Antibiotic Resistance: Understanding and Responding to an Emerging Crisis






Recent human activities have profoundly influenced our global environment, often in ways we did not anticipate. An example is our use of antibiotics. Initially hailed as “magic bullets,” these chemical agents are now used so often that success threatens their long-term utility. Unfortunately, the natural mutability of microbes enables pathogens to develop bullet-proof shields that make antibiotic treatments increasingly ineffective. Our failure to adequately address resistance problems may ultimately push the control of infectious disease back to the pre-penicillin era. Indeed, it is now impractical to simply invent additional antibiotics to replace those lost to resistance. However, ideas have emerged for slowing the development of antibiotic resistance in individual patients and in the human population as a whole. "Antibiotic Resistance" introduces these ideas.

"Antibiotic Resistance" was initially drafted to supplement studies of infectious disease. The problem of resistance tends to be neglected, which puts the well-being of our society at increasing peril. In the course of completing this book, we realized that everyone makes decisions about antibiotic use; therefore, everyone needs to understand how human activities contribute to resistance. Individual patients, medical providers, and agricultural specialists all have a role to play in providing a safer environment. We now aim to make the principles of antibiotic use and effectiveness available to a large audience: farmers, hospital administrators, government regulators, health department personnel, pharmaceutical executives, and especially individual users. (Individual patients pressure their doctors for treatments, and in most cases, patients decide whether to take medicines as prescribed; in countries where prescriptions are not required to purchase antibiotics, patients are major decision makers.) Such diversity in readership poses a challenge.

Fortunately, detailed descriptions of chemical structures, molecular mechanisms, and epidemiological modeling are not required to understand the principles of resistance. We focus on broad concepts supported by examples and descriptions of key experiments. We expect that "Antibiotic Resistance" will be a quick read for persons with knowledge of biology. Those readers can then build on the principles with follow-up reading. Lay readers may find that some terms need to be defined. For them, we have provided a glossary and appendixes covering background concepts.

Our goal with "Antibiotic Resistance" is to point out how human activities contribute to the problem of resistance. Our hope is that an understanding of the complex factors involved in resistance will lead to changes that lengthen antibiotic life spans. An example of the complexity is seen in the traditional practice of setting antibiotic doses only high enough to cure disease. We argue that this practice encourages the emergence of resistance, that more stringent antibiotic regimens are needed to preempt the emergence of resistance. But from an individual patient perspective, using higher doses seems excessive when milder treatment usually cures disease. Why should the individual patient risk toxic side effects to preserve antibiotics for the general population? Antibiotic waste disposal problems are also complex. In principle, environmental contamination with antibiotics exerts selective pressure on microbes. That pressure can lead to the evolution of resistance genes that then spread from one organism to another and eventually reach human pathogens. We do not know how often this scenario occurs, whether it is reversible, or how much we need to improve agricultural and hospital disposal programs to stop the process.
- The Authors -


Contents
Chapter 1 Introduction to the Resistance Problem
  • MRSA Is Putting Resistance in the News
  • Humans Live with Many Pathogens
  • Antibiotics Block Growth and Kill Pathogens
  • Broad-Spectrum Antibiotics Also Perturb Our Microbiomes
  • Antibiotic Resistance Protects Pathogens
  • Antibiotic Resistance Is Widespread
  • Antibiotic Resistance Is Divided into Three Types
  • The Development of New Antibiotics Is Slowing
  • Vaccines Block Disease
  • Perspective

Chapter 2 Working with Pathogens
  • Pathogens Are a Diverse Group of Life Forms
  • Pathogen Numbers Are Measured by Microscopy and by Detecting Growth
  • Molecular Probes Can Be Specific and Highly Sensitive
  • Koch’s Postulates Help Establish That a Pathogen Causes Disease
  • Modern Biology Has Refined Koch’s Postulates
  • Pathogen Studies Focus on Populations

Chapter 3 A Survey of Antibiotics
  • Antibiotics Are Selective Poisons
  • Antibiotics Are Found in a Variety of Ways
  • Antibacterial Agents Usually Attack Specific Targets
  • Antibacterial Agents May Have a Generalized Effect
  • Most Antifungal Agents Attack Membranes and Cell Walls
  • Antiprotozoan Agents Tend to Be Disease-Specific Antihelminth Agents Are Used with a Wide Variety of Worms .
  • Antiviral Agents Are Often Narrow Spectrum
  • Human Immunodeficiency Virus (HIV)
  • Influenza Virus
  • Herpes Virus
  • Antibiotic Classes Evolve
  • Antiseptics and Disinfectants Decontaminate Surfaces

Chapter 4 Dosing to Cure
  • Treatment Strategies Have Been Determined Empirically
  • Susceptibility Testing Guides Antibiotic Choice
  • Testing for Viruses Bypasses Pathogen Growth
  • PK/PD Indices Help Determine Antibiotic Dosage
  • Young Children Are Not Little Adults
  • Toxic Side Effects Are Determined Empirically
  • Duration of Treatment Is Determined Empirically
  • Prophylaxis Preempts Disease
  • Management Programs Control Hospital Antibiotic Policy
  • Self-Medication Is Outside the Guidelines

Chapter 5 Emergence of Resistance
  • Resistance Can Emerge in Individual Patients
  • Spontaneous Mutations Are Nucleotide Sequence Changes
  • Emergence of Spontaneous Resistance Often Arises Stepwise
  • Mutant Selection Window Hypothesis Describes Emergence of Spontaneous Resistance
  • Mutations Can Be Caused (Induced) by Antibiotic Treatment
  • Resistance Arises from Several Molecular Mechanisms
  • Treatment Time Can Contribute to Resistance
  • Mutator Mutations Increase Mutation Frequency
  • Phenotypic Resistance Occurs Without Mutations
  • Resistance May Compromise Antiseptic and Disinfectant Use
  • Viral Resistance Can Arise Readily
  • Resistance Mutations Can Affect Pathogen Fitness
  • Unintended Damage Can Arise from Treatment

Chapter 6 Movement of Resistance Genes Among Pathogens
  • Horizontal Gene Transfer Involves Specific Molecular Events
  • Recombination Involves Breaking and Rejoining of DNA Molecules
  • Plasmids Are Molecular Parasites
  • Some Plasmids Move by Conjugation
  • Bacteriophages Move Bacterial Genes by Transduction
  • Bacterial Transformation Involves Uptake of DNA from the Environment
  • Transposition Moves Genes from One DNA to Another
  • Gene Mobilization Moves Genes from the Chromosome to a Plasmid
  • Integrons Gather Genes into an Expression Site
  • Genomic Islands Help Create Pathogens
  • Plasmid Enzymes Can Be Inhibited

Chapter 7 Transmission of Resistant Disease
  • Spread of Pathogens Is Highly Evolved
  • Infection Control as Local Crisis Management
  • Tuberculosis Is Airborne
  • Airborne Viruses
  • Digestive-Tract Pathogens
  • Direct-Contact Pathogens
  • Arthropod-Borne Pathogens
  • Blood-Borne Infections
  • Multiple-Mode Transmission

Chapter 8 Surveillance
  • Surveillance Is the First Line of Defense
  • The Denominator Effect Lowers Surveillance Accuracy
  • Surveillance Consortia Collect and Process Data
  • Molecular Methods Provide Rapid Pathogen Identification
  • Interpretation of Surveillance Studies
  • Surveillance Indicates Resistance Problems with Gonorrhea
  • Policy Changes Are Occurring in Agricultural Practice

Chapter 9 Making New Antibiotics
  • New Antibiotics Are Temporary Solutions
  • Model Systems Are Used to Speed Drug Discovery
  • Natural Products Are a Source of Antibiotics
  • High-Throughput Screening Accelerates Antibiotic Discovery
  • Rational Drug Design Can Identify Antibiotics
  • New Antibiotics Must Have Few Side Effects
  • Antibiotic Discovery Faces a Fundamental Economic Problem

Chapter 10 Restricting Antibiotic Use and Optimizing Dosing
  • Antibiotic Conservation: Use Less Often When Unnecessary and Higher Amounts When Needed
  • Human Consumption of Antibiotics Correlates with Resistance
  • Limiting Human Consumption of Antibiotics
  • Agricultural Use Contributes to Antibiotic Consumption
  • Antibiotic Contamination of the Environment Is a Byproduct of Usage
  • Clinical Resistance and Resistant Mutants Are Not the Same
  • Dosing to Eradicate Susceptible Cells May Not Halt Emergence of Resistance Keeping Concentrations Above MPC Restricts Mutant Amplification
  • Combining MPC with PK/PD Targets
  • Combination Therapy Restricts Emergence of Resistance
  • Consideration of Resistance During Drug Discovery

Chapter 11 Influenza and Antibiotic Resistance
  • Seasonal Influenza Virus Is Controlled by Vaccines
  • Antiviral Resistance Has Emerged Among Seasonal Influenza Virus
  • Pandemic Influenza Can Be a Killer
  • Avian Flu H5N1 Is a Candidate for Deadly Pandemic Flu
  • Antibiotics May Play an Important Role in Pandemic Influenza
  • Antibiotic Resistance Occurs with Avian Flu H5N1
  • Bacterial Pneumonia May Create Another Resistance Problem

Chapter 12 Avoiding Resistant Pathogens
  • Consumer Perspective Differs from That of Public Health Official or Manufacturer
  • Avoiding Airborne Infection Is Difficult
  • Precautions Can Be Taken with MRSA
  • Sexually Transmitted Infections Require Renewed Attention
  • Arthropod-Borne Infections Are on the Move
  • Contaminated Food Is Common
  • Avoid Rounds of Treatment Interspersed with Pathogen Outgrowth
  • Consume Only with Sound Indications, Choose Optimal Antibiotics
  • Afterword A Course of Action
  • Overuse
  • Dosing
  • Drug Discovery and Surveillance
  • Resistance as a Side Effect

Appendix A Molecules of Life
  • The Action of Molecules Defines Life
  • Proteins Are Molecular Workers
  • DNA Is the Repository of Genetic Information
  • RNA Plays Several Roles in Life Processes
  • Carbohydrates Store Energy, Form Cell Walls, and Make Rigid Structures
  • Lipids Store Energy and Form Membranes
  • Cellular Chemistry Is Organized into Metabolic Pathways

Appendix B Microbial Life Forms
  • Bacteria Lack Nuclei and Other Organelles
  • Fungi Are Eukaryotes Having Cell Walls But Not Chloropasts
  • Parasitic Protozoa Are Eukaryotes Lacking a Cell Wall
  • Helminths Are Parasitic Worms
  • Viruses Are Inert Until They Infect
  • Glossary
  • Literature Cited
  • Index


About the Authors
  • Karl Drlica, Ph.D. is a Principal Investigator at the Public Health Research Institute and Professor of Microbiology & Molecular Genetics at the UMDNJ—New Jersey Medical School in Newark, New Jersey. Dr. Drlica’s laboratory focuses on fluoroquinolone action and resistance with Mycobacteriun tuberculosis and other bacteria, including approaches for slowing the enrichment and amplification of resistant bacterial subpopulations.
  • David S. Perlin, Ph.D. is Executive Director of the Public Health Research Institute and UMDNJ Regional Biocontainment Laboratory, as well as Professor of Microbiology & Molecular Genetics at the New Jersey Medical School in Newark, New Jersey. He is also a Fellow of the New York Academy of Sciences. Dr. Perlin’s laboratory explores mechanisms of antifungal drug resistance, rapid detection of drug-resistant bloodstream pathogens in high-risk patients, and the application of small animal models for the study of respiratory pathogens.

 
Product Details

  • Hardcover: 288 pages
  • Publisher: FT Press; 1 edition (2011)
  • Language: English
  • ISBN-10: 0131387731
  • ISBN-13: 978-0131387737
  • Product Dimensions: 10 x 7.1 x 1 inches
List Price: $49.99 
 
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