Chakrabarti sen anatomy of global stock market crashes; an empirical analysis (2012)

SpringerBriefs in Economics For further volumes: http://www.springer.com/series/8876 Gagari Chakrabarti Chitrakalpa Sen • Anatomy of Global Stock Market Crashes An Empirical Analysis 123 Gagari Chakrabarti Economics Presidency University College Street 86/1 Kolkata 700 073 West Bengal India ISSN 2191-5504 ISBN 978-81-322-0462-6 DOI 10.1007/978-81-322-0463-3 Chitrakalpa Sen G D Goenka Education City Department of Economics G D Goenka World Institute Sohna-Gurgaon Road Gurgaon 122103 India e-ISSN 2191-5512 e-ISBN 978-81-322-0463-3 Springer New Delhi Heidelberg New York Dordrecht London Library of Congress Control Number: 2011944258 Ó The Author(s) 2012 This work is subject to copyright All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed Exempted from this legal reservation are brief excerpts in connection with reviews or scholarly analysis or material supplied specifically for the purpose of being entered and executed on a computer system, for exclusive use by the purchaser of the work Duplication of this publication or parts thereof is permitted only under the provisions of the Copyright Law of the Publisher’s location, in its current version, and permission for use must always be obtained from Springer Permissions for use may be obtained through RightsLink at the Copyright Clearance Center Violations are liable to prosecution under the respective Copyright Law The use of general descriptive names, registered names, trademarks, service marks, etc in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use While the advice and information in this book are believed to be true and accurate at the date of publication, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made The publisher makes no warranty, express or implied, with respect to the material contained herein Printed on acid-free paper Springer is part of Springer Science+Business Media (www.springer.com) Foreword Despite recurrent shocks to the stock market, a disastrous association of stock market with the real sector is required to turn our attention to its importance After the great depression of the 1930s, it is the current financial sector crisis including the stock market crash that has particularly caught our attention Only, this time, the severity and extent of the crash and its effect is deeper and wider since now both financial and real sector, courtesy globalization and technological innovation, stands globally integrated It is said that value and movements of stock market is ultimately determined by the real sector It has also been expressed in the current historical juncture of capitalism that financial sector in general and stock sector in particular exercise considerable control over the real sector Perhaps, both are true Not surprisingly then and despite the dispute which is the primary causal factor, stock market shifts and real sectors shifts tend to move concomitantly, positively during the time of boom and negatively during the bust with each feeding into the other Notwithstanding this state of affairs, much research has also gone into the endogenous factors that generate dynamics within the stock market independent of the real sector Thus it is conjectured that there may be events transpiring in the stock market that may make it implode from within Boom and bubble may thus have to with events that happen in the stock markets which, given the technological transformation of the last two decades, generates speedy decisions– actions that are not only unpredictable, but may also be what are called irrational leading to a path dependent trajectory where the herd mentality of following others take precedence over the rationally calculating decision of cost-benefit The result is a non-linear, chaotic, stock market with self-generating fluctuations and indeterminate equilibrium If the current history of capitalism is about the financial control of stock market, then this endogenously produced cycles bordering on unpredictability and contingency in the stock market only reiterates the unstable nature of the capitalist system per se Moreover, are all of the phases of boom and bubble unique or are there some common factors, such as rising/eroding confidence that are linked with the various cyclic phases? v vi Foreword Distilling the frontier of the debates on these issues, Gagari Chakrabarti and Chitrakalpa Sen produce a fascinating analysis of the history and cause of the cycles of stock market, with particular attention to the current global crisis It will help the reader understand the current nuances of stock markets, its dynamics of booms and busts and, why, even if we may know about the factor of confidence, the trajectory of cycles may lead to indeterminate outcomes This book is a must read for those interested in the role of stock market in the current global economic crisis Kolkata, October 2011 Anjan Chakrabarti Department of Economics University of Calcutta Kolkata India Preface September 15, 2008 did not start as just another day in our lives The world woke up to the news of the collapse of Lehmann Brothers, the fourth largest investment bank in the US and Merrill Lynch, another iconic investment bank, was acquired by Bank of America ‘‘In a period of less than eighteen months Wall Street had gone from celebrating its most profitable age to finding itself on the bank of an epochal devastation Trillions of dollars in wealth had vanished, and the financial landscape was entirely reconfigured’’ (Sorkin 2010).1 Stock prices across the globe were on a downhill path throughout the year 2008 But something was terribly wrong this time The ongoing recession soon turned into a doomsday situation as the whole world plunged into a full blown financial crisis What followed were unanticipated and unprecedented memories of the Great Depression Between October 2008 and March 2009, Dow Jones fell by 52.5%, a breath short of the record 54.5% between 1929 and 1931, at the height of the Great Depression Dow Jones was not alone in this race to the bottom In 2008, Britain’s FTSE recorded its worst fall, a 31.3%; Shanghai’s stock market recorded a 65.2% fall, Germany’s DAX fell by 40.4%, SENSEX went down by 51.9% and Hong Kong stock market saw a fall of 48.3%.2 For all who believed that the good times will never end, were in for a very, very rude shock As the stock market plunged worldwide, the worst nightmare of investors started coming true As the markets fell, then stopped as if catching a breath to its long way down and then fell again, the age old beliefs and rationales about the market that the market knows best started crumbling down all over Best put in the words of Alan Greenspan, ‘‘the whole intellectual edifice, however, collapsed…’’.3 As investors and traders saw the markets come crashing worldwide, economists and researchers, Sorkin A (2010) To big to fail Penguin, India Record stock market falls in 2008 http://bbc.co.uk/news/world/asia_pacific/ Accessed 24 August 2011 As quoted by Alan Greenspan before the committee of Government Oversight and Reform, October 23 2008 http://clipsandcomments.com/wp-content/uploads/2008/10/greenspantestimony-20081023.pdf Accessed 24 August 2011 vii viii Preface dumbfounded by the unexpected development, groped for a suitable explanation And all answers led to one direction … a prolonged misinterpretation of the market behavior, which stood firmly on the traditional belief of the market’s rationality The stock market collapse had a severe ramification on not only other financial markets but also on people’s lives As by-products of the crisis, millions were soon jobless, homeless and suddenly poor all over the world Everybody started believing that the ‘‘invisible hand’’ was dead Under these circumstances, it becomes important both on part of a researcher and a policy maker to understand what actually causes the turbulence This book addresses the dynamics of stock prices and investigates into its underlying characteristics with focus on the last two stock market cycles This study aims to investigate the nature of global stock market dynamics and their association during the financial crises between 1998 and 2011 It identifies two stock market cycles, the first between 1998 and 2003 and the second between 2006 and 2011 The second cycle has been more global in nature Also, several structural breaks are identified during each cycle, for each market The breaks in 2007 and especially in 2008 have been largely global in nature, hinting toward a dynamic interlinkage among the markets The study delves deeper and finds evidence of latent structures in the global stock market around the stock market cycles Some degree of internal association among the markets is also found to be present Finally, the study investigates any possible chaotic nature of the stock markets Results reveal a majority of the markets to be chaotic and all of them being deterministic in nature This is likely to establish, particularly during the years of the global financial crisis, the inefficacy of the traditional asset pricing models as well as traditional policy tools which largely assume linearity Finally, the authors would like to thank Springer Briefs for publishing the manuscript and the anonymous referees for their valuable comments However, it is us who should be held responsible for any flaw in the study Kolkata, India Gurgaon, India Gagari Chakrabarti Chitrakalpa Sen Contents Introduction References Stock Market Cycles and Volatility Regime Switch 2.1 Introduction 2.2 Two Significant Stock Market Cycles 2.2.1 The First Cycle Revisited 2.2.2 The Second Cycle Revisited 2.2.3 The Peak in the Recent Years 2.2.4 Three Peaks and Two Troughs 2.3 Detection of Structural Break in Volatility 2.3.1 Detection of Multiple Structural Breaks in Variance: The ICSS Test 2.3.2 Volatility Breaks in Global Stock Market References 7 9 11 12 16 17 19 24 Crises and Latent Structure in the Global Stock Market 3.1 Introduction 3.2 Exploring the Latent Structure in the Global Stock Market 3.2.1 Methodology 3.2.2 Result for Sub-Period (1998–2005) 3.2.3 Result for Sub-Period (2006–2011) 3.3 Analysis of Intra-Regional Association 3.3.1 Methodology: Granger Causality 3.3.2 Methodology: Dependence Analysis 3.3.3 Results for Phase 3.3.4 Results for Phase 3.4 The Latent Structure and the New Issues Arising References 27 27 28 28 30 32 34 34 36 36 37 43 46 ix x Contents Global Stock Market, Knife-Edge Stability and the Crisis 4.1 Introduction 4.2 Methodology 4.2.1 BDS Test 4.2.2 The State-Space Reconstruction 4.2.3 Mutual Information Criterion: Finding s 4.2.4 False Nearest Neighborhood: Decide the Optimal m 4.2.5 Determinism Test 4.2.6 Maximum Lyapunov Exponent 4.3 Results 4.4 The Dynamics of Global Stock Market: The Emerging Issues References 49 49 51 52 54 55 55 56 57 57 60 61 Antibiotic Discovery and Development Index Boshoff, H.I., 731 Boucher, H.W., 301 Bradford, P.A., 147 Brandl, E., 84, 85 Breidenstein, E.B.M, 679 Briceño, D.F., 651 Brickner, S.J., 275 British Society for Antimicrobial Chemotherapy (BSAC), 1083 Brötz-Oesterhelt, H., 923 Brotzu, G., 22, 85 Brown, D.F.J., 1090 Burckholder, P., 16 Burn wound infections, 693–694 Bush, K., 427, 428 C Cancelarich, J., 155 Carbapenems, 101–102 Carpenter, F.H., 17 Cass, R.T., 229 Cation-adjusted Mueller-Hinton Broth (CA-MHB), 1082 Ceftazidime (CAZ), 774 Ceftobiprole, 1050 Cell-based screening antibiotic discovery dereplication schemes, 903 paper disc process, 902–903 penicillin, 902 streptomycin, 902 vancomycin, 902 Bacillus subtilis biosensor strains, 919–920 bacterial biosensors, 918–919 bacterial cell-based screening techniques, 907–908 cell wall pathway screens agar plate-based screen, 910 bacterial DNA synthesis inhibition, 912 fosfomycin, 910 glycopeptide, 910–911 hypersusceptible mutants, 908, 910 lactivicin, 910 topoisomerase inhibitors, 911 tripeptide reversal assay, 911 E coli biosensors, 920–923 mode-of-action determination antibiotic-treated bacteria, 917–918 DNA microarrays, 916–917 expression profiling, 918 multiapproach method, 925 modern antibiotic discovery programs natural products, 906–907 1113 physicochemical properties, 905–906 target-based genetics/genomics antibiotic discovery, 904–905 prontosil, 901 resistance and resurgent interest, 903–904 sulfonamides, 901 target-based bacterial screening altered target activity, 912–913 antisense downregulation, 914–916 gene promoter regulation, 913–914 target identification mapping antibiotic-resistance, 923–924 multicopy suppressor approach, 924 Cephalosporins antibacterial activity, 90 anti-MRSA, 95–96 Beecham group, 90 first-generation, 91 fourth-generation, 94–95 intravenous infusion, 90 second-generation, 92–93 third-generation, 93–94 Cephalosporium acremonium, 21–22 Cephamycins, 97–98 Cephems, 100 Chain, E., 10, 81, 427, 902 Chitinovorins and cephabacins, 98–99 Chlamydia pneumoniae, 445 Chronic obstructive pulmonary disease, 204 Clinical Laboratory Standards Institute (CLSI), 1072 Clusters of Orthologous Genes (COGS), 883 Coagulase-Negative Staphylococci (CoNS), 762 Colony forming units (CFU), 1046 Committee for Medicinal Products for Human Use (CHMP), 1094–1095 Common Technical Document (CTD), 1088, 1097 Community-acquired bacterial pneumonia (CABP), 205, 214 Community acquired pneumonia (CAP), 163, 172, 769 Complicated intra-abdominal infections (cIAI), 229 Comprehensive Medicinal Chemistry (CMC) database, 800 Conover, L.H., 152 Contigs, 882 Contreras, G.A., 617 Courvalin, P., 515 Coxiella burnetii, 134 Craig, W.A., 326, 1050 Crandon, J.L., 1035 Critical micellar concentration (CMC), 944 1114 Cynamon, M.H., 288 Cystic fibrosis adaptations, 699–700 airway colonization, 699 antimicrobial therapy aerosols, 701 chronic infections, 703–705 colonization and initial infection, 703 combination therapy, 701 treatment strategies, 701 CFTR, 698–699 mortality in, 698 Cystic fibrosis transmembrane conductance regulator (CFTR), 698–699 Cytoplasmic membrane antibacterial agents, 854–855 basic structure, 852 efflux, 856 lipid bilayer membranes, 853–854 permeability coefficient, 853 polycations, 858 target sites derivatization, 855 growth inhibitors, 856 protein-mediated transporter, 856 whole-cell activity, 858 Czaplewski, L.G., 957 D Dalbavancin, 322–323, 534–535 Dath, S., 80 Davies, C., 397 Davies, P., 12 Deinococcus radiodurans, 192–193 Delbrück, M., 1076–1077 de Lencastre, H., 571 Denapaite, D., 593 Derendorf, D., 1055 DeVito, J.A., 913, 914 Diffuse panbronchiolitis/cystic fibrosis, 208–209 Dimethyl sulfoxide (DMSO), 945–946 Diversity-oriented synthesis (DOS), 813 Domagk, G., 6, 26, 34, 83 Dougherty, T.J., 901 Drlica, K., 485 Drug discovery programs microbial sourcing, isolation and strain dereplication biotransformation, 835 environmental metagenome (EDNA) approach, 834–835 fatty acid analysis, 831 genome scanning technology, 832 Index Gram test, 831 high throughput microbial cultivation, 833–834 morphological characteristics, 831 mutation of organisms, 835–836 Rio De Janeiro treaty, 830 synthetic biology, 836–838 novel drug, 829 sensitive and robust biological assays, 828–829 Dubos, R., 10 Duggar, B., 15, 148–150 Dulaney, E., 45, 46, 910 E Efflux-mediated antimicrobial resistance bacterial cells, 349 chromosomal efflux genes, 351 Gram-negative bacteria, 349, 350 ABC family, 358–359 MATE family, 359 MF superfamily, 355–356 RND family (see Resistancenodulation-division) SMR family, 357–358 Gram-positive bacteria, 349–353 mycobacteria, 354–355 soil-dwelling bacteria, 375 Efflux proteins, tet gene Alcaligenes, 551 Alteromonas, 551 Bacillus subtilis, 551 characterization, 549 Chlamydia spp., 550–551 Clostridium perfringens, 552 gram-negative bacteria, 550 Mycobacterium, 551 Egan, W.J., 808 Ehmann, D., 931 Ehrlich, P., 4–6, 34 E I du Pont de Nemours, Company (DuPont), 273–274 Eiznhamer, D.A., 181 Electronic common technical document (eCTD), 1097 Eliopoulos, G.M., 1080 Endocarditis, 622 Endovascular infection, 662 Enright, M.C., 580, 584 Enteric bacteria, 856 Enterobacteriaceae, 165, 436 Acinetobacter spp., 783–784 antibiotic considerations, 672 beta-lactamases, 773 Index ceftazidime resistance, 774 classification and structure capsule, 652 inner membrane, 653 outer membrane, 652–653 clinical syndromes, 671 epidemiology, 671 ESBLs, 773 Escherichia coli antibiotic considerations, 663–666 epidemiology, 659–660 extra-intestinal pathogenic strains, 660–662 intestinal (diarrheagenic) pathogenic strains, 663 microbiology and laboratory diagnosis, 659 Klebsiella pneumoniae antibiotic considerations, 668 clinical syndromes, 667 epidemiology, 666–667 microbiology, 666 mechanisms of resistance b-lactamases (see b-Lactamase) efflux pumps, 658 porin loss, 658–659 target modifications, 657–658 microbiology, 670 P aeruginosa, 774–782 proteus species antibiotic considerations, 670 clinical syndromes, 669–670 epidemiology, 669 microbiology, 668–669 Serratia marcescens antibiotic considerations, 673 clinical syndromes, 673 epidemiology, 673 microbiology, 673 Enterococcus acquired resistance, D-Ala-D-Lac VanA-Type, 518 VanB-Type, 518–521 VanD-Type, 521 acquired resistance, D-Ala-D-Ser VanE-Type, 522–523 VanG-Type, 523 VanL-Type, 523 b-lactams and synergism with aminoglycosides cephalosporins, 625 dose regimen, 625–627 gentamicin and streptomycin, 625 pencillin tolerance, 624–625 cephalosporins, 636 1115 chloramphenicol, 637 epidemiology of bacteremia, 622 colonization, 618–619 colonized individuals vs VRE, 621 endocarditis, 622 intra-abdominal infections, 623 meningitis, 623–624 mortality, 621–622 neonatal infections, 623–624 transmission, 619–621 urinary tract infection, 621–623 glycopeptides molecular typing data, 629–630 vancomycin and teicoplanin, 628 glycylcyclines, 633–634 intrinsic resistance, 524–525 lipoglycopeptides, 634–635 lipopeptides, 630–631 nitrofurantoin, 636–637 oxazolidinones, 631–632 pristinamycins, 632–633 quinolones, 637 Enterococcus faecalis resistant (VRE), 826 Epithelial lining fluid (ELF), 200, 201, 1050 ermB genes, 469, 470 ermC expression A2062 and A2503, 463–464 antibiotic-induced nascent peptidedependent, 464 C3 cladinose, 462 IFVI sequence, 461–462 ketolides, 462 peptidyl-tRNA drop-off, 461 ribosome exit tunnel, 463 ribosome stalling, 461 translational attenuation, 460 Erm-type methyltransferase enzymes, 457 Ernst Chain, 397 Errington, J., 957 Escherichia coli antibiotic considerations, 663–666 epidemiology, 659–660 extra-intestinal pathogenic strains, 660–662 intestinal (diarrheagenic) pathogenic strains, 663 microbiology and laboratory diagnosis, 659 European Committee of Antimicrobial Susceptibility Testing (EUCAST), 1085 European Medicines Agency (EMA), 1080, 1096 European Public Assessment Reports (EPARs), 1094 Extended-spectrum b-lactamases (ESBLs), 654–655, 754 1116 F Far, A.R., 301 Farnet, C.M., 832 FASTA, 883 Felmingham, J., 1090 Fildes, P., 35, 36 Fischer, C., 918, 920 Fisher, S., 931 Flavin, M.T., 181 Fleming, A., 10, 37, 80, 81, 83, 148, 901, 902 Florey, H., 10, 80–82, 902 Fluoroquinolones, 854 See also Quinolone Food and Drug Agency (FDA), 27, 28, 152, 155, 165, 182, 329, 332, 836, 1080, 1096 Fosfomycin, 910 Fox, S., 155 Fractional inhibitory concentration index (FIC), 1080 Friedberg, 917 Friulimicin B, 812 Fujisawa, K., 36, 45, 48, 49 Fulton, J., 82 Fusarium coccineum, 23 G Gale, E.F., 873 Genomic Analysis and Mapping by In vitro Transposition (GAMBIT), 885 Geraci, J.E., 624 Giuseppe Brotzu, 397 GlaxoSmithKline (GSK), 822 Glycopeptide resistance dalbavancin, 534–535 dependence, 528 enterococci (see Enterococcus) expression of, 526–527 mode of action, 515–516 origin of D-Ala:D-Lac ligases, 528–529 D-Ala:D-Ser ligases, 529–530 oritavancin, 533–534 Paenibacillus Popilliae, 525 resistance mechanism, 517 Staphylococcus aureus biological cost, 532–533 VanA-Type vancomycin resistance, dissemination, 533 VISA strains, 530 VRSA Strains, 530–532 Streptomyces coelicolor, 525–526 telavancin, 534 Glycopeptides and lipoglycopeptides Index activity and potency spectrum, 314–317 ADME (see Absorption, distribution, metabolism, and excretion) bacterial resistance mechanisms, 319–320 chemistry chemical modification, 302–303 dalbavancin, 303–304 glycosidic groups, 302 LT-00029 chemical structure, 305 oritavancin, 303–304 PA1409 chemical structure, 305 parvocidin, 303 peptide scaffold and are glycosylated, 302 TD-1792 chemical structure, 305 telavancin, 304 tetramacrocyclic structure, 302 vancomycin, 302 VRE, 304 dalbavancin, 330 mechanism of action bacterial cell wall, 306 cytoplasm, 306 D-alanyl-D-alanine binding pocket, 308 D-alanyl-D-lactate, 309–310 disaccharide-pentapeptide units, 306 enterococcal cell wall, 310 [19F]oritavancin, 308 membrane activities, 311–313 mycin-resistance mechanisms, 307 oritavancin, 309 REDOR experiment, 308 telavancin, 307 transglycosylation and transpeptidation, 306, 307 transpeptidation, 310 ultrastructural changes, 313 MRSA, 301–302 nosocomial infections, 301 pharmacodynamics, 324, 326 protein binding, 317 resistance development, 318–319 time kill, 318 vancomycin and teicoplanin, 327 in vivo activity and pharmacodynamics, 324, 325 Godtfredsen, W., 23 Gram-negative bacteria efflux, 864–866 lipid bilayer deep rough mutants, 861 hydrophobic shell, 859 isolated lipopolysaccharide, 860 novobiocin, 862 permeation rates, 861 Index outer membrane permeability barrier, 864 water-filled channels, 862–864 Gram-negative resistance, 433–435 Gram-positive resistance, 432–433 Gratia, A., 80 Gregory, W.A., 28, 273 Gualtieri, M., 859 H Haemophilus influenzae, 165–166, 772–773, 917 Hajduk, P.J., 992 Hakenbeck, R., 593 Hancock, R.E.W., 679 Harris, S.R., 585 Haydon, D.J., 957, 965 H-13Cheteronuclear multiple quantum spectroscopy (HMQC), 993 Heatley, N., 81, 82 Helicobacter pylori, 445 Hematogenous pyelonephritis, 1019–1020 Hendlin, D., 910 Herzberg, O., 87 Heteronuclear Single Quantum Coherence (HSQC), 980 High resolution Fourier Transform mass spectrometry (HRFTMS), 829 High throughput screening (HTS), 822 assay development, phases of, 933 assay flexibility, 945–946 compound library, 932 constraints pyramid, 934 detection system selection coupling enzyme activity, 936 detection technology platforms, 935 hyperbolic relationship, 937 inorganic phosphate detection, 938 standard curve, 936–937 substrate concentrations, 938–939 target-reaction sensitive chromophores, 936 hit evaluation process artifact assays, 949 compound QC, 950 covalent inhibitors, 951 direct binding assays, 951–952 enzymological mode of inhibition, 953–954 fragment-based methods, 952 promiscuous inhibitors, 951 secondary assays, 949–950 spectrum assays, 950–951 X-ray crystallography/molecular modelling, 952 1117 isozyme selection, 932 primary screening, 946–948 reagent procurement, 932 target biochemistry binding capacity, 941–942 coupling enzymes, 944 detergents, 943–944 enzyme catalysis, 939–940 inhibitors, 940–941 multi-substrate enzymes, 942 plastic microtiter plates, 943 promiscuous inhibitors, 944 rate relationship, 939 single substrate enzymes, 942 Hill, A.V., 873 Hiramatsu, K., 1078 Hitchings, G.H., 36 H-15N heteronuclear single quantum spectroscopy (HSQC), 993 Hobby, G.L., 726 Hooper, D.C., 17, 119 Hospital acquired pneumonia (HAP), 229 Howard Florey, 397 Hu, J., 985 Hunter, J., 80 Huxley, T., 80 I Imada, A., 910 Imipenem resistance (IPM R), 786 Internal transcribed spacer (ITS), 149 Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), 274 Intra-abdominal infections, 623 Investigational new drug application (IND), 1081 In vivo pharmacodynamic modeling animal selection, 1040 dose fractionation studies, 1050–1051 dose-response studies, 1049 drug concentration determination, 1042 evaluable endpoints, 1038–1039 exposure-response studies, 1049–1050 human simulated dosing regimens CFU, 1046 electronic infusion pumps, 1046 Monte Carlo simulation, 1045 pharmacokinetics, 1045 immunocompetent vs immunocompromised models, 1039 inoculum effect, 1037 1118 In vivo pharmacodynamic modeling (cont.) model development agar plates, 1037 animal infection model, 1035 immunosuppression, 1036 inoculation, 1036 mouse strain, 1036 serial dilution, 1037 pharmacodynamic theory, 1047–1048 pharmacokinetic modeling, 1042 protein binding concentration-dependent binding, 1044 free drug exposure-response relationship, 1043 glycylcycline tigecycline, 1044 human equivalent exposures, 1044 neutropenic thigh infection model, 1045 non-specific binding, 1043–1044 tigecycline, 1045 sampling, 1040–1041 timing of antimicrobial therapy, 1038 Isothermal caloremitry (ITC), 1002 J Jacoby, G.A., 119, 428 Jones, C.H., 147 Jones, E., 79 Joubert, J., 80 K Kahne, D., 311 Kern, G., 985 Kerns, R., 485 Kirsch, D.R., 59 Kislak, J.W., 593 Klebsiella aerogene, 42 Klebsiella pneumoniae, 163–165, 168–169 antibiotic considerations, 668 clinical syndromes, 667 epidemiology, 666–667 microbiology, 666 Koch, R., Kostrub, C.F., 229 Kuhn, B., 854 Kushner, S., 26 L Lakaye, B., 872 Lawton, G., 966 Leach, K.L., 289 Lee, A., 870 Lehmann, J., 25 Index Lehoux, D., 301 Lesher, G., 27 Lethal dose (LD), 1015, 1016 Lewis, K., 727 Lieb, W.R., 850, 853, 854 Lilly, E., 18–20, 53, 55, 59, 106, 182 Lim, S.P., 872 Linezolid clinical experience, 280–281 Mycobacterium tuberculosis, 279 pharmacokinetic, 279 PNU-100480, eperezolid, 276–278 SAD and MAD profile, 279 ZyvoxT, 281–282 Lipinski, C.A., 905, 906 Lipopolysaccharide (LPS), 860 Li, X., 924 Lomovskaya, O., 849 Luedemann, G., 17 Luria, S.E., 1076–1077 M Macielag, M.J., 793, 859 Macrolide resistance genes control of expression, 458–459 cost of fitness of resistance, 457–458 ermA erythromycin-dependent, ribosome stalling, 465 mode of action and inducibility, 465–468 structure of, 464, 465 ermB, 469, 470 ermC expression A2062 and A2503, 463–464 antibiotic-induced nascent peptidedependent, 464 C3 cladinose, 462 IFVI sequence, 461–462 ketolides, 462 mutational analysis and biochemical structural studies, 461 ribosome exit tunnel, 463 ribosome stalling, 461 translational attenuation, 460 ermD secondary structure of, 469, 471 transcription attenuation, 471–472 ermS, 472–473 inducibility drug-dependent, 474 leader peptides, 478–479 putative regulatory ORFs, 475–477 Shine-Dalgarno sequences, 474 ribosomes, 455–457 Index Macrolides and Ketolides antimicrobial agents, 181 bactericidal antimicrobial agents, 215 CABP, 214 CEM-101, 214 chronic inflammatory, 215 clinical use anti-inflammatory uses, 208–209 asthma, 208 atherosclerosis, 207 Crohn’s Disease, 208 genital infections, 206 lower-respiratory tract infections, 204–205 mycobacterial infections, AIDS patients, 206 neutrophils, 208 pathogens, 207 skin and soft tissue infections, 205–206 upper respiratory tract infections, 203–204 community-acquired bacterial pneumonia, 215 development history and chemistry azithromycin, 182 cethromycin, 182–184 clarithromycin, 182 erythromycin, 182 gastrointestinal-related side effects, 183 ketolide, 184 Legionnaire’s disease, 182 molecular structures, 182–183 Saccharopolyspora erythraea, 182 telithromycin, 182–184 EP-014887, 214 ESKAPE pathogens, 215 macrolide-resistant organisms, 181 mechanism of action, 191–193 mechanism of resistance esterases, 196 macrolide efflux, 195–196 ribosome-based mutations, 194–195 rRNA methylation, 193–195 Shine-Dalgarno (SD) sequence, 194 MITT, 215 organisms, 214 pharmacokinetics and pharmacodynamics antibacterial activity, 200 AUC, 198–199 AUC/MIC ratio, 202 azithromycin, 198, 202 bacteriostatic effect, 202 cethromycin, 199 clarithromycin, 196–198 concentration-dependent, 202 1119 ELF and alveolar macrophages, 200, 201 erythromycin, 196 ethylsuccinate ester, 196 intracellular pathogens, 200 lipophilic, 200 multiple oral doses, 196–197 PAE, 203 plasma accumulation, 198 telithromycin, 199 upper respiratory tract, 200 safety issues azithromycin, 210–211 drug-drug interactions, 212 erythromycin, 209–210 telithromycin, 211–212 structure-activity relationships, 212 structure-based rational design, 214 TE-802 chemical structures, 213 typical atypical pathogens, 181 in vitro antibacterial activity anaerobic pathogens, 187, 190 Bordetella pertussis, 190 cethromycin, 189 fluoroquinolones, 189 Gram-negative aerobes, 186, 190 gram-positive aerobic bacteria, 184–185 intracellular and atypical pathogens, 188, 190 L pneumophila, 191 M catarrhalis, 190 MICs, 184 MRSA strains, 189 MSSA, 189 penicillin-nonsusceptible pneumococci, 184 ribosomal mutations, 189 S pneumoniae, 184, 189 S pyogenes, 189 Streptococcus spp., 190 Macrolide therapy, 209 Maintenance therapy, 704 Major facilitator (MF) superfamily, 355–356 Malik, M., 485 Mandel, G.L., 624 Mankin, A.S., 455 Manninen reaction, 276 Mannopeptimycins, 812 Margreiter, H., 85 Marketing authorization applications (MAAs), 1093 Marra, A., 1009 Marriott, M., 966 Martin, Y.C., 808 Maurer, P., 593 1120 Mazzariol, A., 870 McGuire, J., 18, 182 McIntosh, T.J., 860, 861 McMurry, L.M., 544 Meagher, A.K., 1063 Mechanism-of-Action (MOA), 824–825 Medeiros, A.A., 428 Mederski-Samaroj, B., 433, 625 Membrane fusion protein (MFP), 349 Mendez, B., 544 Meningitis, 623–624, 662 Merck, 234 Merriken, 1043 Metallo-beta-lactamase (MBL), 443–444, 754 Methicillin, 758 Methicillin-resistant Staphylococcus aureus (MRSA), 189, 229, 814 beta-lactam resistance, 572–573 congruence analysis, 581–582 emergence of, 572 epidemiology and molecular biology, 586 evolutionary history, 585–586 MLST, 579–581 molecular typing techniques, 574–575 PFGE, 575–577 phage types and antibiotics, 574 restriction fragments length polymorphisms (RFLPs), 575 SCCmec typing, 582–585 Spa typing, 577–579 Methicillin-susceptible S aureus (MSSA), 189 Methionyl-tRNA synthetase (MetRS), 972 Microbiological Intend-to-Treat (MITT), 215 Micromonaspora inyoensis, 242 Miller, G.H., 229 Mills, S.D., 901, 923 Minimum bactericidal concentration (MBC), 162, 1074–1075 Minimum inhibitory concentration (MIC), 850 Mode-of-action (MOA), 1087 Mode-of-inhibition (MOI), 1087 Moeck, G., 301 Moellering, R.C., 1080, 1105 Moller, J.K., 557 Moser, H.E., 229, 906 Moult, J., 87 Mouse protection tests (MPTs) acute septicemia model, 1015 analgesics, 1015 anticipated pain, 1014 clinical isolates, 1016–1017 inoculum size, 1017 lethal dose, 1015, 1016 lethalities, 1016 positive and negative control drugs, 1014 Index RTI model, 1016 time course, 1017 Moyed, H.S., 727 Mozer, H.E., 797 Mueller-Hinton Agar (MHA), 1082–1083 Multidrug and toxic compound extrusion (MATE) family, 359 Multi-drug resistance (MDR), 754 Multi-locus sequence typing (MLST), 579–581 Multiple ascending dose (MAD), 279 Murray, B.E., 433, 625 Mutant prevention concentration (MPC), 123–124, 1027 Mycobacterium tuberculosis, 11, 234, 815, 902, 969 Mycoplasma pneumoniae, 445 N Nagano, K., 851, 865, 872 Natural products antibacterial targets, 827 antibiotics drug discovery, 841 MOA, 824–825 resistance and contemporary strategies, 826–827 sources, 822–824 antiseptics, 821 chemistry, 838–840 drug discovery programs microbial sourcing, isolation and strain dereplication, 830–838 novel drug, 829 sensitive and robust biological assays, 828–829 genome sequences, 827 GSK, 822 lead optimization of, 840–841 molecular biology, 827 penicillin, 821 target based screening, 822 traditional and contemporaneous discovery approaches, 825–826 Neisseria gonorrhoeae infection, 239 Neonatal infections, 623–624 New drug application (NDA), 182, 330, 1081 Newton, G.G., 22, 90 Nicholas, R.A., 397 Nichols, W.W., 849, 868 Nicolau, D.P., 1035 Niedercorn, J., 150 Nikaido, H., 851, 852, 854, 860, 862, 863, 865, 870, 872 Index Nitella mucronata, 853 Non-ribosomal peptide synthases (NRPS), 836–837 Normark, S., 870 Nübel, U., 585 Nuclear magnetic resonance (NMR) automation system cryogenic probe, 987 drug discovery, 987 ICONNMR, 987 Larmor frequency, 986 SampleRail system, 987 SampleTrack, 987 Tecan pipetting robot, 987 TopSpin, 987 1D NMR applications alanine binding, 998–1000 ATP binding, 997, 998 enzyme kinetics and compound inhibition, 1002 hit evaluation, 1000–1002 MurC, 996–997 peptidoglycan synthesis pathway, 996 UNAM binding, 997–999 2D NMR applications DNA ligase, 1003–1005 glutamate racemase MurI, 1003 experiments, 988 ligand-target interactions ligand-observed, 988–990 relaxation-edited 1D NMR, 990 STD, 990–992 TRNOE, 990, 991 water-LOGSY, 991, 992 protein-observed NMR chemical shift patterns, 994 HSQC, 993 ligand binding, 994 selective labeling, 993–994 TROSY spectra, 993 screening, 995 Nuclear Overhauser Effect (NOE), 989 Nuermberger, 288 O Oeppinger, H., 83, 85, 86, 90 Oliveira, D.C., 571 Oppolzer, W., 20 Opthalmia neonatum, 80 Ordered-Ter-Ter mechanism, 996 O’Reilly, T., 1014 Oritavancin, 323, 533–534 Osburne, M.S., 64 1121 O’Shea, R., 797, 906 O’Sullivan, J., 910 Oxazolidinone antibacterial agents bacterial resistance dilemma, 272 discovery, 273–274 gram-negative organisms, 272 linezolid clinical experience, 280–281 Mycobacterium tuberculosis, 279 pharmacokinetic, 279 PNU-100480, eperezolid, 276–278 SAD and MAD profile, 279 ZyvoxT, 281–282 MDR bacterial strains, 272 mechanism of action, 289–290 MRSA, 271–272 nosocomial infection, 272 quinolones, 271–272 resistance development E faecium, 290 enterococci, 291 linezolid, 290 ribosomal proteins, 290 staphylococci, 290–291 streptococci, 291–292 SAR AstraZeneca, 288 C-5 side chain, 283–284 extended binding motifs, 285–286 PNU-100480, 288 post-linezolid clinical, 287 radezolid, 286, 288–289 ring replacements, 282–283 torezolid, 289 semi-synthetic/synthetic variations, 271 xenobiotics, 271 P Paenibacillus popilliae, 525 Page, M.G.P., 79 Paine, C.G., 80 Parr, T.R Jr., 301 Pasteur, L., 4, 80 Patti, G.J., 318 PBP mutations Asp345a insertion, 412, 414–415 b2c-b2d loop, 414 C-terminal end, 414 penicillin-resistant strains, 416 saturation mutagenesis, 413–414 structural alterations, 416 structural and biochemical analysis, 417–419 1122 Penicillin-binding proteins b-lactam resistance, 599–600 b-lactams interaction, 595–596 high molecular weight (hmw), 595 low molecular weight (lmw), 595 PBP2a derivatives, 596 PBP3 deletion mutants, 597 PBP2x mutations amino acid alterations, 602 binding efficiency, 602 cefotaxime resistance, 600–601 multistep selection procedure, 600–603 penicillin-binding domain, 602 Q552 E substitution, 603 transpeptidase domain, 602 Penicillins Acremonium strictum, 85 aliphatic compounds, 83 bacterial contamination, 85 beta-lactamase, 84 biosynthetic precursor, 84 broad-spectrum and b-lactamase, 87–89 experimental penams, 89–90 fermentation methods, 84–85 gram-positive bacteria, 83 opthalmia neonatum, 80 oral bioavailability, 86 P chrysogenum, 80–81 production, 82 research, 81–82 staphylococcal penicillinase, 86–87 structures, 85 sulfonamide antibiotic, 83 therapeutic agents, 80–81 turnip infusion, 84 Penicillium notatum, 821, 902 Peptidoglycan, 859 Peptidyl transferase center (PTC), 289–290 Périchon, B., 515 Periodic Safety Update Report (PSURs), 1098 Pfizer, 976 Pharmacokinetic/pharmacodynamic models adaptation models, 1063–1064 antimicrobial drug development, 1056 AUC/MIC ratio, 1064, 1065 model-based drug development, 1055 one population models, 1057–1060 streamlining antimicrobial drug development bacterial growth, 1056 dynamic experiments, 1057 MIC, 1056 Index microdialysis sampling technique, 1056 time-kill curves, 1057 two-population models ciprofloxacin, 1062 genetically-acquired resistance mechanism, 1060 growth inhibition model, 1062 initial inoculum, 1061 MIC model, 1063 net effect model, 1062 robust model, 1061 Phenotypic screening brute force type, 62 DNA replication inhibitors, 63–65 drug screening, 62 folate pathway, 62–63 microbial genetic, 61–62 peptidoglycan synthesis, 61 Pillar, C., 753 Piper, R., 275 Planctomycetes, 445 Platencin, 829, 916 Platensimycin, 829 Plésiat, P., 860 Pneumonia, 662 aminoglycoside tobramycin, 697 antimicrobial therapy, 696 ventilator-associated, 697–698 Pollock, H.M., 1084 Polyketide synthase (PKS), 836 Poole, K., 349, 856 Population analysis profile (PAP), 1078 Post-antibiotic effect (PAE), 203, 1087 Post-antibiotic leukocyte effect (PALE), 1087 Prelog, V., 20 Projan, S.J., 1103 Protein Data Bank (PDB), 971 Proteus P mirabilis, 165, 910 P vulgaris, 165 Proteus species antibiotic considerations, 670 clinical syndromes, 669–670 epidemiology, 669 microbiology, 668–669 Pseudomonas aeruginosa, 907 antimicrobial resistance acquired, 688–689 adaptive, 690–691 intrinsic, 687–689 superbug, 691–692 CAZ and IPM, 780 Citrobacter spp., 778 colistin and polymixin B, 781 Index cystic fibrosis adaptations, 699–700 airway colonization, 699 antimicrobial therapy, 700–705 CFTR, 698–699 mortality in, 698 drug efflux, 779 E cloacae, 778 enterobacteriaceae, 776 hospital-associated antibiotic therapy, 692 bacteremia, 694–696 burn wound infections, 693–694 mechanical ventilation, 692 pneumonia, 696–698 K pneumoniae, 777 multi-drug resistant isolates, 779 pathogenesis alginate, 684–685 biofilm formation, 685–686 exotoxin A, 684 flagellum, 682 lipopolysaccharide, 681–682 proteases, 684 quorum sensing, 686–687 type III secretion, 683 type IV Pili, 683 P mirabilis, 777 S marcescens, 779 Pulsed-field gel electrophoresis (PFGE), 575–577 Q Quinn, J.P., 651 Quinolone antimicrobial activity, 127–128 antimicrobial agents, 119 cell death, 486 ciprofloxacin, 485–486 clinical uses bone and joint infections, 134 ciprofloxacin, 134 Coxiella burnetii, 134 gastrointestinal and abdominal infections, 132–133 levofloxacin, and ofloxacin, 135 neutropenic patients, 135 prophylaxis, 135 respiratory tract infections, 133–134 Rickettsia conorii, 134 sexually transmitted diseases, 131–132 skin and soft-tissue infections, 134 urinary tract infections, 130–131 cross-resistance, 490 1123 DNA gyrase, 486 DNA topoisomerase, 486 efflux-based fluoroquinolone resistance AcrAB-TolC system, E coli, 491–492 gram-negative bacteria, 491 vs mutation frequency, 493 PmrA, 492 Pseudomonas aeruginosa, 492 types of, 491 fluoroquinolone, 119 levofloxacin, 486 mechanism of action, 122–123 mechanisms of resistance chromosomal mechanisms, 123–125 plasmid-mediated mechanisms, 126–127 quinolone resistance, 123 mutant selection window hypothesis experimental support, 498 lethal action and resistant mutant selection, 498–499 pharmacodynamics, 499–501 window description, 496–498 nalidixic acid, 119 permeability-based resistance, 490–491 pharmacodynamics, 129 pharmacokinetics, 128–129 plasmid-mediated resistance forms of, 502 prevalence of, 502, 503 protein-synthesis-dependent chromosome fragmentation, 486 quinolone-induced quinolone resistance, 489–490 quinolone-modifying enzymes, 495 resistance mutations, stepwise accumulation, 488 schematic representation, 486, 487 screening new compounds anti-mutant activity, 501 dual targeting, 501–502 suppression of induced mutants, 502 sources of resistance, 488–489 structure activity relationships, 120–122 topoisomerase-based resistance, 495–496 topoisomerase-protecting protein, 493–494 toxicity, 129–130 Quinolone resistance determining region (QRDR), 124, 364, 657 R Ramu, H., 455 Reller, L.B., 1083 1124 Resistance-nodulation-division (RND) aminoglycosides, 364–365 avoiding efflux, 370–371 biocides, 366–368 b-lactams, 365–366 efflux inhibition, 371–373 EPIs and diagnostics, 375 FQs, 363–364 MexAB-OprM-overproducing strains, 374 MLSK antimicrobials, 360, 363 natural function, 368–369 pump assembly inhibition, 373–374 tetracyclines and glycylcyclines, 366 TolC OMF componen, 374 Resistance trends and susceptibility profiles A baumannii, 785 CoNS, 762 drug resistance, 784 enterobacteriaceae Acinetobacter spp., 783–784 P aeruginosa, 774–782 enterococci E faecalis and E faecium, 762 MSCoNS and MRCoNS, 765 vancomycin resistance, 765 era of antibiotics, 753 bacterial resistance, 753 therapeutic options, 754 gram-positive and gram-negative pathogens, 754 imipenem resistance, 786 infection control procedures, 754 pathogens, 756–758 resistance and antimicrobial activity, 755–756 S aureus, 758–762 streptococci beta-hemolytic streptococci, 765–769 Haemophilus influenzae, 772–773 S pneumoniae, 769–772 United States, 758 Respiratory tract infection (RTI) models, 1016, 1019 Restriction fragments length polymorphisms (RFLPs), 575 Ribosomes Erm-type methyltransferase enzymes, 457 nascent peptide exit tunnel, 455, 456 Rickettsia conorii, 134 Roberts, M., 474, 545 Rocchetta, H.L., 1028 Rotational echo double resonance (REDOR) experiment, 308 Index Rothstein, 911 Roughton, F.J.W., 873 Ruston, S., 957 S Sabina, J., 917 Sahm, D., 753 Salmonella schottmuelleri, 24 Salmonella typhimurium, 855 Salz, T., 485 Sanders, C.C., 1083 Sanderson, J.S.B, 79, 80 Saturation transfer difference (STD), 990–992 SCCmec typing, 582–585 Schaefer, J., 307 Schatz, A., 11, 234, 902 Schmid, M.B., 969 Schurek, K.N., 679 Serine b-Lactamases CTX-M family, 437, 439 enterobacteriaceae, 436 geographical distribution, 437, 438 geographical prevalence, ESBL, 439–442 KPC carbapenemase, 439, 443 non-fermenters, 436–437 serine carbapenemases, 436 Serine carbapenemase (KPC), 754 Serratia marcescens antibiotic considerations, 673 clinical syndromes, 673 epidemiology, 673 microbiology, 673 Shapiro, E., 921 Shaw, K.J., 917 Sheiner, L.B., 1055 Shlaes, D.M., 1105 Shotgun sequencing strategy, 882 Sigler, A., 855 Silver, L.L., 33 Singh, S.B., 821, 907 Single ascending dose (SAD), 279 Sir Alexander Fleming, 397 Skidmore, I., 966 Skin and skin structure infections (SSSI), 756, 758 Skin and soft tissue infections (SSTIs), 280, 662 Small multidrug resistance (SMR) family, 357–358 Smyth, D.S., 586 Snyder, D.S., 860, 861 Snyder, L.B., 283 Spa typing, 577–579 Index Spheroplast formation screens cefoxitin, 47 cell wall-active agents, 45 cephamycin C and thienamycin, 41, 46 D-ala-D-ala ligase, 41, 46 fosfomycin, 44, 46 fosfonochlorin, 47 fosmidomycin, 48 globomycin, 44, 48–49 MEP pathway, 47 mureidomycin, 47 pentalenolactone, 44, 46, 48 peptidoglycan synthesis, 47 Plasmodium falciparum, 48 Plasmodium vinckei, 48 RNA/protein synthesis, 46 SPHERO primary screen, 45–46 thienamycin, 43, 47 Splice Overlap Extension PCR (SOE), 890 Stansly, P.G., 38 Staphylococcus aureus, 24, 167 biological cost, 532–533 bloodstream infections, 758 methicillin, 758 MIC creep, 759 MSSA and MRSA, 761 VanA-Type vancomycin resistance, dissemination, 533 vancomycin, 759 VISA strains, 530 VRSA Strains, 530–532 Stapley, E.O., 38 Stein, W.D., 850, 853, 854, 868, 873 Stephens, A.J., 584 Stokes, N.R., 957 Stone, G.G., 1071 Streptococcus beta-hemolytic streptococci, 765–769 Haemophilus influenzae, 772–773 S pneumoniae, 152, 769–772 (see also Streptococcus pneumoniae) S pyogenes, Streptococcus pneumoniae, 904 community acquired pneumonia, 769 empiric therapy, 772 epidemiological aspects, 593–595 gene transfer, 597–599 mosaic PBP2x genes distribution, 598 murein chemistry, 606–607 non-PBP mutations, 607–608 PBP1a, 604–605 PBP2a, 1b, and 3, 605–606 PBP2b, 603–604 penicillin-binding proteins 1125 b-lactam resistance, 599–600 b-lactams interaction, 595–596 high molecular weight (hmw), 595 low molecular weight (lmw), 595 mutations, 600–603 PBP2a derivatives, 596 PBP3 deletion mutants, 597 penicillin resistance, 606–607 penicillin resistant (PEN R) and MDR isolates, 770 respiratory infections, 769 Streptomyces S aureofaciens, 150 S coelicolor, 525–526 S erythreus, 18 S fradiae, 17 S lincolnensis, 18 S niveus, 20 S orientalis, 19 S rimosus, 16 S roseosporus, 20 S spectabilis, 20 S tenebrarius, 239 Streptomycin aureofaciens, 15 Strominger, J.l., 307 Structure-activity-relationships (SAR), 273–274, 850, 1073 Structure-guided antibacterial drug discovery E coli MetRS, 972 initial chemical matter experimental fragment-based screening, 975–976 in silico screening methods, 977–978 lead optimization, 979–981 maltose binding protein, 974 MurF protein, 973 non-hydrolyzable substrates, 973 protein biochemists, 971 protein structure initiatives, 969–971 sparse matrix screening plates, 973 species selection, 972 target selection, 974–975 Stuart Levy, 544 Subramanian, S.L., 455 Sykes, R., 910 T Tafur, J.D., 651 Takeda, S., 49 Targanta Therapeutics, 755 Targeted dereplication, 840 TB Structural Genomics Consortium (TBSGC), 969 1126 Telavancin, 324, 331–332, 534 Tetracycline, 826, 854 Tetracycline resistance genes amino acid identity, 544 distribution of, 545–548 efflux proteins (see Efflux proteins, tet gene) enzymatic inactivation, 555–556 gene transfer, 558 heterogeneity, 544 mechanism of resistance, 544, 545 mobile elements, 557 Mycobacterium spp., 544 new genes acquisition, 543 ribosomal protection proteins Clostridium perfringens, 554 gram-negative bacteria, 552–553 mosaic tet genes, 555 Neisseria, 554 Streptomycetes, 553 ribosomal protection tet gene, 545 TetU protein, 556–557 transposons, 558–559 Acinetobacter baumannii strain, 559 CTnDOT-like elements, 562 Streptococcus pneumoniae, 558 Streptococcus pyogenes, 560 Tn 916-Tn 1545, 559 Tetracyclines A-377 and chemical isolation, 150 American Cyanamid, 147–148 antibiotic-producing microorganisms, 148 Aureomycin®, 151–153 Bacillus anthracis infection, 155 Bacillus polymyxa, 149 b-hemolytic streptococci, 152 biosynthesis, 153–154 Borrelia burgdorferi, 154 bronzed-colored actinomycete culture, 150 calcium cyanamide manufacture, 148 chlortetracycline, 151–153 Declomycin®, 155 demeclocycline, 155 doxycycline, 154 fermentation samples, 149 glycylcycline and aminomethylcycline antibiotics, 158–159 gram-positive and gram-negative indicator organisms, 149 infectious diseases, 148 inhibiting protein synthesis, 147 intractable diseases, 152 ITS sequences, 149 Lederle’s production site, 148 Lyme disease, 154 methacycline, 154 Index minocycline, 155–158 natural products assay plate, 149–150 oxytetracycline, 152–154 Periostat®, 155 PKS and NRPS, 149 soil microorganisms, 148 soil-screening program, 149 Streptococcus pneumoniae, 152 Streptomyces aureofaciens, 150 Terramycin r, 152 tigecycline (see Tigecycline) Thanassi, D.G., 852, 854 Theorell-Chance kinetics, 233 The Surveillance Network (TSN), 755 Tiberio, V., 80 Tigecycline clinical indications CAP, 172 intra-abdominal infections, 171–172 skin and skin structure infections, 171 mechanism of action, 160 mechanisms of resistance Acinetobacter baumannii, 170 Enterobacteriaceae, 168–169 proteeae and P aeruginosa, 167–168 ribosomal protection mechanisms, 166 S aureus, 167 reference susceptibility test method, 161 susceptibility test data bacterial isolates, 161 biofilm model, 162 bloodstream infection isolates, 161 broad-spectrum activity, 163 CA-MRSA isolates., 162 CAP, 163 carbapenem-resistant, 165 efflux determinants, 164 Enterobacteriaceae, 165 Enterococcus spp, 162 ESBL producers, 163–164 H influenzae, 165–166 K pneumoniae, 164 MBC, 162 M catarrhalis isolates, 166 MIC values, 161–163 pathogens, 165 Proteus mirabilis, 165 Proteus vulgaris, 165 respiratory infections, 166 SENTRY antimicrobial surveillance program, 165 Staphylococcus spp., 161 T.E.ST, 164 vancomycin resistance mechanisms, 163 Index Tigecycline Evaluation and Surveillance Trial (T.E.S.T), 164 TIGRFAM, 884 Tomasz, A., 571 Torres, J.A., 651 Total polar surface area (TPSA), 796 Transferred NOE (TRNOE), 990, 991 Transposon-mediated differential hybridisation (TMDH) method, 887 TRUST surveillance, 755, 756 Tuberculosis bacterial persisters antibiotics insusceptibility, 726 DNA repair, 727–728 HipA, 727 L-form research, 729 phoU gene, 728 planktonic, 728 transposon mutagenesis approach, 728 b-lactam antibiotics, 734 chemotherapy ethambutol, 720 lengthy TB therapy, 721 Mitchison model, 722–723 Tubercle bacilli, 722 Yin-Yang model, 723 diarylquinoline, 736–737 drug development, 729–730 drug resistance, 724–726 gatifloxacin, 734 moxifloxacin, 734 nitroimidazopyran, 737–739 nongrowing persister bacilli, 732–733 novel drug targets energy production pathways, 731 essential genes, 730 NAD metabolism, 731 persister targets, 731 toxin-antitoxin (TA) Modules, 732 virulence factors, 732 oxazolidinones, 739 pyrrole LL-3858, 739–740 rifalazil, 740 rifamycin rifapentine (RPT), 733–734 SQ109, 739 Turnidge, J., 1089 Two-population models persistent bacteria genetically-acquired resistance mechanism, 1060 1127 initial inoculum, 1061 robust model, 1061 resistant bacteria ciprofloxacin, 1062 growth inhibition model, 1062 MIC model, 1063 net effect model, 1062 Tyndall, J., 80, 84 U Umezawa, H., 17, 27, 43 Urban, A., 920 Urinary tract infection (UTI), 229, 621–623, 660–661 V Vancomycin, 902 Vancomycin-intermediate Staphylococcus aureus (VISA), 826, 859 Vancomycin-resistant enterococci (VRE), 304 Veber, D.F., 808 Ventilator-acquired pneumonia (VAP), 229 Villegas, M.V., 651 W Waksman, S.A., 10–12, 17, 25, 37, 234, 902 Waley, S.G., 870 Walker, S., 311 Water-ligand-observed-via-gradient-spectroscopy (Water-LOGSY), 991, 992 Watkins, W.J., 849 White, R.J., Witkin, E., 64 Woods, D., 35, 36 X Xu, Z-Q., 181 Z Zak, O., 1014 Zawadzke, L.E., 1002 Zhang, Y., 719 Zhao, X., 485 Zone of inhibition (ZOI) assays, 59 ... Chapter is an analysis of global stock market behavior around the stock market cycles Starting from a simple analysis of price movements it explores the global trends around these cycles and traces...Gagari Chakrabarti Chitrakalpa Sen • Anatomy of Global Stock Market Crashes An Empirical Analysis 123 Gagari Chakrabarti Economics Presidency University College... Inducible Resistance to Macrolide Antibiotics Sai Lakshmi Subramanian, Haripriya Ramu, and Alexander S Mankin 455 14 Fluoroquinolone Resistance: Mechanisms, Restrictive Dosing, and Anti-Mutant Screening