Maneesh Paul

THE CRITICAL DANGERS OF ANTIMICROBIAL RESISTANCE

admin — Tue, 15 Oct 2024 19:10:20 +0000

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G𝐮𝐚𝐫𝐝𝐢𝐚𝐧𝐬 𝐎𝐟 𝐎𝐮𝐫 𝐇𝐞𝐚𝐥𝐭𝐡: 𝐄𝐦𝐛𝐫𝐚𝐜𝐢𝐧𝐠 𝐀𝐧𝐭𝐢𝐦𝐢𝐜𝐫𝐨𝐛𝐢𝐚𝐥 𝐒𝐭𝐞𝐰𝐚𝐫𝐝𝐬𝐡𝐢𝐩

admin — Tue, 15 Oct 2024 14:35:41 +0000

G𝐮𝐚𝐫𝐝𝐢𝐚𝐧𝐬 𝐎𝐟 𝐎𝐮𝐫 𝐇𝐞𝐚𝐥𝐭𝐡: 𝐄𝐦𝐛𝐫𝐚𝐜𝐢𝐧𝐠 𝐀𝐧𝐭𝐢𝐦𝐢𝐜𝐫𝐨𝐛𝐢𝐚𝐥 𝐒𝐭𝐞𝐰𝐚𝐫𝐝𝐬𝐡𝐢𝐩

Microvioma
October 1, 2023

Antimicrobial resistance is a rising global issue that impacts the efficacy of antibiotics and other antimicrobial treatments. Healthcare experts, veterinarians, farmers, and the general public must all work together to address this problem. Antimicrobial stewardship is a collaborative endeavour that upholds the ideals of One Health, which acknowledges the interdependence of human, animal, and environmental health. In this article, we’ll go into the world of antimicrobial stewardship and explore its significance, key practises, and role in preserving human health.
By encouraging the choice of the best antimicrobial drug regimen, dose, course of treatment, and method of administration, antimicrobial stewardship refers to coordinated initiatives intended to enhance and gauge the proper use of antibiotics. Further it seeks to achieve optimal clinical outcomes related to antimicrobial use, minimize toxicity and other adverse events, reduce the costs of health care for infections, and limit the selection of antimicrobial-resistant strains. antimicrobial stewardship is about using antimicrobials responsibly, which involves promoting actions that balance both the individual’s need for appropriate treatment and the longer-term societal need for sustained access to effective therapy.

Antibiotic resistance is a global crisis. Not only the human population but also food and food animals are equally contributing to antibiotic resistance. Animals also carry bacteria in their gut which might also include antibiotic-resistant bacteria. People can get infections from handling or eating meat or food contaminated with resistant bacteria, from contact with animal waste, and from touching animals without proper handwashing. Antimicrobial stewardship refers to the multifaceted approach (including policies, guidelines, surveillance, prevalence reports, education, and audit of practice) that healthcare organizations have adopted to optimize prescribing.
A comprehensive approach to stop the development of antibiotic resistance must include antimicrobial stewardship as a significant element. Antimicrobial stewardship is a suggested approach to the interrelated issues of rising antibiotic resistance, declining antimicrobial agent availability, and suboptimal use of antibiotics in clinical practice: A critical mission of preservation of antimicrobial utility.

Antibiotic use must be closely monitored due to an increase in multi-drug resistant organisms and a decline in the development of anti-infective agents. An Antimicrobial stewardship program (ASP) is essential in any hospital or healthcare facility to decrease antimicrobial resistance incidence and improve patient care. The ASP is a collaborative effort that involves multiple specialties and departments. A successful ASP changes based on local prescribing trends and resistance patterns while focusing on a patient as an individual.

The ASP programs have the following goals:

To work with healthcare practitioners to prescribe the 5 “D”s of antimicrobial therapy, which are the right Drug, correct Dose, right Drug-route, suitable Duration, and timely De-escalation to pathogen-directed therapy.

To prevent antimicrobial overuse, misuse, and abuse in inpatient, outpatient, and community settings, including the agriculture industry.

To reduce antibiotic-related adverse effects, for example, C.difficile

To minimize resistance

The AMS programs include the following core elements:

Leadership commitment: To dedicate necessary human, financial, and information technology resources, having dedicated time and resources to operate the program effectively.

Accountability: It is necessary to appoint a leader or co-leaders responsible for the results of ASPs activities among clinicians or pharmacists so that someone could take responsibility for managing the program and monitoring its results.

Drug expertise: The participation of pharmacists is critical for leading the efforts to improve antibiotic use. Appoint a pharmacist, ideally as the co-leader of the stewardship program, to lead implementation efforts to improve antibiotic use.

Action Implement: Interventions, such as prospective audit and feedback or pre-authorization, is essential to improve antibiotic use. In addition, staff-pharmacy interventions, drug level monitoring, automatic warning for unnecessary repetition of antibiotic prescription, notification for antibiotic use for more than a reasonable period, detection of interactions between antibiotic-related drugs, and other drugs, and infection- and syndrome-specific interventions could be focused on diagnostic assessment. Microbial testing and antimicrobial susceptibility test are important for the selection of the appropriate empiric antibiotics. A new category of nursing-based actions was added to reflect the important role that nurses can play in hospital antibiotic stewardship efforts.

Tracking: This involves monitoring antibiotic prescribing, the impact of interventions, and resistance patterns. It is also important to collect and analyze the data on the antibiotics used in each medical facility at the government level.

Reporting: Regularly reporting information on antibiotic use and resistance to prescribers, pharmacists, nurses, and hospital leadership. Information about the incidence of antibiotic-resistant bacterial infections is prepared by collaborating with the hospital’s microbiology lab and infection control and healthcare epidemiology department.

Education: Educating prescribers, pharmacists, patients, and nurses about adverse reactions from antibiotics, antibiotic resistance, and optimal prescribing is a core element of ASP.

AMS is one of three “pillars” of an integrated approach to health systems strengthening. The other two are infection prevention and control (IPC) and medicine and patient safety. When applied in conjunction with antimicrobial use surveillance, and the WHO essential medicines list (EML) AWaRe classification (ACCESS, WATCH, RESERVE), AMS helps to control Antimicrobial resistance by optimizing the use of antimicrobials. Linking all three pillars to other key components of infection management and health systems strengthening, such as AMR surveillance and adequate supply of quality assured medicines, promotes equitable and quality health care towards the goal of achieving universal health coverage.

𝐔𝐧𝐫𝐚𝐯𝐞𝐥𝐢𝐧𝐠 𝐭𝐡𝐞 𝐏𝐨𝐰𝐞𝐫 𝐨𝐟 𝐌𝐞𝐭𝐚𝐥𝐥𝐢𝐜 𝐍𝐚𝐧𝐨𝐩𝐚𝐫𝐭𝐢𝐜𝐥𝐞𝐬 𝐢𝐧 𝐅𝐢𝐠𝐡𝐭𝐢𝐧𝐠 𝐀𝐧𝐭𝐢𝐦𝐢𝐜𝐫𝐨𝐛𝐢𝐚𝐥 𝐑𝐞𝐬𝐢𝐬𝐭𝐚𝐧𝐜𝐞: 𝐒𝐢𝐥𝐯𝐞𝐫 𝐚𝐧𝐝 𝐆𝐨𝐥𝐝 𝐍𝐚𝐧𝐨𝐩𝐚𝐫𝐭𝐢𝐜𝐥𝐞𝐬

admin — Tue, 15 Oct 2024 14:31:15 +0000

𝐔𝐧𝐫𝐚𝐯𝐞𝐥𝐢𝐧𝐠 𝐭𝐡𝐞 𝐏𝐨𝐰𝐞𝐫 𝐨𝐟 𝐌𝐞𝐭𝐚𝐥𝐥𝐢𝐜 𝐍𝐚𝐧𝐨𝐩𝐚𝐫𝐭𝐢𝐜𝐥𝐞𝐬 𝐢𝐧 𝐅𝐢𝐠𝐡𝐭𝐢𝐧𝐠 𝐀𝐧𝐭𝐢𝐦𝐢𝐜𝐫𝐨𝐛𝐢𝐚𝐥 𝐑𝐞𝐬𝐢𝐬𝐭𝐚𝐧𝐜𝐞: 𝐒𝐢𝐥𝐯𝐞𝐫 𝐚𝐧𝐝 𝐆𝐨𝐥𝐝 𝐍𝐚𝐧𝐨𝐩𝐚𝐫𝐭𝐢𝐜𝐥𝐞𝐬

Microvioma
October 29, 2023

In the fight against modern medical challenges such as antibiotic resistance and rapidly mutating bacteria, the scientific community is turning towards innovative concepts for solutions. At the forefront of this battle lie metallic nanoparticles, particularly those composed of gold and silver. These nanometrically tiny metallic agents hold immense potential in their ability to combat various bacterial strains. Today, let’s take a deep dive and explore the mechanisms of how these nanoparticle powerhouses stand against pernicious bacteria.

Silver nanoparticles have been recognized as potent antimicrobial agents. Their unique physical and chemical properties have been leveraged against different types of bacteria, showing pronounced antibacterial activity. The complex mechanisms through which they affect bacteria also suggest that they could be a useful tool in combating the problem of antibiotic resistance.

Here are some key points regarding the action of Silver (AgNPs) against bacteria:

1. Interaction with Cellular Structures: AgNPs can interact directly with bacterial cell membranes, leading to structural damage and impaired function, which eventually causes cell death.

2. Release of Silver Ions: Upon interaction with bacteria, AgNPs can release silver ions, which are toxic to bacterial cells. These ions can interact with bacterial proteins and DNA, disrupting essential cellular functions and leading to cell death.

3. Generation of Reactive Oxygen Species: AgNPs can induce the generation of reactive oxygen species within bacterial cells. These ROS can cause oxidative stress and damage to DNA, proteins, and lipids, resulting in cell death.

4. Impact on Bacterial Biofilms: Biofilms form a protective layer for bacteria and render them resistant to antibiotics. AgNPs have shown efficacy in disrupting these biofilms, making the bacteria susceptible to antibiotic action.

5. Inhibition of Cell Division: Some studies suggest that AgNPs can interfere with the bacterial cell division process, inhibiting their proliferation.

6. Size and Shape Effect: The size and shape of AgNPs affect their antibacterial activity. For instance, smaller nanoparticles often exhibit enhanced antibacterial effects due to their increased surface area for interaction.

Gold nanoparticles, owing to their unique physicochemical properties, have gained considerable attention in various fields, including medicine, diagnostics, imaging, and antimicrobial applications. The antimicrobial properties of AuNPs make them potential candidates for combating various bacterial infections and tackling antibiotic resistance.

Here are some key points highlighting the mechanisms of action of AuNPs against bacteria:

1. Interaction with Cellular Structures: Similar to other metallic NPs, AuNPs can interact with bacterial cell walls and membranes, causing structural and functional damages that can potentially lead to cell death.

2. Release of Gold Ions: Upon interaction with bacterial cells, AuNPs can gradually release gold ions, which may interact with critical biomolecules within the bacterial cells, disrupting vital cellular functions and processes.

3. Generation of Reactive Oxygen Species: AuNPs may also promote generation of reactive oxygen species within bacterial cells, causing oxidative stress and potentially leading to DNA, protein and lipid damage within the bacterial cells, thereby resulting in cell death.

4. Photothermal Effects: AuNPs are known for their unique optical properties, including strong light absorption and scattering. Under light irradiation, AuNPs can generate heat, which can kill bacteria, a property that can be used in photothermal therapies.

5. Effect on Bacterial Biofilms: Gold nanoparticles have shown potency in disrupting bacterial biofilms, often responsible for bacterial virulence and resistance to treatments.

6. Delivery of Antibacterial Agents: AuNPs can be functionalized with antibiotics or other antibacterial substances, effectively delivering these agents to bacterial cells and enhancing their antibacterial activity.

In conclusion, the distinctive characteristics of gold and silver nanoparticles – their ability to interact with bacterial cell structures, spur the production of reactive oxygen species, disrupt biofilms, and the distinct photothermal properties held by gold nanoparticles – offer us a unique toolkit in the fight against bacterial infections and antibiotic resistance. By persistently exploring and optimizing these metallic nanoparticles within a framework of rigorous scientific investigation and ethical consideration, we take strides towards a future where the global issue of antimicrobial resistance can be effectively tackled. Thus, the future of antibacterial treatments indeed looks glittering with the promise of gold and silver nanoparticles.

References:

Massironi A, Franco AR, Babo PS, Puppi D, Chiellini F, Reis RL, Gomes ME. Development and characterization of highly stable silver nanoparticles as novel potential antimicrobial agents for wound healing hydrogels. International Journal of Molecular Sciences. 2022 Feb 15;23(4):2161.
Salleh A, Naomi R, Utami ND, Mohammad AW, Mahmoudi E, Mustafa N, Fauzi MB. The potential of silver nanoparticles for antiviral and antibacterial applications: A mechanism of action. Nanomaterials. 2020 Aug 9;10(8):1566.
Xu Z, Zhang C, Wang X, Liu D. Release strategies of silver ions from materials for bacterial killing. ACS applied bio materials. 2021 Jan 11;4(5):3985-99.
Li X, Robinson SM, Gupta A, Saha K, Jiang Z, Moyano DF, Sahar A, Riley MA, Rotello VM. Functional gold nanoparticles as potent antimicrobial agents against multi-drug-resistant bacteria. ACS nano. 2014 Oct 28;8(10):10682-6.
Zhou Y, Kong Y, Kundu S, Cirillo JD, Liang H. Antibacterial activities of gold and silver nanoparticles against Escherichia coli and bacillus Calmette-Guérin. Journal of nanobiotechnology. 2012 Dec;10:1-9.

The Microbiota–Gut–Brain Axis and Alzheimer’s Disease: The Culprit is Neuroinflammation

admin — Tue, 15 Oct 2024 14:25:13 +0000

The Microbiota–Gut–Brain Axis and Alzheimer’s Disease: The Culprit is Neuroinflammation

Microvioma
November 6, 2023

Your gut might hold secrets to Alzheimer’s disease (AD), and neuroinflammation seems to be the chief suspect!

When infections come into play, a plethora of cell signaling pathways get activated, leading to inflammation. If infectious microorganisms break through the blood-brain barrier, it can result in neuronal death and share eerily similar hallmarks with AD. Inflammation is a necessary response for protection, tissue repair, and getting rid of waste. In the AD playbook, neuroinflammation is a significant player, with activated microglia and astrocytes taking center stage. Microglia, brain’s immune warriors, are vital in the neuroinflammation saga. They can morph into different phenotypes depending on the brain’s signals and express innate immune receptors. When these receptors activate, the microglia go into action, producing inflammatory mediators, including reactive oxygen species, nitric oxide, and cytokines. These activated microglia, in the presence of Aβ, migrate to plaques, gobbling up Aβ and triggering an inflammatory response. It’s like a cellular warzone, with pattern recognition receptors as the generals.

But don’t forget about astrocytes, the brain’s unsung heroes, five times more abundant than neurons. These cells help maintain the CNS’s integrity, but when Aβ accumulates, they transform into activated astrocytes. These “super” astrocytes overproduce cytokines and generate oxidative stress, adding more fuel to the fire.

A growing body of evidence suggests that the gut microbiota, the community of microorganisms residing in our digestive system, plays a significant role in the development of the brain. This relationship is often referred to as the “brain-gut-microbiome axis.” It’s a two-way street, where the brain, gut, and gut bacteria influence each other. Let’s dive into the details of this fascinating interplay.

The gut microbiota has the power to influence the brain-gut connection through various mechanisms, including immunological, neuroendocrine, and direct neural pathways. These microorganisms can promote local and systemic inflammation through the release of compounds like lipopolysaccharides (LPS) from pathogenic bacteria and the production of pro-inflammatory cytokines. Moreover, they are capable of generating neurotransmitters and neuromodulators, such as short-chain fatty acids (SCFAs), histamine, serotonin, and gamma-aminobutyric acid (GABA). On the flip side, they can also create neurotoxic metabolites like d-lactic acid and ammonia. These signaling molecules travel through the circulatory system and lymphatic system to reach the central nervous system (CNS), affecting behavior, brain plasticity, and cognitive function. This underscores the gut microbiota’s pivotal role in CNS development, function, and the pathophysiology of chronic brain diseases.

A recent study shed light on how molecules secreted by the gut microbiota contribute to brain inflammation. In the CNS, microglia and astrocytes, two types of immune cells, communicate using molecules like vascular endothelial growth factor B (VEGF-B) and transforming growth factor alpha (TGF-α) to regulate neuroinflammation. This communication is facilitated by a ligand-activated transcription factor called aryl hydrocarbon receptor (AHR), traditionally associated with processing environmental toxins. Interestingly, the deletion of AHR in microglia increased experimental autoimmune encephalitis (EAE) severity, an inflammatory disease in the CNS. AHR’s activation in microglia seems to inhibit CNS inflammation. The study also revealed AHR’s direct involvement in the expression of TGF-α and VEGF-B, which, in turn, affect the inflammatory responses of astrocytes. While TGF-α reduces inflammation in astrocytes, VEGF-B does the opposite. This intricate interplay showcases the profound effects of the gut microbiota on brain inflammation.

Moreover, research demonstrated that supplementing mice with specific tryptophan metabolites and bacterial enzymes reduced CNS inflammation. These molecules can also potentially disrupt communication between specific neural structures of the brain, like dopaminergic neurons.

The connection between the gut microbiota and Alzheimer’s disease (AD) was exemplified in a study using transgenic mouse models. Shifting the gut microbiota diversity of APP transgenic mice led to changes in cerebral amyloid-beta (Aβ) pathology. When germ-free APP transgenic mice were colonized with gut microbiota from conventionally raised APP transgenic mice, cerebral Aβ pathology increased. These findings emphasize the significant role of the gut microbiota in AD pathology.

Intriguingly, many bacteria can synthesize and release neurotransmitters, neuromodulators, and neuropeptides. This hints at the gut microbiota’s involvement in the development of AD pathology. Additionally, chronic inflammation in the gut may disrupt the blood-brain barrier, leading to increased permeability, the generation of pro-inflammatory cytokines, and elevated levels of LPS. In fact, AD patients often exhibit higher LPS levels in their blood. Peripheral inflammation, such as colitis, can exacerbate neuroinflammation and neurodegeneration.

The presence of bacterial amyloid, a component of the gut microbiota, in the CNS contributes to Aβ accumulation, which is closely linked to AD. This suggests that modulating the gut microbiota could be a potential strategy to prevent or reduce the risk of AD.

It’s clear that the gut microbiota influences neuroinflammation, which, in turn, has significant implications for the development of neurodegenerative disorders like AD. The delicate balance in gut microbial diversity can lead to detrimental effects on the brain. Changes in gut composition may help delay or prevent the progression of these disorders. Promising research points to probiotics and specific diets as potential interventions. Understanding these molecular pathways will pave the way for better treatments for neurodegenerative diseases.

In conclusion, the intricate relationship between the gut microbiota and the brain offers a deeper understanding of the complex processes at play in neuroinflammation and neurodegeneration, particularly in the context of Alzheimer’s disease. These findings hold great promise for future therapeutic interventions and shed light on the critical role of gut health in brain function and disease.

Refrences:

Gut Microbiota and Their Neuroinflammatory Implications in Alzheimer’s Disease: https://tinyurl.com/5n6h2jfv

Targeting gut microbiota to alleviate neuroinflammation in Alzheimer’s disease: https://tinyurl.com/2bjr8ndv

The Microbiota–Gut–Brain Axis and Alzheimer’s Disease: Neuroinflammation Is to Blame? : https://tinyurl.com/44hvtj3a

World Prebiotic Awareness

admin — Tue, 15 Oct 2024 14:21:50 +0000

World Prebiotic Awareness

Microvioma
November 7, 2023

In the pursuit of improved human health, prebiotics have grown exceedingly important. These non-digestible substances have the extraordinary ability to alter the gut microbiota, which has a significant impact on a number of facets of human health. Their significance stems from the multifaceted mechanisms through which they operate, and their roles extend from immunomodulation to disease management.

Through the process of rebiosis, or the growth of beneficial bacteria, prebiotics have the ability to affect the gut microbiota. They are able to counteract both pro- and anti-inflammatory reactions. Their capacity to stimulate different immune-related pathways is what causes these effects. For example, prebiotics can secrete regulating interleukin-10 (IL-10) and proinflammatory cytokines by activating the NF-κB pathway through Toll-like receptor 4 (TLR-4). Additionally, they have the ability to inhibit the proinflammatory response by activating the peroxisome proliferator-activated receptor-γ pathway. Furthermore, the prebiotic fermentation process yields short-chain fatty acids (SCFAs), which activate pathways such as NOD-like receptors and the inflammasome. This results in the release of antimicrobial peptides (AMPs), transforming growth factor-β, and anti-inflammatory IL-10.

Prebiotics have a unique ability to influence the host’s immune response both directly and indirectly. The innate immune system, the body’s first line of defense, is impacted by them in different ways. This system includes physical barriers like mucosal membranes as well as immune cells like neutrophils, macrophages, dendritic cells, lymphocytes, and natural killer (NK) cells. Prebiotics have the ability to directly activate immunological and gut-associated epithelial cells, causing either an anti- or pro-inflammatory reaction. Pattern recognition receptors (PRRs), which are found on cell surfaces and are capable of detecting exterior threats, are what trigger these reactions. Then, other transcription factors and signaling pathways, like NF-κB and activator protein 1 (AP-1), activate the genes that code for chemokines and cytokines, controlling inflammation.

Further, by producing SCFAs, prebiotics can indirectly affect the immunological response. When these SCFAs attach to G-protein-coupled receptors (GPCRs), signal transducer and activator of transcription (STAT), mammalian target of rapamycin (mTOR), and mitogen-activated protein kinase (MAPK) are activated. The synthesis of antimicrobial peptides and anti-inflammatory cytokines including TGF-β and IL-10 is triggered by this activation.

Maintaining Gut Barrier Function

The intestinal barrier, consisting of a monolayer of epithelial cells, serves as a selectively permeable defense against microbes, toxins, and antigens. Desmosomes, adhesion junctions, and tight junctions are examples of complex protein networks that are essential to maintaining the integrity of this barrier. If this barrier is compromised, it can lead to long-term inflammation and heightened intestinal permeability, which can make it possible for dangerous compounds like lipopolysaccharides (LPS) to enter the bloodstream.

It has been discovered that prebiotics have a beneficial effect on the intestinal barrier’s functionality. They improve tight junction assembly, which lowers permeability and inhibits the passage of cytokines and LPS. Prebiotics can sometimes trigger the release of peptides similar to glucagon, which improves diseases like type 1 diabetes and obesity, where the gut barrier has been compromised.

Effects of Microbiota on Immune Cells

Prebiotics and SCFAs have a significant impact on gut-dwelling immune cells in addition to epithelial cells. Regulatory T cells (Tregs), neutrophils, macrophages, natural killer (NK) cells, and dendritic cells (DCs) represent a few of these cells.

By exposing other immune cells to antigens, DCs are essential for controlling immunological responses. Prebiotics and SCFAs affect DC maturation, influencing the development of particular immune responses such as Th1, Th2, Th17, or Treg phenotypes. They also increase cytokine release.

Macrophages play a crucial role in preserving the integrity of the intestinal epithelium by being positioned strategically beneath it. Through epigenetic alterations and the suppression of proinflammatory mediators, SCFAs are essential in controlling macrophage polarization and augmenting anti-inflammatory responses. This lowers inflammation and promotes intestinal tolerance.

The regulation of inflammation and immunological tolerance depend on tregs. Prebiotics have been connected to elevated Treg activity, which improves immunity homeostasis and mitigates allergic reactions. This is mediated by both the suppression of histone deacetylase (HDAC) and the engagement of GPCRs by SCFAs.

Prebiotics also affect natural killer cells (NK cells), along with SCFAs can increase their cytotoxicity, improving their resistance to infections and cancer.

Neutrophils, a type of white blood cell, participate in inflammatory responses. SCFAs have been shown to modulate neutrophil function, inhibiting their proinflammatory activities and promoting the resolution of inflammation.

Conclusion

Prebiotics, these remarkable non-digestible compounds, offer a fascinating avenue for immune modulation. Their intricate interaction with the gut microbiota and the host’s immune system goes far beyond their role in gut health. The ability of prebiotics to influence immune cells and gut epithelial cells independently of the gut microbiota is a captivating area of research, shedding light on both pro-inflammatory and anti-inflammatory responses.

As our understanding of prebiotics’ mechanisms deepens, it becomes increasingly evident that these dietary components hold great potential for therapeutic applications in various conditions, particularly those involving immune dysregulation. The concept of prebiotics as a tool to promote immune balance and overall health is an exciting prospect that continues to unfold in the field of scientific inquiry. Prebiotics have the potential to serve as allies in our pursuit of well-being, and further research promises to uncover the full extent of their immunomodulatory powers.

𝐂𝐨𝐦𝐛𝐚𝐭𝐢𝐧𝐠 𝐀𝐧𝐭𝐢𝐦𝐢𝐜𝐫𝐨𝐛𝐢𝐚𝐥 𝐑𝐞𝐬𝐢𝐬𝐭𝐚𝐧𝐜𝐞 𝐭𝐡𝐫𝐨𝐮𝐠𝐡 𝐎𝐧𝐞 𝐇𝐞𝐚𝐥𝐭𝐡 𝐀𝐩𝐩𝐫𝐨𝐚𝐜𝐡: 𝐀 𝐆𝐥𝐨𝐛𝐚𝐥 𝐈𝐦𝐩𝐞𝐫𝐚𝐭𝐢𝐯𝐞

admin — Tue, 15 Oct 2024 14:17:13 +0000

𝐂𝐨𝐦𝐛𝐚𝐭𝐢𝐧𝐠 𝐀𝐧𝐭𝐢𝐦𝐢𝐜𝐫𝐨𝐛𝐢𝐚𝐥 𝐑𝐞𝐬𝐢𝐬𝐭𝐚𝐧𝐜𝐞 𝐭𝐡𝐫𝐨𝐮𝐠𝐡 𝐎𝐧𝐞 𝐇𝐞𝐚𝐥𝐭𝐡 𝐀𝐩𝐩𝐫𝐨𝐚𝐜𝐡: 𝐀 𝐆𝐥𝐨𝐛𝐚𝐥 𝐈𝐦𝐩𝐞𝐫𝐚𝐭𝐢𝐯𝐞

Microvioma
November 19, 2023

Antimicrobials have been a significant part of human and animal health care, used for both therapeutic and prophylactic purposes. The problem arises when these antimicrobials are overused or misused. Over time, some microorganisms develop resistance to these antimicrobials, rendering the treatments ineffective. The widespread use of particular antimicrobials in agriculture is concerning, leading to the evolution of highly-resistant microorganisms that pose significant health risks.

Antimicrobial resistance, a significant global health concern, occurs when microorganisms such as bacteria, fungi, viruses, and parasites develop resistance to the medicines used to treat the infections they cause. This happens primarily due to irresponsible and excessive use of antimicrobials in various sectors such as agriculture, livestock, and human medicine. The importance of addressing antimicrobial resistance cannot be understated as it threatens the effective prevention and treatment of a myriad of infections.

A multidisciplinary and integrative ‘One Health’ approach is deemed as the optimal strategy to address this intricate global issue, linking human, animal, and environmental health. This approach bridges various disciplines to provide comprehensive solutions for health issues affecting these three components of our ecosystem. AMR has severe implications on individuals’ well-being, urging us to perceive and tackle it through different disciplines to streamline it within the One Health framework. Recognizing the interconnection between humans, animals, and their shared environment is a critical step in addressing the escalation of AMR.

Preserving the effectiveness of antibiotics necessitates a harmonized global approach.

The One Health approach believes in enhancing public awareness about the potential harm resulting from overuse and misuse of antimicrobials.

It encourages the adoption of improved and stricter hygiene measures and infection control, reducing the unnecessary use of antimicrobials in agriculture and preventing their spread into the environment.

Moreover, it advocates for promoting new and rapid clinical diagnoses, developing and utilizing vaccines and effective alternatives, further recognizing and increasing the number of professionals working with infectious diseases, and fostering a global coalition for real action against AMR.

The fight against AMR also involves strengthening global surveillance of drug resistance, which needs a clear understanding of antibiotic consumption in humans and animals, current rates of antibiotic resistance, and the molecular basis of AMR. Effective monitoring can guide various health sectors in countering the spread of resistance and contribute to a global image of AMR to direct global health governance and accountability.

As we navigate the era of global health, it is apparent that the One Health approach stands out as a beacon of hope against the looming threat of Antimicrobial Resistance. As AMR continues to escalate, economies, healthcare systems, and livelihoods are at stake. Indeed, the problem of AMR is an urgent global indictment calling for an immediate consensual response. This compels us to rethink and overhaul our current strategies at every level – from consumption and prescription of antimicrobials to their use in food production and environmental systems. Accelerated innovation, sustainable investment in research and development, and stringent control of the types and amounts of antimicrobials used in medical practice, agriculture and livestock are needed.

The combat against AMR is a battle that requires unity and action from all sectors of society. As such, public education campaigns are needed to raise awareness and promote responsible practices surrounding antimicrobial use. Practitioners in both human and animal health sectors should be prudent in antimicrobial prescriptions, advocating for use only when necessary and employing best practices. In conclusion, the complexity of Antimicrobial Resistance requires a comprehensive, robust, and responsive approach – one that recognizes our global interconnectedness and interdependence, and places equal emphasis on animal, human, and environmental health.

In this pivotal moment in human history, a One Health approach is no longer just an option – but an essential path we must adopt, to safeguard our collective health and future.

Reference:

Velazquez-Meza ME, Galarde-López M, Carrillo-Quiróz B, Alpuche-Aranda CM. Antimicrobial resistance: one health approach. Veterinary World. 2022 Mar;15(3):743. https://tinyurl.com/88hceeux

Collignon PJ, McEwen SA. One health—its importance in helping to better control antimicrobial resistance. Tropical medicine and infectious disease. 2019 Jan 29;4(1):22. https://tinyurl.com/3spzpdxv

Hernando-Amado S, Coque TM, Baquero F, Martínez JL. Defining and combating antibiotic resistance from One Health and Global Health perspectives. Nature microbiology. 2019 Sep;4(9):1432-42. https://tinyurl.com/4ftz86ra

𝐂𝐮𝐫𝐛𝐢𝐧𝐠 𝐀𝐧𝐭𝐢𝐦𝐢𝐜𝐫𝐨𝐛𝐢𝐚𝐥 𝐑𝐞𝐬𝐢𝐬𝐭𝐚𝐧𝐜𝐞: 𝐀 𝐏𝐫𝐨𝐚𝐜𝐭𝐢𝐯𝐞 𝐀𝐩𝐩𝐫𝐨𝐚𝐜𝐡 𝐰𝐢𝐭𝐡 𝐀𝐧𝐭𝐢𝐦𝐢𝐜𝐫𝐨𝐛𝐢𝐚𝐥 𝐒𝐭𝐞𝐰𝐚𝐫𝐝𝐬𝐡𝐢𝐩

admin — Tue, 15 Oct 2024 14:12:17 +0000

𝐂𝐮𝐫𝐛𝐢𝐧𝐠 𝐀𝐧𝐭𝐢𝐦𝐢𝐜𝐫𝐨𝐛𝐢𝐚𝐥 𝐑𝐞𝐬𝐢𝐬𝐭𝐚𝐧𝐜𝐞: 𝐀 𝐏𝐫𝐨𝐚𝐜𝐭𝐢𝐯𝐞 𝐀𝐩𝐩𝐫𝐨𝐚𝐜𝐡 𝐰𝐢𝐭𝐡 𝐀𝐧𝐭𝐢𝐦𝐢𝐜𝐫𝐨𝐛𝐢𝐚𝐥 𝐒𝐭𝐞𝐰𝐚𝐫𝐝𝐬𝐡𝐢𝐩

Microvioma
November 20, 2023

Antimicrobial Resistance is a looming global health challenge. It takes the deadly form when microbes mutate and develop resistance to the very medicines designed to destroy them. However, hope abounds in a powerful, targeted strategy known as Antimicrobial Stewardship. AMS programs aim to ensure the optimal selection, dosing, and duration of antimicrobial treatment.

They aspire to drive change in prescribing behavior, reduce unnecessary use of antibiotics, and improve patient health outcomes. It all begins with adopting a prudent approach to antibiotic prescription and use, and here’s how:

1. Optimizing Antimicrobial Prescriptions: AMS encourages healthcare providers not to rush into prescribing antibiotics, but to make careful, considerate choices regarding the right drug, optimal dosage, and suitable duration of therapy. This judicious approach not only improves patient outcomes but also minimizes the risk of developing antibiotic resistance.

2. Emphasizing Education: AMS programs play a significant role in educating both healthcare professionals and patients about the proper antibiotic use and the potential pitfalls of misuse. Understandings of when antibiotics are necessary, the significance of adhering to the prescribed dosage, and the importance of completing courses are all crucial to reducing unnecessary exposure to antibiotics, thus preventing the evolution of resistance.

3.Continuous Monitoring and Reporting: Tracking the use of antimicrobials within healthcare settings provides critical insights into prescribing habits, patterns of resistance, and overall effectiveness of the stewardship interventions. Regular feedback can encourage compliance with recommended practices and help identify areas that need improvement.

4.Enforcing Reassessment of Therapy: Ongoing reevaluation of the initial antibiotic selection is an often overlooked but critical component of AMS programs. This strategy promotes the transition from broad-spectrum antibiotics to narrower agents and encourages the de-escalation or termination of therapy when infection is ruled out. This constant revaluation helps in reducing the unnecessary antibiotic usage.

5.Supporting Non-Antibiotic Strategies: AMS advocates for the use of non-antibiotic measures such as vaccines and infection control practices. These approaches can decrease the prevalence of infections requiring antibiotic treatment, thereby reducing the overall use of antibiotics.

In summary, if intelligently implemented, AMS programs can robustly combat the growing threat of antimicrobial resistance. It takes deliberate and collective effort from all parties involved, including healthcare professionals, patients, and policy-makers. By working together, we can preserve the potency of our current antibiotics, ensuring they remain an effective tool for treating infectious diseases for generations to come. Stepping up to antimicrobial stewardship is not merely an option, but a necessity in our fight against antimicrobial resistance. Let’s commit to using antibiotics responsibly and making the world a safer place for all of us.

Revitalizing Antimicrobial Stewardship: A Gut Microbiome-Centric Approach

admin — Tue, 15 Oct 2024 11:59:14 +0000

Revitalizing Antimicrobial Stewardship: A Gut Microbiome-Centric Approach

Microvioma
November 22, 2023

Antimicrobial stewardship, a critical strategy in the fight against antibiotic resistance, traditionally focuses on optimizing antibiotic use to reduce resistance emergence. A thorough strategy, however, needs to take into account the significant effects that antibiotics have on the commensal gut microbiome. Drug-resistant infections are more likely to colonize environments where antibiotics, especially those classified as broad-spectrum, have disrupted the delicate balance of anaerobic commensals. This microbial imbalance increases the risk of infections in addition to being linked to the development of resistant bacteria. Although reducing the use of broad-spectrum antibiotics is a top priority in current stewardship initiatives, the impact of antibiotics on the microbiome may not be well reflected by their narrow or broad classification.

Therefore, a shift in focus is imperative, considering the relative disruption each antibiotic inflicts on commensal bacteria. Refining treatment choices and improving long-term patient outcomes need integrating microbiome analysis into clinical trials and antibiotic stewardship initiatives. One of the main principles of antimicrobial stewardship is the maintenance of commensal microbiota, which emphasizes the significance it is for protecting human health and stopping the spread of infections that are resistant to antibiotics.

To optimize gut microbiota protection, efforts are being made to create intravenous medicines with limited biliary/fecal excretion, use oral drugs that minimize exposure to the gastrointestinal tract and gut microbiota, and avoid anti-anaerobic antibiotics when clinically feasible. Furthermore, the prospect of completely discontinuing antibiotic therapy exists, particularly in cases where a few doses are needed and a clinical response is unlikely to be affected, is being considered as part of an evolved stewardship paradigm.

One key strategy involves narrowing antibiotic spectra and limiting the duration of use. The diversity of the gut microbiota is greatly impacted by the antibiotics used, with anti-anaerobic drugs causing the most significant disruption. When appropriate, advocating for the prescription of narrower spectrum antibiotics might decrease this disruption and lower the risk of opportunistic infections. Another crucial element is knowing the pharmacokinetics of antibiotics. Diverse antibiotic routes, dosages, and excretions have diverse effects on the gut flora. Compared to intravenous antibiotics, oral antibiotics, particularly those that are highly absorbed and released less through the bile or feces, have less of an effect on the gut microbiota. It’s critical to customize antibiotic prescriptions to reduce disturbance by taking into account elements including absorption, excretion, and risk for resistance, is vital for effective stewardship.

Modulating the gut microbiota to avoid infections is a new field. In certain clinical contexts, strategies to lower the risk of infection are taken into consideration, such as Fecal Microbiota Transplant (FMT), Selective Oropharyngeal Decontamination, Selective Digestive Decontamination, and Pre-Operative Oral Antibiotic Preparation.

Microbiome protection therapies, such as FMT and probiotics, are emerging as potential strategies to mitigate the negative effects of antibiotic exposure on the gut microbiome. The exceptional effectiveness of FMT in treating recurrent 𝘊𝘭𝘰𝘴𝘵𝘳𝘪𝘥𝘪𝘶𝘮 𝘥𝘪𝘧𝘧𝘪𝘤𝘪𝘭𝘦 infection (CDI) highlights the significance of reestablishing a healthy microbiome in order to ward against infections. Early probiotic administration combined with antibiotics has been shown to significantly lower the risk of CDI, indicating a possible path toward microbiome protection.

The creation of quick, affordable tests that can detect disruptions in the gut microbiota is thought to be essential for providing at-risk patients with microbiome-protective treatments. Furthermore, novel strategies such as the use of oral β-lactamases and chemically ensnaring antibiotics in the gastrointestinal tract are being investigated to stop the selection of antibiotic-resistant bacteria and preserve the health of the gut microbiome.

Topical and local administration of antibiotics, as well as alternative routes such as transdermal and nebulized administration, are being investigated to reduce systemic exposure and subsequent gut microbiome impact. Another potentially effective tactic to reduce ecologically-induced negative effects on the human microbiome is the development of precise, very-narrow-spectrum agents.

In conclusion, antimicrobial stewardship practices directly intersect with the gut microbiome. By tailoring antibiotic prescriptions, exploring targeted delivery methods, and considering modulation strategies, stewardship efforts aim not only to combat infections but also to safeguard the delicate equilibrium of the gut microbiota and curb the emergence of antibiotic resistance. Preserving the efficacy of antimicrobials and solving the worldwide health crisis will require integrating the gut microbiota into antimicrobial medication development and improving stewardship methods.

Read Further:

Rethinking antimicrobial stewardship paradigms in the context of the gut microbiome: https://tinyurl.com/bdep52me

Gut Microbiota Modulation: Implications for Infection Control and Antimicrobial Stewardship: https://tinyurl.com/a2bhjrpm

Protect commensal gut bacteria to improve antimicrobial stewardship: https://tinyurl.com/ynm9m79m

Can Understanding Gut Microbiome Dynamics Combat Antimicrobial Resistance?

admin — Tue, 15 Oct 2024 11:55:08 +0000

Can Understanding Gut Microbiome Dynamics Combat Antimicrobial Resistance?

Microvioma
November 23, 2023

Antibiotic resistance (AR) poses a severe threat to global public health, claiming an estimated millions of lives globally. Resistance is acquired by bacteria either by horizontal gene transfer (HGT), in which genetic elements containing resistance genes are transferred between bacteria, or through mutations. The dynamics of AR are significantly influenced by the human gut microbiota, a varied ecology found in the gastrointestinal tract.

The gut microbiota, primarily composed of symbiotic bacteria, can harbor opportunistic pathogens. Importantly, the human gut microbiota serves as a reservoir for AR determinants, collectively known as the ‘gut resistome.’ Tetracycline, beta-lactam, and macrolide resistance genes are among the many types of AR genes found in the gut microbiota, as shown by high-throughput DNA sequencing. Interestingly, the gut microbiota can be disproportionately affected by antibiotics such as tetracyclines and macrolides, potentially impacting the resistome during therapy.

Among the prominent gut commensals, Bacteroides strains exhibit high resistance rates, particularly to beta-lactams and tetracyclines. The spread of AR within the gut microbiota is dynamic, as evidenced by the transmission of resistance genes like tetQ via conjugative transposons like CTnDOT. It is imperative to take actions to slow down the growth of the gut resistome.

Antimicrobial resistance (AMR) dynamics in the human body are largely influenced by the gut microbiome resistome, which is made up of intrinsic and mobile resistance genes. Through integration into mobile genetic elements, intrinsic resistance genes can become mobile-resistant even in the absence of prior exposure. Particular genomic regions known as Resistance Islands serve as an example of the intricacy of mobile resistomes. For instance, the 𝘈𝘤𝘪𝘯𝘦𝘵𝘰𝘣𝘢𝘤𝘵𝘦𝘳 𝘣𝘢𝘶𝘮𝘢𝘯𝘯𝘪 Resistance Island, an 86-kb genomic island, hosts 45 antimicrobial resistance genes, enabling microbes to resist antibiotics through various mechanisms such as disabling antibiotic influx, active efflux pump-driven antibiotic expulsion, modification of antibiotic target sites, and degradation of intracellular antibiotics. This highlights the intricate interplay between intrinsic and mobile resistance in the gut microbiome.

Understanding the factors that shape and spread ARGs in the gut microbiome is crucial due to its diverse regulatory role in the human body. The gut microbiota exhibits a dynamic nature due to its exposure to all foods and drugs taken, underscoring the necessity of cataloging ARGs for thorough investigation and problem-solving. One of the most important ways that ARGs spread across the gut microbiome is by conjugation, transduction, and transformation, or horizontal gene transfer (HGT) via MGEs.

In the mammalian gut, transformation—the reception of naked DNA from the surrounding environment—occurs infrequently, but if the acquired DNA contains ARGs, the bacterium becomes resistant. Within the same phylogenetic taxa, conjugation—which entails the creation of a mating bridge for ARG transfer—occurs more frequently. Notably, increased inflammation of the gut boosts ARG transfer between commensals and other pathogens. Conversely, in the healthy gut, intestinal epithelial cells produce compounds that hinder conjugation, reducing ARG transfer.

Transduction, where ARGs are encoded in bacteriophages incorporated into the host, emerges as a significant player in the gut resistome. This is corroborated by the quantity of bacteria and phages in the digestive system; research indicates that the phages of mice treated with antibiotics have higher ARG isolates. The complex relationship that exists between AMR and the gut microbiota highlights how crucial it is to comprehend these mechanisms in order to create focused plans of action for reducing the widespread problem of antibiotic resistance.

The misuse of antimicrobial drugs in medical, environmental, and animal settings has severely disrupted the gut microbiota’s natural community. This disruption shows up as increased bacterial translocation and mucus layer malfunction. As a result, these changed circumstances set off a series of immunological reactions that begin with dendritic cell activation. and macrophages through microorganism-associated molecular patterns (MAMPs) recognized by Toll-like receptors (TLRs). This recognition induces neutrophil chemotaxis and the production of interleukin (IL), leading to local inflammation and eventual damage to epithelial cells.

As a consequence of this immune activation, antigen-presenting cells (APC) present antigens to prime and sustain T-cell responses, while B cells inhibit the production of Ig A by plasma cells. Overall in all, the outcome is an inflammatory condition that eventually plays a role in the emergence of chronic illnesses. A number of treatment strategies have been investigated to mitigate these negative consequences. One possible treatment option for bacterial strain disruptions in the gut microbiota is phage therapy, which uses bacteriophages to target particular strains of the bacteria. Furthermore, it appears that fecal microbiota transplantation and the ingestion of functional foods enhanced with probiotics and prebiotics are viable approaches to reestablish homeostasis and a balanced microbiome. These therapies have the capacity to target specific bacterial taxa, providing a holistic approach to counteract the consequences of antimicrobial abuse on the gut microbiota and prevent the associated complications of chronic inflammation.

Further Reading:

Human microbiomes and antibiotic resistance: https://tinyurl.com/38rr73c7

Antibiotic resistance in the commensal human gut microbiota: https://tinyurl.com/3c8zrc5t

Metagenomics of Antimicrobial Resistance in Gut Microbiome: https://tinyurl.com/5n89hwbz

Potential Elimination of Human Gut Resistome by Exploiting the Benefits of Functional Foods: https://tinyurl.com/mwy3hs26

Championing Antimicrobial Stewardship: A Fight for a Healthier Future

admin — Tue, 15 Oct 2024 11:30:56 +0000

Championing Antimicrobial Stewardship: A Fight for a Healthier Future

Microvioma
November 24, 2023

The threat of antimicrobial resistance looms globally, posing an enormous challenge to the treatment of infectious diseases. Behind this lurking health crisis lies the misuse and overuse of antibiotics, both in humans and animals, further catalyzing bacterial resistance. As we navigate these choppy waters, implementing a comprehensive and robust Antimicrobial Stewardship Program becomes imperative.

An Antimicrobial Stewardship Program is not just about judicious and rational antibiotic usage. It is a multidimensional endeavor involving the selection, dosing, route, and duration of antimicrobial treatment, all aimed towards achieving the best clinical outcomes with minimal adverse effects and the least impact on subsequent resistance. Through intricate layers of education, monitoring, and direct intervention, ASPs strive to effect crucial changes in prescribing behaviors. The benefits of Antimicrobial Stewardship are manifold. Reduced antibiotic resistance, improved patient outcomes, decreased side effects, and lower healthcare costs stand paramount. By systematically reducing unnecessary antibiotic use, we conserve the efficacy of existing antimicrobials, curbing the rise of resistance. ASPs also pinpoint inappropriate antimicrobial use, spot therapeutic failures, and streamline processes to improve patient care.

Strategizing an effective ASP begins with assembling a dedicated stewardship team. This team incorporates physicians, pharmacists, microbiologists, infection control specialists, and even information system experts. Their joint collaboration roots ASP in the very structure of healthcare provision. Providing these professionals with training and support to assume stewardship responsibilities is integral to the program’s success.

The implementation of an Antimicrobial Stewardship Program provides several benefits, including:

1. Improved Patient Outcomes: By ensuring appropriate prescribing, ASPs can help reduce treatment failures, improve cure rates, and decrease complications.

2. Reduced Antimicrobial Resistance: ASPs help conserve the efficacy of existing antimicrobials by discouraging unnecessary or inappropriate antibiotic use, thereby reducing the development of resistant organisms.

3. Cost-effectiveness: Through more judicious use of antimicrobials and higher cure rates, ASPs can substantially reduce healthcare costs, including those associated with long-term care for antibiotic-resistant infections.

4. Reduction in Adverse Drug Events: By encouraging a more rational use of antibiotics, ASPs can minimize the risk of adverse drug events, including antibiotic-associated side effects.

5. Reduced Spread of Infections: ASPs can help prevent the spread of multi-drug resistant organisms within healthcare settings, reducing the incidence and spread of difficult-to-treat infections.

6. Preservation of Antimicrobial Drugs: ASP initiatives help preserve the effectiveness of existing antibiotics for future use, by ensuring they are used appropriately and sparingly.

7. Educational Benefits: ASPs can provide valuable educational opportunities for healthcare providers, improving understanding of antibiotic use and resistance.

Actions taken under an ASP can range from prior authorization of particular antimicrobials, prospective audit with intervention and feedback, to continuous education about antimicrobial resistance and judicious antimicrobial use. Strategies also encompass the development and implementation of clinical guidelines and pathways for common infectious disease syndromes.

The next challenge is the smooth execution of the stewardship program. Regular and vigilant monitoring of antibiotic use forms the foundation of this stage. Advanced technological tools like electronic medical records can provide real-time prescription data, aiding in the identification of potentially unnecessary prescriptions.

ASP isn’t a solo endeavor. Active engagement of the entire healthcare team must be encouraged. The program’s purpose and importance should be effectively communicated through continuous education and discussions, leading to the ultimate adherence to the stewardship guidelines. In conclusion, Antimicrobial Stewardship is our best defensive line against the mounting menace of antimicrobial resistance. With meticulous planning, diligent implementation, and dedicated follow-through, effective antibiotic stewardship can be achieved. When done right, ASPs have the potential to significantly improve patient outcomes, reduce healthcare costs, and most importantly, safeguard our existing antibiotics for future use.

Let’s embrace this fight against antimicrobial resistance together, ensuring a healthier, more secure future for all. Through shared knowledge, collaboration and vigilance, we can sustain the power of antibiotics and keep a global health crisis at bay.