Antibiotic resistance. Understanding and responding to an emerging crisis

Contents......Page 8
About the Authors......Page 14
Preface......Page 16
MRSA Is Putting Resistance in the News......Page 18
Humans Live with Many Pathogens......Page 21
Antibiotics Block Growth and Kill Pathogens......Page 23
Broad-Spectrum Antibiotics Also Perturb Our Microbiomes......Page 24
Antibiotic Resistance Protects Pathogens......Page 25
Antibiotic Resistance Is Widespread......Page 26
The Development of New Antibiotics Is Slowing......Page 29
Vaccines Block Disease......Page 30
Perspective......Page 31
Pathogens Are a Diverse Group of Life Forms......Page 34
Pathogen Numbers Are Measured by Microscopy and by Detecting Growth......Page 35
Molecular Probes Can Be Specific and Highly Sensitive......Page 40
Koch’s Postulates Help Establish That a Pathogen Causes Disease......Page 41
Modern Biology Has Refined Koch’s Postulates......Page 43
Pathogen Studies Focus on Populations......Page 45
Perspective......Page 46
Antibiotics Are Selective Poisons......Page 48
Antibiotics Are Found in a Variety of Ways......Page 49
Antibacterial Agents Usually Attack Specific Targets......Page 54
Antibacterial Agents May Have a Generalized Effect......Page 57
Most Antifungal Agents Attack Membranes and Cell Walls......Page 58
Antiprotozoan Agents Tend to Be Disease-Specific......Page 60
Antiviral Agents Are Often Narrow Spectrum......Page 62
Human Immunodeficiency Virus (HIV)......Page 63
Influenza Virus......Page 65
Herpes Virus......Page 66
Antibiotic Classes Evolve......Page 67
Antiseptics and Disinfectants Decontaminate Surfaces......Page 69
Perspective......Page 70
Treatment Strategies Have Been Determined Empirically......Page 72
Susceptibility Testing Guides Antibiotic Choice......Page 74
PK/PD Indices Help Determine Antibiotic Dosage......Page 79
Young Children Are Not Little Adults......Page 82
Toxic Side Effects Are Determined Empirically......Page 83
Prophylaxis Preempts Disease......Page 84
Management Programs Control Hospital Antibiotic Policy......Page 85
Self-Medication Is Outside the Guidelines......Page 86
Perspective......Page 87
Resistance Can Emerge in Individual Patients......Page 90
Spontaneous Mutations Are Nucleotide Sequence Changes......Page 91
Emergence of Spontaneous Resistance Often Arises Stepwise......Page 92
Mutant Selection Window Hypothesis Describes Emergence of Spontaneous Resistance......Page 94
Mutations Can Be Caused (Induced) by Antibiotic Treatment......Page 96
Resistance Arises from Several Molecular Mechanisms......Page 97
Treatment Time Can Contribute to Resistance......Page 99
Mutator Mutations Increase Mutation Frequency......Page 100
Viral Resistance Can Arise Readily......Page 101
Resistance Mutations Can Affect Pathogen Fitness......Page 103
Unintended Damage Can Arise from Treatment......Page 104
Perspective......Page 106
Horizontal Gene Transfer Involves Specific Molecular Events......Page 108
Recombination Involves Breaking and Rejoining of DNA Molecules......Page 109
Plasmids Are Molecular Parasites......Page 111
Some Plasmids Move by Conjugation......Page 112
Bacteriophages Move Bacterial Genes by Transduction......Page 113
Bacterial Transformation Involves Uptake of DNA from the Environment......Page 115
Gene Mobilization Moves Genes from the Chromosome to a Plasmid......Page 116
Integrons Gather Genes into an Expression Site......Page 118
Genomic Islands Help Create Pathogens......Page 119
Perspective......Page 120
Spread of Pathogens Is Highly Evolved......Page 122
Infection Control as Local Crisis Management......Page 123
Tuberculosis Is Airborne......Page 124
Airborne Viruses......Page 131
Digestive-Tract Pathogens......Page 132
Direct-Contact Pathogens......Page 133
Arthropod-Borne Pathogens......Page 135
Multiple-Mode Transmission......Page 138
Perspective......Page 140
Surveillance Is the First Line of Defense......Page 142
The Denominator Effect Lowers Surveillance Accuracy......Page 143
Surveillance Consortia Collect and Process Data......Page 144
Molecular Methods Provide Rapid Pathogen Identification......Page 145
Interpretation of Surveillance Studies......Page 149
Policy Changes Are Occurring in Agricultural Practice......Page 150
Perspective......Page 154
New Antibiotics Are Temporary Solutions......Page 156
Model Systems Are Used to Speed Drug Discovery......Page 157
Natural Products Are a Source of Antibiotics......Page 158
High-Throughput Screening Accelerates Antibiotic Discovery......Page 160
Rational Drug Design Can Identify Antibiotics......Page 161
New Antibiotics Must Have Few Side Effects......Page 162
Antibiotic Discovery Faces a Fundamental Economic Problem......Page 163
Perspective......Page 164
Antibiotic Conservation: Use Less Often When Unnecessary and Higher Amounts When Needed......Page 166
Human Consumption of Antibiotics Correlates with Resistance......Page 167
Limiting Human Consumption of Antibiotics......Page 169
Antibiotic Contamination of the Environment Is a Byproduct of Usage......Page 172
Clinical Resistance and Resistant Mutants Are Not the Same......Page 174
Dosing to Eradicate Susceptible Cells May Not Halt Emergence of Resistance......Page 175
Keeping Concentrations Above MPC Restricts Mutant Amplification......Page 176
Combining MPC with PK/PD Targets......Page 177
Combination Therapy Restricts Emergence of Resistance......Page 179
Consideration of Resistance During Drug Discovery......Page 180
Perspective......Page 181
Seasonal Influenza Virus Is Controlled by Vaccines......Page 184
Antiviral Resistance Has Emerged Among Seasonal Influenza Virus......Page 185
Pandemic Influenza Can Be a Killer......Page 187
Avian Flu H5N1 Is a Candidate for Deadly Pandemic Flu......Page 188
Antibiotics May Play an Important Role in Pandemic Influenza......Page 189
Antibiotic Resistance Occurs with Avian Flu H5N1......Page 190
Bacterial Pneumonia May Create Another Resistance Problem......Page 192
Perspective......Page 193
Consumer Perspective Differs from That of Public Health Official or Manufacturer......Page 194
Avoiding Airborne Infection Is Difficult......Page 195
Precautions Can Be Taken with MRSA......Page 199
Sexually Transmitted Infections Require Renewed Attention......Page 202
Arthropod-Borne Infections Are on the Move......Page 203
Contaminated Food Is Common......Page 205
Avoid Rounds of Treatment Interspersed with Pathogen Outgrowth......Page 213
Consume Only with Sound Indications, Choose Optimal Antibiotics......Page 214
Perspective......Page 216
Overuse......Page 220
Dosing......Page 221
Drug Discovery and Surveillance......Page 222
Resistance as a Side Effect......Page 223
The Action of Molecules Defines Life......Page 224
Proteins Are Molecular Workers......Page 225
DNA Is the Repository of Genetic Information......Page 226
RNA Plays Several Roles in Life Processes......Page 232
Carbohydrates Store Energy, Form Cell Walls, and Make Rigid Structures......Page 235
Lipids Store Energy and Form Membranes......Page 236
Cellular Chemistry Is Organized into Metabolic Pathways......Page 237
Bacteria Lack Nuclei and Other Organelles......Page 238
Fungi Are Eukaryotes Having Cell Walls But Not Chloropasts......Page 239
Parasitic Protozoa Are Eukaryotes Lacking a Cell Wall......Page 240
Viruses Are Inert Until They Infect......Page 241
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Y......Page 248
Literature Cited......Page 250
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