10.01.2015
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2 Market Overview and Dynamics 2.1 Market Size and Forecast 2.1.1 Impact of COVID-19 on the Market 2.2 Major Growth Drivers 2.3 Market Restraints and Challenges 2.4 Emerging Opportunities and Market Trends 2.5 Porter's five Forces Analysis. 3 Segmentation of Global Market by Drug Class 3.1 Market Overview by Drug Class 3.2 Cephalosporin 3.3 Penicillin 3.4 Macrolides 3.5 Fluoroquinolones 3.6 Quinolones 3.7 Monobactam 3.8 Aminoglycosides 3.9 Carbapenem 3.10 Other Drug Classes. 4 Segmentation of Global Market by Action Mechanism 4.1 Market Overview by Action Mechanism 4.2 Cell Wall Synthesis Inhibitors 4.3 Mycolic Acid Inhibitors 4.4 RNA Synthesis Inhibitors 4.5 DNA Synthesis Inhibitors 4.6 Protein Synthesis Inhibitors 4.7 Other Mechanisms. 5 Segmentation of Global Market by Drug Origin 5.1 Market Overview by Drug Origin 5.2 Natural Antibiotics 5.3 Semi-synthetic Antibiotics 5.4 Synthetic Antibiotics. 6 Segmentation of Global Market by Activity Spectrum 6.1 Market Overview by Activity Spectrum 6.2 Broad-spectrum Antibiotics 6.3 Narrow-spectrum Antibiotics. 7 Segmentation of Global Market by Route of Administration 7.1 Market Overview by Route of Administration 7.2 Oral Administration 7.3 Intravenous Administration 7.4 Other Administration Routes. 8 Segmentation of Global Market by Drug Type 8.1 Market Overview by Drug Type 8.2 Brand Antibiotics 8.3 Generic Antibiotics. 10 Competitive Landscape 10.1 Overview of Key Vendors 10.2 New Product Launch, Partnership, Investment, and M&A 10.3 Company Profiles. Abbott Laboratories Astellas Pharma AstraZeneca Plc Bayer AG Bristol Myers Squibb Company Cipla Inc. 11 Investing in Global Market: Risk Assessment and Management 11.1 Risk Evaluation of Global Market 11.2 Critical Success Factors (CSFs) For more information about this report visit https://www.researchandmarkets.com/r/dad9v5. Research and Markets also offers Custom Research services providing focused, comprehensive and tailored research. Gene test can predict risk of medications causing liver injury. Organoid-related discovery may also help drug makers screen potential pharmaceuticals. CINCINNATI–Scientists who were working on a way to determine the viability of batches of tiny liver organoids have discovered a testing method that may have far broader implications. 7, 2020, in Nature Medicine , reports identifying a “polygenic risk score” that shows when a drug, be it an approved medication or an experimental one, poses a risk of drug-induced liver injury (DILI). The work was conducted by consortium of scientists from Cincinnati Children’s, Tokyo Medical and Dental University, Takeda Pharmaceutical Co. in Japan, and several other research centers in Japan, Europe and the US. The findings take a large step toward solving a problem that has frustrated drug developers for years. “So far we have had no reliable way of determining in advance whether a medication that usually works well in most people might cause liver injury among a few,” says Jorge Bezerra, MD, Director, Division of Gastroenterology, Hepatology and Nutrition at Cincinnati Children’s. “That has caused a number of promising medications to fail during clinical trials, and in rare cases, also can cause serious injury from approved medications. If we could predict which individuals would be most at-risk, we could prescribe more medications with more confidence,” says Bezerra, who was not involved with the study. Now that reliable test might be just around the corner. “Our genetic score will potentially benefit people directly as a consumer diagnostic-like application, such as 23andMe and others. People could take the genetic test and know their risk of developing DILI,” says corresponding author Takanori Takebe, MD, an organoid expert at Cincinnati Children’s who has been studying ways to grow liver “buds” for large-scale use in research. The team developed the risk score by re-analyzing hundreds of genome-wide association studies (GWAS) that had identified a long list of gene variants that might indicate a likelihood of a poor reaction in the liver to various compounds. By combining the data and applying several mathematical weighting methods, the team found a formula that appears to work. The risk score takes more than 20,000 gene variants into account. The team confirmed the score’s prediction power in cell culture, in organoid tissue and by using patient genomic data already on file. The score was valid in tests involving more than a dozen medications: cyclosporine, bosentan, troglitazone, diclofenac, flutamide, ketoconazole, carbamazepine, amoxicillin-clavulanate, methapyrilene. The test works for different types of drugs because the score focuses on a set of common mechanisms involved in how the liver metabolizes a drug, including oxidant stress pathways in liver cells and endoplasmic reticulum (ER) stress–a disruption of cell function that happens when proteins cannot fold properly. For clinicians, this would allow them to run a quick genetic test to identify patients at higher risk of liver injury before prescribing medications. The results might prompt a doctor to change the dosage, order more frequent follow-up tests to catch early signs of liver damage, or switch medications entirely. For drug research, the test could help exclude people of high risk of liver injury from a clinical trial so that the benefits of a medication can be more accurately assessed. Liver toxicity has caused a number of drug failures over the years. Takebe says both patients and the drug maker were disappointed when a potential diabetes treatment called fasigliam was withdrawn in 2014 during phase 3 clinical trials. Some of the participants (at a rate equivalent to about 1 in 10,000) experienced elevated enzyme levels that suggested potential liver injury. While such risks may appear low, at the time there was no way to predict which people would develop DILI, making the drug unacceptably dangerous. But the new polygenic risk score would make it possible to produce liver organoids that exhibit key risk variants to determine if a drug is harmful before people ever take it. Takebe and colleagues demonstrated how to produce liver buds on a mass scale in 2017 in a study published in Cell Reports . The team has improved upon the process since, reporting success in 2019 in Cell Metabolism at engineering liver organoids that model disease. However, more research involving a more-diverse population is needed to confirm the initial findings and to scale up a DILI screening test for potentially widespread use, Takebe says. In addition to Cincinnati Children’s, collaborators on this study included experts from Yokohama City University, the T-CiRA Joint Program, Takeda Pharmaceutical Company, and the Tokyo Medical and Dental University in Japan; Nottingham and Newcastle Universities in the United Kingdom; the Icahn School of Medicine at Mount Sinai in New York, and the University of North Carolina, Funding sources primarily include Takeda Pharmaceutical Company via the T-CiRA program (Director, Shinya Yamanaka).Sources also include the National Institutes of Health (UG3 DK119982), , the New York Stem Cell Foundation, Cincinnati Children’s Research Foundation, the Dr. Ralph and Marian Falk Medical Research Trust Awards Program, the Takeda Science Foundation, the Mitsubishi Foundation award, and AMED JP19fk0210037, JP19bm0704025, JP19fk0210060, JP19bm0404045 and JSPS JP18H02800,19K22416. Media Contact Tim Bonfield [email protected] The Open Biotechnology Journal. Online Submission Submit Abstract Online Submit Issue Proposal Aims and Scope Abstracted / Indexed in View Published Contents. New Journal Website Journal Home Editorial Board Board Recruitment Workflow Instructions for Authors Plagiarism Prevention Editorial Policies Publishing Ethics and Rectitude Quick Track Option Reviewer Guidelines Peer Review Workflow Guidelines for Guest Editors Publication Fee Publication Cycle - Process Flowchart Archiving Policies. Antimicrobials Misuse/Overuse: Adverse Effect, Mechanism, Challenges and Strategies to Combat Resistance. Mittal 1 , 2 , * , Rohit Bhardwaj 1 , Priya Mishra 3 , Satyendra K. Overuse and misuse of antibiotics are the first risk factors for the development of antibiotics resistance. Inadequate professional competence of health care physicians might worsen the complications associated with antibiotics resistance. Antibiotic resistance is a global issue; however, the epicenter of this misfortune is Asian regions due to the easy accessibility of the strongest antibiotics without prescriptions or diagnoses. High effectiveness and easy accessibility of antibiotics lead to overuse/misuse and encouraging bacteria to develop the resistance. The over-usage and mis-usage of antibiotics are antibiotic abuse, which increase the potentially serious impact on human health. Bestowing to WHO guidelines, the resistance has led to spread worldwide and classifying resistance is a serious health problem. Furthermore, resistance claims uncertainty to predict the future. This review summarizes the major antibiotics involved in drug resistance, mechanism, prescribed dosage with a disease condition, proposed policies and guidelines to combat antibiotic resistance associated problems. Identifiers and Pagination: Article History: © 2020 Mittal et al . open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: (https://creativecommons.org/licenses/by/4.0/legalcode). This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. * Address correspondence to this author at the Amity Institute of Pharmacy (AIP), Lab no-G-01, Block-L-1, Amity Institute of Pharmacy, Amity University, Noida, Uttar Pradesh (UP), India -201313; Tel: 0120-4735655; E-mail: akmittal@amity.edu; amitkrbiotech@gmail.com. Open Peer Review Details Manuscript submitted on 3-3-2020 Original Manuscript Antimicrobials Misuse/Overuse: Adverse Effect, Mechanism, Challenges and Strategies to Combat Resistance. Antimicrobial Resistance (AMR) has emerged as a major risk to public health estimated to cause 1 crore deaths annually by 2050 [ 1 Dixit A, Kumar N, Kumar S, Trigun V. Antimicrobial resistance: Progress in the decade since emergence of New Delhi metallo-?-lactamase in India. Annually, more than 50,000 newborns die from sepsis due to resistance against first-line antibiotics [ 1 Dixit A, Kumar N, Kumar S, Trigun V. Antimicrobial resistance: Progress in the decade since emergence of New Delhi metallo-?-lactamase in India. Carbapenem resistance in Klebsiella pneumoniae due to the New Delhi Metallo-?-lactamase. [http://dx.doi.org/10.1093/cid/ciq178] [PMID: 21258100] ]. The overuse and misuse of antibiotics are vital issues contributing to the development of antibiotic resistance, causing potentially serious effects on human health [ 3 de Carvalho CC, Caramujo MJ. Ancient procedures for the high-tech World: health benefits and antimicrobial compounds from the Mediterranean Empires. Open Biotechnol J 2008; 2(1) [http://dx.doi.org/10.2174/1874070700802010235] ]. Several countries are facing the emergence of drug-resistant bacteria, which are completely resistant to available antibiotics. Most of the countries are preparing a country-specific action plan for the management of AMR globally, according to WHO guidelines [ 1 Dixit A, Kumar N, Kumar S, Trigun V. Antimicrobial resistance: Progress in the decade since emergence of New Delhi metallo-?-lactamase in India. Carbapenem resistance in Klebsiella pneumoniae due to the New Delhi Metallo-?-lactamase. [http://dx.doi.org/10.1093/cid/ciq178] [PMID: 21258100] ]. Asian countries have the largest burdens of drug-resistant strains worldwide [ 4 Porter G, Grills N. Medication misuse in India: A major public health issue in India. [http://dx.doi.org/10.1093/pubmed/fdv072] [PMID: 26060236] ]. Furthermore, India is one of the major consumers of antibiotics in the world and their overuse and misuse are rambling [ 4 Porter G, Grills N. Medication misuse in India: A major public health issue in India. [http://dx.doi.org/10.1093/pubmed/fdv072] [PMID: 26060236] ]. Besides, India is at one of the top rates of resistance against antimicrobials that are used for the treatment of humans and farm animals [ 5 Van Boeckel TP, Brower C, Gilbert M, et al. Global trends in antimicrobial use in food animals. [http://dx.doi.org/10.1073/pnas.1503141112] [PMID: 25792457] ]. Currently, antibiotics are also utilizing against the treatment of several species of fungi and protozoans infections, but the impact of these is very toxic to humans and animals [ 6 Waksman SA. Antibiotics' effectiveness and easy access can lead to overuse or misuse prompting to develop resistance in microorganisms. In addition, inappropriate antibiotic dosages have also contributed to the emergence of antibiotic-resistant bacterial strains [ 7 Lewis R. Unappropriated practices of antibiotics have long been believed to fuel AMR, but newer research showed that simply lowering consumption is not enough [ 8 Cunha CB. Antimicrobial stewardship programs: Principles and practice. [http://dx.doi.org/10.1016/j.mcna.2018.04.003] [PMID: 30126571] ]. Significant problems are arising due to the development of antibiotic-resistant strains of bacteria and further creation of multidrug-resistant bacterial spp [ 9 Magiorakos AP, Srinivasan A, Carey RB, et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: An international expert proposal for interim standard definitions for acquired resistance. [http://dx.doi.org/10.1111/j.1469-0691.2011.03570.x] [PMID: 21793988] ]. The multidrug-resistant bacterial spp., having resistance to multiple antibiotics, can cause life-threatening infections [ 10 Bassetti M, Righi E. For example, overuse of fluoroquinolone and other associated antibiotics can also lead to such kind of antibiotic resistance in bacteria [ 11 Fair RJ, Tor Y. Antibiotics and bacterial resistance in the 21st century. Developments of superbugs are the result of such kinds of antibiotic associated evils [ 12 Alpert PT. Superbugs: antibiotic resistance is becoming a major public health concern. In addition, few antibiotics have been associated with adverse side effects, including mild to very serious symptoms that depend upon treated microbial sps and individual patients [ 13 Torok E, Moran E, Cooke F. Oxford handbook of infectious diseases and microbiology 2016. [http://dx.doi.org/10.1093/med/9780199671328.001.0001] ]. The antibiotics can sometimes alter the host microbiota and lead to chronic infection and inflammation [ 14 Langdon A, Crook N, Dantas G. The effects of antibiotics on the microbiome throughout development and alternative approaches for therapeutic modulation. [http://dx.doi.org/10.1186/s13073-016-0294-z] [PMID: 27074706] ]. Usually, antibiotics side-effects are fever, nausea and major allergic reactions, including photo-dermatitis and anaphylaxis. The common side-effect of antibiotics is diarrhea, due to the misbalancing of the intestinal flora species or overgrowth of pathogenic bacteria [ 15 Bhattacharya S.
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