans, animals, and agriculture significantly contributes to the development and spread of AMR. There are several causes and contributing factors to antimicrobial resistance include.
2.1. Natural or Biological Causes
The natural causes of antimicrobial resistance arise from the inherent characteristics and adaptability of microorganisms. These causes include:
2.1.1. Selective Pressure
Selective pressure refers to the survival and replication advantage of microorganisms that carry resistance genes when exposed to antimicrobial agents 15. When antimicrobials are used, susceptible microorganisms are either killed or inhibited, allowing resistant strains to survive and multiply 16. These resistant strains become the dominant type within the microbial population. Over time, this selective pressure can lead to the proliferation of antimicrobial-resistant microorganisms 17,18.
2.1.2. Mutation
Microorganisms have a remarkable ability to reproduce rapidly, allowing them to adapt and evolve quickly in response to changing environmental conditions, including exposure to antimicrobial agents 19,20. During replication, genetic mutations can occur spontaneously, resulting in changes in the DNA of the microorganism. Some of these mutations may confer resistance to specific antimicrobial agents, providing a survival advantage to the mutated microorganism 21,22.
2.1.3. Gene Transfer
Microorganisms, particularly bacteria, have the capability to acquire resistance genes from other microorganisms, including those of the same or distinct species 23–25. Gene transfer can occur through different mechanisms, such as horizontal gene transfer (HGT). In HGT, genetic material, including resistance genes, can be transferred between bacteria, even if they are not closely related. This transfer can happen through three processes: conjugation, transformation, and transduction. 25–28. Gene transfer allows bacteria to rapidly acquire resistance genes, which can make them resistant to antimicrobial agents. 27,29.
2.2. Misuse and Overuse of Antibiotics
The misuse and overuse of antibiotics represent an alarming challenge that drives the emergence and propagation of antimicrobial resistance (AMR), a phenomenon in which microorganisms, notably bacteria, develop resistance to once-effective drugs 6–8,30–32. Within the context of human medicine, antibiotics are frequently employed inappropriately, particularly for viral infections, despite their ineffectiveness against non-bacterial pathogens 33. This misguided practice exposes bacteria needlessly, creating opportunities for the development of resistance mechanisms, thereby diminishing the efficacy of antibiotics 10,16,34. The incomplete adherence to prescribed antibiotic treatment regimens allows surviving bacteria to potentially acquire resistance to the initially effective drugs 35. In agriculture, excessive use of antibiotics for livestock growth promotion and disease prevention contributes to the proliferation of antibiotic-resistant bacteria 36,37. The transmission of these resilient pathogens to humans through the food chain and environmental pathways represents a serious and imminent threat to public health 38. To address the complex issue of antimicrobial resistance (AMR), we need to take a comprehensive and collaborative approach that includes educating healthcare professionals and the public about the importance of using antibiotics appropriately 39. The implementation of rigorous measures across healthcare and agriculture sectors can effectively combat the growing threat of antimicrobial resistance (AMR) by preserving the efficacy of antibiotics10–14,40.
2.3. Lack of New Antibiotics
In recent times, the creation of new drugs to fight against harmful microorganisms is decreasing, and this poses a significant problem 41,42. These drugs play a crucial role in treating infections caused by bacteria, viruses, and other microbes. However, the number of new antibiotics being developed is declining rapidly 41–43. The consequences of this decline are worsened by the fact that many microorganisms are becoming resistant to existing antimicrobial drugs 44, 45. The number of new drugs entering the market decreases and the prevalence of drug resistance continues to rise, there is a growing concern about the possibility of a future shortage of effective treatments 41,42,46. The shortage of effective treatments is a cause for concern because it means that infections that were once easily treated may become more difficult to control 47. Simple infections could become life-threatening, and medical procedures such as surgeries, organ transplants, and cancer treatments could become riskier due to the lack of effective antimicrobials to prevent and treat infections 48,49. Solving this issue requires a coordinated effort from the scientific community, pharmaceutical companies, and policymakers to promote the research and development of new antimicrobial drugs. 50. Finding innovative solutions is crucial to combat antimicrobial resistance and ensure a continuous supply of effective treatments to fight against harmful infections 51,52.
2.4. Global Travel and Trade
Global travel and trade play a significant role in the spread of AMR worldwide 53,54. When people travel internationally, they can unknowingly carry resistant bacteria with them. These bacteria can be present in their bodies without causing any symptoms. As a result, when infected individuals visit other countries, they can introduce these resistant strains of bacteria to new populations 53–56. AMR can also be transmitted through contaminated food, water, or other goods traded between countries. If these items are contaminated with resistant bacteria, they can act as carriers, spreading the bacteria to various parts of the world 56–58. The global dissemination of resistant strains is a significant concern. It means that once a particular strain of bacteria becomes resistant to antibiotics in one location, it can quickly spread to other regions. This can make it challenging to control and treat infections, as the available drugs may no longer be effective against these resistant strains 53–59. To tackle this problem effectively, it is crucial to raise awareness about AMR and implement preventive measures. This includes improving infection control practices, promoting responsible use of antibiotics, and implementing strict regulations on the trade and transportation of goods to minimize the risk of transmitting resistant bacteria 40,51,52,60.
2.5. Agricultural Use of Antibiotics
The use of antibiotics in agriculture has raised significant concerns regarding their potential impact on human health 61. Antibiotics are commonly administered to livestock for two main reasons: growth promotion and disease prevention. This widespread practice carries significant risks 61,62. The utilization of antibiotics in agriculture has been strongly associated with the emergence and dissemination of antibiotic-resistant bacteria 63. When animals are treated with these drugs, the bacteria present in their bodies can develop mechanisms to resist the effects of the antibiotics. Over time, this can give rise to the development of superbugs that are challenging to treat, posing a threat to both animal and human health 64,65. The consequences of antibiotic-resistant bacteria are extensive and extend to various aspects. Resistant bacteria have the potential to contaminate meat and other animal-derived products, effectively entering the human food chain 66. These bacteria can spread through environmental contamination, affecting soil, water, and crops. This poses a substantial threat to human health, as infections caused by antibiotic-resistant bacteria are more challenging to treat and can result in increased morbidity and mortality rates 58,67. The use of antibiotics in agriculture is a growing concern due to the potential for antibiotic resistance. There is a need for stricter regulations and oversight to ensure that antibiotics are used appropriately and that the risk of antibiotic resistance is minimized. It is also important to find sustainable practices that reduce the need for antibiotics in agriculture, while still meeting the demands of food production 68.
2.6. Lack of Diagnostic Tools
The lack of diagnostic tools in healthcare settings presents a significant challenge when it comes to timely and accurate diagnosis of infections 69. This issue can have profound consequences, as delayed or incorrect diagnosis often leads to the inappropriate use of antibiotics 69,70. In the absence of efficient diagnostic tests, healthcare providers may opt for broad-spectrum antibiotics as a precautionary measure rather than administering targeted therapy 71. Broad-spectrum antibiotics are effective against a wide range of bacteria but do not target the microorganism causing the infection 72. This approach increases the likelihood of unnecessary antibiotic use, which in turn contributes to the development and spread of antibiotic resistance 72,73. Rapid and accurate diagnostic tools are essential for identifying the specific pathogens that cause infections. This information allows healthcare professionals to prescribe the most effective treatment, including targeted antibiotics, which can help to improve patient outcomes and reduce the spread of antibiotic resistance 74. With accurate diagnostics, the choice of antibiotics can be tailored to the specific infection, reducing the unnecessary use of broad-spectrum drugs, and mitigating the risk of antibiotic resistance 74,75. Improved diagnostic tools, such as point-of-care tests or molecular diagnostics, offer healthcare providers real-time information, enabling them to make well-informed decisions regarding treatment options 76. By ensuring precise diagnoses, these tools have the potential to optimize antibiotic use, minimize resistance, and improve patient outcomes 76,77.
2.7. Poor Public Awareness and Education
Poor public awareness and education regarding the proper use of antibiotics and the consequence of antimicrobial resistance is a significant factor contributing to the development and spread of this global health crisis 78. The lack of understanding about the appropriate use of antibiotics leads to misuse and overuse of these drugs, which accelerates the emergence of drug-resistant bacteria 79. A significant challenge lies in the common misconception among many individuals who believe that antibiotics are effective in treating viral infections like the common cold or flu. This misconception leads to unnecessary antibiotic prescriptions and contributes to the development of antibiotic resistance 80,81. Additionally, patients often fail to complete the full course of antibiotics as prescribed, further promoting the survival of drug-resistant bacteria 82,83. Insufficient knowledge about the consequences of antimicrobial resistance also hampers efforts to control its spread 84. When individuals are unaware of the potential dangers, they may neglect taking preventive measures, such as practicing good hygiene and infection control. This lack of awareness allows resistant bacteria to thrive and spread in communities, healthcare settings, and the environment 85. Efforts to address poor public awareness and education should focus on increasing knowledge about the appropriate use of antibiotics, emphasizing the importance of completing prescribed courses, and promoting alternatives to antibiotics where possible 86. By improving public awareness and education on these critical issues, we can empower individuals to make informed decisions about antibiotic use and take proactive measures to prevent the spread of antimicrobial resistance 86,87.
3. Detection Methodologies for Antimicrobial Resistance
Detection methodologies for antimicrobial resistance have evolved to address the growing public health concern of antimicrobial resistance. Detecting AMR is crucial for effective treatment and containment of resistant infections. Here are some methodologies used for detecting AMR
3.1. Phenotypic Methods
Phenotypic techniques for identifying antimicrobial resistance are essential tools used in microbiology to determine the susceptibility of bacterial or fungal pathogens to various antimicrobial agents 88. These techniques involve growing the microorganisms in the presence of specific antibiotics or antifungal drugs and observing their growth response to assess their susceptibility or resistance 89. Here are some common phenotypic techniques used for identifying antimicrobial resistance:
3.1.1. Disk Diffusion
The Disk Diffusion Test, also known as the Kirby-Bauer Test, is a fundamental method employed in clinical microbiology to assess the susceptibility of bacteria to various antibiotics 90. This technique involves placing paper disks, impregnated with specific antibiotics of known concentrations, onto an agar plate inoculated with the target bacteria. Over time, the antibiotics diffuse from the disks into the surrounding agar medium. After incubation, a clear "zone of inhibition" appears around each disk, representing the area where bacterial growth is inhibited due to the antibiotic's action. Larger zones indicate greater susceptibility of the bacteria to the antibiotic, suggesting effective inhibition of their growth 91. This rapid and cost-effective test is a valuable tool for clinicians to select the most appropriate antibiotic therapy for bacterial infections. However, it is important to complement this method with other techniques to get a comprehensive understanding of antimicrobial resistance patterns. By using a combination of approaches, we can get a more in-depth analysis of resistance profiles, which will help us to make better treatment decisions and effectively manage infections 91,92.
3.1.2. Broth Dilution
The Broth Dilution Method is a fundamental technique used in microbiology to determine the Minimum Inhibitory Concentration (MIC) of antibiotics against a specific microorganism. In this method, the antibiotic of interest is serially diluted in liquid growth medium, creating a range of concentrations. The test organism is then exposed to these dilutions and incubated for a defined period. MIC is defined as the lowest concentration of the antibiotic that completely inhibits visible growth of the microorganism. A higher MIC value suggests reduced susceptibility or resistance, indicating that higher concentrations of the antibiotic are required to inhibit the growth of the microorganism effectively 91–93. The Broth Dilution Method provides essential quantitative data for clinicians and researchers, enabling the selection of appropriate antibiotic dosages to combat infections effectively and contribute to the management of antimicrobial resistance 94.
3.1.3. Etest
Epsilometer testing, commonly known as Etest, has emerged as a versatile and reliable method for assessing the minimum inhibitory concentration (MIC) of antibiotics against bacterial strains. Combining elements of the traditional disk diffusion and broth dilution techniques, the Etest involves the placement of an Etest strip impregnated with a continuous gradient of the antibiotic on an agar plate inoculated with the test organism 91,95. As the antibiotic diffuses into the agar, an elliptical zone of inhibition forms, and the point at which the ellipse intersects the Etest strip represents the MIC value. This approach offers a quantitative assessment of antibiotic susceptibility, aiding in the identification of resistant pathogens and the determination of optimal treatment regimens. The Etest's simplicity, accuracy, and ability to evaluate multiple antibiotics simultaneously make it an invaluable tool in clinical laboratories and research settings for combating antimicrobial resistance 91,95,96.
3.2. Genotypic Methods
Molecular diagnostics for genotypic detection of antibiotic resistance has revolutionized the field of antimicrobial susceptibility testing. These methods leverage advanced molecular techniques to identify specific antibiotic resistance genes rapidly and accurately in microorganisms, aiding in the precise characterization of antimicrobial resistance (AMR) profiles 91,97.
Polymerase Chain Reaction (PCR) is a well-established molecular method used in genotypic detection. It amplifies specific DNA sequences, including known resistance genes, allowing for the targeted identification of resistance determinants. PCR is a rapid and reliable technique, commonly used in clinical laboratories to detect a wide range of resistance genes 91,98.
DNA microarrays are another powerful tool for genotypic detection. These microarrays contain immobilized DNA probes that can hybridize with DNA samples, enabling simultaneous detection of multiple resistance genes 91,99. By analyzing the hybridization patterns, researchers can identify the presence of known resistance markers in a single test, making DNA microarrays a high-throughput option for AMR detection 100.
Next-generation sequencing (NGS) represents an innovative technology in genotypic detection. NGS allows for the complete sequencing of microbial genomes, providing a comprehensive view of all genetic elements, including resistance genes and mutations 101. This technology enables the identification of both known and novel resistance mechanisms, enhancing our understanding of AMR and supporting the development of new antimicrobial therapies 101,102.
Commercially available molecular diagnostic platforms have streamlined the detection of antibiotic resistance genes, making it faster and more accurate than traditional methods. These approaches play a crucial role in guiding appropriate antibiotic therapy, preventing the spread of resistant infections, and informing infection control measures. They are invaluable tools in the ongoing fight against antimicrobial resistance 103.
3.3. Innovative and Rapid Antimicrobial Susceptibility Testing (AST) Systems
In recent years, innovative and rapid antimicrobial susceptibility testing (AST) systems have emerged to address the urgent need for faster and more efficient ways to combat antimicrobial resistance. These innovative approaches aim to significantly reduce testing time and quickly identify bacterial susceptibility to antibiotics, enabling timely and targeted treatment decisions 91,92,104,105. One class of rapid AST systems utilizes phenotypic analysis, where the growth characteristics of bacteria are assessed in the presence of antibiotics 106. Some methods, like the Accelerate Pheno™ system, employ rapid phenotypic analysis combined with automated imaging and artificial intelligence algorithms to detect bacterial growth inhibition within hours. Such systems offer substantial time savings compared to conventional culture-based methods, which can take up to 24-48 hours or longer for results 107. Other innovative AST systems incorporate microfluidic technology, where bacteria are exposed to a panel of antibiotics in tiny, controlled chambers 108. The growth or inhibition of bacteria is continuously monitored, providing real-time data on susceptibility patterns, and enabling quicker identification of effective antibiotic options 109. Some AST systems leverage advanced molecular techniques, such as DNA-based methods or mass spectrometry, to rapidly detect specific resistance genes or protein markers 110. Novel approaches in AST can provide valuable information on antibiotic resistance within a matter of hours by analyzing the genetic or proteomic profiles of bacteria. These new approaches represent a significant advancement in the fight against antimicrobial resistance. They enhance patient care by expediting the identification of effective treatments, support antibiotic stewardship efforts, and contribute to global efforts in tackling the challenge of antimicrobial resistance 111.
3.4. Bioinformatics’ Approaches
It plays a pivotal role in the identification and analysis of antibiotic resistance genes in clinical samples using metagenomic next-generation sequencing 112. Metagenomic sequencing involves the direct sequencing of genetic material extracted from complex microbial communities present in the clinical sample. This powerful technique provides a comprehensive view of the diverse microbial populations, including potential pathogens and antibiotic-resistant strains 112,113. After metagenomic sequencing, vast amounts of sequencing data are generated, requiring sophisticated bioinformatics tools for analysis. Alignment and assembly methods are employed to match the sequencing reads to reference databases of known antibiotic resistance genes. These tools allow researchers to identify specific resistance genes present in microbial communities 114,115. Bioinformatics also enable the characterization of novel or previously undiscovered resistance genes. By comparing the sequencing data to comprehensive databases, researchers can detect genetic variations and mutations that might confer antibiotic resistance 116,117. Bioinformatics approaches are indispensable for extracting meaningful insights from metagenomic NGS data, contributing significantly to our understanding of antimicrobial resistance in clinical settings. They offer powerful tools to inform clinicians and public health officials in making informed decisions regarding antibiotic use, infection control strategies, and the development of novel antimicrobial therapies to combat the threat of antibiotic resistance 114–118.
4. Challenges in Addressing Antimicrobial Resistance
Antimicrobial resistance is a pressing global health challenge that threatens the effectiveness of antimicrobial drugs used to combat infections in humans, animals, and plants. The rise of AMR has led to limited treatment options, the development of multidrug-resistant organisms, inadequate surveillance and data collection, issues with antibiotic stewardship and prescribing practices, and a need for improved global coordination and collaboration.
4.1. Limited Treatment Options
Limited treatment options remain a major challenge in combating AMR. The increasing ineffectiveness of once-reliable antimicrobial treatments has left medical practitioners grappling with a reduced arsenal against infectious diseases 119. Pathogens, in their relentless evolution, have developed mechanisms to withstand the effects of previously successful antimicrobials, rendering them less potent or even entirely ineffective 120. Compounding this problem is the alarming scarcity of new antimicrobial drugs in the clinical development pipeline. Pharmaceutical companies and researchers face significant challenges in discovering and bringing new drugs to market, resulting in a stagnation of potential solutions to combat AMR 50,121. To effectively confront this crisis, urgent action is necessary in the form of intensified research and innovation. The scientific community must unite to explore novel antimicrobial agents, harnessing innovative technologies and interdisciplinary approaches 122. Genomics, nanotechnology, and other emerging fields offer promising avenues for developing targeted and efficient antimicrobial treatments. Prioritizing the development of new antimicrobial agents and implementing comprehensive strategies, we can hope to stem the tide of AMR and safeguard the future of modern medicine 123.
4.2. Development of Multidrug-Resistant Organisms
The misuse and overuse of antimicrobial drugs in various sectors, including human medicine, animal husbandry, and agriculture have contributed significantly to the development and dissemination of drug-resistant pathogens 31,32,124,125. When antibiotics are used indiscriminately or prescribed inappropriately, bacteria can evolve and develop resistance, rendering these once-effective drugs powerless against infections 33,34,126. In human medicine, the inappropriate prescription and improper use of antibiotics have fueled the evolution of resistant bacteria, making once-treatable infections much harder to manage 33,34,125,127. The agricultural industry's routine use of antimicrobials in livestock and crops has also facilitated the proliferation of resistant strains, as these drugs can enter the environment and food chain 36,37,124,125,128. Collaborative initiatives between healthcare, veterinary, and agricultural sectors are crucial to implementing effective interventions. Safeguarding the effectiveness of antimicrobials requires a collective commitment to combat the misuse of these life-saving drugs. By adopting a comprehensive approach, we can work towards mitigating the rapid rise of resistance and preserving the effectiveness of our antimicrobial arsenal for future generations 12–14,129.
4.3. Inadequate Surveillance and Data Collection
In the battle against AMR, one major obstacle is the lack of adequate surveillance and data collection systems. Without accurate and up-to-date information on the prevalence of resistant pathogens, it becomes challenging to devise effective management strategies and monitor the impact of interventions 130. Timely and precise data play a pivotal role in guiding healthcare professionals' treatment decisions 131. Understanding which antibiotics remain effective in specific regions and against certain pathogens is crucial to avoid the misuse of antibiotics and prevent the further development of resistance 132. Additionally, having access to comprehensive data allows researchers and policymakers to identify emerging trends and patterns of AMR, facilitating the development of targeted solutions 133. It is essential to bolster surveillance networks and data collection efforts on a global scale to address this critical issue. By establishing robust surveillance systems, we can gather comprehensive information on antimicrobial resistance in different healthcare settings, veterinary practices, and communities 134. Fostering collaboration among countries and organizations to share data can provide a more comprehensive understanding of AMR's global impact and allow for the implementation of coordinated strategies 135.
4.4. Antibiotic Stewardship and Prescribing Practices
Antibiotic stewardship and responsible prescribing practices are pivotal in the fight against antimicrobial resistance. To effectively curb the rise of drug-resistant microbes, it is crucial to optimize the use of antibiotics through evidence-based prescribing guidelines 136. Healthcare professionals must be judicious in their prescription decisions, prescribing antibiotics only when necessary and ensuring appropriate dosages and treatment durations 137. Avoiding unnecessary antibiotic use reduces selective pressure on microbes, minimizing the chances of resistance development 17,18,138. Patient education on the proper use of antibiotics, including the importance of completing prescribed courses and not sharing or using leftover antibiotics, is vital 139. Encouraging patients to consult their healthcare providers before demanding antibiotics for illnesses that do not require them is also essential in preserving the effectiveness of these life-saving drugs 140. Beyond healthcare professionals and patients, policymakers also have a critical role to play. They must enact and enforce policies that support antibiotic stewardship initiatives, incentivize research into new antimicrobial agents, and promote the development of diagnostic tools to better target antibiotic treatments. A collaborative effort involving healthcare professionals, policymakers, and the public is essential in promoting prudent antibiotic use. By adopting these responsible practices, we can slow down the development of AMR, extend the lifespan of existing antibiotics and safeguard their effectiveness in treating infectious diseases 136,141,142.
4.5. Global Coordination and Collaboration
The global challenge of antimicrobial resistance demands a unified and collaborative response, transcending geographical and political boundaries. AMR knows no borders; therefore, effective solutions can only be achieved through shared knowledge, best practices, and resources among nations, international organizations, and research institutions 143,144. Collaborative efforts foster a collective understanding of AMR's complexities, enabling a more comprehensive approach to combat this threat 145. The One Health approach stands out as a crucial initiative in this regard, acknowledging the interdependence of human, animal, and environmental health in the spread of AMR. By recognizing these interconnected systems, we can address the various pathways through which AMR disseminates and formulates holistic strategies that encompass both human and veterinary medicine, agriculture, and environmental practices 11–14,146. Global coordination in AMR research and response is essential for developing innovative solutions, identifying new antimicrobial agents, and improving diagnostic techniques. It also facilitates the sharing of data and expertise, enabling rapid response to emerging AMR threats. By working together, we can pool our collective strengths, experiences, and resources, forging a powerful alliance against AMR. A united front, grounded in global coordination and collaboration, offers the best chance to curb the spread of antimicrobial resistance and ensure a sustainable future for healthcare and disease management worldwide 144,145,147.
5. Societal Implications of Antimicrobial Resistance
5.1. Increased healthcare costs
The emergence of antimicrobial resistance presents substantial hurdles to healthcare systems worldwide and carries extensive implications for society at large. One of the major consequences is the substantial increase in healthcare costs. As per recent estimates, AMR is projected to impose an enormous economic burden on the world economy, reaching an alarming $100 trillion by the year 2050. These costs encompass several factors, such as the expenses incurred in treating infections that are no longer responsive to standard antibiotics 148. The development of new antimicrobial drugs involves substantial financial investments and research efforts, further adding to the economic strain. The impact of AMR on productivity cannot be overlooked, as it leads to extended hospital stays, delayed recovery periods, and increased absenteeism from work due to prolonged illness 149. The consequences of AMR extend beyond economic ramifications and affect public health significantly. Healthcare delivery and infection control systems face immense challenges in managing and preventing the spread of resistant infections, resulting in compromised patient care and potentially overwhelming healthcare facilities 149,150. AMR also has the potential to spark widespread infections and pandemics, posing a global health threat. Addressing these societal implications necessitates a concerted effort from governments, healthcare professionals, researchers, and the public to implement robust strategies for antimicrobial stewardship, infection prevention, and the development of new therapeutic approaches 51,52,60,86,87,141,142,151.
5.2. Higher morbidity and mortality rates
Antimicrobial resistance poses a significant threat to public health, and one of its key societal implications is the potential for higher morbidity and mortality rates. Currently, AMR is already responsible for causing millions of deaths annually, and this number is projected to surge if effective interventions are not implemented. The emergence of drug-resistant pathogens undermines the efficacy of existing antibiotics, rendering once-treatable infections untreatable, thus exacerbating the toll of infectious diseases on human lives 31,32,119,125,152. AMR not only affects individuals but also imposes significant burdens on healthcare systems and economies. Treating drug-resistant infections requires more extensive and costly interventions, leading to increased healthcare costs. AMR also impacts healthcare delivery and infection control measures, making it challenging to manage outbreaks and prevent the spread of resistant strains 119,153. The rise of AMR also has severe economic implications, as the economic burden on society escalates due to prolonged illnesses, prolonged hospital stays and the need for more expensive treatments. The potential for widespread infections and pandemics looms large as AMR can facilitate the rapid dissemination of resistant microbes on a global scale 154. The societal implication of AMR demands a multifaceted approach encompassing improved antimicrobial stewardship, infection prevention and control measures, development of novel antimicrobial agents and enhanced international collaboration 136,141,142,155.
5.3. Potential for widespread infections and pandemics
AMR presents a critical concern for global public health due to its potential to foster widespread infections and pandemics. The increased resistance of microorganisms to antimicrobial drugs can facilitate the rapid transmission of infectious diseases among individuals and communities. As these pathogens become more resilient to conventional treatments, the likelihood of containing and controlling outbreaks diminishes significantly 119,125,152,156. One of the major concerns with AMR is its ability to promote the spread of infections. Resistant microorganisms can proliferate rapidly and spread between individuals, communities, and even across borders, facilitated by travel and global connectivity. This means that infections that were once manageable can become difficult to control, leading to larger outbreaks and potential pandemics 119,153–157. The rise of AMR can increase morbidity and mortality rates significantly. When infections become resistant to frontline treatments, individuals are at greater risk of severe illnesses and complications, which can lead to higher death rates. This, in turn, puts additional strain on healthcare systems, resulting in increased healthcare costs and economic burdens on society. To combat the potential consequences of AMR, a multifaceted approach is required, including responsible use of antimicrobials, investment in research and development of new drugs, improved infection prevention and control measures, and international cooperation to address this global health challenge. Staying vigilant and updated on the latest scientific research and policies is crucial to mitigate the potential impact of AMR on society and public health 31,32,119,125,152–158.
6. Conclusion
This study extensively explored the vital concerns of Antimicrobial Resistance (AMR), revealing crucial insights that illuminate the origins, methods of detection, hurdles, and wider consequences for society. Our findings underscore the urgent need to address AMR using collaborative and multifaceted strategies. By harnessing the power of diverse disciplines, such as medicine, microbiology, policy, and public health, we can develop comprehensive solutions to this pressing problem. Addressing AMR demands collective action at various levels. Strengthening surveillance systems for early detection, promoting the judicious use of antibiotics, and enhancing public awareness are pivotal steps. Fostering research on novel antimicrobial agents and treatment alternatives is paramount. Policymakers should enact stringent regulations to curb misuse and incentivize pharmaceutical innovation. As we look ahead, a unified effort is essential to effectively combat AMR. By implementing the recommendations outlined in this study and fostering ongoing collaboration between scientists, healthcare professionals, policymakers, and the public, we can forge a path towards a future where the threat of AMR is mitigated, safeguarding both current and future generations.
References
- Blaser, M.J.; Cardon, Z.G.; Cho, M.K.; et al. Toward a predictive understanding of earth’s microbiomes to address 21st century challenges. mBio 2016, 7. [Google Scholar] [CrossRef] [PubMed]
- Maraz, K.M.; Khan, R.A. An overview on impact and application of microorganisms on human health, medicine and environment. GSC Biological and Pharmaceutical Sciences 2021, 16, 089–104. [Google Scholar] [CrossRef]
- Di Martino, P. Antimicrobial agents and microbial ecology. AIMS Microbiol 2022, 8, 1–4. [Google Scholar] [CrossRef] [PubMed]
- Sánchez-López, E.; Gomes, D.; Esteruelas, G.; et al. Metal-based nanoparticles as antimicrobial agents: An overview. Nanomaterials 2020, 10. [Google Scholar] [CrossRef] [PubMed]
- Pokharel, S.; Shrestha, P.; Adhikari, B. Antimicrobial use in food animals and human health: Time to implement ‘One Health’ approach. Antimicrob Resist Infect Control 2020, 9. [Google Scholar] [CrossRef] [PubMed]
- Sandhya, S.M.; Rekha, A.G.S. Issue:3 Citation. 2019. Available online: www.ijppr.humanjournals.com.
- Dadgostar, P. Antimicrobial resistance: Implications and costs. Infect Drug Resist 2019, 12, 3903–3910. [Google Scholar] [CrossRef] [PubMed]
- EClinicalMedicine. Antimicrobial resistance: A top ten global public health threat. EClinicalMedicine 2021, 41. [Google Scholar]
- Cheng, G.; Ning, J.; Ahmed, S.; et al. Selection and dissemination of antimicrobial resistance in Agri-food production. Antimicrob Resist Infect Control 2019, 8. [Google Scholar] [CrossRef]
- Samtiya, M.; Matthews, K.R.; Dhewa, T.; Puniya, A.K. Antimicrobial Resistance in the Food Chain: Trends, Mechanisms, Pathways, and Possible Regulation Strategies. Foods 2022, 11. [Google Scholar] [CrossRef]
- Ogyu, A.; Chan, O.; Littmann, J.; et al. National action to combat AMR: A One-Health approach to assess policy priorities in action plans. BMJ Glob Health 2020, 5. [Google Scholar] [CrossRef]
- Anon. The Need for a One Health Approach to Zoonotic Diseases and Antimicrobial Resistance. Available online: https://cdn.who.int/media/.
- Velazquez-Meza, M.E.; Galarde-López, M.; Carrillo-Quiróz, B.; Alpuche-Aranda, C.M. Antimicrobial resistance: One Health approach. Vet World 2022, 15, 743–749. [Google Scholar] [CrossRef] [PubMed]
- McEwen, S.A.; Collignon, P.J. Antimicrobial Resistance: A One Health Perspective. Microbiol Spectr 2018, 6. [Google Scholar] [CrossRef]
- Tello, A.; Austin, B.; Telfer, T.C. Selective pressure of antibiotic pollution on bacteria of importance to public health. Environ Health Perspect 2012, 120, 1100–1106. [Google Scholar] [CrossRef] [PubMed]
- Tenover, F.C. Mechanisms of Antimicrobial Resistance in Bacteria. American Journal of Medicine 2006, 119. [Google Scholar]
- Dougherty, T.J.; Pucci, M.J.; Bronson, J.J.; Davison, D.B.; Barrett, J.F. Antimicrobial resistance - Why do we have it and what can we do about it? Expert Opin Investig Drugs 2000, 9, 1707–1709. [Google Scholar] [CrossRef] [PubMed]
- Pablos-Mendez, A.; Lessnau, K. Chapter 5 Clinical mismanagement and other factors producing antituberculosis drug resistance. 2000.
- Geisel, N.; Vilar, J.M.G.; Rubi, J.M. Optimal resting-growth strategies of microbial populations in fluctuating environments. PLoS One 2011, 6. [Google Scholar] [CrossRef] [PubMed]
- Mozhayskiy, V.; Tagkopoulos, I. Guided evolution of in silico microbial populations in complex environments accelerates evolutionary rates through a step-wise adaptation. BMC Bioinformatics 2012, 13. [Google Scholar] [CrossRef] [PubMed]
- Babic, M.; Bonomo, R.A. Mutations as a Basis of Antimicrobial Resistance. In Antimicrobial Drug Resistance; Humana Press, 2009; pp. 65–74. [Google Scholar]
- Schrader, S.M.; Botella, H.; Jansen, R.; et al. Multiform antimicrobial resistance from a metabolic mutation. 2021. Available online: https://www.science.org.
- Djordjevic, S.P.; Stokes, H.W.; Chowdhury, P.R. Mobile elements, zoonotic pathogens and commensal bacteria: Conduits for the delivery of resistance genes into humans, production animals and soil microbiota. Front Microbiol 2013, 4. [Google Scholar] [CrossRef]
- Kristiansson, E.; Fick, J.; Janzon, A.; et al. Pyrosequencing of antibiotic-contaminated river sediments reveals high levels of resistance and gene transfer elements. PLoS One 2011, 6. [Google Scholar] [CrossRef]
- Gandon, S.; Vale, P.F. The evolution of resistance against good and bad infections. J Evol Biol 2014, 27, 303–312. [Google Scholar] [CrossRef]
- Nazarian, P.; Tran, F.; Boedicker, J.Q. Modeling multispecies gene flow dynamics reveals the unique roles of different horizontal gene transfer mechanisms. Front Microbiol 2018, 9. [Google Scholar] [CrossRef] [PubMed]
- Milka, M.; Awkew, A. Role of Horizontal Gene Transfer in Bacteria. Online; 2018. Available online: www.iiste.org.
- Burmeister, A.R. Horizontal Gene Transfer. Evol Med Public Health 2015, 2015, 193–194. [Google Scholar] [CrossRef] [PubMed]
- Wang, Y.; Batra, A.; Schulenburg, H.; Dagan, T. Gene sharing among plasmids and chromosomes reveals barriers for antibiotic resistance gene transfer. Philosophical Transactions of the Royal Society B: Biological Sciences 2022, 377. [Google Scholar] [CrossRef] [PubMed]
- Bright-Ponte, S.J. Antimicrobial use data collection in animal agriculture. Zoonoses Public Health 2020, 67, 1–5. [Google Scholar] [CrossRef] [PubMed]
- Shallcross, L.J. Editorials: Antibiotic overuse: A key driver of antimicrobial resistance. British Journal of General Practice 2014, 64, 604–605. [Google Scholar] [CrossRef] [PubMed]
- Manohar, P.; Loh, B.; Leptihn, S. Will the Overuse of Antibiotics during the Coronavirus Pandemic Accelerate Antimicrobial Resistance of Bacteria? Infectious Microbes and Diseases 2020, 2, 87–88. [Google Scholar] [CrossRef]
- Richards, J. Emergence & spread of Multiresistant Organisms - Can Infection Control measures help? Int J Infect Control 2009, 5. [Google Scholar]
- Munita, J.M.; Arias, C.A. Mechanisms of Antibiotic Resistance Kudva, I.T.; Zhang, Q.; eds. Microbiol Spectr 2016, 4. Available online: https://journals.asm.org/doi/10.1128/microbiolspec.VMBF-0016-2015.
- Windels, E.M.; Michiels, J.E.; Van Den Bergh, B.; Fauvart, M.; Michiels, J. Antibiotics: Combatting Tolerance To Stop Resistance. 2019. [CrossRef]
- Economou, V.; Gousia, P. Agriculture and food animals as a source of antimicrobial-resistant bacteria. Infect Drug Resist 2015, 8, 49–61. [Google Scholar] [CrossRef]
- Karimi, A.; Shulman, C.; Tchoudnovski, D.; Tobis, M. An Agricultural Perspective for Combating Antibiotic Resistance: A Literature Review. Undergraduate Research in Natural and Clinical Science and Technology (URNCST) Journal 2020, 4, 1–10. [Google Scholar] [CrossRef]
- Antunes, P.; Novais, C.; Peixe, L. Food-to-Humans Bacterial Transmission. Microbiol Spectr 2020, 8. [Google Scholar] [CrossRef]
- Sartelli, M.; Hardcastle, T.C.; Catena, F.; et al. Antibiotic use in low and middle-income countries and the challenges of antimicrobial resistance in surgery. Antibiotics 2020, 9, 1–12. [Google Scholar] [CrossRef] [PubMed]
- Harbarth, S.; Balkhy, H.H.; Goossens, H.; et al. Antimicrobial resistance: One world, one fight! Antimicrob Resist Infect Control 2015, 4. [Google Scholar] [CrossRef]
- Wei Zheng, C.; Zheng, W.; Sun, W.; Simeonov, A. Themed Section: Inventing New Therapies Without Reinventing the Wheel: The Power of Drug Repurposing REVIEW ARTICLE Drug repurposing screens and synergistic drug-combinations for infectious diseases. BJP British Journal of Pharmacology British Journal of Pharmacology 2018, 175, 181. [Google Scholar]
- Spellberg, B.; Powers, J.H.; Brass, E.P.; Miller, L.G.; Edwards, J.E. Trends in Antimicrobial Drug Development: Implications for the Future. 2004. Available online: https://academic.oup.com/cid/article/38/9/1279/317267.
- Overbye, K.M.; Barrett, J.F. Antibiotics: Where did we go wrong? Drug Discov Today 2005, 10, 45–52. [Google Scholar] [CrossRef]
- Kalayci, S. Antimicrobial Properties of Various Non-Antibiotic Drugs against Microorganisms. J Bioanal Biomed 2016, 8. [Google Scholar] [CrossRef]
- Ross-Gillespie, A.; Kümmerli, R. ‘Evolution-Proofing’ Antibacterials. Evol Med Public Health 2014, 2014, 134–135. [Google Scholar] [CrossRef]
- Costantino, L.; Barlocco, D. Challenges in the design of multitarget drugs against multifactorial pathologies: A new life for medicinal chemistry? Future Med Chem 2013, 5, 5–7. [Google Scholar] [CrossRef]
- Leviton, I. Commentary on ‘the impact of anti-infective drug shortages on hospitals in the United States: Trends and causes’. Clinical Infectious Diseases 2012, 54, 692–693. [Google Scholar] [CrossRef]
- Bow, E.J. There should be no ESKAPE for febrile neutropenic cancer patients: The dearth of effective antibacterial drugs threatens anticancer efficacy. Journal of Antimicrobial Chemotherapy 2013, 68, 492–495. [Google Scholar] [CrossRef]
- Lesho, E.P.; Laguio-Vila, M. The Slow-Motion Catastrophe of Antimicrobial Resistance and Practical Interventions for All Prescribers. Mayo Clin Proc 2019, 94, 1040–1047. [Google Scholar] [CrossRef]
- Mossialos, E.; Renwick, M.; Mossialos, E. Fostering R&D of novel antibiotics and other technologies to prevent and treat infection. Available online: https://academic.oup.com/eurpub/article/30/Supplement_5/ckaa165.1203/5913902.
- Kaur, I. Novel Strategies to Combat Antimicrobial Resistance. Journal of Infectious Diseases & Therapy 2016, 4. [Google Scholar]
- Kpokiri, E.E.; Budak, J.Z.; Chang, C.C.; et al. Innovative strategies to fight antimicrobial resistance: Crowdsourcing to expand medical training. F1000Res 2020, 9. [Google Scholar] [CrossRef]
- Langelier, C.; Graves, M.; Kalantar, K.; et al. Article Summary Line: Metagenomic study of enteric microbiota collected longitudinally from international travelers revealed an increase in antimicrobial resistance genes and changes in discrete microbial populations following travel. Running Title: Microbiome and Resistome Dynamics in Travelers Title: Microbiome and Antimicrobial Resistance Gene Dynamics in International Travelers. [CrossRef]
- Sridhar, S.; Turbett, S.E.; Harris, J.B.; Larocque, R.C. Antimicrobial-resistant bacteria in international travelers. Curr Opin Infect Dis 2021, 34, 423–431. [Google Scholar] [CrossRef] [PubMed]
- Bokhary, H.; Pangesti, K.N.A.; Rashid, H.; Abd El Ghany, M.; Hill-Cawthorne, G.A. Travel-related antimicrobial resistance: A systematic review. Trop Med Infect Dis 2021, 6. [Google Scholar] [CrossRef] [PubMed]
- Rogers, B.A.; Aminzadeh, Z.; Hayashi, Y.; Paterson, D.L. Country-to-country transfer of patients and the risk of multi-resistant bacterial infection. Clinical Infectious Diseases 2011, 53, 49–56. [Google Scholar] [CrossRef] [PubMed]
- Frost, I.; Van Boeckel, T.P.; Pires, J.; Craig, J.; Laxminarayan, R. Global geographic trends in antimicrobial resistance: The role of international travel. J Travel Med 2019, 26. [Google Scholar] [CrossRef]
- Skandalis, N.; Maeusli, M.; Papafotis, D.; et al. Environmental spread of antibiotic resistance. Antibiotics 2021, 10. [Google Scholar] [CrossRef]
- Molton, J.S.; Tambyah, P.A.; Ang, B.S.P.; Ling, M.L.; Fisher, D.A. The global spread of healthcare-associated multidrug-resistant bacteria: A perspective from Asia. Clinical Infectious Diseases 2013, 56, 1310–1318. [Google Scholar]
- Godman, B.; Egwuenu, A.; Haque, M.; et al. Strategies to improve antimicrobial utilization with a special focus on developing countries. Life 2021, 11. [Google Scholar] [CrossRef]
- Singer, R.S.; Williams-Nguyen, J. Human health impacts of antibiotic use in agriculture: A push for improved causal inference. Curr Opin Microbiol 2014, 19, 1–8. [Google Scholar] [CrossRef]
- Chattopadhyay, M.K. Use of antibiotics as feed additives: A burning question. Front Microbiol 2014, 5. [Google Scholar] [CrossRef] [PubMed]
- Cantón, R.; Morosini, M.I. Emergence and spread of antibiotic resistance following exposure to antibiotics. FEMS Microbiol Rev 2011, 35, 977–991. [Google Scholar] [CrossRef] [PubMed]
- Aarestrup, F.M. Antimicrobial resistance in bacteria of animal origin. ASM Press; 2006.
- Tollefson, L. Impact of Antimicrobial Use in Animals and Regulatory Response.
- Addis, M. A Review on Antibiotic Resistant and Implication on Food Chain. 2015, 42. Available online: www.iiste.org.
- Ishii, S. Ecology of pathogens and antibiotic-resistant bacteria in environments: Challenges and opportunities. Microbes Environ 2019, 34, 1–4. [Google Scholar] [CrossRef] [PubMed]
- Wallinga, D. Today’s food system: How healthy is it? J Hunger Environ Nutr 2009, 4, 251–281. [Google Scholar] [CrossRef] [PubMed]
- Wilson, M.L. Infectious diseases and pathology: Opportunities and challenges. Am J Clin Pathol 2006, 125, 654–655. [Google Scholar] [CrossRef] [PubMed]
- Mitsakakis, K.; D’Acremont, V.; Hin, S.; von Stetten, F.; Zengerle, R. Diagnostic tools for tackling febrile illness and enhancing patient management. Microelectron Eng 2018, 201, 26–59. [Google Scholar] [CrossRef] [PubMed]
- Trevas, D.; Caliendo, A.M.; Hanson, K.; Levy, J.; Ginocchio, C.C. Diagnostic Tests Can Stem the Threat of Antimicrobial Resistance: Infectious Disease Professionals Can Help. Clinical Infectious Diseases 2021, 72, E893–E900. [Google Scholar] [CrossRef]
- Paharik, A.E.; Schreiber, H.L.; Spaulding, C.N.; Dodson, K.W.; Hultgren, S.J. Narrowing the spectrum: The new frontier of precision antimicrobials. Genome Med 2017, 9. [Google Scholar] [CrossRef]
- Yang, B.; Fang, D.; Lv, Q.; Wang, Z.; Liu, Y. Targeted Therapeutic Strategies in the Battle Against Pathogenic Bacteria. Front Pharmacol 2021, 12. [Google Scholar] [CrossRef]
- Anon. Rapid Detection of Pathogens.
- Brink, A.J.; van Wyk, J.; Moodley, V.M.; et al. The role of appropriate diagnostic testing in acute respiratory tract infections: An antibiotic stewardship strategy to minimise diagnostic uncertainty in primary care. South African Medical Journal 2016, 106, 554–561. [Google Scholar] [CrossRef]
- Kozel, T.R.; Burnham-Marusich, A.R. Point-of-Care Testing for Infectious Diseases: Past, Present, and Future. 2017. Available online: https://journals.asm.org/journal/jcm.
- Lisby, J.G.; Schneider, U.V. Point of care testing for infectious disease: Ownership and quality. Journal of Antimicrobial Chemotherapy 2021, 76, III28–III32. [Google Scholar] [CrossRef] [PubMed]
- Shami, A.Y. Antimicrobial resistance strategies: Are we approaching the end? J Pure Appl Microbiol 2020, 14, 93–102. [Google Scholar] [CrossRef]
- Bbosa, G.S.; Mwebaza, N.; Odda, J.; Kyegombe, D.B.; Ntale, M. Antibiotics/antibacterial drug use, their marketing and promotion during the post-antibiotic golden age and their role in emergence of bacterial resistance. Health N Hav 2014, 06, 410–425. [Google Scholar] [CrossRef]
- Thomas, M.G. New Zealand Medical Journal ‘Just say no’-reducing the use of antibiotics for colds, bronchitis and sinusitis. 2000.
- McCullough, A.R.; Parekh, S.; Rathbone, J.; Del Mar, C.B.; Hoffmann, T.C. A systematic review of the public’s knowledge and beliefs about antibiotic resistance. Journal of Antimicrobial Chemotherapy 2016, 71, 27–33. [Google Scholar] [CrossRef] [PubMed]
- Davey, P.; Pagliari, C.; Hayes, A. The patient’s role in the spread and control of bacterial resistance to antibiotics. Clinical Microbiology and Infection 2002, 8, 43–68. [Google Scholar] [CrossRef] [PubMed]
- De Sá, F.; Fiol, D.; Barberato-Filho, S.; Lopes, C.; Inês De Toledo, M. Level of patient information on antibiotic use. 2010.
- Wise, R.; Blaser, M.; Carrs, O.; et al. The urgent need for new antibacterial agents. Journal of Antimicrobial Chemotherapy 2011, 66, 1939–1940. [Google Scholar] [CrossRef] [PubMed]
- Cave, R.; Cole, J.; Mkrtchyan, H.V. Surveillance and prevalence of antimicrobial resistant bacteria from public settings within urban built environments: Challenges and opportunities for hygiene and infection control. Environ Int 2021, 157. [Google Scholar] [CrossRef]
- Ancillotti, M.; Eriksson, S.; Veldwijk, J.; Nihlén Fahlquist, J.; Andersson, D.I.; Godskesen, T. Public awareness and individual responsibility needed for judicious use of antibiotics: A qualitative study of public beliefs and perceptions. BMC Public Health 2018, 18. [Google Scholar] [CrossRef]
- Mathew, P.; Sivaraman, S.; Chandy, S. Communication strategies for improving public awareness on appropriate antibiotic use: Bridging a vital gap for action on antibiotic resistance. J Family Med Prim Care 2019, 8, 1867. [Google Scholar] [CrossRef]
- Vaz, C.P. ; MM A, AG R. Current and Novel Methods in Clinical Microbiology: Advantages and Pitfalls when Facing the Menace of Antimicrobial Resistance. J Med Microbiol Diagn 2018, 7. [Google Scholar]
- Gilbert, P.; Collier, P.J.; Brown, M.R.W. MINIREVIEW Influence of Growth Rate on Susceptibility to Antimicrobial Agents: Biofilms, Cell Cycle, Dormancy, and Stringent Response. 1990.
- Yao, H.; Liu, J.; Jiang, X.; Chen, F.; Lu, X.; Zhang, J. Analysis of the clinical effect of combined drug susceptibility to guide medication for carbapenem-resistant klebsiella pneumoniae patients based on the Kirby–Bauer disk diffusion method. Infect Drug Resist 2021, 14, 79–87. [Google Scholar] [CrossRef] [PubMed]
- Khan, Z.A.; Siddiqui, M.F.; Park, S. Current and emerging methods of antibiotic susceptibility testing. Diagnostics 2019, 9. [Google Scholar] [CrossRef] [PubMed]
- Jorgensen, J.H.; Ferraro, M.J. Antimicrobial Susceptibility Testing: A Review of General Principles and Contemporary Practices. Clinical Infectious Diseases 2009, 49, 1749–1755. [Google Scholar] [CrossRef] [PubMed]
- Tan, R.; Yu, A.; Liu, Z.; et al. Prediction of Minimal Inhibitory Concentration of Meropenem Against Klebsiella pneumoniae Using Metagenomic Data. Front Microbiol 2021, 12. [Google Scholar] [CrossRef] [PubMed]
- Witebsky, F.G.; Maclowry, J.D.; French, S.S. Broth Dilution Minimum Inhibitory Concentrations: Rationale for Use of Selected Antimicrobial Concentrations. 1979. Available online: https://journals.asm.org/journal/jcm.
- Dannaoui, E.; Espinel-Ingroff, A. Antifungal susceptibly testing by concentration gradient strip etest method for fungal isolates: A review. Journal of Fungi 2019, 5. [Google Scholar] [CrossRef] [PubMed]
- Conceição, N.; Rodrigues, W.F.; De Oliveira,, K.L.P.; et al. Beta-lactams susceptibility testing of penicillin-resistant, ampicillin-susceptible Enterococcus faecalis isolates: A comparative assessment of Etest and disk diffusion methods against broth dilution. Ann Clin Microbiol Antimicrob 2020, 19. [Google Scholar] [CrossRef] [PubMed]
- Yee, R.; Bard, J.D.; Simner, P.J. The genotype-to-phenotype dilemma: How should laboratories approach discordant susceptibility results? J Clin Microbiol 2021, 59. [Google Scholar] [CrossRef]
- Park, S.; Rana, A.; Sung, W.; Munir, M. Competitiveness of Quantitative Polymerase Chain Reaction (qPCR) and Droplet Digital Polymerase Chain Reaction (ddPCR) Technologies, with a Particular Focus on Detection of Antibiotic Resistance Genes (ARGs). Appl Microbiol 2021, 1, 426–444. [Google Scholar] [CrossRef]
- Taguchi, T.; Ishikawa, M.; Ichikawa, M.; et al. Amplification-free detection of bacterial genes using a signaling probe-based DNA microarray. Biosens Bioelectron 2021, 194. [Google Scholar] [CrossRef]
- Frye, J.G.; Jesse, T.; Long, F.; et al. DNA microarray detection of antimicrobial resistance genes in diverse bacteria. Int J Antimicrob Agents 2006, 27, 138–151. [Google Scholar] [CrossRef]
- Besser, J.; Carleton, H.A.; Gerner-Smidt, P.; Lindsey, R.L.; Trees, E. Next-generation sequencing technologies and their application to the study and control of bacterial infections. Clinical Microbiology and Infection 2018, 24, 335–341. [Google Scholar] [CrossRef] [PubMed]
- Petrillo, M.; Fabbri, M.; Kagkli, D.M.; et al. A roadmap for the generation of benchmarking resources for antimicrobial resistance detection using next generation sequencing. F1000Res 2021, 10, 80. [Google Scholar] [CrossRef] [PubMed]
- Li, Y.; Yang, X.; Zhao, W. Emerging Microtechnologies and Automated Systems for Rapid Bacterial Identification and Antibiotic Susceptibility Testing. SLAS Technol 2017, 22, 585–608. [Google Scholar] [CrossRef]
- Arena, F.; Viaggi, B.; Galli, L.; Rossolini, G.M. Antibiotic susceptibility testing: Present and future. Pediatric Infectious Disease Journal 2015, 34, 1128–1130. [Google Scholar] [CrossRef] [PubMed]
- Shin, D.J.; Andini, N.; Hsieh, K.; Yang, S.; Wang, T.-H. Emerging Analytical Techniques for Rapid Pathogen Identification and Susceptibility Testing. Annual Review of Analytical Chemistry 11, 47. [CrossRef]
- Chen, J.; Tomasek, M.; Cruz, A.; et al. Feasibility and potential significance of rapid in vitro qualitative phenotypic antimicrobial susceptibility testing of gram-negative bacilli with the ProMax system. PLoS One 2021, 16. [Google Scholar] [CrossRef]
- Matic, N.; Willey, B.; Gascon, B.; et al. Clinical Impact of Rapid Identification (ID) and Phenotypic Antimicrobial Susceptibility Testing (AST) by Accelerate PhenoTM System (AXDX) for Gram-negative (GNB) Bloodstream Infections. Open Forum Infect Dis 2017, 4, S595. [Google Scholar] [CrossRef]
- Hwang, J.H.; Lee, S.Y.; Choi, J. Microscopic analysis of bacterial inoculum effect using micropatterned biochip. Antibiotics 2021, 10. [Google Scholar] [CrossRef]
- Syal, K.; Mo, M.; Yu, H.; et al. Current and emerging techniques for antibiotic susceptibility tests. Theranostics 2017, 7, 1795–1805. [Google Scholar] [CrossRef]
- Liu, T.; Lu, Y.; Gau, V.; Liao, J.C.; Wong, P.K. Rapid Antimicrobial Susceptibility Testing with Electrokinetics Enhanced Biosensors for Diagnosis of Acute Bacterial Infections. Ann Biomed Eng 2014, 42, 2314–2321. [Google Scholar] [CrossRef]
- Khaledi, A.; Weimann, A.; Schniederjans, M.; et al. Predicting antimicrobial resistance in Pseudomonas aeruginosa with machine learning-enabled molecular diagnostics. EMBO Mol Med 2020, 12. [Google Scholar] [CrossRef] [PubMed]
- Li, Y.; Yang, Q.; Ding, J. Metagenomic Next-generation Sequencing: Application in Infectious Diseases. Explor Res Hypothesis Med 2022, 7, 19–24. [Google Scholar] [CrossRef]
- Ruppé, E.; Charretier, Y.; Lazarevic, V.; Schrenzel, J. Integrating metagenomics in the routine lab. In: Application and Integration of Omics-powered Diagnostics in Clinical and Public Health Microbiology. Springer International Publishing, 2021, 133–152.
- Queyrel, M.; Prifti, E.; Templier, A.; Zucker, J.-D. Towards End-To-End Disease Prediction from Raw Metagenomic Data.
- McCall, C.; Xagoraraki, I. Comparative study of sequence aligners for detecting antibiotic resistance in bacterial metagenomes. Lett Appl Microbiol 2018, 66, 162–168. [Google Scholar] [CrossRef] [PubMed]
- Berglund, F.; Böhm, M.E.; Martinsson, A.; et al. Comprehensive screening of genomic and metagenomic data reveals a large diversity of tetracycline resistance genes. Microb Genom 2020, 6, 1–14. [Google Scholar] [CrossRef] [PubMed]
- Van Camp, P.J.; Haslam, D.B.; Porollo, A. Bioinformatics approaches to the understanding of molecular mechanisms in antimicrobial resistance. Int J Mol Sci 2020, 21. [Google Scholar] [CrossRef]
- Peng, Z.; Mao, Y.; Zhang, N.; Zhang, L.; Wang, Z.; Han, M. Utilizing Metagenomic Data and Bioinformatic Tools for Elucidating Antibiotic Resistance Genes in Environment. Front Environ Sci 2021, 9. [Google Scholar] [CrossRef]
- Hocking, L.; Ali, G.C.; D’Angelo, C.; et al. A rapid evidence assessment exploring whether antimicrobial resistance complicates non-infectious health conditions and healthcare services, 2010–2020. JAC Antimicrob Resist 2021, 3. [Google Scholar]
- Antonelli, G.; Cappelli, L.; Cinelli, P.; et al. Strategies to tackle antimicrobial resistance: The example of escherichia coli and pseudomonas aeruginosa. Int J Mol Sci 2021, 22. [Google Scholar] [CrossRef]
- Payne, D.J.; Miller, L.F.; Findlay, D.; Anderson, J.; Marks, L. Time for a change: Addressing R&D and commercialization challenges for antibacterials. Philosophical Transactions of the Royal Society B: Biological Sciences 2015, 370. [Google Scholar]
- Miethke, M.; Pieroni, M.; Weber, T.; et al. Towards the sustainable discovery and development of new antibiotics. Nat Rev Chem 2021, 5, 726–749. [Google Scholar] [CrossRef]
- Mantravadi, P.K.; Kalesh, K.A.; Dobson, R.C.J.; Hudson, A.O.; Parthasarathy, A. The quest for novel antimicrobial compounds: Emerging trends in research, development, and technologies. Antibiotics 2019, 8. [Google Scholar] [CrossRef] [PubMed]
- Pagani, L.; Pieri, A.; Aschbacher, R.; et al. Country income is only one of the tiles: The global journey of antimicrobial resistance among humans, animals, and environment. Antibiotics 2020, 9, 1–13. [Google Scholar]
- Ma, F.; Xu, S.; Tang, Z.; Li, Z.; Zhang, L. Use of antimicrobials in food animals and impact of transmission of antimicrobial resistance on humans. Biosaf Health 2021, 3, 32–38. [Google Scholar] [CrossRef]
- Hotinger, J.A.; Morris, S.T.; May, A.E. The case against antibiotics and for anti-virulence therapeutics. Microorganisms 2021, 9. [Google Scholar] [CrossRef] [PubMed]
- Mir, S.; Brett, D.; Adam de la, B.; Martha, K. Antibiotics Overuse and Bacterial Resistance. Annals of Microbiology and Research 2019, 3. [Google Scholar] [CrossRef]
- Mann, A.; Nehra, K.; Rana, J.S.; Dahiya, T. Antibiotic resistance in agriculture: Perspectives on upcoming strategies to overcome upsurge in resistance. Curr Res Microb Sci 2021, 2. [Google Scholar] [CrossRef] [PubMed]
- Picchioni, F.; Aurino, E.; Aleksandrowicz, L.; et al. Roads to interdisciplinarity – working at the nexus among food systems, nutrition and health: 1st annual Agriculture, Nutrition and Health (ANH) Academy Week, Addis Ababa (Ethiopia), 20–24 June 2016. Food Secur 2017, 9, 181–189. [Google Scholar] [CrossRef]
- Davies, S.C.; Oxlade, C. Innovate to secure the future: The future of modern medicine. Future Healthc J 2021, 8, e251–e256. [Google Scholar] [CrossRef]
- Meid, A.D.; Ruff, C.; Wirbka, L.; et al. Using the causal inference framework to support individualized drug treatment decisions based on observational healthcare data. Clin Epidemiol 2020, 12, 1223–1234. [Google Scholar] [CrossRef]
- Keet, R.; Rip, D. Listeria monocytogenes isolates from western cape, south africa exhibit resistance to multiple antibiotics and contradicts certain global resistance patterns. AIMS Microbiol 2021, 7, 40–58. [Google Scholar] [CrossRef]
- Ashley, E.A.; Shetty, N.; Patel, J.; et al. Harnessing alternative sources of antimicrobial resistance data to support surveillance in low-resource settings. Journal of Antimicrobial Chemotherapy 2019, 74, 541–546. [Google Scholar] [CrossRef] [PubMed]
- Zhang, M.; Wang, C.; O, A.M. A Bayesian Latent Class Mixture Model With Censoring for Correlation Analysis in Antimicrobial Resistance Across Populations. 2020. [CrossRef]
- Acharya, K.P.; Subramanya, S.H.; Pitout, J.D.D. Inclusion of next-generation leaders and cost-effective precision diagnostic techniques are vital in combatting antimicrobial resistance in low- And middle-income countries. JAC Antimicrob Resist 2020, 2. [Google Scholar] [CrossRef] [PubMed]
- Rajesh, A.; Mohanan, H.; Thomas, R.P. A Review on Antimicrobial Stewardship Programs in Multiple Care Settings. J Pharm Res Int 2021, 264–270. [Google Scholar] [CrossRef]
- Yates, T.D.; Davis, M.E.; Taylor, Y.J.; et al. Not a magic pill: A qualitative exploration of provider perspectives on antibiotic prescribing in the outpatient setting. BMC Fam Pract 2018, 19. [Google Scholar] [CrossRef] [PubMed]
- Banamah, O.B.; Alsamih, M.F.; Alshehri, H.H.; et al. Chances and prevention of antibiotic resistance in primary health care: Literature review. Int J Community Med Public Health 2021, 8, 875. [Google Scholar] [CrossRef]
- Palin, V.; Welfare, W.; Ashcroft, D.M.; Van Staa, T.P. Shorter and Longer Courses of Antibiotics for Common Infections and the Association with Reductions of Infection-Related Complications including Hospital Admissions. Clinical Infectious Diseases 2021, 73, 1805–1812. [Google Scholar] [CrossRef] [PubMed]
- Fleming-Dutra, K.E.; Mangione-Smith, R.; Hicks, L.A. How to Prescribe Fewer Unnecessary Antibiotics: Talking Points That Work with Patients and Their Families. 2016. Available online: www.aafp.org/afp.
- Harbarth, S.; Hackett, J. Introduction: DRIVE-AB’s definitions and indicators to monitor responsible antibiotic use. Journal of Antimicrobial Chemotherapy 2018, 73, vi2. [Google Scholar] [CrossRef]
- Littmann, J.; Rid, A.; Buyx, A. Tackling anti-microbial resistance: Ethical framework for rational antibiotic use. Eur J Public Health 2018, 28, 359–363. [Google Scholar] [CrossRef]
- Lomazzi, M.; Moore, M.; Johnson, A.; Balasegaram, M.; Borisch, B. Antimicrobial resistance - Moving forward? BMC Public Health 2019, 19. [Google Scholar] [CrossRef]
- Joshi, M.P.; Hafner, T.; Twesigye, G.; et al. Strengthening multisectoral coordination on antimicrobial resistance: A landscape analysis of efforts in 11 countries. J Pharm Policy Pract 2021, 14. [Google Scholar] [CrossRef]
- Joshi, M.P.; Chintu, C.; Mpundu, M.; et al. Multidisciplinary and multisectoral coalitions as catalysts for action against antimicrobial resistance: Implementation experiences at national and regional levels. Glob Public Health 2018, 13, 1781–1795. [Google Scholar] [CrossRef] [PubMed]
- Humboldt-Dachroeden, S.; Mantovani, A. Assessing environmental factors within the one health approach. Medicina (Lithuania) 2021, 57. [Google Scholar] [CrossRef] [PubMed]
- Ruckert, A.; Fafard, P.; Hindmarch, S.; et al. Governing antimicrobial resistance: A narrative review of global governance mechanisms. J Public Health Policy 2020, 41, 515–528. [Google Scholar] [CrossRef] [PubMed]
- Cama, J.; Leszczynski, R.; Tang, P.K.; et al. To Push or to Pull? in a Post-COVID World, Supporting and Incentivizing Antimicrobial Drug Development Must Become a Governmental Priority. ACS Infect Dis 2021, 7, 2029–2042. [Google Scholar] [CrossRef]
- Metsemakers, W.J.; Zalavras, C.; Schwarz, E.M.; Chen, A.F.; Trampuz, A.; Moriarty, T.F. Antimicrobial Resistance, the COVID-19 Pandemic, and Lessons for the Orthopaedic Community. Journal of Bone and Joint Surgery 2021, 103, 4–9. [Google Scholar] [CrossRef]
- Sturm, L.; Flood, M.; Montoya, A.; Mody, L.; Cassone, M. Updates on Infection Control in Alternative Health Care Settings. Infect Dis Clin North Am 2021, 35, 803–825. [Google Scholar] [CrossRef]
- Cars, O.; Chandy, S.J.; Mpundu, M.; Peralta, A.Q.; Zorzet, A.; So, A.D. Resetting the agenda for antibiotic resistance through a health systems perspective. Lancet Glob Health 2021, 9, e1022–e1027. [Google Scholar] [CrossRef]
- Mancuso, G.; Midiri, A.; Gerace, E.; Biondo, C. Bacterial antibiotic resistance: The most critical pathogens. Pathogens 2021, 10. [Google Scholar] [CrossRef]
- Ruiz, J. Microbes, Infection and Chemotherapy IDEAS AND OPINIONS. 2021.
- Jung, H.; Yang, J.; Kim, E.; Lee, J. The effect of mid-to-long-term hospitalization on the catastrophic health expenditure: Focusing on the mediating effect of earned income loss. Healthcare (Switzerland) 2021, 9. [Google Scholar] [CrossRef]
- Rodríguez-Baño, J.; Rossolini, G.M.; Schultsz, C.; et al. Antimicrobial resistance research in a post-pandemic world: Insights on antimicrobial resistance research in the COVID-19 pandemic. J Glob Antimicrob Resist 2021, 25, 5–7. [Google Scholar] [CrossRef]
- Viegas, C.; Viegas, S. Special issue “antimicrobial resistance: From the environment to human health”. Microorganisms 2021, 9. [Google Scholar] [CrossRef] [PubMed]
- Wozniak, T.M.; Smith-Vaughan, H.; Andrews, R. Convergence of surveillance blind spots with antimicrobial resistance hotspots. Aust N Z J Public Health 2021, 45, 541–542. [Google Scholar] [CrossRef] [PubMed]
- Littmann, J.; Viens, A.M.; Silva, D.S. The Super-Wicked Problem of Antimicrobial Resistance. In:, 2020, 421–443.
|
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).