DOCSLIB.ORG

(12) Patent Application Publication (10) Pub. No.: US 2010/0062974 A1 Laronde Et Al

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
(12) Patent Application Publication (10) Pub. No.: US 2010/0062974 A1 Laronde Et Al US 2010.0062974A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2010/0062974 A1 LaRonde et al. (43) Pub. Date: Mar. 11, 2010 (54) COMBINATION THERAPY FOR THE Publication Classification TREATMENT OF BACTERAL INFECTIONS (51) Int. Cl. (75) Inventors: Frank LaRonde, Toronto (CA); st 4.5 CR Hanje Chen, Toronto (CA); Selva ( .01) Sinnadurai, Scarborough (CA) A63/496 (2006.01) A63L/7048 (2006.01) Correspondence Address: A63L/43 (2006.01) CLARK & ELBNG LLP A6II 3/42 (2006.01) 101 FEDERAL STREET A63L/464 (2006.01) A6IP3 L/10 (2006.01) (73) Assignee: Interface Biologics, Inc., Toronto (CA) (52) U.S. Cl. .......... 514/8: 514/635: 514/253.08: 514/40: 514/197; 514/380: 514/399 (21) Appl. No.: 12/419,733 (22) Filed: Apr. 7, 2009 (57) ABSTRACT O O The invention features a method for treating a Subject diag Related U.S. Application Data nosed with, or at risk of developing, a bacterial infection by (60) Provisional application No. 61/123,231, filed on Apr. administering to the Subject a combination of biologically 7, 2008. active agents. US 2010/0062974 A1 Mar. 11, 2010 COMBINATION THERAPY FOR THE ond agent selected from fluoroquinolones, aminoglycosides, TREATMENT OF BACTERAL INFECTIONS B-lactams, glycopeptide antibiotics, Sulfonamides, and anti fungal azoles. CROSS-REFERENCE TO RELATED 0008. The invention further features a composition includ APPLICATIONS ing a biodegradable polymer having a first repeating unit and 0001. This application claims benefit from U.S. Provi a second repeating unit, the first repeating unit including a sional Application No. 61/123,231, filed Apr. 7, 2008, hereby membrane active biocide and the second repeating unit incorporated by reference. including a second agent selected from fluoroquinolones, aminoglycosides, B-lactams, glycopeptide antibiotics, Sul BACKGROUND OF THE INVENTION fonamides, and antifungal azoles. 0009. The invention also features a composition including 0002 The present invention relates to the field of antibac (i) a biodegradable polymer including a repeating unit includ terial therapy. ing a membrane active biocide and (ii) a second agent 0003. The use of antibiotics by humans can be seen as an selected from fluoroquinolones, aminoglycosides, B-lactams, evolutionary experiment of enormous magnitude, a window glycopeptide antibiotics, Sulfonamides, and antifungal from which to view not-quite-natural selection operating in azoles. real time. Within 50 years, the number of species and strains 0010. In a related aspect the invention features a compo of pathogenic and commensal bacteria resistant to antibiotics sition including (i) a biodegradable polymer including a and the number of antibiotics to which they are resistant has repeating unit including a second agent selected from fluoro increased virtually monotonically world-wide. As a result, quinolones, aminoglycosides, B-lactams, glycopeptide anti infections that had been readily treatable by chemotherapy biotics, Sulfonamides, and antifungal azoles and (ii) a mem may no longer be so. It is clear that the evolution and spread brane active biocide. of resistance can be attributed to the use and overuse of antibiotics. Increased resistance of bacterial infections to 0011. The invention further features a composition includ antibiotic treatment has been extensively documented and has ing (i) a first biodegradable polymer including a repeating now become a generally recognized medical problem, par unit including a membrane active biocide and (ii) a second ticularly with nosocomial infections. See, for example, Jones biodegradable polymer including a repeating unit including a et al., Diagn. Microbiol. Infect. Dis. 31:379-388, 1998; Mur second agent selected from fluoroquinolones, aminoglyco ray, Adv. Intern. Med. 42:339-367, 1997; and Nakae, Micro sides, B-lactams, glycopeptide antibiotics, Sulfonamides, and biologia 13:273-284, 1997. antifungal azoles. 0004 Throughout the developed world there is public and 0012. The invention further features a method of reducing governmental concern about the increasing prevalence of bacterial growth on a Surface by contacting the Surface with a antimicrobial resistance to chemotherapy in bacteria that composition including a membrane active biocide and a sec cause diseases in humans. Many pathogens exist for which ond agent selected from fluoroquinolones, aminoglycosides, there are few effective treatments, and the number of strains B-lactams, glycopeptide antibiotics, Sulfonamides, and anti resistant to available drugs is continually increasing. New fungal azoles in amounts that together are effective to reduce antimicrobial agents and improved methods are thus needed bacterial growth. for the treatment and prevention of infections by such patho 0013 The invention also features a method of reducing genS. bacterial growth on a surface by coating the Surface with a biodegradable polymer including a first repeating unit and a SUMMARY OF THE INVENTION second repeating unit, the first repeating unit including a 0005 We have discovered that a combination of a mem membrane active biocide and the second repeating unit brane active biocide (e.g., chlorhexidine) and a second agent including a second agent selected from fluoroquinolones, selected from fluoroquinolones, aminoglycosides, B-lactams, aminoglycosides, B-lactams, glycopeptide antibiotics, Sul glycopeptide antibiotics, Sulfonamides, and antifungal azoles fonamides, and antifungal azoles. is more effective in treating bacterial infections and reducing 0014. The invention further features a method of reducing bacterial growth than either agent alone. We have also dis fungal growth on a Surface by contacting the Surface with a covered that a combination of a Sulfonamide (e.g., Sul composition including a membrane active biocide and a sec famethoxazole) and a second agent selected from B-lactams ond agent selected from fluoroquinolones, aminoglycosides, and antifungal azoles is more effective in treating bacterial B-lactams, glycopeptide antibiotics, Sulfonamides, and anti infections and reducing bacterial growth than either agent fungal azoles in amounts that together are effective to reduce alone. Thus, the invention features compositions, methods, fungal growth. and kits including these effective combinations, which can be 0015 The invention also features a method of reducing useful for the treatment and prevention of infections. fungal growth on a surface by coating the Surface with a 0006. Accordingly, in a first aspect the invention features a biodegradable polymer including a first repeating unit and a composition including a membrane active biocide and a sec second repeating unit, the first repeating unit including a ond agent selected from fluoroquinolones, aminoglycosides, membrane active biocide and the second repeating unit B-lactams, glycopeptide antibiotics, Sulfonamides, and anti including a second agent selected from fluoroquinolones, fungal azoles in amounts that together are sufficient in vivo to aminoglycosides, B-lactams, glycopeptide antibiotics, Sul treat a bacterial infection. fonamides, and antifungal azoles. 0007. In a related aspect, the invention features a biode 0016. In certain embodiments of the above methods, the gradable polymer including a first repeating unit and a second Surface is, for example, a surface of an implantable medical repeating unit, the first repeating unit including a membrane device (e.g., a cardiac-assist device, a catheter, a stent, a active biocide and the second repeating unit including a sec prosthetic implant, a Suture, a cuff, a mesh, a hernia patch, a US 2010/0062974 A1 Mar. 11, 2010 wound dressing, a bandage, an artificial sphincter, or a drug 0025. The invention also features a kit including: (i) an delivery device) or any other surface described herein. implantable medical device; (ii) a composition including a 0017. The invention also features a method of treating a membrane active biocide and a second agent selected from bacterial infection in a Subject, the method including admin fluoroquinolones, aminoglycosides, 3-lactams, glycopeptide istering a membrane active biocide and a second agent antibiotics, Sulfonamides, and antifungal azoles; and (iii) selected from fluoroquinolones, aminoglycosides, B-lactams, instructions for coating the implantable medical device with glycopeptide antibiotics, Sulfonamides, and antifungal azoles the composition. to the Subject in amounts that together are sufficient in vivo to 0026. In certain embodiments of the kits of the invention, treat the bacterial infection. the composition is a biodegradable polymer including a first 0018. The invention also features a method of treating a repeating unit and a second repeating unit, the first repeating fungal infection in a Subject, the method including adminis unit including a membrane active biocide and the second tering a membrane active biocide and a second agent selected repeating unit including the second agent. Alternatively, the from fluoroquinolones, aminoglycosides, 3-lactams, glyco composition is a mixture of (i) a biodegradable polymer peptide antibiotics, Sulfonamides, and antifungal azoles to the including a repeating unit including a membrane active bio Subject in amounts that together are sufficient in Vivo to treat cide and (ii) the secondagent, a mixture of (i) a biodegradable the fungal infection. polymer including a repeating unit including the secondagent and (ii) a membrane active biocide; or a mixture of (i) a first 0019. In certain embodiments, the membrane active
Load more

Recommended publications
  • Comparison Between the Molecular and Crystal Structures of a Benzylpenicillin Ester and Its Corresponding Sulfoxide with Drastically Reduced Biological Activity
    Comparison between the Molecular and Crystal Structures of a Benzylpenicillin Ester and its Corresponding Sulfoxide with Drastically Reduced Biological Activity Harald Labischinski*, Dieter Naumann Robert-Koch-Institut des Bundesgesundheitsamtes, Nordufer 20, D-1000 Berlin (West) 65 Gerhard Barnickel3, Wolfgang Dreißig, Wojciech Gruszecki, Andreas Hofer, and Hans Bradaczek Institut für Kristallographie, Freie Universität Berlin, Takustraße 6, D-1000 Berlin (West) 33 Z. Naturforsch. 42b, 367-375 (1987); received June 30/0ctober 14, 1986 X-Ray, Penicillin G, Penicillin G Sulfoxide, Thiazolidine Ring Conformation, Structure Activity Relationships A comparative X-ray structure determination was performed to elucidate possible conforma- tional differences between penicillins and penicillin sulfoxides. Penicillin-G-acetoxy-methylester and its Iß-oxide were used as model substances, because the only chemical difference between both compounds resides in the thiazolidine ring sulfur oxidation. On the basis of the X-ray data as well as of infrared measurements it is discussed that the drastically reduced biological activity of the penicillin-G-sulfoxide might be related to conformational differences in thiazolidine ring puckering or, even more simply, to the geometric position of the sulfoxide oxygen atom, both of which may hamper the proper reaction of the sulfoxide with its target enzyme(s). Introduction transformation, i.e. no penetration problems nor /3-Lactam antibiotics, although being in therapeut- any destruction by ß-lactamases should occur): First, ical use for more than 40 years, still provide the most the chemical reactivity leading to the acylation of the widely used antibacterial drugs. An enormous target enzyme might be changed or, secondly the amount of chemical modifications of the originally ability for proper interaction with the protein might discovered penicillin G structure has been syn- be affected by conformational factors.
    [Show full text]
  • Consideration of Antibacterial Medicines As Part Of
    Consideration of antibacterial medicines as part of the revisions to 2019 WHO Model List of Essential Medicines for adults (EML) and Model List of Essential Medicines for children (EMLc) Section 6.2 Antibacterials including Access, Watch and Reserve Lists of antibiotics This summary has been prepared by the Health Technologies and Pharmaceuticals (HTP) programme at the WHO Regional Office for Europe. It is intended to communicate changes to the 2019 WHO Model List of Essential Medicines for adults (EML) and Model List of Essential Medicines for children (EMLc) to national counterparts involved in the evidence-based selection of medicines for inclusion in national essential medicines lists (NEMLs), lists of medicines for inclusion in reimbursement programs, and medicine formularies for use in primary, secondary and tertiary care. This document does not replace the full report of the WHO Expert Committee on Selection and Use of Essential Medicines (see The selection and use of essential medicines: report of the WHO Expert Committee on Selection and Use of Essential Medicines, 2019 (including the 21st WHO Model List of Essential Medicines and the 7th WHO Model List of Essential Medicines for Children). Geneva: World Health Organization; 2019 (WHO Technical Report Series, No. 1021). Licence: CC BY-NC-SA 3.0 IGO: https://apps.who.int/iris/bitstream/handle/10665/330668/9789241210300-eng.pdf?ua=1) and Corrigenda (March 2020) – TRS1021 (https://www.who.int/medicines/publications/essentialmedicines/TRS1021_corrigenda_March2020. pdf?ua=1). Executive summary of the report: https://apps.who.int/iris/bitstream/handle/10665/325773/WHO- MVP-EMP-IAU-2019.05-eng.pdf?ua=1.
    [Show full text]
  • EMA/CVMP/158366/2019 Committee for Medicinal Products for Veterinary Use
    Ref. Ares(2019)6843167 - 05/11/2019 31 October 2019 EMA/CVMP/158366/2019 Committee for Medicinal Products for Veterinary Use Advice on implementing measures under Article 37(4) of Regulation (EU) 2019/6 on veterinary medicinal products – Criteria for the designation of antimicrobials to be reserved for treatment of certain infections in humans Official address Domenico Scarlattilaan 6 ● 1083 HS Amsterdam ● The Netherlands Address for visits and deliveries Refer to www.ema.europa.eu/how-to-find-us Send us a question Go to www.ema.europa.eu/contact Telephone +31 (0)88 781 6000 An agency of the European Union © European Medicines Agency, 2019. Reproduction is authorised provided the source is acknowledged. Introduction On 6 February 2019, the European Commission sent a request to the European Medicines Agency (EMA) for a report on the criteria for the designation of antimicrobials to be reserved for the treatment of certain infections in humans in order to preserve the efficacy of those antimicrobials. The Agency was requested to provide a report by 31 October 2019 containing recommendations to the Commission as to which criteria should be used to determine those antimicrobials to be reserved for treatment of certain infections in humans (this is also referred to as ‘criteria for designating antimicrobials for human use’, ‘restricting antimicrobials to human use’, or ‘reserved for human use only’). The Committee for Medicinal Products for Veterinary Use (CVMP) formed an expert group to prepare the scientific report. The group was composed of seven experts selected from the European network of experts, on the basis of recommendations from the national competent authorities, one expert nominated from European Food Safety Authority (EFSA), one expert nominated by European Centre for Disease Prevention and Control (ECDC), one expert with expertise on human infectious diseases, and two Agency staff members with expertise on development of antimicrobial resistance .
    [Show full text]
  • The Effects of Combination Antibiotic Therapy on Methicillin-Resistant Staphylococcus Aureus Presented by Kasra Nick Fallah In
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by UT Digital Repository The Effects of Combination Antibiotic Therapy on Methicillin-Resistant Staphylococcus aureus Presented by Kasra Nick Fallah in partial fulfillment of the requirements for completion of the Health Science Scholars honors program in the College of Natural Sciences at The University of Texas at Austin Spring 2018 Gregory C. Palmer, Ph.D. Date Supervising Professor Texas Institute for Discovery Education in Science Department of Medical Education Ruth Buskirk, Ph.D. Date Biology Honors Advisor Biological Sciences, College of Natural Sciences Table of Contents Abstract (3) Chapter 1: Literature Review (4) 1.1: The History of Antibiotics (4) 1.1.1: The Discovery of Penicillin (4) 1.1.2: The Different Classes of Antibiotics (7) 1.1.3: The Mechanisms of Action of Antibiotics (13) 1.2: Antibiotic Resistance (16) 1.2.1: The Rise of Antibiotic Resistance (16) 1.2.2: Mechanisms of Resistance (17) 1.2.3: How Antibiotic Resistance Spreads (20) 1.2.4: Methicillin-Resistant Staphylococcus aureus (21) 1.3: Streptomyces (24) 1.3.1: Selman Waksman (24) 1.3.2: Streptomyces: A Possible Solution to Antibiotic Resistance (25) 1.4: Combination Antibiotic Therapy (27) 1.4.1: The Positive/Negative Effects of Combination Antibiotic Therapy (27) 1.4.2: Drug Interactions (29) 1.4.3: Antibiotic Stewardship (30) Chapter 2: Research Manuscript (32) 2.1: Introduction (32) 1 2.2: Methods (35) 2.2.1: Strains, Media, and Growth Conditions (35) 2.2.2: Bacterial Strain Isolation and Identification (35) 2.2.3: Ethyl acetate Extractions (36) 2.2.4: Disc Assays (36) 2.3: Results & Discussion (38) 2.3.1: Isolation of Bacteria (38) 2.3.2: Organic Extractions (41) 2.3.3: Inhibition of MSSA and MRSA (41) 2.3.4: Inhibitory effect of the antibiotic produced by S.
    [Show full text]
  • Point Prevalence Survey of Healthcare-Associated Infections and Antimicrobial Use in European Acute-Care Hospitals
    Point prevalence survey of healthcare- associated infections and antimicrobial use in European acute- care hospitals Codebook v1.0 July 2016 Point prevalence survey of healthcare-associated infections and antimicrobial use in European acute-care hospitals About Public Health England Public Health England exists to protect and improve the nation's health and wellbeing, and reduce health inequalities. It does this through world-class science, knowledge and intelligence, advocacy, partnerships and the delivery of specialist public health services. PHE is an operationally autonomous executive agency of the Department of Health. Public Health England Wellington House 133-155 Waterloo Road London SE1 8UG Tel: 020 7654 8000 www.gov.uk/phe Twitter: @PHE_uk Facebook: www.facebook.com/PublicHealthEngland Prepared by: PHE PPS England Team For queries relating to this document, please contact: [email protected] © Crown copyright 2016 You may re-use this information (excluding logos) free of charge in any format or medium, under the terms of the Open Government Licence v3.0. To view this licence, visit OGL or email [email protected]. Where we have identified any third party copyright information you will need to obtain permission from the copyright holders concerned. Published July 2016 PHE publications gateway number: 2016185 Point prevalence survey of healthcare-associated infections and antimicrobial use in European acute-care hospitals Contents About Public Health England 2 Recommended case finding algorithm for healthcare-associated
    [Show full text]
  • ARCH-Vet Anresis.Ch
    Usage of Antibiotics and Occurrence of Antibiotic Resistance in Bacteria from Humans and Animals in Switzerland Joint report 2013 ARCH-Vet anresis.ch Publishing details © Federal Office of Public Health FOPH Published by: Federal Office of Public Health FOPH Publication date: November 2015 Editors: Federal Office of Public Health FOPH, Division Communicable Diseases. Elisabetta Peduzzi, Judith Klomp, Virginie Masserey Design and layout: diff. Marke & Kommunikation GmbH, Bern FOPH publication number: 2015-OEG-17 Source: SFBL, Distribution of Publications, CH-3003 Bern www.bundespublikationen.admin.ch Order number: 316.402.eng Internet: www.bag.admin.ch/star www.blv.admin.ch/gesundheit_tiere/04661/04666 Table of contents 1 Foreword 4 Vorwort 5 Avant-propos 6 Prefazione 7 2 Summary 10 Zusammenfassung 12 Synthèse 14 Sintesi 17 3 Introduction 20 3.1 Antibiotic resistance 20 3.2 About anresis.ch 20 3.3 About ARCH-Vet 21 3.4 Guidance for readers 21 4 Abbreviations 24 5 Antibacterial consumption in human medicine 26 5.1 Hospital care 26 5.2 Outpatient care 31 5.3 Discussion 32 6 Antibacterial sales in veterinary medicines 36 6.1 Total antibacterial sales for use in animals 36 6.2 Antibacterial sales – pets 37 6.3 Antibacterial sales – food producing animals 38 6.4 Discussion 40 7 Resistance in bacteria from human clinical isolates 42 7.1 Escherichia coli 42 7.2 Klebsiella pneumoniae 44 7.3 Pseudomonas aeruginosa 48 7.4 Acinetobacter spp. 49 7.5 Streptococcus pneumoniae 52 7.6 Enterococci 54 7.7 Staphylococcus aureus 55 Table of contents 1 8 Resistance in zoonotic bacteria 58 8.1 Salmonella spp.
    [Show full text]
  • European Surveillance of Healthcare-Associated Infections in Intensive Care Units
    TECHNICAL DOCUMENT European surveillance of healthcare-associated infections in intensive care units HAI-Net ICU protocol Protocol version 1.02 www.ecdc.europa.eu ECDC TECHNICAL DOCUMENT European surveillance of healthcare- associated infections in intensive care units HAI-Net ICU protocol, version 1.02 This technical document of the European Centre for Disease Prevention and Control (ECDC) was coordinated by Carl Suetens. In accordance with the Staff Regulations for Officials and Conditions of Employment of Other Servants of the European Union and the ECDC Independence Policy, ECDC staff members shall not, in the performance of their duties, deal with a matter in which, directly or indirectly, they have any personal interest such as to impair their independence. This is version 1.02 of the HAI-Net ICU protocol. Differences between versions 1.01 (December 2010) and 1.02 are purely editorial. Suggested citation: European Centre for Disease Prevention and Control. European surveillance of healthcare- associated infections in intensive care units – HAI-Net ICU protocol, version 1.02. Stockholm: ECDC; 2015. Stockholm, March 2015 ISBN 978-92-9193-627-4 doi 10.2900/371526 Catalogue number TQ-04-15-186-EN-N © European Centre for Disease Prevention and Control, 2015 Reproduction is authorised, provided the source is acknowledged. TECHNICAL DOCUMENT HAI-Net ICU protocol, version 1.02 Table of contents Abbreviations ...............................................................................................................................................
    [Show full text]
  • Guidelines for Atcvet Classification 2012
    Guidelines for ATCvet classification 2012 ISSN 1020-9891 ISBN 978-82-8082-479-0 Suggested citation: WHO Collaborating Centre for Drug Statistics Methodology, Guidelines for ATCvet classification 2012. Oslo, 2012. © Copyright WHO Collaborating Centre for Drug Statistics Methodology, Oslo, Norway. Use of all or parts of the material requires reference to the WHO Collaborating Centre for Drug Statistics Methodology. Copying and distribution for commercial purposes is not allowed. Changing or manipulating the material is not allowed. Guidelines for ATCvet classification 14th edition WHO Collaborating Centre for Drug Statistics Methodology Norwegian Institute of Public Health P.O.Box 4404 Nydalen N-0403 Oslo Norway Telephone: +47 21078160 Telefax: +47 21078146 E-mail: [email protected] Website: www.whocc.no Previous editions: 1992: Guidelines on ATCvet classification, 1st edition1) 1995: Guidelines on ATCvet classification, 2nd edition1) 1999: Guidelines on ATCvet classification, 3rd edition1) 2002: Guidelines for ATCvet classification, 4th edition2) 2003: Guidelines for ATCvet classification, 5th edition2) 2004: Guidelines for ATCvet classification, 6th edition2) 2005: Guidelines for ATCvet classification, 7th edition2) 2006: Guidelines for ATCvet classification, 8th edition2) 2007: Guidelines for ATCvet classification, 9th edition2) 2008: Guidelines for ATCvet classification, 10th edition2) 2009: Guidelines for ATCvet classification, 11th edition2) 2010: Guidelines for ATCvet classification, 12th edition2) 2011: Guidelines for ATCvet classification, 13th edition2) 1) Published by the Nordic Council on Medicines 2) Published by the WHO Collaborating Centre for Drug Statistics Methodology Preface The Anatomical Therapeutic Chemical classification system for veterinary medicinal products, ATCvet, has been developed by the Nordic Council on Medicines (NLN) in collaboration with the NLN’s ATCvet working group, consisting of experts from the Nordic countries.
    [Show full text]
  • Part I Betalactams, Aminoglycosides, Quinolones
    Antibiotics – agents - part I betalactams, aminoglycosides, quinolones Vlastimil Jindrák Oddělení klinické mikrobiologie a antibiotická stanice Nemocnice Na Homolce, Praha 13.12. 2004 Antibiotika - katedra farmakologie 2. LF UK - 2 1 Antibiotics - antimicrobial agents • antibacterial agents • antifungal agents • antiviral agents • antiparasitic agents 13.12. 2004 Antibiotika - katedra farmakologie 2. LF UK - 2 2 Classification of antibiotics main groups of antibacterial agents betalactams chloramphenicol aminoglycosides tetracyklines quinolones rifamycins glycopeptides sulfonamides and trimethoprim macrolides, azalides polypeptides lincosamides nitroimidazoles ketolides nitrofurans streptogramines oxazolidinones 13.12. 2004 Antibiotika - katedra farmakologie 2. LF UK - 2 3 Classification of antibiotics antimycobacterial agents antibiotics active against mycobacteria streptomycine, rifampicin, fluoroquinolones specific antimycobacterial agents PAS (para-aminosalicylic acid) isoniazid ethambutol etionamid, pyrazinamid kapreomycin, cykloserin 13.12. 2004 Antibiotika - katedra farmakologie 2. LF UK - 2 4 Classification of antibiotics antifungal agents polyens amphotericin B, nystatine azoles fluconazole, itraconazole, voriconazole, ketoconazole echinocandines caspofungin others flucytosine, griseofulvin 13.12. 2004 Antibiotika - katedra farmakologie 2. LF UK - 2 5 Classification of antibiotics antiviral agents antivirotics nucleoside analogs: aciclovir, valaciclovir, famciclovir, ganciclovir neuraminidase inhibitors: oseltamivir, zanamivir
    [Show full text]
  • Glycopeptide Antibiotics: Structure and Mechanisms of Action
    Journal of Bacteriology and Virology 2015. Vol. 45, No. 2 p.67 – 78 http://dx.doi.org/10.4167/jbv.2015.45.2.67 Review Article Glycopeptide Antibiotics: Structure and Mechanisms of Action * Hee-Kyoung Kang1 and Yoonkyung Park1,2 1Department of Biomedical Sciences, Chosun University, Gwangju; 2Research Center for Proteinaceous Materials, Chosun University, Gwangju, Korea Glycopeptides of the clinically important antibiotic drugs are glycosylated cyclic or polycyclic nonribosomal peptides. Glycopeptides such as vancomycin and teicoplanin are often used for the treatment of gram-positive bacteria in patients. The increased incidence of drug resistance and inadequacy of these therapeutics against gram-positive bacterial infections would be the formation and clinical development of more variable second generation of glycopeptide antibiotics: semisynthetic lipoglycopeptide analogs such as telavancin, dalbavancin, and oritavancin with improved activity and better pharmacokinetic properties. In this review, we describe the development of and bacterial resistance to vancomycin, teicoplanin, and semisynthetic glycopeptides (teicoplanin, dalbavancin, and oritavancin). The clinical influence of resistance to glycopeptides, particularly vancomycin, are also discussed. Key Words: Glycopeptide; Resistance; Vancomycin; Teicoplanin; Dalbavancin (vancomycin-intermediate S. aureus, VISA or glycopeptide- INTRODUCTION intermediate S. aureus, GISA) has caused researchers to develop the second-generation glycopeptides and caused a Glycopeptides are the most prevalent class of thera- flurry of activity targeted at understanding the mechanisms peutics that are used for the treatment against as severe of bacterial resistance and the evolution of glycopeptide infections caused by Gram-positive pathogens, such as antibiotics (1, 2). enterococci, methicillin-resistant Staphylococcus aureus Glycopeptides are glycosylated cyclic or polycyclic non- (MRSA), and Clostridium difficile.
    [Show full text]
  • 1 Cephalosporins and Vancomycin
    Alice Prince CEPHALOSPORINS AND VANCOMYCIN CEPHALOSPORINS These compounds are closely related in structure, mechanism of action, spectrum of activity and pharmacology to the penicillins. They are produced by fungi and synthetic modification. I. CHEMISTRY Contains 6-membered dihydrothiazine ring. Substitutions at position 3 generally affect pharmacology; substitutions at position 7 affect antibacterial activity, but this is not invariably true. 1 II. MECHANISM OF ACTION Cephalosporins are bactericidal. They inhibit enzymatic reactions necessary for stable bacterial cell walls by binding to PBPs. Bacterial cells must be growing. III. PHARMACOLOGIC PROPERTIES OF CEPHALOSPORINS Peak blood level Percentage Drug (µg/ml) Protein Binding T½ (hr) [CSF] µg/ml Cefazolin 1g 188 70 - 85% 1.4 ---------------- Cefuroxime 1.5g 100 50% 1.3 1.1 - 18 Cefoxitin 1g 110 70% 0.7-0.9 ---------------- Cefotaxime 1g 100 13 - 38% 1.0 6 – 11 (2g)* Ceftriaxone 1g 150 83 - 96% 5.8-8.7 1.3 - 44 Ceftazidime 1g 90 < 10% 1.9 2 – 42 *non-inflamed meninges CSF level 0.01-0.7 µg/ml IV. MECHANISM OF RESISTANCE TO CEPHALOSPORINS A. Failure to reach receptor sites, permeability. B. Destroyed by β-lactamase. Some gram-negative bacteria produce large amounts of β- lactamase constitutively. C. Failure to bind to penicillin binding proteins, in gram negative and gram positive organisms. V. ANTIMICROBIAL ACTIVITY The cephalosporins have been grouped into "generations" corresponding to their development by the pharmaceutical industry in response to clinical needs. In general, the later generations of cephalosporins have greater gram-negative activity at the expense of gram-positive activity. A. First generation agents Cefazolin Cephalothin Cephalexin (oral) Cefaclor (oral) All of these drugs inhibit gram-positive cocci (S.
    [Show full text]
  • Author Section
    AUTHOR SECTION patients with new onset of fever, demographic, clinical, and laborato- Mycoplasma spp. Overall, the spectrum of antibacterial activity indi- ry variables were obtained during the 2 days after inclusion, while cates a potential role for this combination in the treatment of diffi- microbiological results for a follow-up period of 7 days were collect- cult-to-treat Gram-positive infections, including those caused by ed. Patients were followed up for survival or death, up to a maximum multidrug-resistant organisms. Since this activity extends to Gram- of 28 days after inclusion. MEASUREMENTS AND RESULTS: Of negative respiratory bacteria, quinupristin/dalfopristin may also find all patients, 95% had SIRS, 44% had sepsis with a microbiologically a role in the treatment of atypical, as well as typical, pneumonia. confirmed infection, and 9% died. A model with a set of variables all significantly (p<0.01) contributing to the prediction of mortality was Boubaker A. et al. [Investigation of the urinary tract in children in nuclear med- derived.The set included the presence of hospital-acquired fever, the icine]. Rev Med Suisse Romande. 2000; 120(3) : 251-7.p Abstract: peak respiratory rate, the nadir score on the Glasgow coma scale, and The early detection of urologic abnormalities by antenatal sonogra- the nadir albumin plasma level within the first 2 days after inclusion. phy has resulted in the investigation of many infants and neonates for This set of variables predicted mortality for febrile patients with suspicion of either obstructive uropathy or reflux nephropathy. microbiologically confirmed infection even better.The predictive val- Nuclear medicine techniques allow to assess renal parenchyma ues for mortality of SIRS and sepsis were less than that of our set of integrity, to detect pyelonephritic scars and to measure absolute and variables.
    [Show full text]