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21st Century Challenges in Antimicrobial Therapy and Stewardship

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    Book

  • November 2020
  • Bentham Science Publishers Ltd
  • ID: 5215263
21st Century Challenges in Antimicrobial Therapy and Stewardship addresses selected topics that are of importance in the practice of infectious disease management. The text starts by illustrating the global landscape of antimicrobial drug resistance, which influences antimicrobial use and therapeutic decisions in the clinic. The contributors explain the reasons for the spread of antibiotic resistance, the pharmacology of antibiotics of different classes, innovative drug delivery methods which can improve the efficacy and safety of new drug candidates and achieve targeted drug delivery as well as drug resistance monitoring techniques and issues in the practice of antimicrobial stewardship and infection control.

Key Features:
  • 14 organized chapters on several aspects of antimicrobial therapy and stewardship
  • Introductory knowledge on global antimicrobial trends
  • Coverage of molecular basis of antimicrobial resistance in gram positive, gram negative and fungal microbes
  • Focused coverage on new developments in antimicrobial drug development, drug delivery, formulation and diagnostic tools
  • Information on unmet needs of patients and clinicians, including the treatment of difficult infections
  • Comprehensive coverage of issues in antimicrobial stewardship

21st Century Challenges in Antimicrobial Therapy and Stewardship brings to readers - healthcare administrators, educators, pharmacists, clinicians and students, alike - the knowledge of the molecular basis of antimicrobial drug therapy, drug resistance in pathogens and current practices in antimicrobial stewardship programs.

This knowledge, in turn, fosters an awareness among healthcare industry participants to collaborate in an interprofessional environment to combat multi drug resistance.

Table of Contents

Preface

List of Contributors

Chapter 1 Global Landscape of Microbial Resistance
  • Elsayed Aboulmagd, Mervat A. Kassem and Alaa Abouelfetouh
  • Global Nature of Amr Problem
  • Causes of Amr
  • Antibiotic Misuse as a Driver of Resistance
  • Use of Sub-Therapeutic Concentrations of Antibiotics in Animals as Growth Promoters
  • Antibiotics as Environmental Waste
  • Selective Pressure, Gene Transfer and Mutation
  • Types and Mechanisms of Amr
  • Intrinsic Resistance
  • Acquired Resistance
  • Multidrug Resistance Caused by Altered Physiological States
  • Consequences of Amr
  • Treatment Failure and Loss of Activity
  • High Morbidity and Mortality and Ensuing Economic Cost
  • How to Mitigate the Amr Problem?
  • Surveillance and Antimicrobial Stewardship
  • Chemical Modifications and Discovery of New Antibiotics
  • Alternative Approaches to Treat Resistant Infections
  • Conclusion
  • Consent for Publication
  • Conflict of Interest
  • Acknowledgements
  • References

Chapter 2 Innovative Drug Delivery Systems for Antimicrobial
  • Agents
  • Vaishnavi Parikh and Pardeep Gupta
  • Introduction
  • Mechanism of Microbial Resistance
  • Antimicrobial Molecule Modification
  • A Barrier to the Antibiotic Target
  • Change of Target Sites
  • Resistance due to Global Cell Adaptive Processes
  • Advances in Drug Delivery Systems
  • Nanotechnology and Nanoengineering
  • Mechanism of Antibacterial Activity of Nanomaterials
  • Applications of Nanomaterials
  • Antimicrobial Peptides (Amp)
  • Mechanism of Antibacterial Activity of Antimicrobial Peptides
  • Gene Editing Technologies
  • Summary
  • Consent for Publication
  • Conflict of Interest
  • Acknowledgements
  • References

Chapter 3 Alternative Routes of Antimicrobial Administration
  • Michael J. Cawley
  • Introduction
  • Aerosol
  • Intramuscular
  • Intracerebroventricular
  • Ophthalmic
  • Topical
  • Bone
  • Rectal
  • Compounded Antimicrobial Agents
  • Conclusion
  • Clinical Case Scenarios
  • Case 1
  • Case 2
  • Case 3
  • Consent for Publication
  • Conflict of Interest
  • Acknowledgements
  • References

Chapter 4 Molecular Basis of Resistance I
  • Adebowale O. Adeluola and Kolawole S. Oyedeji
  • Means of Bacterial Propagation
  • Transformation
  • Conjugation
  • Transduction
  • Mechanisms/Basis of Antimicrobial Resistance
  • Antibiotic Modification
  • Alterations in the Primary Site of Action
  • Reduction in Drug Accumulation in Bacterial Cells
  • Production of Alternative Target
  • Molecular Basis of Resistance
  • Drug Inactivation or Modification: Enzymatic Degradation of Antibiotics
  • Streptogramin Acetyltransferases
  • Phosphotransferases Kinases
  • Aminoglycoside Kinases
  • Macrolide Kinases
  • Nucleotidyltransferases
  • Glycosyltransferases
  • Dna Gyrase and Topoisomerase Iv
  • Other Mechanisms of Resistance
  • Alteration of Target/Binding Sites - Penicillin Binding Proteins (Pbp)
  • Reduced Drug Accumulation and Increasing Active Efflux
  • Proteins of the Outer Membrane Porins
  • Efflux Pump Activity
  • Alteration of Metabolic Pathway
  • Mitigating Bacterial Molecular Resistance Mechanism
  • Basic Overview of Pharmacokinetic and Pharmacodynamic
  • Principles
  • Routes of Antimicrobial Administration
  • Conclusion
  • Consent for Publication
  • Conflict of Interest
  • Acknowledgements
  • References

Chapter 5 Molecular Basis of Resistance Ii
  • Diaa Alrahmany and Islam M. Ghazi
  • Introduction
  • Development of Resistance
  • Mechanisms of Resistance
  • Decreased Antimicrobial Uptake (Porins-Mediated Resistance)
  • Efflux Pumps Mediated Resistance
  • Target Modification/Bypass/Protection
  • Biofilm Production
  • Genetic Elements of Biofilm
  • Enzymatic Inactivation of Antibiotics
  • Conclusion
  • Consent for Publication
  • Conflict of Interest
  • Acknowledgements
  • References

Chapter 6 Molecular Basis of Resistance Iii
  • Islam M. Ghazi, Diaa Alrahmany and Wasim S. El Nekidy
  • Introduction
  • Antifungal Agents’ Mode of Action
  • Azoles
  • Echinocandins
  • Polyenes
  • Nucleoside Analogues
  • Allylamines and Thiocarbamates
  • Susceptibility Testing
  • Fungal Resistance
  • Molecular and Genetic Basis for Fungal Resistance
  • Azole Antifungals
  • Echinocandins
  • Polyenes
  • Nucleoside Analogues
  • Implications of Antifungal Resistance
  • Future Insights into Combating Fungal Resistance
  • Consent for Publication
  • Conflict of Interest
  • Acknowledgements
  • References

Chapter 7 Evolving Rapid Diagnostics Tools
  • Diaa Alrahmany and Islam M. Ghazi
  • Introduction
  • Microscopy-Based Methods
  • Gram-Stain
  • Acid-Fast and Modified Acid-Fast Stain
  • Wet Mounts
  • Immunoassays
  • Manually-Performed Immunoassay-Based Techniques
  • Lateral Flow Immune-Assays (Lfia)
  • Nucleic Acid Lateral Flow Immune-Assay (Nalfia)
  • Flow-Through Assay Fta
  • Agglutination Test
  • Dipstick
  • Automated Immunoassays
  • Enzyme-Linked Immunosorbent Assays (Elisa)
  • Radioimmunoassay (Ria)
  • Fluorescence Immunoassays (Fia)
  • Nucleic Acid Probe-Based Techniques
  • Peptide Nucleic Acid (Pna) Fluorescence in Situ Hybridization (Fish)
  • Nucleic Acid Amplification-Based Techniques
  • Real-Time Polymerase Chain Reaction (Rt-Pcr)
  • Real-Time Multiplex Pcr (X-Rt-Pcr)
  • Spectrometry Based Techniques
  • Matrix-Assisted Laser Desorption Ionization Time-Of-Flight Mass Spectrometry (Malditof-
  • Ms)
  • Maldi- Imaging Mass Spectrometry (Maldi-Ims)
  • Future Rdts in Development
  • Microfluidics (Lab-On-A-Chip)
  • Whole-Genome Sequencing (Wgs)
  • Milestones in the Implementation of Rapid Diagnostics
  • Positioning and Priorities
  • Infrastructure and Logistic Challenges
  • Cost-Effectiveness Challenges
  • Laboratory Stewardship
  • Clinical Pearls
  • Consent for Publication
  • Conflict of Interest
  • Acknowledgements
  • References

Chapter 8 Therapeutic Options for Difficult to Treat Bacteria And
  • Candida Auris
  • Viktorija O. Barr, Alyssa Christensen, Morgan Anderson and Addison Pang
  • Introduction
  • Gram-Positive Organisms
  • Methicillin-Resistant Staphylococcus Aureus (Mrsa)
  • Resistance Mechanisms
  • Treatment Options
  • Vancomycin-Resistant Enterococcus Spp. (Vre)
  • Resistance Mechanisms
  • Treatment Options
  • Gram-Negative Organisms
  • Enterobacteriaceae
  • Resistance Mechanisms
  • Extended Spectrum Β-Lactamases (Esbl's) and Ampc's
  • Treatment Options
  • Carbapenamase Resistant Enterobactereaciae (Cre)
  • Treatment Options
  • Multi-Drug Resistant Pseudomonas Aeruginosa
  • Resistance Mechanism
  • Resistance Prevention
  • Treatment Options
  • Multi-Drug Resistant Acinteobacter Baumanii
  • Resistance Mechanisms
  • Treatment Options
  • Cefiderocol
  • Eravacycline
  • Plazomicin
  • Practical Application
  • Candida Auris
  • Resistance Mechanisms
  • Treatment Options
  • Consent for Publication
  • Conflict of Interest
  • Acknowledgements
  • References

Chapter 9 Antimicrobial Therapeutic Drug Monitoring
  • Rim W. Rafeh, Kamilia Abdelraouf, Nisrine Haddad, Nesrine Rizk and Ahmed F. El-
  • Yazbi
  • Introduction
  • Tdm: Rationale and Drug Characteristics
  • Mechanistic Basis of Tdm
  • In Vitro Infection Models
  • In Vivo Infection Models
  • Dose-Fractionation Studies
  • Dose-Ranging Studies
  • Efficacy of Human-Simulated Exposures
  • Limitations of in Vivo Assessments and Outcome Translation
  • Models of Population Kinetics
  • Antimicrobial Tdm in Special Patient Population: Clinical
  • Necessity Vs. Investigational Luxury
  • Critically Ill Patients
  • Obese and Overweight Patients
  • Tdm Using Alternative Biological Matrices
  • Tdm of Antimicrobials to Avoid Emergence of Resistance
  • Common and Recent Tdm Recommendations for Specific
  • Antibiotics and Antibiotic Classes
  • Vancomycin
  • Aminoglycosides
  • Beta Lactams
  • Linezolid
  • Fluoroquinolones
  • Concluding Remarks
  • Abbreviations
  • Consent for Publication
  • Conflict of Interest

Author

  • Islam M. Ghazi
  • Michael J. Cawley