Current challenges in antimicrobial drugs

Current challenges in antimicrobial drugs

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  CURRENT CHALLENGES INANTIMICROBIAL DRUGS ANTIMICROBIAL DRUGS IN THE ENVIRONMENT: THE INDIAN SCENARIO A J A F R I N A Y S H A I M . S c . , M I C R O B I O L O G Y D E P A R T M E N T O F M I C R O B I O L O G Y A N D B I O T E C H N O L O G Y T H A S S I M B E E V I A B D U L K A D E R C O L L E G E F O R W O M E N , K I L A K A R A I
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  C O N T E N T S • INTRODUCTION • REPORTEDRATES OF AMR IN INDIA • AMR IN PEOPLE • AMR IN FOOD AND ANIMALS • AMR IN ENVIRONMENT • STEPS TAKEN TO CURB AMR IN THE ENVIRONMENT • Nano-Strategies to Fight Multidrug Resistant Bacteria — “A Battle of the Titans” • CONCLUSION • REFERENCES
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  INTRODUCTION 1 • Antibiotic resistancehappens when germs like bacteria and fungi develop the ability to defeat the drugs designed to kill them. 2 • In this fight against AMR, it is important to realize the contribution by all the following four spheres: humans, animals, food and environment. 3 • India has been referred to as ‘the AMR capital of the world’ With 7,00,000 people losing battle to antimicrobial resistance (AMR) per year and another 10 million projected to die from it by 2050, AMR alone is killing more people than cancer
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  REPORTED RATE OFAMR IN INDIA 1 • 2152 studies published by Indian institutions on AMR. 2 • AMR in humans • Overall 1040 studies were conducted on AMR in humans. The studies categorized as social were mainly focused on understanding. The knowledge, attitudes, practices, and ethical issues involving antibiotic use in the general public and among healthcare. Animals 3% Diagnostics 1% Environment 4% Humans 48% Miscellaneou s 12% Novel Agents 18% One Health 1% Review/Edit orial 13% Social 4% Clinical 13% Surveilance 83%
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  REPORTED RATE OFAMR IN INDIA 3 • AMR in animals • Overall, 70 studies were conducted on AMR in animals. • According to the statistics of 2015, India was the largest producer of milk and the second largest producer of fish in the world the poultry consumption in India is expected to rise by 577 per cent between year 2000 and 2030 • Examining alternative practices of food, animal, rearing and their economic impacts Understanding transmission resistance spreads from food animals to humans. Fish 16% Pultry 24% Livestock 30% Others 30%
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  REPORTED RATE OFAMR IN INDIA 4 • AMR in environment • A total of 90 studies were conducted on environmental AMR. • The presence of antimicrobial residues in various environmental sources such as rivers, recreational water, sewage treatment plants, hospital effluents, and industrial effluents. Studies examining antibiotic. Fresh Water 11% Hospital Effluent 10% Industry Effluent 7% Other 37% River Water 22% Sewage 13% 11.50% 56.60% 46.80% 67.30% 16.20% 56.60% 41.80% 70.90% 0.00% 10.00% 20.00% 30.00% 40.00% 50.00% 60.00% 70.00% 80.00% E. koli K. pneumoniae P. aeruginosa A. baumannii ResistancePercentage Gandra S et. al 2016 ICMR 2015
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  STEPS TAKEN TOCURB AMR IN THE ENVIRONMENT YEAR ACTIVITY 2010 Establishment of the National Task Force on AMR Containment 2011 Publication of the Situation Analysis on AMR 2011 Publication of National Policy on AMR Containment 2011 Jaipur Declaration on AMR Containment 2011 The Food Safety and Standards (Contaminants, Toxins and Residues) Regulations, by FSSAI 2011 Establishment of the National Programme on AMR Containment under the Twelfth Five Year Plan (2012–2017) 2012 National Program on Antimicrobial Stewardship, Prevention of Infection and Control (ASPIC) by ICMR 2013 Establishment of a National AMR Surveillance Network by NCDC and ICMR 2014 Inclusion of antibiotics in Schedule H1 category to avoid nonprescription sales of antibiotics 2016 Launch of the Red Line Campaign on Antibiotics to create awareness regarding rational usage of antibiotics 2016 Publication of National Treatment Guidelines for Antimicrobial Use in Infectious Diseases by NCDC 2016 National address by prime minister on the issue of antibiotic resistance in his Man Ki Baat (a radio program hosted by the Honourable Prime Minister of India) in August 2017 Publication of the National Action Plan for Containment of AMR and Delhi Declaration 2017 The Food Safety and Standards (Contaminants, Toxins and Residues) Regulations in food animals
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  NANO-STRATEGIES TO FIGHTMULTIDRUG RESISTANT BACTERIA - “A BATTLE OF THE TITANS” 1 • Recent advances in nanotechnology offer new prospects to develop novel formulations based on distinct types of nanoparticles (NPs) with different sizes and shapes and exhibit flexible antimicrobial properties. 2 • NPs exert their multitude of mechanisms, such as: • direct interaction with the bacterial cell wall; • inhibition of biofilm formation; • triggering of innate as well as adaptive host immune responses; • generation of reactive oxygen species (ROS); and • induction of intracellular effects
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  NANOPARTICLES (NPs) SIZE TARGETEDBACTERIA AND ANTIBIOTIC RESISTANCE ANTIBACTERIAL MECHANISMS FACTORS AFFECTING ANTIMICROBIAL ACTIVITY / TOXICITY REFERENCES Gold (Au) NP 1 - 100 nm Methicillin-resistant Staphylococcus aureus (MRSA) Loss of membrane potential, disruption of the respiratory chain, reduced ATPase activity, decline in tRNA binding to ribosome subunit, bacterial membrane disruption, generation of holes in the cell wall Roughness and Particle Size (Chen et al., 2014; Dizajet al., 2014; Rudramurthy et al., 2016; Hemeg, 2017; Zaidi et al., 2017) Silver (Ag) NP 1 - 100 nm Staphylococcus epidermidis, MRSA, vancomycin- resistant Enterococcus (VRE), extended-spectrum beta- lactamase (ESBL)-producing organisms, MDR Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, carbapenemand polymyxin B-resistant baumannii, carbapenemresistant P. aeruginosa A. and carbapenem- resistant Enterobacteriaceae (CRE) Reactive oxygen species (ROS) generation, lipid peroxidation, inhibition of cytochromes in the electron transport chain, bacterial membrane disintegration, inhibition of cell wall synthesis, increase in membrane permeability, dissipation of proton gradient resulting in lysis, adhesion to cell surface causing lipid and protein damage, ribosome destabilization, intercalation between DNA bases Particle Size and Shape of Particles (Dizaj et al., 2014; Cavassin et al., 2015; Rudramurthy et al., 2016; Hemeg, 2017; Zaidi et al., 2017) Copper (Cu) NP 2 - 350 nm MDR E. coil, A. baumannii Dissipation of cell membrane potential, ROS generation, lipid peroxidation, protein oxidation, DNA degradation Particle Size and Concentration (Chatterjee et al., 2014; Dizaj et al., 2014; Cavassin et al., 2015; Hemeg, 2017; Zaidi et al., 2017) Silica (Si) NP 20 - 400 nm MRSA Disruption of cell walls through ROS Particle Size, Shape and Stability (Dizaj et al., 2014; Zaidi et al., 2017) Aluminum (Al) NP 10 - 100 nm E. coli Disruption of cell walls through ROS (Rudramurthy et al., 2016; Hemeg, 2017) Iron oxide NP 1- 100 nm MDR E. coli, K. pneumoniae, MRSA ROS-generated oxidative stress: superoxide radicals (021, singlet oxygen (r02), hydroxyl radicals (OH-), hydrogen peroxide (H202) Has high chemical activity, tends to aggregate, oxidized by air resulting in loss of magnetism and dispersibility (Rudramurthy et al., 2016; Zaidi et al., 2017) Zinc oxide (ZnO) NP 10 - 100 nm Enterobacter aerogenes, E. coli, Klebsiella oxytoca, K. pneumoniae, MRSA, ESBL-producing E. coli, K. pneumoniae ROS production, disruption of membrane, adsorption to cell surface, and lipid and protein damage Particle Size and Concentration (Vandebriel and De Jong, 2012; Cavassin et al., 2015; Rudramurthy et al., 2016; Hemeg, 2017) Titanium doxide (TiO2) NP 30 - 45 nm E. coil, P aeruginosa, S. aureus, Enterococcus faecium ROS generation, adsorption to the cell surface Crystal Structure, Shape and Size (Rudramurthy at al., 2016; Hemeg, 2017) Magnesium Oxide (MgO) NP 15 - 100 nm S. aureus, E coli ROS generation, lipid peroxidation, electrostatic interaction, alkaline effect Particle Size, pH and Concentration (Rudramurthy et al., 2016) NANO-STRATEGIES TO FIGHT MULTIDRUG RESISTANT BACTERIA - “A BATTLE OF THE TITANS”
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  3 • The majorityof amputations in diabetic patients, which today represent greatest barrier to healing formation of biofilm. • There is an urgent need for novel anti-biofilm strategies and novel antimicrobial agents and, in this scenario, silver nanotechnology has received tremendous attention. NANO-STRATEGIES TO FIGHT MULTIDRUG RESISTANT BACTERIA - “A BATTLE OF THE TITANS”
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  CONCLUSION 1 • In theenvironment of India AMR posing a continuously increasing threat , urgent steps are necessary to halt its progress and spread. 2 • A multisectoral and multidisciplinary approach with combined efforts and supervision is required to tackle this problem. 3 • Infections causing non-healing wounds still remain a serious challenge, and clinical data indicate the presence of biofilm. • Effective anti-biofilm treatment are necessary and, in this scenario, nanotechnology offers novel approaches with unique properties.
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  REFERENCES • Antimicrobial resistancein the environment: The Indian scenario. Neelam Taneja and Megha Sharma -2018doi: 10.4103/ijmr.IJMR_331_18 • Scoping Report on Antimicrobial Resistance in India, November 2017 • Antimicrobial Silver Nanoparticles for Wound Healing Application: Progress and Future Trends Federica Paladini and Mauro Pollini 2019 Aug 9.doi: 10.3390/ma12162540