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OfficialreprintfromUpToDate
www.uptodate.com2015UpToDate
Cephalosporins
Author
StephenBCalderwood,MD

SectionEditor
DavidCHooper,MD

DeputyEditor
AllysonBloom,MD

Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.
Literaturereviewcurrentthrough:Dec2014.|Thistopiclastupdated:Jan12,2015.
INTRODUCTIONBetalactamantibioticsareamongthemostcommonlyprescribeddrugs,groupedtogether
baseduponasharedstructuralfeature,thebetalactamring.Cephalosporinscoverabroadrangeoforganisms,
aregenerallywelltolerated,andareeasytoadministerthus,theseagentsarefrequentlyusedbetalactamdrugs.
Theclassification,spectrumofactivity,andpharmacologyofthecephalosporinswillbereviewedhere.
Thespectrumofactivityofcephalosporinscombinedwithbetalactamaseinhibitorsarediscussedseparately.
(See"Combinationbetalactamaseinhibitors,carbapenems,andmonobactams".)
Themechanismsofactionandresistanceandmajoradversereactionsofthebetalactamantibiotics,andthe
penicillinsandotherbetalactamdrugsarealsodiscussedseparately.(See"Betalactamantibiotics:Mechanisms
ofactionandresistanceandadverseeffects"and"Penicillins"and"Extendedspectrumbetalactamases".)
CLASSIFICATIONOFCEPHALOSPORINSCephalosporinsincludethecloselyrelatedcephamycin
compounds.Theparenteralagentsarecommonlyclassifiedintothefollowingcategories:
Firstgeneration(cefazolin)
Secondgeneration
A.SubgroupwithactivityagainstHaemophilusinfluenzae(cefuroxime)
B.CephamycinsubgroupwithactivityagainstBacteroidesspp(cefoxitinandcefotetan)
Thirdgeneration
A.SubgroupwithbroadgramnegativeactivitybutpooractivityagainstPseudomonasaeruginosa
(cefotaxime,ceftriaxone,andceftizoxime)
B.SubgroupwithbroadgramnegativeactivityincludinggoodactivityagainstPseudomonasaeruginosa
(ceftazidime)
Fourthgeneration(cefepime)
Fifthgeneration(ceftaroline)
SPECTRUMOFACTIVITYANDCLINICALUSEMostoftheavailablecephalosporinsaresemisynthetic
derivativesofcephalosporinC,acompoundwithantibacterialactivityproducedbythefungusCephalosporium.
Thecloselyrelatedcephamycincompounds(derivedfromStreptomycesspp)areregardedasmembersofthe
cephalosporinclass.Inclinicalpractice,theseantibioticshavefrequentlybeengroupedintofive"generations"
basedupontheirspectrumofactivityagainstaerobicandfacultativegramnegativebacilliandgrampositive
bacteria.
Parenteralagents
FirstgenerationCephalothinistheoldestofthefirstgenerationcephalosporinsandwaspreviouslyused
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astheprototypeofthisgroup.Cephalothinwasactiveagainstmostgrampositivecocci(includingpenicillinase
producingstaphylococci),butdidnothaveclinicallyusefulactivityagainstenterococci,Listeria,oxacillinresistant
staphylococci[1],orpenicillinresistantpneumococci[24].(See"Microbiologyofmethicillinresistant
Staphylococcusaureus"and"ResistanceofStreptococcuspneumoniaetobetalactamantibiotics".)
CephalothinwasactiveagainstmoststrainsofEscherichiacoli,Proteusmirabilis,andKlebsiellapneumoniae,but
hadlittleactivityagainstindolepositiveProteus,Enterobacter,Serratia,andthenonentericgramnegativebacilli
suchasAcinetobactersppandPseudomonasaeruginosa.Gramnegativecocci(suchasthegonococcusand
meningococcus)andH.influenzaeweregenerallyresistant.Cephalothinwasactiveagainstmostofthecommon
anaerobicpathogens,withcertainexceptionssuchasBacteroidesspecies,particularlyB.fragilis.
Cefazolinhasasimilarspectrumofactivitytocephalothin,isavailableworldwide,andisnowtheonlyparenteral
firstgenerationcephalosporinavailableintheUnitedStates.Cefazolinachievessubstantiallyhigherserumlevels
thancephalothin,andhasalongerhalflifeofelimination.Cefazolinislessstablethancephalothininvitrotothe
typeApenicillinaseofstaphylococci[5]therelevanceofthisforclinicaltherapy,however,isnotcertain.
SecondgenerationThesecondgenerationcephalosporinsaresomewhatlessactiveagainstcertaingram
positivecoccithanthefirstgenerationagentsbutaremoreactiveagainstcertaingramnegativebacilli.This
generationofcompoundscanbedividedintotwosubgroups,onewithactivityagainstH.influenzaeandtheother,
thecephamycins,withactivityagainstBacteroides.
ActivityagainstHaemophilusinfluenzaeInthefirstsubgroup,cefuroximeisavailableparenterallyand
ismoreactivethancefazolininvitroagainststrainsofEnterobacterandindolepositiveProteus.However,this
agentinducesthechromosomalbetalactamasesoftheseorganisms,leadingtoresistanceandfailuresofclinical
therapy[6].(See"Betalactamantibiotics:Mechanismsofactionandresistanceandadverseeffects",sectionon
'Mechanismsofbacterialresistance'.)
CefuroximeisalsomoreactivethancefazolinagainstH.influenzae,andcefuroximeisquitestabletotheTEM
betalactamaseinampicillinresistantstrains.AlthoughcefuroximeisapprovedforthetherapyofH.influenzae
meningitis,delayedresponsesandtreatmentfailureshaveoccurred,andathirdgenerationcephalosporinisnow
preferredfortherapyofmeningitisduetoampicillinresistantstrains[7].Cefuroximeisalsohighlyactiveagainst
betalactamaseproducingMoraxellacatarrhalis.
Cephamycinsubgroup(activeagainstBacteroides)Thecephamycinsubgroupofthesecond
generationcephalosporinsincludescefoxitinandcefotetan.ThissubgroupisactiveagainstmoststrainsofE.coli,
P.mirabilis,andKlebsiella,likethefirstgenerationcephalosporins.Thecephamycinsarequitestabletomany
plasmidmediatedbetalactamases,buttheactivityofthisgroupagainstEnterobacterandindolepositiveProteus
islimitedbyinductionofchromosomalcephalosporinasesofthesespeciesandselectionofstablyderepressed
mutants[6].
Unlikethefirstgenerationcephalosporins,thecephamycinsareactiveagainstmanystrainsofBacteroides.The
combinationofactivityagainstcommonaerobicandfacultativegramnegativebacilliplusBacteroideshasledto
theuseofthecephamycinsintheprophylaxisandtherapyofinfectionsintheabdominalandpelviccavities
(wheretheseorganismspredominate)[8].Thecephamycinshavenoclearadvantagesoverthefirstgeneration
cephalosporinsforinfectionsoutsideoftheabdominalandpelvicareas.
Overallresistanceratestocephamycinsrangefrom10to80percentfordifferentmembersoftheBacteroides
fragilisgroup,comparedwith15to30percentforclindamycin,andessentiallynoresistanceforthecarbapenems,
chloramphenicol,ormetronidazole[9].
ThirdgenerationThethirdgenerationcephalosporinclass[10]ismarkedbystabilitytothecommonbeta
lactamasesofgramnegativebacilli,andthesecompoundsarehighlyactiveagainstEnterobacteriaceae(E.coli,
Proteusmirabilis,indolepositiveProteus,Klebsiella,Enterobacter,Serratia,Citrobacter),Neisseria,andH.
influenzae.TheyarethetherapyofchoiceforgramnegativemeningitisduetosusceptibleEnterobacteriaceae.
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Thirdgenerationcephalosporinsmayalsobeusefulalternativestotheaminoglycosidesintreatinggramnegative
infectionsresistanttootherbetalactams,particularlyinthepatientwithrenaldysfunction.However,mutantsof
Enterobacter,indolepositiveProteus,Serratia,andCitrobacter,withstablederepressionofthechromosomalbeta
lactamase,areresistanttotheseantibiotics[6,11].Eveniftheseorganisms(Enterobacter,indolepositiveProteus,
Serratia,andCitrobacter)testsusceptibletocephalosporins,useofathirdgenerationcephalosporinasasingle
agentfortreatmentofseriousinfectionsduetothesebacteriacanleadtotheemergenceofresistanceduring
therapy.
Thethirdgenerationcephalosporinsarelessactiveagainstmostgrampositiveorganismsthanthefirstgeneration
cephalosporinsandareinactiveagainstenterococci,Listeria,oxacillinresistantstaphylococci,andAcinetobacter.
Cefotaximeandceftriaxoneareusuallyactiveagainstpneumococciwithintermediatesusceptibilitytopenicillin,
butstrainsfullyresistanttopenicillinareoftenresistanttothethirdgenerationcephalosporinsaswell.In1998,for
example,25percentofstrainsofS.pneumoniaeintheUnitedStateswereintermediatelyorfullyresistantto
penicillin,and14percentwereresistanttothirdgenerationcephalosporins[24,1214].(See"Resistanceof
Streptococcuspneumoniaetobetalactamantibiotics".)
Treatmentwiththirdgenerationcephalosporinsmaybecomplicatedbysuperinfection(particularlywithenterococci
orCandida)orbytheemergenceofresistanceontherapy(particularlywhenusedassingleagentsfor
Enterobacter,indolepositiveProteus,orP.aeruginosainfections)[15].
Thirdgenerationcephalosporinsarenotcurrentlyrecommendedforprophylacticuseinsurgery.
PooractivityagainstPseudomonasOnesubgroupofthethirdgenerationcephalosporins,including
cefotaximeandceftriaxone,haspooractivityagainstP.aeruginosa.Withinthissubgroup,cefotaximehasthe
shortestserumhalflife(1hour)becauseofpartialmetabolisminthelivertodesacetylcefotaxime.However,this
metabolitealsohasantibacterialactivityandalongerhalflifeinserum(1.7hours),allowingdosingeverysix
hours.
Ceftriaxonehasthelongestserumhalflifeofthisgroup(6.4hours)andcanbeadministeredonceortwiceaday.
Ceftriaxonehasbeenparticularlyrecommendedforthetherapyofpenicillinresistantgonorrhea,Lymedisease
involvingthecentralnervoussystemorjoints,meningitisduetoampicillinresistantH.influenzae,andmeningitis
inchildren[7,16].Oneofthecomplicationsofceftriaxonetherapy,however,hasbeentheformationinthebiliary
tractof"sludge"composedofceftriaxonecrystals,causingthesyndromeofbiliarypseudolithiasis[17].
ActivityagainstPseudomonasTheothersubgroupofthethirdgenerationcephalosporins,including
cefoperazoneandceftazidime,hasactivityagainstP.aeruginosa.Cefoperazonewasthefirstavailabledrugin
thissubgroup,butiscurrentlynotusedasoftenduetodecreasedstabilitytotheplasmidmediatedbeta
lactamasesofgramnegativebacillithatmakeitlessactiveagainstEnterobacteriaceaethantheotherthird
generationcephalosporins.Thenewermemberofthesubgroup,ceftazidime,isquitestabletothecommon
plasmidmediatedbetalactamasesandishighlyactiveagainstEnterobacteriaceae,Neisseria,andH.influenzae.
CeftazidimeisalsoparticularlyactiveagainstP.aeruginosaandisaneffectivetherapyforseriousinfectionsdue
toP.aeruginosawhentheorganismisresistanttotheantipseudomonalpenicillinsorthepatientispenicillin
allergic.Inaddition,itiseffectivetherapyformeningitiscausedbyP.aeruginosa.Aswiththeantipseudomonal
penicillins,however,ceftazidimeshouldgenerallybegivenatleastinitiallyincombinationwithanaminoglycoside
fortreatmentofseriousP.aeruginosainfection.Ceftazidimehaspooractivityagainstgrampositiveorganisms
andshouldbereservedforuseininfectionsprovenorhighlysuspectedtobeduetoP.aeruginosa.
CefoperazonecontainsanNmethylthiotetrazole(NMTT)sidechain.ThisNMTTgroupcandissociatefromthe
parentantibioticinsolutionorinvivoandcompetitivelyinhibitvitaminKaction,leadingtoprolongationofthe
prothrombintimeandbleeding[18].Thissidechainisalsoassociatedwithadisulfiramlikereactiontoalcohol.
FourthgenerationCefepimeisthefourthgenerationcephalosporincurrentlyavailable.Ithasapositively
chargedquaternaryammoniumattachedtothedihydrothiazonering,whichresultsinbetterpenetrationthroughthe
outermembraneofgramnegativebacteriaandaloweraffinitythanthethirdgenerationcephalosporinsforcertain
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chromosomalbetalactamasesofgramnegativebacilli.
Cefepimehassimilaractivitytocefotaximeandceftriaxoneagainstpneumococci(includingpenicillinintermediate
strains)andoxacillinsensitiveS.aureus.Liketheearlierthirdgenerationagents,itisactiveagainstthe
Enterobacteriaceae,Neisseria,andH.influenzaebuthasgreateractivityagainstthegramnegativeentericsthat
haveabroadspectrum,inducible,chromosomalAmpCbetalactamase(Enterobacter,indolepositiveProteus,
Citrobacter,andSerratia)[19].Theroleofcefepimeintherapyofinfectionsduetostablyderepressedmutantsof
theseorganismshasnotyetbeenfullydefined,butpreliminarydatasuggestthatitmaybeeffective[20,21].Ina
studyof96patientswithinfectionsduetolaboratoryconfirmedAmpCbetalactamaseproducingorganisms,96
percentoftheisolatesweresusceptibletocefepime[20].Amongpatientswhoreceivedcefepime,the30day
mortalityrateanddurationofhospitalizationweresimilartothoseobservedinamatchedsubsetofpatientswho
receivedmeropenem.
CefepimeisasactiveasceftazidimeforPseudomonasaeruginosa,andisactiveagainstsomeceftazidime
resistantisolates.Aswiththeantipseudomonalpenicillins,cefepimeshouldgenerallybegivenincombination
withanaminoglycosidefortreatmentofseriousP.aeruginosainfection.Therehasnotbeenenoughclinical
experiencewithcefepimeinmeningitistorecommenditsroutineuseforthispurpose.Itisalsonotcurrently
recommendedforprophylacticuseinsurgery.Acinetobacterisolatesarefrequentlyresistanttocefepime.
Despitethesepotentialadvantagesoverthirdgenerationcephalosporins,especiallyagainstorganismswith
inducible,chromosomalresistance,comparativetrialsofthirdandfourthgenerationcephalosporinshavenotyet
beenperformed.
AreviewbytheUnitedStatesFoodandDrugAdministration(FDA)ofcefepimesafetydatawasinitiatedin2007
followingfindingsofametaanalysisthatraisedconcernregardingincreasedallcausemortalityassociatedwith
cefepimeuse(riskratio1.26,95%CI1.081.49)[22].TheFDAreviewedthesestudydata,conductedadditional
analysesbasedonotherdata,anddeterminedthatthedatadonotindicateahigherrateofdeathincefepime
treatedpatients[23].Cefepimeremainsanappropriatetherapyforitsapprovedindications[24].
Treatmentwithcefepimemaybecomplicatedbysuperinfection(particularlywithenterococciorCandida)[15].
Cefepimeusealsocarriesariskofseizures(specificallynonconvulsivestatusepilepticus),particularlyinpatients
withrenalfailureforwhomthedoseisnotappropriatelyadjusteddownwards[25].(See"Betalactamantibiotics:
Mechanismsofactionandresistanceandadverseeffects",sectionon'Neurologicreactions'.)
FifthgenerationCeftarolineisafifthgenerationcephalosporinwhoseactivemetabolitehasaspectrumof
invitroactivitysimilartoceftriaxonebutwithimprovedgrampositiveactivity.Inparticular,ceftarolinehashigher
affinityforPBP2ainoxacillinresistantstaphylococci,andhasactivityagainstMRSA,aswellasvancomycin
intermediateStaphylococcusaureus(VISA)andheteroVISA.Inaddition,ceftarolinehasactivityfor
Streptococcuspneumoniaethatisintermediateorresistanttopenicillinorceftriaxone.Ceftarolineisnotactivefor
enterococcinoragainstAmpCoverproducingorESBLproducingEnterobacteriaceae,Pseudomonasaeruginosa,
Acinetobacterbaumannii,orBacteroidesfragilis.Severalrandomized,doubleblindcontrolledclinicaltrialshave
suggestedthatceftarolineisnoninferiortovancomycinplusaztreonamfortreatmentofcomplicatedskinandsoft
tissueinfectionsincludingthoseduetoMRSA,andtoceftriaxonefortherapyofcommunityacquiredpneumonia
[2628].TheefficacyofthisantiMRSAcephalosporinisnotyetknownforhospitalacquiredMRSApneumoniaor
forbacteremia.(See"Antibioticstudiesforthetreatmentofcommunityacquiredpneumoniainadults",sectionon
'Ceftarolineversusceftriaxone'and"Pharmacologyofantimicrobialagentsfortreatmentofmethicillinresistant
Staphylococcusaureusandvancomycinresistantenterococcus",sectionon'Ceftaroline'.)
Ceftobiproleisaninvestigationalcephalosporinalsocapableofbindingtopenicillinbindingprotein2a,theprotein
conferringS.aureusresistancetobetalactamantibiotics[29].Itcanalsobindpenicillinbindingprotein2xin
penicillinresistantS.pneumoniae.Ithasinvitroactivitysimilartothatofceftazidimeorcefepimeagainst
Enterobacteriaceaeitalsohasactivityagainstenterococci[30,31].Inaddition,ceftobiproleappearstohavealow
potentialforselectionofresistance[32].
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ClinicaltrialdataontheseagentsforuseinMRSAinfectionsaredetailedseparately.(See"Treatmentofinvasive
methicillinresistantStaphylococcusaureusinfectionsinadults",sectionon'Ceftobiprole'and"Treatmentof
invasivemethicillinresistantStaphylococcusaureusinfectionsinadults",sectionon'Ceftaroline'.)
OralagentsCephalosporinsavailablefororaluseincludecephalexin,cefadroxil,cefaclor,cefuroximeaxetil,
cefprozil,cefixime,cefpodoximeproxetil,ceftibuten,cefdinir,andcefditoren.
Cefadroxilhasalongerserumhalflifethancephalexinandisgenerallygiveninadoseof500to1000mgevery12
hours.Theoralcephalosporinsarepoorlyactiveagainstpenicillinresistantpneumococci[2].
Theoralsecondgenerationcephalosporins,cefaclor,cefuroximeaxetil,andcefprozil,haveimprovedactivity
againstH.influenzaecomparedwiththefirstgenerationoralcephalosporinsandmaybeusefulintreatingotitis,
sinusitis,andrespiratorytractinfections.
Theoralthirdgenerationcephalosporins,cefixime,cefpodoximeproxetil,ceftibuten,cefdinir,andcefditoren,are
activeagainststreptococci,H.influenzae(includingbetalactamaseproducingstrains),andM.catarrhalis.They
aremoreactivethantheotheroralcephalosporinsagainstentericgramnegativebacilli,includingE.coli,P.
mirabilis,andKlebsiella.However,theyhavepooractivityagainstmoststrainsofEnterobacter,Acinetobacter,P.
aeruginosa,andtheanaerobes.Cefiximeandceftibutenhavelittleactivityagainststaphylococci,butcefpodoxime
proxetilandcefdinirhavemoreactivity.Ceftibutenisalsoonlyweaklyactiveagainstpneumococci.Itsspectrum
ofactivityisotherwisesimilartothoseofcefdinirandcefpodoxime.
Theseantibioticsarerelativelystabletomanyplasmidmediatedbetalactamasesbutaremuchlessstableto
commonchromosomallymediatedcephalosporinases.Althoughtheseantibioticsarepromotedasoralthird
generationcephalosporins,theyarelessactiveagainsttheentericgramnegativebacillithantheparenteralthirdor
fourthgenerationcephalosporins.Theseantibioticsarerecommendedastherapyforotitismedia,upperandlower
respiratorytractinfections,andurinarytractinfections(cefixime,cefpodoxime,andcefdinir).Theseindicationsare
sharedwiththeoralsecondgenerationcephalosporins,amoxicillinclavulanate,andtrimethoprim
sulfamethoxazole.Cefiximeandceftibutenhavelittleornoactivityagainststaphylococciincontrasttosomeof
theseotheragents.
PHARMACOLOGYManyoftheavailableparenteralcephalosporinshaveshortserumhalflives(generallyone
hourorless)andshouldbeadministeredonaneveryfourhourbasiswhentreatingserioussystemicinfectionsin
patientswithnormalrenalfunction(table1).Certaincephalosporinshavelongerserumhalflivesandmaybe
dosedlessfrequently(eg,cefazolinQ8handceftriaxoneQ24h).Allofthecephalosporinsexceptcefoperazone
andceftriaxonerequiredosemodificationinthepresenceofsevererenalfailure(table1).
Allofthecephalosporinsachievetherapeuticlevelsinpleural,pericardial,peritoneal,andsynovialfluids,andurine.
Biliaryconcentrationsexceedserumlevels(intheabsenceofobstruction)andareparticularlyhighforcefazolin,
cefoperazone,andceftriaxone.
Firstandsecondgenerationcephalosporins(exceptcefuroxime)penetratethecerebrospinalfluid(CSF)barrier
poorlyandshouldnotbeusedtotreatinfectionsofthecentralnervoussystem.Thethirdgeneration
cephalosporinsachievemuchmorereliableCSFlevelsinpatientswithmeningealirritation.PeakCSF
concentrationsofseveralcephalosporinsgivenatmeningealdosesareshowninthetable(table2).Cefotaxime,
ceftriaxone,andceftazidimeareapprovedforthetreatmentofbacterialmeningitis.
Fatalreactionsduetocalciumceftriaxoneprecipitatesinthelungsandkidneysofneonateshavebeenreported.
Ceftriaxoneshouldnotbereconstitutedormixedwithacalciumcontainingproduct(eg,Ringer'sorHartmann's
solutionorparenteralnutrition).Inaddition,ceftriaxoneshouldbeavoidedininfantsaged28daysiftheyare
receivingorexpectedtoreceiveintravenouscalciumcontainingproducts.However,ceftriaxoneandcalcium
containingproductsmaybeusedconcomitantlyinpatientsaged>28days,providedthattheinfusionlinesare
thoroughlyflushedbetweeninfusions[33].
SUMMARY
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Firstgenerationcephalosporins,includingcefazolin,areactiveagainstmostgrampositivecocciexceptfor
enterococci,oxacillinresistantstaphylococci,andpenicillinresistantpneumococci.Theyarealsoactive
againstmoststrainsofEscherichiacoli,Proteusmirabilis,andKlebsiellapneumoniae.(See'Firstgeneration'
above.)
Thesecondgenerationcephalosporinsincludetwosubgroups.Onesubgrouphasactivityagainst
HaemophilusinfluenzaeandMoraxellacatarrhalis.Theothersubgroupconsistsofthecephamycins,which
areactiveagainstmanystrainsofBacteroides.(See'Secondgeneration'above.)
Thirdgenerationcephalosporinshavelessactivityagainstmostgrampositiveorganismsthanfirstgeneration
agentsbutarehighlyactiveagainstEnterobacteriaceae,Neisseria,andH.influenzae.Ceftazidimeand
cefoperazonearealsoactiveagainstPseudomonasaeruginosa.Thefourthgenerationcefepimehassimilar
activityasthethirdgenerationcephalosporins,includingagainstP.aeruginosa,withtheadditionofgreater
activityagainstentericgramnegativerodsthathaveaninduciblechromosomalbetalactamase.(See'Third
generation'aboveand'Fourthgeneration'above.)
Thefifthgenerationcephalosporinshaveactivityagainstoxacillinresistantstaphylococci,penicillinresistant
pneumococci,andentericgramnegativerods.(See'Fifthgeneration'above.)
Oralcephalosporinsarealsodividedintodifferentgenerationsandtheirspectraofactivitygenerallymirror
thoseparenteralagentsofthecorrespondinggeneration.However,oralthirdgenerationdrugsarelessactive
againstentericgramnegativebacteriathantheparenteralthirdgenerationcephalosporins.Secondandthird
generationoralcephalosporinshavesimilarindications,namelyotitismedia,respiratorytractinfections,and
urinarytractinfections.(See'Oralagents'above.)
Manyoftheavailableparenteralcephalosporinshaveshortserumhalflivesandrequirefrequent
administration.Allofthecephalosporinsexceptcefoperazoneandceftriaxonerequiredosemodificationin
thepresenceofsevererenalfailure(table1).(See'Pharmacology'above.)
Allofthecephalosporinsachievetherapeuticlevelsinpleural,pericardial,peritoneal,andsynovialfluids,and
urine.Firstandsecondgenerationcephalosporinsenterintocerebrospinalfluidpoorly.Thirdgeneration
cephalosporinsachievemorereliablecerebrospinalfluidlevelsinpatientswithmeningealirritation.(See
'Pharmacology'above.)
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adjustmentsforkidneyimpairment,June26,2012.http://www.fda.gov/Drugs/DrugSafety/ucm309661.htm
(AccessedonJune27,2012).
26. CoreyGR,WilcoxM,TalbotGH,etal.IntegratedanalysisofCANVAS1and2:phase3,multicenter,
randomized,doubleblindstudiestoevaluatethesafetyandefficacyofceftarolineversusvancomycinplus
aztreonamincomplicatedskinandskinstructureinfection.ClinInfectDis201051:641.
27. FileTMJr,LowDE,EckburgPB,etal.IntegratedanalysisofFOCUS1andFOCUS2:randomized,
doubledblinded,multicenterphase3trialsoftheefficacyandsafetyofceftarolinefosamilversus
ceftriaxoneinpatientswithcommunityacquiredpneumonia.ClinInfectDis201051:1395.
28. FileTMJr,WilcoxMH,SteinGE.Summaryofceftarolinefosamilclinicaltrialstudiesandclinicalsafety.
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30. BushK,HeepM,MacielagMJ,NoelGJ.AntiMRSAbetalactamsindevelopment,withafocuson
ceftobiprole:thefirstantiMRSAbetalactamtodemonstrateclinicalefficacy.ExpertOpinInvestigDrugs
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broadspectrumcephalosporin.AntimicrobAgentsChemother200549:4210.
33. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafety
InformationforHeathcareProfessionals/ucm084263.htm(AccessedonJune08,2009).
Topic480Version15.0

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GRAPHICS
Doseofparenteralcephalosporinswithadjustmentsforrenalfailure
Glomerularfiltrationrate(GFR)mL/min*
Drug

>50(normalrenal
function)

1050

<10

Removalby
dialysis

Cefazolin

12gQ8h

0.51gQ12h

0.51gQ24h

Yes(HD),No(PD)

Cefuroxime

0.751.5gQ68h

0.751.5gQ

0.75gQ24h

Yes(HD,PD)

812h
Cefoxitin

12gQ46h

12gQ812h

0.51gQ24h

Yes(HD),No(PD)

Cefotetan

12gQ12h

12gQ24h

12gQ48h

Yes(HD)

Cefotaxime

12gQ6h

12gQ812h

12gQ1224
h

Yes(HD),No(PD)

Ceftizoxime

12gQ68h

0.251gQ8
12h

0.251gQ24
h

Yes(HD),No(PD)

Ceftriaxone

12gQ1224h

NC

NC

No(HD)

Ceftazidime

12gQ8h

12gQ1224

0.51gQ24

Yes(HD,PD)

48h

Cefepime

12gQ812h

0.52gQ12
24h

0.251gQ24
h

Yes(HD)

Ceftaroline

600mgQ12h

300400mgQ
12h

200400mgQ
12h

Yes(HD)

HD:hemodialysisPD:peritonealdialysisNC:nochange.
*Usualadultdosingandrenaladjustmentsshownareformoderatetosevereinfections.Forspecific
dosingrecommendations,seerelateddiseasetreatmenttopicsandLexiCompdruginformationincluded
withUpToDate.
NotavailableintheUnitedStatesorCanada.
1hourinfusion.
Graphic58411Version7.0

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PeakCSFconcentrationsofcephalosporinsinbacterialmeningitis
Cephalothin

0.160.31g/mL

Cefoxitin

<1.5612.5g/mL

Cefuroxime

4.39.3g/mL

Cefotaxime

6.827.2g/mL

Ceftriaxone

242g/mL

Ceftazidime

2.530g/mL

Graphic62934Version3.0

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Disclosures
Disclosures:StephenBCalderwood,MDConsultant/AdvisoryBoards:Pulmatrix[Inhaledantimicrobial
products(Notcurrentlyreleased)].PatentHolder:VaccineTechnologies[Cholera(Choleravaccines)].
EquityOwnership/StockOptions:PharmAthene[Biodefense(Anthrax)].DavidCHooper,MD
Consultant/AdvisoryBoards:Bacterioscan[Urinediagnostics]Cepheid[Rapiddiagnostics
(GeneExpert)]FabPharma[Antibacterials]Cubist[Antibacterials(Daptomycin)].AllysonBloom,MD
EmployeeofUpToDate,Inc.
Contributordisclosuresarereviewedforconflictsofinterestbytheeditorialgroup.Whenfound,theseare
addressedbyvettingthroughamultilevelreviewprocess,andthroughrequirementsforreferencestobe
providedtosupportthecontent.Appropriatelyreferencedcontentisrequiredofallauthorsandmust
conformtoUpToDatestandardsofevidence.
Conflictofinterestpolicy

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