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Antibiotics and Drug Resistance 2008

¸®¼­Ä¡»ç BioPharm Reports (Technology and Markets Ltd)
¹ßÇàÀÏ 2008³â 01¿ù »óǰÄÚµå 62222
ÆäÀÌÁö Á¤º¸ 174 Pages
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Abstract

New drug innovation and the strategy to combat antibiotic resistance mechanisms Updated Quarterly

Introduction:This report reviews new drug innovation and strategy to combat antibiotic resistance mechanisms. This embraces current research-stage activities, patents published in the last five years, the entire pharmaceutical development pipeline and today' s existing armoury of anti-bacterial drugs. The report reviews around 400+ pipeline antibiotics and anti-bacterial technologies (from pre-clinical to Phase III/initial launch), 350+ antibiotic patents published between Jan 2002 and Jan 2008 and more than 200 fully launched antibiotics. It identifies and discusses new antibiotics, technologies and strategies at the anti-bacterial mechanistic level, that are specifically being developed to combat resistance mechanisms. The opportunities which they potentially offer in tackling the increasing global threat of antibiotic resistance, are discussed.

Overview: This report gives a comprehensive and detailed review of pipeline, emerging and current antibiotics and anti-bacterial technologies and their potential to provide more effective long-term therapies. More than 900 drugs, drug candidates and developmental compounds are identified, discussed and classified on the basis of their mode of action, developmental stage, activities and capabilities and by companies and research groups responsible for taking these activities forward. Moreover, they are considered in terms of their importance and potential to combat resistant pathogens, as part of the global effort to find alternatives to current antibiotics, which have lost or are losing their effectiveness against common and serious pathogens. The report looks in depth at current developments and thinking on how antibiotic resistance can be tackled technically and strategically, from improvements to existing drugs and drug combinations, to novel molecules, new and more promising drug targets and approaches to tackling resistance at its source. More detailed information on this report is given in the printable Report Description, which is linked to this page.

Combating Antibiotic Resistance: This review examines more than 370 pipeline candidates and 340 antibiotic patents, published between Jan 2002 and Jan 2008. These patents were selected from more than 1800 patents citing "anti-infectives", published over the same period. Strategies being developed to combat resistance mechanisms include the identification of new selective targets, the selection of targets which may preclude genomic/phenotypic adaptation by bacteria, or where this is considered more difficult, combined activity molecules, molecules which inhibit stress-induced mutational emergence of resistance genes in response to synthetic antibiotics, novel antibacterial technologies, new targeting strategies and synthetic or semi-synthetic approaches vs. drugs of natural origin. Other areas reviewed include virulence targeting, the dissemination of adaptable traits, predicting resistance and the developing importance of pathogenomics.

Table of Contents

Executive Summary

1 INTRODUCTION

  • 1.1 Background
  • 1.2 Antibiotic Resistance
  • 1.3 Resistance Mechanisms
  • 1.4 The Resistome
  • 1.5 Pathogenomics
  • 1.6 Antibiotics, Strategies and Targets
  • 1.7 The Cost of Antibiotic Resistance
  • 1.8 Global Surveillance
  • 1.9 This Report

2 ANTIBIOTIC RESISTANCE: GLOBAL FIGURES AND TRENDS

  • Summary
  • 2.1 Antibiotic Resistance
  • 2.2 Europe
    • 2.2.1 Escherichia coli
    • 2.2.2 Streptococcus pneumoniae
    • 2.2.3 Staphylococcus aureus
    • 2.2.4 Enterococci
    • 2.2.5 Klebsiella pneumoniae
    • 2.2.6 Pseudomonas aeruginosa
  • 2.3 England and Wales
    • 2.3.1 Gram-positive cocci
    • 2.3.2 Gram-negative bacilli
    • 2.3.3 Other pathogens
  • 2.4 Other countries
  • 2.5 China
  • 2.6 USA
  • 2.7 Kuwait
  • 2.8 Discussion

3 FULLY LAUNCHED ANTI-BACTERIALS

  • 3.1 Current Anti-Infectives
  • 3.2 Anti-bacterials
  • 3.3 Bacterial Cell Wall Inhibitors
  • 3.4 Immune Stimulators
  • 3.5 30S/50S Ribosomal Subunit Inhibitors
  • 3.6 DNA Gyrase/Topoisomerase Inhibitors
  • 3.7 Other Antibiotics
  • 3.8 Discussion

4 PIPELINE ANTI-BACTERIALS

  • 4.1 Pipeline Anti-Infectives
  • 4.2 Developmental Stage
  • 4.3 Mechanisms of Action
  • 4.4 Phase III and Beyond (Late Stage)
  • 4.5 Pre-Clinical to Phase II (Early Stage)
    • 4.5.1 Established Classes
    • 4.5.2 New Classes
  • 4.6 Anti-bacterial Groups
    • 4.6.1 Immune-acting agents
    • 4.6.2 Cell wall inhibitors
    • 4.6.3 DNA topoisomerase ATP hydrolysing inhibitors
    • 4.6.4 Protein 50S ribosomal subunit inhibitors
    • 4.6.5 Protein 30S ribosomal subunit inhibitors
    • 4.6.6 Protein synthesis antagonists
    • 4.6.7 DNA directed DNA polymerase inhibitors
    • 4.6.8 DNA antagonists
    • 4.6.9 DNA topoisomerase IV inhibitors
    • 4.6.10 B anthracis protective antigen inhibitors
    • 4.6.11 Chelating agents
    • 4.6.12 Defensin agonists
    • 4.6.13 Deformylase inhibitors
    • 4.6.14 General pump inhibitors
    • 4.6.15 FABI inhibitors
    • 4.6.16 Membrane integrity antagonists
    • 4.6.17 Membrane permeability enhancers
    • 4.6.18 Dihydrofolate reductase inhibitors
    • 4.6.19 DNA synthesis inhibitors
    • 4.6.20 Lactamase-A inhibitors
    • 4.6.21 Adenosinetriphosphate synthase inhibitors
    • 4.6.22 Deg protease inhibitors
    • 4.6.23 Fab F inhibitors
    • 4.6.24 Gene expression inhibitors
    • 4.6.25 Glutamate racemase inhibitors
    • 4.6.26 Glycosyl transferase inhibitors
    • 4.6.27 Heat shock protein 90 antagonists
    • 4.6.28 Kinase inhibitors
    • 4.6.29 Lipoteichoic acid antagonists
    • 4.6.30 PcrV inhibitors
    • 4.6.31 Peptidyltransferase inhibitors
  • 4.7 Notable pipeline candidates
    • 4.7.1 Pre-registered and Registered
    • 4.7.2 Phase III
    • 4.7.3 Early-stage
  • 4.8 Discussion

5 EMERGING ANTI-BACTERIALS

  • 5.1 Patents
  • 5.2 Antibiotic Classes
    • 5.2.1 Macrolide
    • 5.2.2 Beta-lactam
    • 5.2.3 Peptides
    • 5.2.4 Cephalosporins
    • 5.2.5 Combined antimicrobiols
    • 5.2.6 Carbapenems
    • 5.2.7 Quinolones
    • 5.2.8 General
    • 5.2.9 Vaccines (therapeutic)
    • 5.2.10 Lytics
    • 5.2.11 Bioenhancers
    • 5.2.12 Lactamase inhibitors
    • 5.2.13 Oxazolidinones
    • 5.2.14 Tetracyclines
    • 5.2.15 Natural products
    • 5.2.16 Aminoglycosides
    • 5.2.17 Quorum sensing
    • 5.2.18 Rifamycins
    • 5.2.19 ABC transporter modulator
    • 5.2.20 Glycopeptides
    • 5.2.21 Other technologies
    • 5.2.22 Patent filings organisations
  • 5.3 Discussion

6 COMBATING RESISTANCE MECHANISMS

  • 6.1 Background
  • 6.2 New Targets and Mechanisms
  • 6.3 Multiple Activities
  • 6.4 Circumventing Resistance
  • 6.5 Resistance Mutations
  • 6.6 Virulence
  • 6.7 Other Technologies
  • 6.8 Discussion

CHAPTER 7 COMPANIES AND ORIGINATORS

  • 7.1 Companies

FIGURES

  • Figure 2.1 Escherichia coli: Combined resistance (fluoroquinolones, third-generation cephalosporins and aminoglycosides) by country 2001-2005. Only countries that reported 20 isolates or more per year for at least 3 years were included. The arrows indicate significant trends (Source: EARSS).
  • Figure 2.2 Streptococcus pneumoniae: Dual resistance to penicillin and erythromycin by country, 1999-2005. Only countries that reported 20 isolates or more per year for at least 3 years were included. The arrows indicate significant trends (Source: EARSS).
  • Figure 2.3 Staphylococcus aureus: Resistance to methicillin by country, 1999-2005. Only countries that reported 20 isolates or more per year for at least 3 years were included. The arrows indicate significant trends (Source: EARSS).
  • Figure 2.4 Staphylococcus aureus: MRSA levels in England and Wales, 1992-2005. (Source UK Health Protection Agency, Trends in Antimicrobiol Resistance in England and Wales, 2004-2005).
  • Figure 2.5 Enterococcus faecalis: Trends in high aminoglycoside resistance by country 2001-2005. Only countries that reported 20 isolates or more per year for at least 3 years were included. The arrows indicate significant trends (Source: EARSS).
  • Figure 2.6 Klebsiella pneumoniae: Trends in high aminoglycoside resistance by country in 2002 and 2005. Only countries that reported 20 isolates or more per year for at least 3 years were included (Source: EARSS).
  • Figure 2.7 Pseudomonas aeruginosa: Trends in high aminoglycoside resistance by country in 2002 and 2005. Only countries that reported 20 isolates or more per year for at least 3 years were included (Source: EARSS).
  • Figure 2.8 Antibiotic resistance of gram-positive cocci in England and Wales, 2004-2005 (Source: UK Health Protection Agency, Trends in Antimicrobiol Resistance in England and Wales, 2004-2005.
  • Figure 2.9 Antibiotic resistance of gram-negative bacilli in England and Wales, 2004-2005 (Source: UK Health Protection Agency, Trends in Antimicrobiol Resistance in England and Wales, 2004-2005.
  • Figure 2.10 Antibiotic resistance of other bacteria in England and Wales, 2004-2005 (Source: UK Health Protection Agency, Trends in Antimicrobiol Resistance in England and Wales, 2004-2005).
  • Figure 2.11 Antibiotic resistance of Staphylococcus, Streptococcus, Escherichia coli and Enterococcus in the US, Egypt and Tunisia (Source: Frimodt-Møller et al., Danish Medical Bulletin Vol. 54, May 2007)
  • Figure 3.1 Current, fully launched anti-infectives (Independent Research, Pharmaprojects 2007)
  • Figure 3.2 Categories of fully approved anti-bacterial therapeutics (Independent Research, Pharmaprojects 2007)

TABLES

  • Table 2.1 EARSS surveillance programme: countries and country codes
  • Table 3.1a. Fully launched antibiotics - bacterial cell wall inhibitors (β-lactams) (Source: Company Research May 2007, Pharmaprojects May 2007)
  • Table 3.1b. Approved antibiotics - bacterial cell wall inhibitors (β-lactams) (Source: Company Research May 2007, Pharmaprojects May 2007)
  • Table 3.2a. Approved antibiotics - Immune Stimulators/Modulators (Source: Company Research May 2007, Pharmaprojects May 2007)
  • Table 3.2b. Approved antibiotics - Immune Stimulators/Modulators (Source: Company Research May 2007, Pharmaprojects May 2007)
  • Table 3.3 Approved antibiotics - Protein 30S/50S Ribosomal Subunit Inhibitors (Source: Company Research May 2007, Pharmaprojects May 2007)
  • Table 3.4 Approved antibiotics - DNA topoisomerase ATP hydrolysing inhibitor (Source: Company Research May 2007, Pharmaprojects May 2007)
  • Table 3.5a Approved antibiotics - Other antibiotics (Source: Company Research May 2007, Pharmaprojects May 2007)
  • Table 3.5b Approved antibiotics - Other antibiotics (Source: Company Research May 2007, Pharmaprojects May 2007)
  • Table 3.5c Approved antibiotics - Other antibiotics (Source: Company Research May 2007, Pharmaprojects May 2007)
  • 3.8 Discussion
  • Table 4.1 Pipeline Anti-Infectives (Source: Company Research May 2007, Pharmaprojects May 2007)
  • Table 4.2 Pipeline Anti-infectives (Source: Company Research May 2007, Pharmaprojects May 2007)
  • Table 4.3 Pipeline Anti-Infectives (Source: Company Research May 2007, Pharmaprojects May 2007)
  • Figure 7.1 The top 20 companies with fully launched anti-bacterials (Source: Independent Research, Pharmaprojects 2007)
  • Figure 7.2 The top 20 anti-bacterial development companies, representing candidates in the development pipeline (pre-clinical to Phase III/initial launch) (Source: Independent Research, Pharmaprojects 2007)
  • Figure 7.3 The top 20 anti-bacterial patent filing organisations of 340 patents selected for analysis in this report. (Source: Delphion)

APPENDICES

  • Appendix 1 Escherichia coli: trends of aminopenicillin resistance by country, 2001-2005. Only countries that reported 20 isolates or more per year for at least 3 years were included. The arrows indicate significant trends. See page X for country codes (Source: EARSS).
  • Appendix 2 Escherichia coli: trends in 3rd generation cephalosporin resistance by country, 2001-2005. Only countries that reported 20 isolates or more per year for at least 3 years were included. The arrows indicate significant trends. See page X for country codes (Source: EARSS).
  • Appendix 3 Escherichia coli: trends of fluoroquinolones resistance by country, 2001-2005. Only countries that reported 20 isolates or more per year for at least 3 years were included. The arrows indicate significant trends. See page X for country codes (Source: EARSS).
  • Appendix 4 Escherichia coli: trends of aminoglycoside resistance by country, 2001-2005. Only countries that reported 20 isolates or more per year for at least 3 years were included. The arrows indicate significant trends. See page X for country codes (Source: EARSS).
  • Appendix 5 Streptococcus pneumoniae: Resistance to penicillin by country, 1999-2005. Only countries that reported 20 isolates or more per year for at least 3 years were included. The arrows indicate significant trends. See page X for country codes (Source: EARSS).
  • Appendix 6 Streptococcus pneumoniae: Resistance to erythromycin by country, 1999-2005. Only countries that reported 20 isolates or more per year for at least 3 years were included. The arrows indicate significant trends. See page X for country codes (Source: EARSS).
  • Appendix 7 Anti-bacterials on the drug development pipeline (Source: Company Research May 2007, Pharmaprojects May 2007)
  • Appendix 8 Patent Application for Antibiotics and Anti-bacterials 2002-2007 (Source: Delphion, WIPO)
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