Details

Antibiotic Drug Resistance


Antibiotic Drug Resistance


1. Aufl.

von: José-Luis Capelo-Martínez, Gilberto Igrejas

226,99 €

Verlag: Wiley
Format: PDF
Veröffentl.: 20.08.2019
ISBN/EAN: 9781119282532
Sprache: englisch
Anzahl Seiten: 720

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Beschreibungen

<p>This book presents a thorough and authoritative overview of the multifaceted field of antibiotic science – offering guidance to translate research into tools for prevention, diagnosis, and treatment of infectious diseases. </p> <ul> <li>Provides readers with knowledge about the broad field of drug resistance</li> <li>Offers guidance to translate research into tools for prevention, diagnosis, and treatment of infectious diseases</li> <li>Links strategies to analyze microbes to the development of new drugs, socioeconomic impacts to therapeutic strategies, and public policies to antibiotic-resistance-prevention strategies</li> </ul>
<p>List of Contributors xix</p> <p>Preface xxv</p> <p>About the Editors xxvii</p> <p><b>Part I Current Antibiotics and Their Mechanism of Action 1</b></p> <p><b>1 Resistance to Aminoglycosides: Glycomics and the Link to the Human Gut Microbiome 3<br /></b><i>Viviana G. Correia, Benedita A. Pinheiro, Ana Luísa Carvalho, and Angelina S. Palma</i></p> <p>1.1 Aminoglycosides as Antimicrobial Drugs 3</p> <p>1.1.1 The Structure of Aminoglycosides 5</p> <p>1.1.2 Mechanisms of Action 8</p> <p>1.2 Mechanisms of Resistance 10</p> <p>1.2.1 Aminoglycoside‐Modifying Enzymes 10</p> <p>1.2.2 Mutation or Modification of Ribosomal Target Sequences 13</p> <p>1.2.3 Changes in Uptake and Efflux 14</p> <p>1.3 Development of New AGAs: The Potential of Glycomics 16</p> <p>1.3.1 Exploitation of Carbohydrate Chemistry to Study Structure–Activity Relationship of Aminoglycoside Derivatives 17</p> <p>1.3.2 Aminoglycoside Microarrays to Screen Interactions of Antibiotics with RNAs and Proteins 18</p> <p>1.4 Influence of the Human Microbiome in Aminoglycoside Resistance 20</p> <p>1.4.1 The Effect of Antibiotic‐Induced Alterations 21</p> <p>1.4.2 A Reservoir of Antibiotic Resistance 24</p> <p>1.4.3 Strategies to Modulate the Human Microbiome 25</p> <p>1.5 Conclusions and Outlook 26</p> <p>Acknowledgments 27</p> <p>References 28</p> <p><b>2 Mechanisms of Action and of Resistance to Quinolones 39<br /></b><i>José L. Martínez</i></p> <p>2.1 Introduction 39</p> <p>2.2 Mechanism of Action of Quinolones 40</p> <p>2.3 Mutations in the Genes Encoding the Targets of Quinolones 41</p> <p>2.4 Multidrug Efflux Pumps and Quinolone Resistance 42</p> <p>2.5 Transferable Quinolone Resistance 43</p> <p>2.6 <i>Stenotrophomonas maltophilia</i> and Its Uncommon Mechanisms of Resistance to Quinolones 46</p> <p>Acknowledgments 47</p> <p>References 47</p> <p><b>3 Beta‐Lactams 57<br /></b><i>Luz Balsalobre, Ana Blanco, and Teresa Alarcón</i></p> <p>3.1 Introduction 57</p> <p>3.2 Chemical Structure 58</p> <p>3.3 Classification and Spectrum of Activity 59</p> <p>3.3.1 Penicillins 59</p> <p>3.3.2 Cephalosporins 61</p> <p>3.3.3 Monobactams 63</p> <p>3.3.4 Carbapenems 64</p> <p>3.3.5 Beta‐Lactam Associated with Beta‐Lactamase Inhibitors 64</p> <p>3.4 Mechanism of Action 66</p> <p>3.5 Activity of Beta‐Lactams Against Multiresistant Bacteria 68</p> <p>3.6 Conclusions 70</p> <p>References 70</p> <p><b>4 Glycopeptide Antibiotics: Mechanism of Action and Recent Developments 73<br /></b><i>Paramita Sarkar and Jayanta Haldar</i></p> <p>4.1 Introduction 73</p> <p>4.2 Naturally Occurring Glycopeptide Antibiotics 75</p> <p>4.3 Mechanism of Action of Glycopeptide Antibiotics 76</p> <p>4.4 Resistance to Glycopeptides 78</p> <p>4.5 Second‐Generation Glycopeptides 79</p> <p>4.5.1 Telavancin 79</p> <p>4.5.2 Dalbavancin 80</p> <p>4.5.3 Oritavancin 80</p> <p>4.6 Strategies to Overcome Resistance to Glycopeptides 81</p> <p>4.6.1 Modifications That Enhance the Binding Affinity to Target Pentapeptide 81</p> <p>4.6.2 Incorporation of Lipophilicity 85</p> <p>4.6.3 Incorporation of Lipophilic Cationic Moieties to Impart Membrane Disruption Properties 86</p> <p>4.6.4 Incorporation of Metal Chelating Moiety to Vancomycin to Impart New Mechanism of Action 88</p> <p>4.7 Glycopeptides Under Clinical Trials 88</p> <p>4.8 Glycopeptide Antibiotics: The Challenges 90</p> <p>References 91</p> <p><b>5 Current Macrolide Antibiotics and Their Mechanisms of Action 97<br /></b><i>S. Lohsen and D.S. Stephens</i></p> <p>5.1 Introduction 97</p> <p>5.2 Structure of Macrolides 99</p> <p>5.3 Macrolide Mechanisms of Action 101</p> <p>5.4 Clinical Use of Macrolides 104</p> <p>5.5 Next‐Generation Macrolides and Future Use 107</p> <p>References 109</p> <p><b>Part II Mechanism of Antibiotic Resistance 119</b></p> <p><b>6 Impact of Key and Secondary Drug Resistance Mutations on Structure and Activity of β‐Lactamases 121<br /></b><i>Egorov Alexey, Ulyashova Mariya, and Rubtsova Maya</i></p> <p>6.1 Introduction 121</p> <p>6.2 Structure of the Protein Globule of TEM‐Type β‐Lactamases: Catalytic and Mutated Residues 122</p> <p>6.2.1 Catalytic Site of β‐Lactamase TEM‐1 124</p> <p>6.2.2 Mutations Causing Phenotypes of TEM‐Type β‐Lactamases 125</p> <p>6.3 Effect of the Key Mutations on Activity of TEM‐Type β‐Lactamases 127</p> <p>6.3.1 Single Key Mutations in TEM‐Type ESBLs (2be) 128</p> <p>6.3.2 Combinations of Key Mutations in TEM‐Type ESBLs (2be) 130</p> <p>6.3.3 Key Mutations in IRT TEM‐Type β‐Lactamases (2br) 131</p> <p>6.3.4 Single Key Mutations in IRT TEM‐Type β‐Lactamases (2br) 131</p> <p>6.3.5 Combinations of Key Mutations in IRT TEM‐Type β‐Lactamases (2br) 133</p> <p>6.3.6 Combinations of Key ESBL and IRT Mutations in CMT TEM‐Type β‐Lactamases (2ber) 133</p> <p>6.4 Effect of Secondary Mutations on the Stability of TEM‐Type β‐Lactamases 134</p> <p>6.5 Conclusions 135</p> <p>Abbreviations 136</p> <p>References 137</p> <p><b>7 Acquired Resistance from Gene Transfer 141<br /></b><i>Elisabeth Grohmann, Verena Kohler, and Ankita Vaishampayan</i></p> <p>7.1 Introduction 141</p> <p>7.2 Horizonal Gene Transfer: A Brief Overview 143</p> <p>7.2.1 Transformation 144</p> <p>7.2.2 Transduction 144</p> <p>7.2.3 Conjugation 145</p> <p>7.3 Conjugative Transfer Mechanisms 145</p> <p>7.3.1 Conjugative Transfer of Plasmids 146</p> <p>7.3.2 Conjugative Transfer of Integrative Conjugative Elements 148</p> <p>7.3.3 Conjugative Transfer of Other Integrative Elements 150</p> <p>7.4 Antibiotic Resistances and Their Transfer 151</p> <p>7.4.1 Dissemination of Carbapenem Resistance Among Bacterial Pathogens 151</p> <p>7.4.2 Dissemination of Cephalosporin Resistance Among Bacterial Pathogens 153</p> <p>7.4.3 Dissemination of Methicillin Resistance Among Bacterial Pathogens 153</p> <p>7.4.4 Dissemination of Vancomycin Resistance Among Bacterial Pathogens 154</p> <p>7.4.5 Dissemination of Fluoroquinolone Resistance Among Bacterial Pathogens 154</p> <p>7.4.6 Dissemination of Penicillin and Ampicillin Resistance Among Bacterial Pathogens 155</p> <p>7.5 Nanotubes Involved in Acquisition of Antibiotic Resistances 155</p> <p>7.6 Conclusions and Outlook 156</p> <p>Abbreviations 156</p> <p>References 157</p> <p><b>8 Antimicrobial Efflux Pumps 167<br /></b><i>Manuel F. Varela</i></p> <p>8.1 Bacterial Antimicrobial Efflux Pumps 167</p> <p>8.1.1 Active Drug Efflux Systems 167</p> <p>8.1.2 Secondary Active Drug Transporters 169</p> <p>References 173</p> <p><b>9 Bacterial Persistence in Biofilms and Antibiotics: Mechanisms Involved 181<br /></b><i>Anne Jolivet‐Gougeon and Martine Bonnaure‐Mallet</i></p> <p>9.1 Introduction 181</p> <p>9.2 Reasons for Failure of Antibiotics in Biofilms 182</p> <p>9.2.1 Failure of Antibiotics to Penetrate Biofilm: Active Antibiotics on the Biofilm 182</p> <p>9.2.2 Outer Membrane Vesicles (OMVs) 183</p> <p>9.2.3 Horizontal Transfer of Encoding β‐Lactamase Genes 184</p> <p>9.2.4 Influence of Subinhibitory Concentrations of Antibiotics on Biofilm 184</p> <p>9.2.5 Small Colony Variants (SCVs), Persistence (Persisters), and Toxin–Antitoxin (TA) Systems 186</p> <p>9.2.6 Quorum Sensing: Bacterial Metabolites 191</p> <p>9.2.7 Extracellular DNA 191</p> <p>9.2.8 Nutrient Limitation 192</p> <p>9.2.9 SOS Inducers (Antibiotics and Others) 192</p> <p>9.2.10 Hypermutator Phenotype 192</p> <p>9.2.11 Multidrug Efflux Pumps 193</p> <p>9.3 Usual and Innovative Means to Overcome Biofilm Resistance in Biofilms 193</p> <p>9.3.1 Antibiotics (Bacteriocins) Natural and Synthetic Molecules: Phages 194</p> <p>9.3.2 Efflux Pump Inhibitors 195</p> <p>9.3.3 Anti‐Persisters: Quorum‐Sensing Inhibitors 195</p> <p>9.3.4 Enzymes 196</p> <p>9.3.5 Electrical Methods 196</p> <p>9.3.6 Photodynamic Therapy 196</p> <p>9.4 Conclusion 197</p> <p>Acknowledgments 197</p> <p>Conflict of Interest 197</p> <p>References 197</p> <p><b>Part III Socio-Economical Perspectives and Impact of AR 211</b></p> <p><b>10 Sources of Antibiotic Resistance: Zoonotic, Human, Environment 213<br /></b><i>Ivone Vaz‐Moreira, Catarina Ferreira, Olga C. Nunes, and Célia M. Manaia</i></p> <p>10.1 The Antibiotic Era 213</p> <p>10.2 Intrinsic and Acquired Antibiotic Resistance 214</p> <p>10.3 The Natural Antibiotic Resistome 215</p> <p>10.4 The Contaminant Resistome 215</p> <p>10.5 Evolution of Antibiotics Usage 216</p> <p>10.6 Antibiotic Resistance Evolution 219</p> <p>10.7 Stressors for Antibiotic Resistance 219</p> <p>10.8 Paths of Antibiotic Resistance Dissemination 221</p> <p>10.9 Antibiotic Resistance in Humans and Animals 224</p> <p>10.10 Final Considerations 227</p> <p>References 228</p> <p><b>11 Antibiotic Resistance: Immunity‐Acquired Resistance: Evolution of Antimicrobial Resistance Among Extended‐Spectrum β‐Lactamases and Carbapenemases in Klebsiella pneumonia and Escherichia coli 239<br /></b><i>Isabel Carvalho, Nuno Silva, João Carrola, Vanessa Silva, Carol Currie, Gilberto Igrejas, and Patrícia Poeta</i></p> <p>11.1 Overview of Antibiotic Resistance as a Worldwide Health Problem 239</p> <p>11.2 Objectives 241</p> <p>11.3 Causes of Antimicrobial Resistance 242</p> <p>11.4 <i>Enterobacteriaceae</i>: General Characterization 243</p> <p>11.4.1 Escherichia coli 243</p> <p>11.4.2 <i>Klebsiella pneumoniae</i> 244</p> <p>11.5 Current Antibiotic Resistance Threats 245</p> <p>11.5.1 Carbapenem‐Resistant <i>Enterobacteriaceae</i> 245</p> <p>11.5.2 Extended‐Spectrum β‐Lactamase 247</p> <p>11.6 Consequences and Future Strategies to Brace the Antibiotic Backbone 250</p> <p>11.7 Concluding Remarks and Future Perspectives 251</p> <p>Acknowledgments 252</p> <p>References 252</p> <p><b>12 Extended‐Spectrum‐β‐Lactamase and Carbapenemase‐Producing Enterobacteriaceae in Food‐Producing Animals in Europe: An Impact on Public Health? 261<br /></b><i>Nuno Silva, Isabel Carvalho, Carol Currie, Margarida Sousa, Gilberto Igrejas, and Patrícia Poeta</i></p> <p>12.1 Extended‐Spectrum β‐Lactamase 261</p> <p>12.1.1 ESBL‐Producing <i>Enterobacteriaceae</i> in Food Animals 262</p> <p>12.2 Carbapenemases 265</p> <p>12.3 Concluding Remarks 267</p> <p>References 268</p> <p><b>Part IV Therapeutic Strategy for Overcoming AR 275</b></p> <p><b>13 AR Mechanism‐Based Drug Design 277<br /></b><i>Mire Zloh</i></p> <p>13.1 Introduction 277</p> <p>13.2 Drug Design Principles 279</p> <p>13.3 Identification of Novel Targets and Novel Mechanisms of Action 282</p> <p>13.4 Efflux Pump Inhibitors 286</p> <p>13.5 Design of Inhibitors of Drug‐Modifying Enzymes 294</p> <p>13.6 Antimicrobial Peptides 297</p> <p>13.7 Other Approaches to Overcome Bacterial Resistance 299</p> <p>13.8 Conclusion 300</p> <p>References 300</p> <p><b>14 Antibiotics from Natural Sources 311<br /></b><i>David J. Newman</i></p> <p>14.1 Introduction 311</p> <p>14.1.1 The Origin of Microbial Resistance Gene Products 311</p> <p>14.2 Organization of the Following Sections 312</p> <p>14.3 Peptidic Antibiotics (Both Cyclic and Acyclic) 312</p> <p>14.3.1 Tyrocidines, Gramacidins, and Derivatives 312</p> <p>14.3.2 Streptogramins and Derivatives: Cyclic Peptides 313</p> <p>14.3.3 Arylomycins (Lipopeptide and Modification, Preclinical) 313</p> <p>14.3.4 Daptomycin (Cyclic Depsilipopeptide) 314</p> <p>14.3.5 Colistins (Cyclic Peptides with a Lipid Tail) 315</p> <p>14.3.6 Glycopeptides 317</p> <p>14.3.7 Host Defense Peptides 319</p> <p>14.4 β‐Lactams: Development, Activities, and Chemistry 321</p> <p>14.4.1 Combinations with β‐Lactamase Inhibitors 322</p> <p>14.5 Aminoglycosides 323</p> <p>14.5.1 Streptomycin 323</p> <p>14.5.2 Plazomicin 323</p> <p>14.6 Early Tetracyclines: Aureomycin and Terramycin 324</p> <p>14.6.1 Semisynthetic Tetracyclines from 2005 324</p> <p>14.7 Erythromycin Macrolides 326</p> <p>14.7.1 Recent Semisynthetic Macrolides 326</p> <p>14.8 Current Methods of “Discovering Novel Antibiotics” 328</p> <p>14.8.1 Introduction 328</p> <p>14.8.2 Initial Rate‐Limiting Step (Irrespective of Methods) 328</p> <p>14.8.3 Genomic Analyses of Whole Microbes 329</p> <p>14.8.4 Isolated Genomics 329</p> <p>14.8.5 New Sources (and Old Ones?) for Investigation 331</p> <p>14.8.6 “Baiting” for Microbes 331</p> <p>14.8.7 Use of Elicitors 333</p> <p>14.9 Conclusions 333</p> <p>14.9.1 Funding? 334</p> <p>14.9.2 The “Take‐Home Lesson” 334</p> <p>References 334</p> <p><b>15 Bacteriophage Proteins as Antimicrobials to Combat Antibiotic Resistance 343<br /></b><i>Hugo Oliveira, Luís D. R. Melo, and Sílvio B. Santos</i></p> <p>15.1 Introduction 343</p> <p>15.2 Polysaccharide Depolymerases 346</p> <p>15.2.1 Depolymerase Structure 348</p> <p>15.2.2 Depolymerase Classification 349</p> <p>15.2.3 Depolymerase Activity Assessment 350</p> <p>15.2.4 Depolymerases as Antimicrobials 351</p> <p>15.2.5 Remarks on Depolymerases 355</p> <p>15.3 Peptidoglycan‐Degrading Enzymes 356</p> <p>15.3.1 Virion‐Associated Lysins (VALs) 358</p> <p>15.3.2 Gram‐Positive Targeting Endolysins 365</p> <p>15.3.3 Gram‐Negative Targeting Endolysins 374</p> <p>15.4 Holins 388</p> <p>15.4.1 Holin Structure 388</p> <p>15.4.2 Holins as Antimicrobials 389</p> <p>15.4.3 Remarks on Holins 390</p> <p>15.5 Final Considerations 390</p> <p>References 392</p> <p><b>16 Antibiotic Modification Addressing Resistance 407<br /></b><i>Haotian Bai and Shu Wang</i></p> <p>16.1 Chemical Synthesis of New Antibiotics 407</p> <p>16.2 Antibiotic Modification with Targeted Groups 413</p> <p>16.3 Antibiotic Modification with Photo‐Switching Units 417</p> <p>16.4 Antibiotic Modification by Supramolecular Chemistry 420</p> <p>16.5 Antibiotic Modification by Complexed with Other Materials 423</p> <p>16.6 Conclusion 425</p> <p>References 425</p> <p><b>17 Sensitizing Agents to Restore Antibiotic Resistance 429<br /></b><i>Anton Gadelii, Karl‐Omar Hassan, and Anders P. Hakansson</i></p> <p>17.1 Introduction 429</p> <p>17.2 Sensitizing Strategies Directly Targeting Resistance Mechanisms 430</p> <p>17.2.1 Inhibition of β‐Lactamases 430</p> <p>17.2.2 Drug Efflux Pump Inhibitors (EPIs) 433</p> <p>17.3 Sensitizing Strategies Circumventing Resistance Mechanisms 435</p> <p>17.3.1 Manipulating Bacterial Homeostasis 435</p> <p>17.3.2 Cell Wall/Membrane Proteins 437</p> <p>17.3.3 Biofilms and Quorum Sensing 438</p> <p>17.3.4 Persister Cells 440</p> <p>17.3.5 Targeting Nonessential Genes/Proteins 441</p> <p>17.3.6 Bacteriophages 441</p> <p>17.4 Using and Strengthening the Human Immune System Against Resistant Bacteria 441</p> <p>17.4.1 Strengthening Host Immune System Function 441</p> <p>17.4.2 Antimicrobial Peptides (AMPs) 443</p> <p>17.5 Conclusion 443</p> <p>References 444</p> <p><b>18 Repurposing Antibiotics to Treat Resistant Gram‐Negative Pathogens 453<br /></b><i>Frank Schweizer</i></p> <p>18.1 Introduction 453</p> <p>18.2 Anti‐Virulence Strategy 454</p> <p>18.3 Antibiotic Combination Strategy 454</p> <p>18.4 Antibiotic–Antibiotic Combination Approach 455</p> <p>18.5 Antibiotic–Adjuvant Combination Approach 456</p> <p>18.6 β‐Lactam and β‐Lactamase Inhibitor Combination 456</p> <p>18.7 Imipenem–Cilastatin/Relebactam Triple Combination 457</p> <p>18.8 Aspergillomarasmine A 458</p> <p>18.9 Intrinsic Resistance Challenges and Strategies to Overcome Them 458</p> <p>18.10 Repurposing of Hydrophobic Antibiotics with High Molecular Weight by Enhancing Outer Membrane Permeability Using Polybasic Adjuvants 461</p> <p>18.11 Repurposing of Hydrophobic Antibiotics with Large Molecular Weight and Other Antibacterials as Antipseudomonal Agents Using Polybasic Adjuvants 464</p> <p>18.12 Repurposing of Antibiotics as Potent Agents Against MDR GNB 467</p> <p>18.13 Outlook and Conclusions 468</p> <p>References 468</p> <p><b>19 Nontraditional Medicines for Treatment of Antibiotic Resistance 477<br /></b><i>Ana Paula Guedes Frazzon, Michele Bertoni Mann, and Jeverson Frazzon</i></p> <p>19.1 Introduction 477</p> <p>19.2 Antibodies 478</p> <p>19.2.1 Raxibacumab Versus <i>Bacillus anthracis</i> 478</p> <p>19.2.2 Bezlotoxumab Versus <i>Clostridium difficile</i> 479</p> <p>19.2.3 Panobacumab Versus <i>Pseudomonas aeruginosa</i> 479</p> <p>19.2.4 LC10 Versus <i>Staphylococcus aureus</i> 480</p> <p>19.3 Immunomodulators 481</p> <p>19.3.1 Antibodies plus Polymyxins 481</p> <p>19.3.2 Antibodies plus Vitamin D 482</p> <p>19.3.3 Antibodies plus Clavanin 482</p> <p>19.3.4 Antibodies plus Reltecimod 483</p> <p>19.4 Potentiators of Antibiotic Activity 483</p> <p>19.4.1 Antibiotic–Antibiotic Combinations 484</p> <p>19.4.2 Pairing of Antibiotic with Nonantibiotic 485</p> <p>19.5 Bacteriophages 488</p> <p>19.5.1 Life Cycles of Bacteriophages 488</p> <p>19.5.2 Bacteriophage Therapy 489</p> <p>19.5.3 Phage Enzymes 490</p> <p>19.5.4 Concerns About the Application of Phage to Treat Bacteria 491</p> <p>19.6 Therapy with Essential Oils 491</p> <p>19.7 Microbiota‐Based Therapy 495</p> <p>19.7.1 Microbiota Modulation 495</p> <p>19.7.1.1 Probiotics 496</p> <p>19.7.1.2 Prebiotics 496</p> <p>19.7.2 Stool Microbiota Transplant 496</p> <p>Further Reading 497</p> <p><b>20 Therapeutic Options for Treatment of Infections by Pathogenic Biofilms 503<br /></b><i>Bruna de Oliveira Costa, Osmar Nascimento Silva, and Octávio Luiz Franco</i></p> <p>20.1 Introduction 503</p> <p>20.2 Antibiotic Therapy for the Treatment of Pathogenic Biofilms 504</p> <p>20.2.1 Monotherapy 504</p> <p>20.2.2 Antibiotic Combination Therapy 505</p> <p>20.3 New Findings for the Treatment of Pathogenic Biofilms 507</p> <p>20.3.1 AMPs Applied to Treatment Pathogenic Biofilms 507</p> <p>20.3.2 Bacteriophage Therapy Anti‐Biofilm 514</p> <p>20.3.3 Nanotechnology Applied to the Treatment of Pathogenic Biofilms 517</p> <p>20.4 Conclusion and Future Directions 519</p> <p>References 520</p> <p><b>Part V Strategies to Prevent the Spread of AR 533</b></p> <p><b>21 Rapid Analytical Methods to Identify Antibiotic‐Resistant Bacteria 535<br /></b><i>John B. Sutherland, Fatemeh Rafii, Jackson O. Lay, Jr., and Anna J. Williams</i></p> <p>21.1 Introduction 535</p> <p>21.2 Standard Methods for Antibiotic Sensitivity Testing 536</p> <p>21.3 Rapid Cultural Methods 537</p> <p>21.4 Rapid Serological Methods 540</p> <p>21.5 Rapid Molecular (Genetic) Methods 540</p> <p>21.6 Mass Spectrometric Methods 545</p> <p>21.7 Flow Cytometric Methods 549</p> <p>21.8 Conclusions 550</p> <p>Acknowledgments 553</p> <p>References 553</p> <p><b>22 Effective Methods for Disinfection and Sterilization 567<br /></b><i>Lucía Fernández, Diana Gutiérrez, Beatriz Martínez, Ana Rodríguez, and Pilar García</i></p> <p>22.1 Introduction 567</p> <p>22.2 Disinfection and Sterilization: Methods and Factors Involved in Their Efficacy 569</p> <p>22.2.1 Methods of Sterilization and Disinfection 570</p> <p>22.2.2 Factors Influencing Disinfection and Sterilization Efficacy 570</p> <p>22.3 Resistance to Disinfectants 571</p> <p>22.3.1 Molecular Mechanisms of Biocide Resistance 571</p> <p>22.3.2 Biofilms 572</p> <p>22.3.3 Cross‐Resistance Between Antibiotics and Disinfectants 574</p> <p>22.4 New Technologies as Alternatives to Classical Disinfectants 575</p> <p>22.4.1 Chemical and Physical Disinfectants 575</p> <p>22.4.2 Antimicrobial Surfaces 578</p> <p>22.4.3 Biological Disinfectants 578</p> <p>22.5 Current Legislation 579</p> <p>22.6 Conclusions 581</p> <p>References 582</p> <p><b>23 Strategies to Prevent the Spread of Antibiotic Resistance: Understanding the Role of Antibiotics in Nature and Their Rational Use 589<br /></b><i>Rustam Aminov</i></p> <p>23.1 Introduction 589</p> <p>23.2 Agriculture as the Largest Consumer of Antimicrobials 590</p> <p>23.3 Antimicrobials and Antimicrobial Resistance 591</p> <p>23.4 First‐Generation Tetracyclines: Discovery and Usage 592</p> <p>23.5 Tetracycline Resistance Mechanisms 593</p> <p>23.6 Phylogeny of Tetracycline Resistance Genes 593</p> <p>23.7 Second‐Generation Tetracyclines 595</p> <p>23.8 Third‐Generation Tetracyclines 595</p> <p>23.9 Resistance to Third‐Generation Tetracyclines 596</p> <p>23.10 Other Potential Resistance Mechanisms Toward Third‐Generation Tetracyclines 597</p> <p>23.11 Evolutionary Aspect of <i>tet</i>(X) 598</p> <p>23.12 Ecological Aspects of <i>tet</i>(X) 599</p> <p>23.13 Antibiotics and Antibiotic Resistance as Integral Parts of Microbial Diversity 602</p> <p>23.14 The Role of Antibiotics in Natural Ecosystems 604</p> <p>23.15 Low‐Dose Antibiotics: Phenotypic Effects 605</p> <p>23.16 Low‐Dose Antibiotics: Genetic Effects 606</p> <p>23.17 Regulation of Antibiotic Synthesis in Antibiotic Producers 608</p> <p>23.18 Convergent Evolution of Antibiotics as Signaling Molecules 610</p> <p>23.19 Carbapenems: Convergent Evolution and Regulation in Different Bacteria 611</p> <p>23.20 Antibiotics and Antibiotic Resistance: Environmental and Anthropogenic Contexts 614</p> <p>23.21 Conclusions 615</p> <p>Conflict of Interest 616</p> <p>References 616</p> <p><b>Part VI Public Policy 637</b></p> <p><b>24 Strategies to Reduce or Eliminate Resistant Pathogens in the Environment 639<br /></b><i>Johan Bengtsson‐Palme and Stefanie Heß</i></p> <p>24.1 Introduction 639</p> <p>24.2 Sources of Resistant Bacteria in the Environment 640</p> <p>24.3 Sewage and Wastewater 641</p> <p>24.3.1 Sewage Treatment Plants 641</p> <p>24.3.2 Non‐Treated Sewage 643</p> <p>24.3.3 Industrial Wastewater Effluents 643</p> <p>24.3.4 Environmental Antibiotic Resistance is a Poverty Problem 644</p> <p>24.4 Agriculture 646</p> <p>24.4.1 Intensive, Large‐Scale Animal Husbandry 646</p> <p>24.4.2 Manure Application 647</p> <p>24.4.3 Agriculture in Developing Countries 647</p> <p>24.4.4 Aquaculture 648</p> <p>24.5 <i>De Novo</i> Resistance Selection 649</p> <p>24.6 Relevant Risk Scenarios 649</p> <p>24.7 Management Options 653</p> <p>24.7.1 Possible Interventions on the Level of Releases of Resistant Bacteria 653</p> <p>24.7.2 Restricting Transmission of Resistant Bacteria from the Environment 657</p> <p>24.7.3 Better Agriculture Practices to Sustain the Lifespans of Antibiotics 658</p> <p>24.7.4 Limiting Selection for Resistance in the Environment 659</p> <p>24.8 Final Remarks 661</p> <p>Acknowledgments 662</p> <p>Conflict of Interest 662</p> <p>References 662</p> <p>Index 675</p>
<p><b>JOSÉ-LUIS CAPELO-MARTÍNEZ P<small>H</small>D</b>, is Associate Professor in the Department of Chemistry of the Faculty of Science and Technology of the NOVA University of Lisbon. <p><b>GILBERTO IGREJAS P<small>H</small>D</b>, is an Associate Professor with habilitation in the Department of Genetics and Biotechnology at the University of Trás-os-Montes and Alto Douro in Portugal.
<p><b>A COMPREHENSIVE REVIEW OF THE MULTIFACETED FIELD OF ANTIBIOTIC SCIENCE</b> <p>In recent years bacterial resistance to antibiotics has reached new and disturbing heights. <i>Antibiotic Drug Resistance</i> offers a comprehensive overview of the complex field of antibiotic science. The authors—noted experts in the field—present an authoritative guide that translates current research into tools for prevention, diagnosis, and treatment of infectious diseases. <p><i>Antibiotic Drug Resistance</i> explores the significant challenge of resistance to antibiotic drugs and examines a wide range of topics. The book addresses the mechanisms of action of the antibiotics used today such as aminoglycosides, quinolones, betalactams, glycopeptides, and macrolides. The authors explore the strategies devoted to overcoming antibiotic resistance and include information on new techniques for designing drugs, antibiotics from natural sources, approaches based on antimicrobials and bacteriophages, and more. This important book: <ul> <li>Provides the essential knowledge about the broad field of drug resistance</li> <li>Offers information on the tools for prevention, diagnosis, and treatment of infectious diseases</li> <li>Links strategies to analyze microbes to the development of new drugs</li> <li>Offers data on sensitizing agents to restore antibiotic activity, non-traditional medicines, and therapeutic options to treat infections caused by pathogenic bilfilms</li> </ul> <p>Written for pharmaceutical and medicinal chemists, microbiologists, biochemists, and others, <i>Antibiotic Drug Resistance</i> offers information on the current antibiotics and their mechanism of action and mechanism of antibiotic resistance. It also provides material on a socio-economic perspective, therapeutic approaches, prevention strategies, and public policy.

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