Table Of Content

ANTIBIOTICS AND ANTIBIOTIC RESISTANCE ANTIBIOTICS AND ANTIBIOTIC RESISTANCE Ola Sko¨ld, M.D., Ph.D. ProfessorofMicrobiology UppsalaUniversity AJOHNWILEY&SONS,INC.,PUBLICATION Copyright©2011byJohnWiley&Sons,Inc.Allrightsreserved PublishedbyJohnWiley&Sons,Inc.,Hoboken,NewJersey PublishedsimultaneouslyinCanada Nopartofthispublicationmaybereproduced,storedinaretrievalsystem,ortransmittedin anyformorbyanymeans,electronic,mechanical,photocopying,recording,scanning,or otherwise,exceptaspermittedunderSection107or108ofthe1976UnitedStatesCopyright Act,withouteitherthepriorwrittenpermissionofthePublisher,orauthorizationthrough paymentoftheappropriateper-copyfeetotheCopyrightClearanceCenter,Inc.,222 RosewoodDrive,Danvers,MA01923,(978)750-8400,fax(978)750-4470,oronthewebat www.copyright.com.RequeststothePublisherforpermissionshouldbeaddressedtothe PermissionsDepartment,JohnWiley&Sons,Inc.,111RiverStreet,Hoboken,NJ07030,(201) 748-6011,fax(201)748-6008,oronlineathttp://www.wiley.com/go/permission. LimitofLiability/DisclaimerofWarranty:Whilethepublisherandauthorhaveusedtheir besteffortsinpreparingthisbook,theymakenorepresentationsorwarrantieswithrespectto theaccuracyorcompletenessofthecontentsofthisbookandspecificallydisclaimanyimplied warrantiesofmerchantabilityorfitnessforaparticularpurpose.Nowarrantymaybecreated orextendedbysalesrepresentativesorwrittensalesmaterials.Theadviceandstrategies containedhereinmaynotbesuitableforyoursituation.Youshouldconsultwitha professionalwhereappropriate.Neitherthepublishernorauthorshallbeliableforanylossof profitoranyothercommercialdamages,includingbutnotlimitedtospecial,incidental, consequential,orotherdamages. Forgeneralinformationonourotherproductsandservicesorfortechnicalsupport,please contactourCustomerCareDepartmentwithintheUnitedStatesat(800)762-2974,outsidethe UnitedStatesat(317)572-3993orfax(317)572-4002. Wileyalsopublishesitsbooksinavarietyofelectronicformats.Somecontentthatappearsin printmaynotbeavailableinelectronicformats.FormoreinformationaboutWileyproducts, visitourwebsiteatwww.wiley.com. LibraryofCongressCataloging-in-PublicationData: Sko¨ld,Ola. [Antibiotikaochantibiotikaresistens.English] Antibioticsandantibioticresistance/OlaSko¨ld. p.;cm. Translationof:Antibiotikaochantibiotikaresistens/OlaSko¨ld.c2006. Includesindex. ISBN978-0-470-43850-3(cloth) 1. Antibiotics.2. Drugresistanceinmicroorganisms. I.Title. [DNLM:1. Anti-BacterialAgents.2. DrugResistance,Microbial. QV350] RM267.S555132011 615(cid:2).329–dc22 2011002200 PrintedintheUnitedStatesofAmerica ePDFISBN:978-1-118-07556-2 oBookISBN:978-1-118-07560-9 ePubISBN:978-1-118-07558-6 10987654321 TothememoryofJ.B.Neilands,ProfessorofBiochemistry, UniversityofCalifornia,Berkeley ‘‘ThefinestGentlemanofScienceIevermet’’ CONTENTS Preface xiii 1 ANTIBIOTICS:THEGREATESTTRIUMPH OF SCIENTIFICMEDICINE 1 Selectivity 3 DevelopmentofResistance 4 Sulfonamide:TheFirstAntibacterialAgentActing Selectively 5 ChemotherapeuticsandAntibiotics 9 Penicillin:TheFirstAntibiotic 9 TheFirstTherapeuticTrial 12 RediscoveryofPenicillinbyaBasicScientific Approach 13 Betalactams 14 Streptomycin:TheSecondAntibioticintheHistory ofAntibacterialAgents 16 TheFirstRemedyforTuberculosis 18 Conclusion 19 vii viii CONTENTS 2 DISTRIBUTIONOF ANTIBIOTICS 21 QuantitativeEvaluationofAntibioticsConsumption 22 DefinedDailyDoses 22 InternationalDistributionofAntibiotics: AScandinavianExample 22 ControlofAntibioticsOveruse 25 3 SULFONAMIDES AND TRIMETHOPRIM 29 GeneralAspectsRegardingtheDevelopment ofResistance 30 Sulfonamides 32 SulfonamidesasRemedies 32 ResistancetoSulfonamide 34 ResistancetoSulfonamidesinNeisseriameningitidis 35 CharacterizationoftheSulfonamide-Resistant DihydropteroateSynthaseinN.meningitidis 40 CharacterizationoftheOtherSulfonamide-Resistant DihydropteroateSynthaseinN.meningitidis 42 ResistancetoSulfonamidesinStreptococcus pyogenes 44 ResistancetoSulfonamidesinCampylobacterjejuni 46 ResistancetoSulfonamidesinStreptococcus pneumoniae 46 ResistancetoSulfonamidesinPneumocystisjiroveci (carinii) 47 ResistancetoSulfonamidesinStaphylococcusaureus andS.haemolyticus 48 ResistancetoSulfonamidesinMycobacteriumleprae 49 Plasmid-BorneResistancetoSulfonamides 49 Trimethoprim 51 CONTENTS ix InnateResistancetoTrimethoprim 55 ChromosomalResistancetoTrimethoprim 56 Plasmid-BorneResistancetoTrimethoprim 59 PossiblePathogenicityChangeinC.jejuniby AcquiringTrimethoprimResistanceGenes 65 ExperimentalTestoftheReversibilityof TrimethoprimResistance 66 Conclusion 67 4 PENICILLINSAND OTHER BETALACTAMS 69 TheBetalactamRing:TheCharacteristic ofallBetalactams 70 TheAntibacterialMechanismofBetalactams 73 Penicillins 74 PenicillinswithanEnlargedSpectrum 75 PenicillinsStabletoPenicillinases 77 CounteractingResistancebytheInhibition ofBetalactamases 80 OtherAntibacterialBetalactams 81 Cephalosporins 81 Monobactams 84 Thienamycins 85 Betalactamases 87 HorizontalSpreadofBetalactamases 87 Penicillin-BindingProteins 90 ResistancetoBetalactamsbyChangesinthePBPs 91 AVeryOldProphecyCameTrue 94 5 GLYCOPEPTIDES 95 MechanismofAntibacterialAction 96 x CONTENTS Resistance 98 AvoparcinandClinicalResistancetoGlycopeptides 100 VancomycinasanAntibioticofLastResort 101 6 AMINOGLYCOSIDES 103 TheAntibacterialMechanismofStreptomycin 104 BactericidalEffect 106 ClinicalSideEffects 106 BacterialResistancetoAminoglycosides 109 HorizontalSpreadofAminoglycosideResistance 110 Conclusion 113 7 OTHER ANTIBIOTICSINTERFERING WITH BACTERIALPROTEINSYNTHESIS 115 Chloramphenicol 115 ClinicalSideEffects 117 BacterialResistancetoChloramphenicol 117 Tetracyclines 119 MechanismofAction 120 ClinicalSideEffects 121 BacterialResistancetoTetracyclines 121 ErythromycinandRelatedAntibiotics 123 Macrolides 123 ResistancetoErythromycin 124 ClinicalUseofMacrolides 125 Lincosamides 125 Streptogramins 126 FusidicAcid 128 CONTENTS xi Linezolid 129 Conclusion 131 8 QUINOLONES 133 TheEffectofQuinolonesonBacteria 134 ClinicalUseofQuinolones 136 BacterialResistancetoQuinolones 139 MutationalResistance 139 ResistancebyQuinoloneEfflux 140 TransferablePlasmid-BorneResistance 140 Conclusion 145 9 ANTIBACTERIALAGENTSNOT RELATED TOTHE LARGE ANTIBIOTICFAMILIES 147 RemediesforTuberculosis 147 Rifampicin 149 MechanismofAction 150 Resistance 151 Plasmid-BorneResistance 151 OtherAgentsAgainstTuberculosis 152 IsoniazidorIsonicotinicAcidHydrazide 153 Pyrazinamide 154 Ethambutol 155 Cycloserine 156 para-AminosalicylicAcid 157 TuberculostaticDrugsRecruitedfromEarlier KnownGroupsofAntibioticsFoundOriginally withOtherAntibacterialSpectra 158 xii CONTENTS Diarylquinolines 159 TheBattleAgainstTuberculosis 159 Nitrofurantoin 161 Nitroimidazoles 161 Phosphomycin 163 Conclusion 165 10 MECHANISMS FOR THE HORIZONTALSPREAD OF ANTIBIOTICRESISTANCEAMONG BACTERIA 167 TransferableResistance:Conjugation 167 MutationalResistance 170 Plasmid-BorneResistanceAgainstAntibacterial Agents 171 Plasmids 173 TheOriginofRPlasmids 176 Transposons 178 Integrons 182 11 HOW TOMANAGE ANTIBIOTICRESISTANCE 187 CrossResistanceBetweenRelatedAntibiotics 188 TheEvolutionofAntibacterialResistance 188 HowtoCounteractResistanceDevelopment 190 CurtailingtheUseofAntibiotics 191 IntroductionofTrulyNewAntibacterialAgents 193 AntibacterialPeptides 193 InhibitionofPathogenicity 197 InhibitionofBacterialFattyAcidSynthesis 198 ResistanceDevelopmentAccelerates 200 Index 203

Description:

This book, which is the translated version of a Swedish book, combines a general introduction of a variety of antibiotics with a more in-depth discussion of resistance. The focus on resistance in learning about antibiotics will help future scientists recognize the problem antibiotics resistance pose