頭孢菌素類抗生素(英文)Cephalosporin-Antibiotics

CephalosporinAntibioticsFirstdiscoveredin1945fromaCephalosporiumfungiCommercialdrugsderivedsemi-syntheticallyFrom7-aminocephalosporanicacid-producedbyfermentationSimilartopenicillins–4GenerationsDerivativesacylatedatthe7-aminogroupReasonsforsyntheticmodificationinclude:IncreasedacidstabilityImprovedpharmacokinetics(oralabsorption)BroadenantimicrobialspectrumIncreasedactivity(decreasedresistanceduetodestruction)ImprovedpenetrationIncreasedreceptoraffinityDecreasedallergenicityIncreasedtoleranceduetoparenteraladministrationCephalosporinAntibioticsFirstTransitionfromfirstgenerationtothirdgenerationagentsreflectsBroadeningoftheGram(-)organismspectrumLossofefficacyagainstGram(+)organismsGreaterefficacyagainstresistantorganisms(butincreasedcost)MOA:Inhibitcellwallsynthesis

osmoticallyinducedcelllysisUsuallybactericidal–afunctionofdosage,organismsusceptibility,tissueconcentrations,andgrowthrateCrossallergenicitywithpenicillinsis5-16%Druginteractions:Alcoholusemayproducedadisulfiramlikereaction-NMTTAminoglycosidenephrotoxicitycanbeincreasedAnticoagulanteffectscanbepotentiated-NMTTAntacidscandecreaseplasmaconcentrationsoforalagentsLoopdiureticnephrotoxicitycanbeincreasedMonitorrenalfunctionsinceallarerenallyexcreted

CefoperazonetheexceptionCephalosporinAntibioticsTransitionfromfirstgeneratiClassifiedbyGenerations-explosiveadvancesFirstGenerationEpitomizedbycefazolinGoodactivityagainstGram(+)ModestGram(-)activitySecondGenerationIncreasedGram(-)activitySomeactiveagainstbaccillusfragilis(highlyresistantanaerobe)ThirdGeneration-costvs.efficacy“Broad”spectrumwithhighpenicillinaseresistanceGreaterGram(-)spectrumLessactivethanG1againstmostGram(+)MoreactivethanG1againstenterobacterFourthGeneration-CefepimeExtendedrangeofactivitycomparedtoG3–MoreGram(+)Increasedstabilityagainstb-lactamasesVERYusefulforGram(-)strainsresistanttoG3CephalosporinAntibioticsClassifiedbyGenerations-exCephalosporinAntibioticsCephalosporinAntibioticsG1PO:Cephalexin,Cephradine,CephadroxilParenteral:Cefapirin,CefazolinG2PO:Cefaclor,Loracarbef,Cefprozil,CefuroximeParenteral:Cefmetazole,Cefotetan,Cefonacid, Cefamandol,CefoxitinG3PO:Cefpodoxime,Cefixime,Cefdinir,CeftitbutenParenteral:Cefotaxime,Ceftizoxime,Ceftriaxone, Ceftazidime,CefaperazoneG4-CefepimeCephalosporinAntibioticsG1CephalosporinAntibioticsCephalosporinDeactivationDeactivatedCephalosporinCephalosporinDeactivationDeac1stGenerationCephalosporinsIndications:Respiratorytractinfections,Otitismedia,skinandskinstructureinfections,Boneinfections,Gram(-)UTI.Usedforstaphorstrepinfectioninpatientswithmildhypersensitivitytopenicillins!

Gram(+)aerobicbacteria-limitedGram(-)Oraluseonly,10%proteinbound,>90%excretedrenallyunchangedOneoftheTop200Indications:Oral-Respiratorytractinfections,Otitismedia,skinandskinstructureinfections,Boneinfections,GUinfections,UTI;Parenteral–Septicemia;pre-,post-orintraoperativeprophylaxisOralorIV/IMuse,17%proteinbound,>90%excretedrenallyunchangedGenerallyallareinactivatedbyb-lactamasesPartialhydrogenation1stGenerationCephalosporinsI1stGenerationCephalosporinsGenerallyallareinactivatedbyb-lactamasesIndications:UTI,pharyngitisandtonsillitisduetogroupAb-hemolyticStreptococcus,skinandskinstructureinfections.Oraluseonly,20%proteinbound,>90%excretedrenallyunchangedProlongedhalf-lifeallowsonce-a-daydosingIndications:Respiratorytractinfections,skinandskinstructureinfections,Osteomyelitis,UTI,Septicemia,pre-,post-orintraoperativeprophylaxisIV/IMuseonly,50%proteinbound,70%excretedrenallyunchangedMethicillinsubstitute.

ComparativelyresistanttoStaph.penicillinase

1stGenerationCephalosporinsG1stGenerationCephalosporinsGenerallyallareinactivatedbyb-lactamasesIndications:Respiratorytractinfections,GUinfections,skinandskinstructureinfections,Biliarytractinfections,boneandjointinfections,Septicemia,endocarditits;pre-,post-orintraoperativeprophylaxis.Usedforstaphorstrepinfectioninpatientswithmildhypersensitivitytopenicillins!NOTformeningitis(can’tcrossBBB).IM/IVuseonly,adjustdoseasafunctionofcreatinineclearancewith80%excretedrenallyunchanged,86%proteinboundLongerhalf-lifethanCephapirin,lessirritatingoninjection,heat/lightunstable1stGenerationCephalosporinsG2ndGenerationCephalosporinsIndications:

Respiratorytractinfections,Otitismedia,skinandskinstructureinfections,UTIExtendedreleasetabs:acutebacterialexacerbationsofchronicbronchitis,secondaryinfectionsasaresultofacutebronchitis,pharyngitisandtonsillitisOraluseonly,25%proteinbound,85%excretedunchangedrenallyRefrigeratesuspensionMOSTsusceptibletob-lactamasesinitsclass!CarbonIsostereofcefaclorIndications:Secondarybacterialinfectionofacutebronchitits,pneumonia;Otitismedia,acutemaxillarysinusitis,pharyngitis,tonsillitis,skinandskinstructureinfection,UTIsuchascystitisandpyelonephritisOraluseonly,25%proteinbound,>90%excretedunchangedintheurineStoresuspensionatroomtemperatureVariableresistancetob-lactamase,moreGram(-)activity2ndGenerationCephalosporinsI2ndGenerationCephalosporinsVariableresistancetob-lactamase,moreGram(-)activityIndications:pharyngitis,tonsillitis,otitismedia,acutesinusitis,acuteandchronicbronchitis,uncomplicatedskinandskinstructureinfectionsOraluseonly,36%proteinbound,60%renalexcretionunchanged-dosageadjustmentnecessaryinrenalfailure-creatinineclearance<30use50%theusualdosageSimilartoCefaclorwithimprovedpotencyTop200drugAmoxicillinlikegroupTransformhereimpartsGram(-)activity2ndGenerationCephalosporinsV2ndGenerationCephalosporinsVariableresistancetob-lactamase,moreGram(-)activityIndications:Lowerrespiratorytractinfections,UTI,intra-abdominalinfections,GUinfections,skinandskinstructureinfections,boneandjointinfections,Septicemia,pre-,post-orintraoperativeprophylaxisDoNOTmixinthesameIVasaminoglycosides,stabilityofreconstitutedsolutionisafunctionofthediluentused,IVuseonly,73%proteinbound,85%excretedunchangedintheurineIndications:ORAL:Respiratorytractinfections,UTI,earlyLymedisease,uncomplicatedgonorrhea,skinandskinstructureinfections;PARENTERAL:Asaboveplussepticemia,meningitis,boneandjointinfections,mixedinfections.CommunityacquiredpneumoniaOralorIV/IMuse,50%proteinbound,upto100%excretedintheurineunchanged-reducedosageinrenalimpairmentbasedoncreatinineclearance,maybetakenwithfood,DoNOTmixinthesameIVasaminoglycosidesorusesodiumbicarbonateinjectionasdiluent,doNOTchewtabletsduetoverybadtaste—swallowwholeTop200drugCancrosstheBBB–meningitisNotusedasceftriaxone&cefotaximepreferredCephamycin:Anaerobicactivity2ndGenerationCephalosporinsV2ndGenerationCephalosporinsVariableresistancetob-lactamase,moreGram(-)activityIndications:UTI,lowerrespiratoryinfections,skinandskinstructureinfections,intra-abdominalinfections,pre-operativeprophylaxisIM/IVuseonly,65%proteinbound,85%recoveredunchangedintheurineDoNOTmixinthesameIVwithaminoglycosidesIndications:UTI,lowerrespiratoryinfections,skinandskinstructureinfections,intra-abdominalinfections,peri-operativeprophylaxis,GUinfections,boneandjointinfectionsWatchfornephrotoxicitywhenusewithaminoglycosides-besuretoadjustdosageinrenalfailurebasedoncreatinineclearanceanddoNOTmixinthesameIVIM/IVonly,90%proteinbound,81%recoveredunchangedfromtheurineTheseagents+cefoxitinhavereasonableanaerobicactivity:Peritonitis&diverticulitis2ndGenerationCephalosporinsV2ndGenerationCephalosporinsVariableresistancetob-lactamase,moreGram(-)activityIndications:Lowerrespiratoryinfection,UTI,skinandskinstructures,septicemia,boneandjointinfections,pre-operativeprophylaxisIV/IMuseonly,90%proteinbound,99%excretedunchangedintheurine----dosageadjustmentnecessaryinrenalfailureAdmixincompatibilitywithaminoglycosidesLongerhalf-lifethanotherG2,lowerGram(+)potencyIndications:Lowerrespiratoryinfection,UTI,peritonitis,skinandskinstructures,septicemia,boneandjointinfections;pre-,intra-andpost-operativeprophylaxisAdmixincompatibilitywithaminoglycosidesIV/IMuseonly,dosagereductionnecessarybasedonrenalfunctionNMTT–bleedinganddisulfuramproblemsNMTT2ndGenerationCephalosporinsVDiesterprodrug!!-extendedspectrumagentIndications:acutecommunity-acquiredpneumonia,chronicbronchitis,acuteotitismedia,pharyngitis,tonsilllitis,acuteuretheral,cervicalorrectalgonorrheabutNOTpharyngealdisease;skinandskinstructureinfections,UTIUsefulincirrhosispatients—nodosageadjustmentneeded,renalfailurenecessitatesdosageadjustmentOraluseonly,29%proteinbound,33%excretedunchangedintheurineIndications:UTI,otitismedia,pharyngitis,tonsillitis,acuteandacutechronicbronchitis,cervicalorurethralgonorrheaOraluseonly,65%proteinbound,50%excretedunchangedintheurineDOC–gonorrhea–single400mgdose3rdGenerationCephalosporinsDiesterprodrug!!-extendedspe

Indications:Communityacquiredpneumonia,acuteexacerbationofchronicbronchitits,acutemaxillarysinusitis,pharnygitis,tonsillitis,skinandskinstructureinfections,acuteotitismediaOraluseonly,70%proteinbound,17%excretedunchangedintheurinebutdosagestillneedsreducedinrenalfailureIndications:acutebacterialexacerbationsofchronicbronchitis,acutebacterialotitismediacausedbyH.influenza,pharyngitisandtonsillititscausedbyS.pyogenesOraluseonly,65%proteinbound,56%excretedunchangedintheurine-dosageadjustmentasafunctionofcreatinineclearance3rdGenerationCephalosporinsCeftibutenIndications:CommunityacquiIndications:Lowerrespiratoryinfection,UTI,gynecologicalinfection,bacteremia/septicemia,skinandskinstructureinfections,intra-abdominalinfections,boneorjointinfections,meningitisorotherCNSinfections,perioperativeprophylaxisCDCrecommendedtreatmentforgonorrheaIM/IV,40%proteinbound,60%renalexcretedunchanged–adjustwithrenalfx3rdGenerationCephalosporins3rdGenerationCephalosporinsIndications:Lowerrespiratoryinfection,UTI,gonorrheaandPID,septicemia,skinandskinstructureinfections,intra-abdominalinfections,boneorjointinfections,meningitisIM/IVuseonly,30%proteinbound,80%excretedunchangedintheurine---dosagereductionnecessaryinrenalfailureIndications:Lowerrespiratoryinfection,UTI,gonorrheaandPID,septicemia,skinandskinstructureinfections,intra-abdominalinfections,boneorjointinfections,meningitis,surgicalprophylaxis,effectiveintreatingLymediseaseinfectioncausingneurologicalcomplications,arthritisandcardititsrefractorytoPenGDOC–Gonorrhea–singleinjectionIM/IVuseonly,95%proteinbound,67%excretedunchangedintheurine3rdGenerationCephalosporinsIndications:LowerrespiratorIndications:Lowerrespiratoryinfections,skinandskinstructureinfections,UTI,bacterialsepticemia,boneandjointinfections,gynecologicalinfections,intra-abdominalinfections,CNSinfections,concomitantantibiotictherapyinimmunocompromisedpatientsRenalexcretion---adjustdosageasafunctionofGFR—90%unchangedSodiumbicarbonatesolutionisNOTrecommendedasadiluent,doNOTmixwithaminoglycosidesIM/IVuseonly,<10%proteinboundIndications:Respiratorytractinfections,peritonititsandotherintra-abdominalinfections,bacterialsepticemia,skinandskinstructureinfections,PID,endometritis,UTI IM/IVonly,93%proteinbound,30% excretionunchangedintheurine Extensivelyexcretedinthebile—monitorserum concentrationsinhighdosesinthecaseof hepaticdiseaseorbiliaryobstruction

Renalfailure-nodoseadjustmentexceptin highdoses3rdGenerationCephalosporinsIndications:Lowerrespirator4thGenerationCephalosporinsIndications:UTI,skinandskinstructureinfections,pneumonia(moderatetosevere),complicatedintra-abdominalinfections,empiricaltherapyforfebrileneutropenicpatients,pediatricpatients2monthsto