This is a free sample of content from Antibiotics and Antibiotic Resistance. Click here for more information on how to buy the book. Index A Antifolates. See also specific drugs AAC(60)-Ib-cr, 185 novel compounds, 378–379 ACHN-975 overview, 373–374 clinical studies, 163–164 resistance mechanisms medicinal chemistry, 166 sulfamethoxazole, 378 structure, 162 trimethoprim, 374–378 AcrAB-TolC, 180 Apramycin, structure, 230 AcrD, 236 Arbekacin, 237–238 AdeRS, 257 Avibactam, structure, 38 AFN-1252 Azithromycin mechanism of action, 148, 153 resistance, 291, 295 resistance, 153 structure, 272 structure, 149 Aztreonam, structure, 36 AIM-1, 74 Amicoumacin A, 222 Amikacin B indications, 240 BaeSR, 257 structure, 230 BAL30072, 36 synthesis, 4 BB-78495, 162 Aminoglycosides. See also specific drugs BC-3205, 341, 344 historical perspective, 229–230 BC-7013, 341, 344 indications, 239–241 b-Lactamase. See also specific enzymes mechanism of action, 232 classification novel drugs, 237 class A, 67–71 pharmacodynamics, 238–239 class B, 69–74 pharmacokinetics, 238–239 class C, 69, 74 resistance mechanisms class D, 70, 74–77 aminoglycoside-modifying enzymes evolution of antibiotic resistance, 4 acetyltransferases, 233–235 historical perspective, 67 nucleotidyltransferases, 235 inhibitors phosphotransferases, 235 overview, 37–39 efflux-mediated resistance, 236 structures, 38 molecular epidemiology, 236–237 nomenclature, 67 overview, 17, 233 b-Lactams. See also specific classes and antibiotics ribosomal RNA modifications, 235–236 Enterococcus faecium–resistancemechanisms, 52–54 spectrum of activity, 230–232 mechanism of action, 24–25, 45–46, 65–66 structures, 230 monocyclic b-lactams, 36–37 targets, 17 Mycobacterium tuberculosis–resistance Amoxicillin, structure, 27 mechanisms, 56–57 AmpC, 74 penicillin-binding proteins Ampicillin, structure, 26 Enterococcus faecium,52–53 Antibiotic resistance dating Mycobacterium tuberculosis,56 challenges, 9 peptidoglycan assembly enzymology, 46–48 experimental evidence for old resistance, 11–12 Staphylococcus aureus,54–55 phylogenetics, 11 Staphylococcus pneumoniae sequencing techniques, 9–10 overview, 48–49 technology impact, 10–11 resistance proteins, 49–52 Antibiotic restriction, guidelines, 5 targets, 45–46, 65–66 397 © 2016 by Cold Spring Harbor Laboratory Press. All rights reserved. This is a free sample of content from Antibiotics and Antibiotic Resistance. Click here for more information on how to buy the book. Index b-Lactams. See also specific classes and resistance, 164–165 antibiotics (Continued) structural basis of species specificity and kinetics, popularity, 23–24 166–167 Staphylococcus aureus–resistance structure, 162 mechanisms, 54–56 Chloramphenicol, 17, 311–312, 316–317, 321–322, 326 Staphylococcus pneumoniae–resistance 5-Chloro-2-phenoxyphenol mechanisms, 48 mechanism of action, 148 targets and resistance mechanisms, 17, 66–67 structure, 149 Biapenem, 35 Chlortetracycline, structure, 248 Blasticidin S, 225 Ciprofloxacin. See Fluoroquinolones Brachybacterium, phylogenetic analysis of resistance, 12 Clarithromycin resistance, 295 structure, 272 C Clavulanic acid, 38 Capreomycin, 223 Clindamycin, 311, 316 Carbapenems. See also specific drugs Clomocycline, 248 historical perspective, 34–36 Clostridium difficile types and structures, 35 clinical features of infection, 383–384 Carbenicillin, 27 fidaxomicin therapy. See Fidaxomicin Cathelicidin microbial peptide (CRAMP), 130 LFF571 therapy. See LFF571 Cefaclor, 29 rifaximin therapy, 209 Cefazolin, 30 Cloxacillin, 26 Cefdinir, 30 CmlB1, 326 Cefepime, 31 Cmr, 323 Cefixime, 29 CRAMP. See Cathelicidin microbial peptide Cefoperazone, 30 CTX, 70 Cefotaxime, 30 Cycloheximide, 344 Cefoxitin, 32 Cystic fibrosis (CF), tobramycin therapy, 240 Cefpoxime, 29 Ceftaroline, 31 Ceftazidime, 31 D Ceftibutin, 29 Dalbavancin Ceftobiprole, 31 historical perspective, 83 Ceftolozane resistance mechanisms, 90–91 structure, 31 structure, 82 uses, 33 Dalfopristin, 310–311, 316 Ceftriaxone, 30 Daptomycin Cefuroxime, 30 historical perspective, 109–110 Cephalexin, 29 mechanism of action, 112–114 Cephalosporin, 357 resistance Cephalosporins. See also specific drugs Enterococcus faecalis, 118–120 historical perspective, 28, 33 Enterococcus faecium, 118–120 types and structures, 29–32 overview of mechanisms, 17, 114 uses, 28, 33 Staphylococcus aureus, 114–118 CF. See Cystic fibrosis structure, 110–111 Cfr, 347 synthesis, 110–112 cfr, 327–329 targets, 17 CG400462 Demethylchlorotetracycline, 248 mechanism of action, 148 DHFR. See Dihydrofolate reductase structure, 149 DHPS. See Dihydropteroate synthase CG400549 Dihydrofolate reductase (DHFR), 373–375, 377 mechanism of action, 148, 153 Dihydropteroate synthase (DHPS), 373–374, 378–379 structure, 149 DIM-1, 74 CHIR-090 Dityromycin, 222 bacterial defense effects of inhibition, 169 Doripenem, 35 medicinal chemistry, 165–166 Doxycycline, 248 398 © 2016 by Cold Spring Harbor Laboratory Press. All rights reserved. This is a free sample of content from Antibiotics and Antibiotic Resistance. Click here for more information on how to buy the book. Index E FIM-1, 74 eat(A), 325 Florfenicol, 311–312, 315, 317, 326 Edeine, 218 Fluoroquinolones Elongation factors historical perspective, 173–174 fusidic acid targeting of Ef-G, 18, 225, 355, 360–363 mechanism of action, 174–177 LFF571 targeting of Ef-Tu, 389–392 resistance translation, 219–225 mechanisms EmrR, 181 permeation alterations, 178–182 Enoyl-acyl carrier protein reductase (FabI) inhibitors. plasmid-mediated resistance, 182–186 See also specific inhibitors PMQR determinants, 186 bisubstrate inhibitors, 148–152 target enzyme mutational alteration, mechanism of action, 18 177–178 NAD(P)–FabI-binding inhibitors overview, 4, 17 product complex binders, 152–153 targets, 17 substrate complex binders, 153–154 Folate pathway inhibitors. See Antifolates prospects for study, 154–155 FomA, 104 types and structures, 146–147 FomB, 104 Enterococcus faecalis, daptomycin resistance, 118–120 FosA3, 103, 105 Enterococcus faecium FosB, 103 b-lactam-resistance mechanisms, 52–54 Fosfomycin daptomycin resistance, 118–120 historical perspective, 97–98 Eravacycline mechanism of action, 98–100 clinical studies, 262 resistance development, 249 clinical considerations structure, 248 combination therapy, 104–105 Ere(A), 287–288 overview, 104 Ere(B), 287–288 modifying enzymes, 102–104 Erm, 272, 274, 281–283 mutational resistance, 100–101 Ertapenem, 35 overview of mechanisms, 18 Erythromycin spectrum of activity, 98 resistance, 295 target, 18 structure, 272 uptake, 100 5-Ethyl-2-phenoxyphenol FosX, 104 mechanism of action, 148 fus genes, 364–366 structure, 149 Fusidic acid EttA, 347 mechanism of action, 18, 225, 355, 360–363 ExPortal, 131 pH effects and intracellular activity, 360–361 prospects for study, 369 resistance F cross-resistance with other antibiotics, 366 FabI inhibitors. See Enoyl-acyl carrier protein development, 363–364 reductase inhibitors dosing optimization for prevention, FDX. See Fidaxomicin 366–368 FepA, 180 mechanisms, 18, 363–366 FepR, 180 prevalence, 358–359 Fidaxomicin (FDX) spectrum of activity, 356–360 efficacy against Clostridium difficile, 386 structure, 356 historical perspective, 384–385 mechanism of action, 385–386 prospects for study, 392–393 G resistance GE2270A, 220 frequencies, 387 GE2832, 223 mechanisms, 18, 387–389 GE81112, 218 resistant Clostridium difficile features, 389 Gene transfer structure, 386 bacteria, 4–5 target, 18, 385 horizontal gene transfer, 18 399 © 2016 by Cold Spring Harbor Laboratory Press. All rights reserved. This is a free sample of content from Antibiotics and Antibiotic Resistance. Click here for more information on how to buy the book. Index Genomics, antibacterial drug target identification, LFF571 16–17 historical perspective, 385 Gentamycin, 222 mechanism of action, 389–391 Gentamycin C1a, 230 prospects for study, 392–393 GES b-lactamases, 71 resistance GIM-1, 74 frequencies, 391–392 Glycopeptide antibiotics. See also specific antibiotics mechanisms, 391–392 antibacterial spectrum, 84 structure, 386 historical perspective, 83 Limecycline, 248 mechanisms of action, 84–87 Lincomycins, 17, 310–311 overview, 81, 83 Lincosamides. See also specific drugs resistance mechanisms, 87–91 indications, 310 structures, 82 mechanism of action, 313–315 GSK2251052, 19 prospects for study, 328, 330 GyrA, 177 resistance GyrB, 177 efflux genes multidrug transporters, 323 specific exporters, 323–325 H enzymatic inactivation, 319, 321 HE. See Hepatic encephalopathy mechanisms, 315, 317 Helvoic acid, 357 prevalence, 315–317 Hepatic encephalopathy (HE), rifaximin therapy, ribosomal mutations, 317–319 206–207 target site modifications and resistance, 327 structures, 311 Linezolid, 327 I Lipopolysaccharide (LPS) IBS. See Irritable bowel syndrome LpxC inhibitors. See LpxC inhibitors Iclaprim, 375, 378 modifications in polymyxin resistance, Imipenem, 35 132–137 IMP, 72–73 lmr genes, 324 InhA, 150 Lon protease, tetracycline resistance, 258 Initiation factors, translation, 216–219 LPS. See Lipopolysaccharide Irritable bowel syndrome (IBS), rifaximin therapy, LpxC inhibitors. See also specific inhibitors 205–206 adaptation to alteration of lipopolysaccharide Isoniazid synthesis, 167–168 mechanism of action, 148, 150 bacterial defense effects of inhibition, 168–169 resistance mechanisms, 150–152 clinical studies, 162–163 structure, 149 historical perspective, 160–162 lipid A biosynthesis, 159–160 medicinal chemistry, 165–166 J overview, 18 Josamycin, 273 Pseudomonas aeruginosa studies, 162 resistance, 164–165