Antibiotics Acting on the Translational Machinery
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Swedres-Svarm 2019
2019 SWEDRES|SVARM Sales of antibiotics and occurrence of antibiotic resistance in Sweden 2 SWEDRES |SVARM 2019 A report on Swedish Antibiotic Sales and Resistance in Human Medicine (Swedres) and Swedish Veterinary Antibiotic Resistance Monitoring (Svarm) Published by: Public Health Agency of Sweden and National Veterinary Institute Editors: Olov Aspevall and Vendela Wiener, Public Health Agency of Sweden Oskar Nilsson and Märit Pringle, National Veterinary Institute Addresses: The Public Health Agency of Sweden Solna. SE-171 82 Solna, Sweden Östersund. Box 505, SE-831 26 Östersund, Sweden Phone: +46 (0) 10 205 20 00 Fax: +46 (0) 8 32 83 30 E-mail: [email protected] www.folkhalsomyndigheten.se National Veterinary Institute SE-751 89 Uppsala, Sweden Phone: +46 (0) 18 67 40 00 Fax: +46 (0) 18 30 91 62 E-mail: [email protected] www.sva.se Text, tables and figures may be cited and reprinted only with reference to this report. Images, photographs and illustrations are protected by copyright. Suggested citation: Swedres-Svarm 2019. Sales of antibiotics and occurrence of resistance in Sweden. Solna/Uppsala ISSN1650-6332 ISSN 1650-6332 Article no. 19088 This title and previous Swedres and Svarm reports are available for downloading at www.folkhalsomyndigheten.se/ Scan the QR code to open Swedres-Svarm 2019 as a pdf in publicerat-material/ or at www.sva.se/swedres-svarm/ your mobile device, for reading and sharing. Use the camera in you’re mobile device or download a free Layout: Dsign Grafisk Form, Helen Eriksson AB QR code reader such as i-nigma in the App Store for Apple Print: Taberg Media Group, Taberg 2020 devices or in Google Play. -
Writer Master Template
Nabriva Therapeutics AG Clinical Protocol NAB-BC-3781-3102 Clinical Protocol No. NAB-BC-3781-3102 A Phase 3, Randomized, Double-Blind, Double-Dummy Study to Compare the Efficacy and Safety of Oral Lefamulin (BC-3781) Versus Oral Moxifloxacin in Adults With Community-Acquired Bacterial Pneumonia US IND 125546 (Oral) EudraCT Number 2015-004782-92 Protocol Status Version Date Original 1.0 21-Dec-2015 Amendment 1 2.0 17-Feb-2016 Amendment 2 3.0 17-Mar-2016 The information contained herein is the property of Nabriva Therapeutics AG and may not be produced, published, or disclosed to others without written authorization of Nabriva Therapeutics AG. V3.0: 17-Mar-2016 Page 1 of 102 Confidential Information Nabriva Therapeutics AG Clinical Protocol NAB-BC-3781-3102 SPONSOR RELATED CONTACT DETAILS A Phase 3, Randomized, Double-Blind, Double-Dummy Study to Compare the Efficacy and Safety of Oral Lefamulin (BC-3781) Versus Oral Moxifloxacin in Adults With Community-Acquired Bacterial Pneumonia (Protocol NAB-BC-3781-3102 with Amendments 1 and 2) Sponsor: Nabriva Therapeutics AG Leberstraße 20 1110 Vienna Austria Sponsor’s Study Managers: Patricia Spera, PhD Nabriva Therapeutics US, Inc. 1000 Continental Drive, Suite 600 King of Prussia, PA 19406 USA Tel: +1 610 816 6656 Cell: +1 610 209 5574 Email: [email protected] Claudia Lell, PhD Nabriva Therapeutics AG Leberstraße 20 1110 Vienna Austria Tel: +43 1 74093 1242 Cell: +43 664 9631469 Email: [email protected] Sponsor’s Medical Officer: Leanne Gasink, MD Senior Director, Clinical Development and Medical Affairs Nabriva Therapeutics AG Nabriva Therapeutics US, Inc. -
Characterization of a Novel Gene, Srpa, Conferring Resistance to Streptogramin A, 2 Pleuromutilins, and Lincosamides in Streptococcus Suis1
bioRxiv preprint doi: https://doi.org/10.1101/2020.08.07.241059; this version posted August 7, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 1 Characterization of a novel gene, srpA, conferring resistance to streptogramin A, 2 pleuromutilins, and lincosamides in Streptococcus suis1 3 Chaoyang Zhang,a Lu Liu,a Peng Zhang,a Jingpo Cui,a Xiaoxia Qin, a Lichao Ma,a Kun Han,a 4 Zhanhui Wang b, Shaolin Wang b, Shuangyang Ding b, Zhangqi Shen a,b 5 6 a Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Veterinary 7 Medicine, China Agricultural University, Beijing, China. 8 b Beijing Key Laboratory of Detection Technology for Animal-Derived Food Safety and Beijing 9 Laboratory for Food Quality and Safety, China Agricultural University, Beijing, China 10 11 Address correspondence to Zhangqi Shen, [email protected]; 12 13 14 15 1 Abbreviations: Multidrug-resistant (MDR), methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecium (VRE), peptidyl-transferase center (PTC), transmembrane domains (TMDs), valnemulin (VAL), enrofloxacin (ENR), fluorescence polarization immunoassay (FPIA), nucleotide-binding sites (NBSs), fluorescence polarization (FP), carbonyl cyanide m- chlorophenylhydrazone (CCCP) bioRxiv preprint doi: https://doi.org/10.1101/2020.08.07.241059; this version posted August 7, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 16 Abstract 17 Antimicrobial resistance is undoubtedly one of the greatest global health threats. -
Third ESVAC Report
Sales of veterinary antimicrobial agents in 25 EU/EEA countries in 2011 Third ESVAC report An agency of the European Union The mission of the European Medicines Agency is to foster scientific excellence in the evaluation and supervision of medicines, for the benefit of public and animal health. Legal role Guiding principles The European Medicines Agency is the European Union • We are strongly committed to public and animal (EU) body responsible for coordinating the existing health. scientific resources put at its disposal by Member States • We make independent recommendations based on for the evaluation, supervision and pharmacovigilance scientific evidence, using state-of-the-art knowledge of medicinal products. and expertise in our field. • We support research and innovation to stimulate the The Agency provides the Member States and the development of better medicines. institutions of the EU the best-possible scientific advice on any question relating to the evaluation of the quality, • We value the contribution of our partners and stake- safety and efficacy of medicinal products for human or holders to our work. veterinary use referred to it in accordance with the • We assure continual improvement of our processes provisions of EU legislation relating to medicinal prod- and procedures, in accordance with recognised quality ucts. standards. • We adhere to high standards of professional and Principal activities personal integrity. Working with the Member States and the European • We communicate in an open, transparent manner Commission as partners in a European medicines with all of our partners, stakeholders and colleagues. network, the European Medicines Agency: • We promote the well-being, motivation and ongoing professional development of every member of the • provides independent, science-based recommenda- Agency. -
Inhibition of Peptide Bond Formation by Pleuromutilins: the Structure of the 50S Ribosomal Subunit from Deinococcus Radiodurans in Complex with Tiamulin
Blackwell Science, LtdOxford, UKMMIMolecular Microbiology0950-382XBlackwell Publishing Ltd, 2004? 200454512871294Original ArticleStructure of 50S ribosomal subunit in complex with TiamulinF. Schlünzen et al. Molecular Microbiology (2004) 54(5), 1287–1294 doi:10.1111/j.1365-2958.2004.04346.x Inhibition of peptide bond formation by pleuromutilins: the structure of the 50S ribosomal subunit from Deinococcus radiodurans in complex with tiamulin Frank Schlünzen,1 Erez Pyetan,2,3 Paola Fucini,1 clic nucleus composed of a cyclo-pentanone, cyclo-hexyl Ada Yonath2,3 and Jörg M. Harms2* and cyclo-octane, and a (((2-(diethylamino)ethyl)thio)- 1Max-Planck Institute for Molecular Genetics, D-14195 acetic acid) side-chain on C14 of the octane ring (Fig. 1A). Berlin, Germany. The drug is soluble in water and readily absorbed; it is 2Max-Planck-Research-Unit for Ribosome Structure, D- therefore one of the few antibiotics that can be easily 22607 Hamburg, Germany. administered to animals. So far, pleuromutilin derivatives 3Weizmann Institute of Science, IL-76100 Rehovot, Israel. are only employed in veterinary practice and most fre- quently to treat swine dysentery. However, the increasing number of pathogens resistant to common antibiotics has Summary raised a new interest in pleuromutilin derivatives, which Tiamulin, a prominent member of the pleuromutilin may be suitable for human therapy (Brooks et al., 2001; class of antibiotics, is a potent inhibitor of protein Bacque et al., 2002; 2003; Pearson et al., 2002; Springer synthesis in bacteria. Up to now the effect of pleuro- et al., 2003). mutilins on the ribosome has not been determined Early biochemical and genetic studies of the antimicro- on a molecular level. -
Reflection Paper on the Use of Macrolides, Lincosamides And
14 November 2011 EMA/CVMP/SAGAM/741087/2009 Committee for Medicinal Products for Veterinary Use (CVMP) Reflection paper on the use of macrolides, lincosamides and streptogramins (MLS) in food-producing animals in the European Union: development of resistance and impact on human and animal health Draft agreed by Scientific Advisory Group on Antimicrobials (SAGAM) 2-3 June 2010 Adoption by CVMP for release for consultation 10 November 2010 End of consultation (for comments) 28 February 2011 Agreed by Scientific Advisory Group on Antimicrobials (SAGAM) 22 September 2011 Adoption by CVMP 12 October 2011 7 Westferry Circus ● Canary Wharf ● London E14 4HB ● United Kingdom Telephone +44 (0)20 7418 8400 Facsimile +44 (0)20 7418 8416 E-mail [email protected] Website www.ema.europa.eu An agency of the European Union © European Medicines Agency, 2011. Reproduction is authorised provided the source is acknowledged. Reflection paper on the use of macrolides, lincosamides and streptogramins (MLS) in food-producing animals in the European Union: development of resistance and impact on human and animal health CVMP recommendations for action Macrolides and lincosamides are used for treatment of diseases that are common in food producing animals including medication of large groups of animals. They are critically important for animal health and therefore it is highly important that they are used prudently to contain resistance against major animal pathogens. In addition, MLS are listed by WHO (AGISAR, 2009) as critically important for the treatment of certain zoonotic infections in humans and risk mitigation measures are needed to reduce the risk for spread of resistance between animals and humans. -
Swedres-Svarm 2005
SVARM Swedish Veterinary Antimicrobial Resistance Monitoring Preface .............................................................................................4 Summary ..........................................................................................6 Sammanfattning................................................................................7 Use of antimicrobials (SVARM 2005) .................................................8 Resistance in zoonotic bacteria ......................................................13 Salmonella ..........................................................................................................13 Campylobacter ...................................................................................................16 Resistance in indicator bacteria ......................................................18 Escherichia coli ...................................................................................................18 Enterococcus .....................................................................................................22 Resistance in animal pathogens ......................................................32 Pig ......................................................................................................................32 Cattle ..................................................................................................................33 Horse ..................................................................................................................36 Dog -
Antibiotics and Antibiotic Resistance
This is a free sample of content from Antibiotics and Antibiotic Resistance. Click here for more information on how to buy the book. Index A Antifolates. See also specific drugs AAC(60)-Ib-cr, 185 novel compounds, 378–379 ACHN-975 overview, 373–374 clinical studies, 163–164 resistance mechanisms medicinal chemistry, 166 sulfamethoxazole, 378 structure, 162 trimethoprim, 374–378 AcrAB-TolC, 180 Apramycin, structure, 230 AcrD, 236 Arbekacin, 237–238 AdeRS, 257 Avibactam, structure, 38 AFN-1252 Azithromycin mechanism of action, 148, 153 resistance, 291, 295 resistance, 153 structure, 272 structure, 149 Aztreonam, structure, 36 AIM-1, 74 Amicoumacin A, 222 Amikacin B indications, 240 BaeSR, 257 structure, 230 BAL30072, 36 synthesis, 4 BB-78495, 162 Aminoglycosides. See also specific drugs BC-3205, 341, 344 historical perspective, 229–230 BC-7013, 341, 344 indications, 239–241 b-Lactamase. See also specific enzymes mechanism of action, 232 classification novel drugs, 237 class A, 67–71 pharmacodynamics, 238–239 class B, 69–74 pharmacokinetics, 238–239 class C, 69, 74 resistance mechanisms class D, 70, 74–77 aminoglycoside-modifying enzymes evolution of antibiotic resistance, 4 acetyltransferases, 233–235 historical perspective, 67 nucleotidyltransferases, 235 inhibitors phosphotransferases, 235 overview, 37–39 efflux-mediated resistance, 236 structures, 38 molecular epidemiology, 236–237 nomenclature, 67 overview, 17, 233 b-Lactams. See also specific classes and antibiotics ribosomal RNA modifications, 235–236 Enterococcus faecium–resistancemechanisms, -
In Vitro Antibacterial Spectrum of BC-7013, a Novel Pleuromutilin Derivative for Topical Use in Humans Nabriva Therapeutics AG Leberstrasse 20 ICAAC 2009 D.J
F1-1521 In Vitro Antibacterial Spectrum of BC-7013, a Novel Pleuromutilin Derivative for Topical Use in Humans Nabriva Therapeutics AG Leberstrasse 20 ICAAC 2009 D.J. BIEDENBACH1, R.N. JONES1, Z. IVEZIC-SCHOENFELD2, S. PAUKNER2, R. NOVAK2 1112 Vienna, Austria Tel.: +43 (0)1 74093 0 1 JMI Laboratories, North Liberty, Iowa, USA Fax.: +43 (0)1 74093 1900 2 Nabriva Therapeutics AG, Vienna, Austria www.nabriva.com Table 1. Antibacterial spectrum of BC-7013 and topical comparator antibiotics tested against Gram-positive bacteria Abstract Methods % susceptible/ % susceptible/ Conclusions Antimicrobial agent MIC MIC Range Antimicrobial agent MIC MIC Range 50 90 resistant a 50 90 resistant a Background: BC-7013 [14-O-[(3-Hydroxymethyl-phenylsulfanyl)-acetyl]-mutilin] is a novel Organism Collection: The activity of BC-7013 was determined against bacterial pathogens • BC-7013 was the most active compound against common Gram- semi-synthetic pleuromutilin derivative that inhibits prokaryotic protein synthesis. BC-7013 is in causing uSSSI. Organisms included strains isolated from patients in either the United States S. aureus (303) CoNS (105) early stage of clinical development for the topical treatment of uncomplicated skin and skin (USA, 52.3%) or European (47.6%) medical centers (n=67) primarily during 2006 to 2007. Less BC-7013 0.015 0.03 0.008 – 0.03 - / - BC-7013 0.03 0.06 0.008 – >8 - / - positive bacterial pathogens such as S. aureus, S. pyogenes and S. structure infections (uSSSI). We assessed BC-7013 activity against a wide range of clinical commonly isolated species and those organisms w ith characterized resistance mechanism were Retapamulin 0.12 0.12 0.03 – 0.12 - / - Retapamulin 0.06 0.5 0.015 – >8 - / - agalactiae when compared with other topical antibiotics. -
Lefamulin the Potential for 1 Antibiotic Rather Than 2 in CABP March 13, 2018
Lefamulin The potential for 1 antibiotic rather than 2 in CABP March 13, 2018 Prof. Mark H. Wilcox Professor of Medical Microbiology Leeds Teaching Hospitals & University of Leeds Confidential Disclosures Mark H. Wilcox has received Consulting fees from Abbott Laboratories, Actelion, Antabio, AiCuris, Astellas, Astra-Zeneca, Bayer, Biomèrieux, Cambimune, Cerexa, Da Volterra, The European Tissue Symposium, Ferring, The Medicines Company, MedImmune, Menarini, Merck, Meridian, Motif Biosciences, Nabriva, Paratek, Pfizer, Qiagen, Roche, Surface Skins, Sanofi-Pasteur, Seres, Summit, Synthetic Biologics, and Valneva Lecture fees from Abbott, Alere, Allergan, Astellas, Astra-Zeneca, Merck, Pfizer, Roche, and Seres Grant support from Abbott, Actelion, Astellas, Biomèrieux, Cubist, Da Volterra, Merck, MicroPharm, Morphochem AG, Sanofi-Pasteur, Seres, Spero, Summit, and The European Tissue Symposium Confidential Pleuromutilin Antibacterial Agents • Pleuromutilin antibiotics inhibit translation and are O OH R O 14 semisynthetic derivatives of the naturally occurring tricyclic H diterpenoid pleuromutilin isolated from an edible mushroom – Veterinary use: tiamulin and valnemulin (oral treatment of dysentery O Pleuromutilin R = OH and respiratory infections in swine and poultry) Pleurotus mutilus (Clitopilus – Human use: retapamulin (topical treatment of uSSSTI caused by scyphoides) MSSA or Streptococcus spp) Source: James Lindsey's Ecology of Commanster Site, 2006 • Lefamulin was discovered by Nabriva and is the first systemic CH2 pleuromutilin for -
Concept Paper
Concept Paper: Potential Approach for Ranking of Antimicrobial Drugs According to Their Importance in Human Medicine: A Risk Management Tool for Antimicrobial New Animal Drugs Introduction This concept paper discusses a potential approach to considering the human medical importance of antimicrobial drugs when assessing and managing antimicrobial resistance risks associated with the use of antimicrobial drugs in animals. In 2003, FDA established a list ranking antimicrobial drugs according to their relative importance in human medicine primarily for the purpose of supporting a qualitative risk assessment process outlined in agency guidance. It was envisioned by the Agency at the time the current medical importance rankings list was published that it would periodically reassess the rankings to align with contemporary science and current human clinical practices. To that end, this paper describes a potential revised process for ranking antimicrobial drugs according to their relative importance in human medicine, potential revised criteria to determine the medical importance rankings, and the list of antimicrobial drug medical importance rankings that would result if those criteria were to be used. Disclaimer: This concept paper is for discussion purposes only. The intent of this concept paper is to obtain public comment and early input on a potential approach to consider the human medical importance of antimicrobial drugs when assessing and managing antimicrobial resistance risks associated with the use of antimicrobial drugs in animals. This concept paper does not contain recommendations and does not constitute draft or final guidance by the Food and Drug Administration. It should not be used for any purpose other than to facilitate public comment. -
19 June 2019
Belgian Veterinary Surveillance of Antibacterial Consumption National consumption report 2018 Publication : 19 June 2019 1 SUMMARY This annual BelVet-SAC report is now published for the 10th time and describes the antibacterial use in animals in Belgium in 2018 and the evolution since 2011. For the first time this report combines sales data (collected at the level of the wholesalers- distributors and the compound feed producers) and usage data (collected at herd level). This allows to dig deeper into AMU at species and herd level in Belgium. With -12,8% mg antimicrobial/kg biomass in comparison to 2017, 2018 marks the largest reduction in total sales of antimicrobials for animals in Belgium since 2011. This obviously continues the decreasing trend of the previous years, resulting in a cumulative reduction of -35,4% mg/kg since 2011. This reduction is evenly split over a reduction in pharmaceuticals (-13,2% mg/kg) and antibacterial premixes (-9,2% mg/kg). It is speculated that the large reduction observed in 2018 might partly be due to the effect of extra stock (of pharmaceuticals) taken during 2017 by wholesalers-distributors and veterinarians in anticipation of the increase in the antimicrobial tax for Marketing Authorisation Holders, which became effective on the 1st of April 2018. When comparing the results achieved in 2018 with the AMCRA 2020 reduction targets, the goal of reducing the overall AMU in animals with 50% by 2020 has not been achieved yet, however, the objective comes in range with still 14,6% to reduce over the next two years. Considering the large reduction observed in total AMU in 2018, it is not surprising that also in the pig sector a substantial reduction of -8,3% mg/kg between 2017 and 2018 is observed based upon the usage data.