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OfficialreprintfromUpToDate
www.uptodate.com2016UpToDate

Cephalosporins
Author
StephenBCalderwood,MD

SectionEditor
DavidCHooper,MD

DeputyEditor
AllysonBloom,MD

Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.
Literaturereviewcurrentthrough:Feb2016.|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
astheprototypeofthisgroup.Cephalothinwasactiveagainstmostgrampositivecocci(includingpenicillinase
producingstaphylococci),butdidnothaveclinicallyusefulactivityagainstenterococci,Listeria,oxacillinresistant
staphylococci[1],orpenicillinresistantpneumococci[24].(See"MethicillinresistantStaphylococcusaureus
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(MRSA):Microbiology"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.
Thirdgenerationcephalosporinsmayalsobeusefulalternativestotheaminoglycosidesintreatinggramnegative
infectionsresistanttootherbetalactams,particularlyinthepatientwithrenaldysfunction.However,mutantsof
Enterobacter,indolepositiveProteus,Serratia,andCitrobacter,withstablederepressionofthechromosomalbeta
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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.Cefoperazonewasthefirstavailabledruginthis
subgroup,butiscurrentlynotusedasoftenduetodecreasedstabilitytotheplasmidmediatedbetalactamasesof
gramnegativebacillithatmakeitlessactiveagainstEnterobacteriaceaethantheotherthirdgeneration
cephalosporins.Thenewermemberofthesubgroup,ceftazidime,isquitestabletothecommonplasmidmediated
betalactamasesandishighlyactiveagainstEnterobacteriaceae,Neisseria,andH.influenzae.Ceftazidimeis
alsoparticularlyactiveagainstP.aeruginosaandisaneffectivetherapyforseriousinfectionsduetoP.aeruginosa
whentheorganismisresistanttotheantipseudomonalpenicillinsorthepatientispenicillinallergic.Inaddition,it
iseffectivetherapyformeningitiscausedbyP.aeruginosa.Aswiththeantipseudomonalpenicillins,however,
ceftazidimeshouldgenerallybegivenatleastinitiallyincombinationwithanaminoglycosidefortreatmentof
seriousP.aeruginosainfection.Ceftazidimehaspooractivityagainstgrampositiveorganismsandshouldbe
reservedforuseininfectionsprovenorhighlysuspectedtobeduetoP.aeruginosa.
CefoperazonecontainsanNmethylthiotetrazole(NMTT)sidechain.ThisNMTTgroupcandissociatefromthe
parentantibioticinsolutionorinvivoandcompetitivelyinhibitvitaminKaction,leadingtoprolongationofthe
prothrombintimeandbleeding[18].Thissidechainisalsoassociatedwithadisulfiramlikereactiontoalcohol.
FourthgenerationCefepimeisthefourthgenerationcephalosporincurrentlyavailable.Ithasapositively
chargedquaternaryammoniumattachedtothedihydrothiazonering,whichresultsinbetterpenetrationthroughthe
outermembraneofgramnegativebacteriaandaloweraffinitythanthethirdgenerationcephalosporinsforcertain
chromosomalbetalactamasesofgramnegativebacilli.
Cefepimehassimilaractivitytocefotaximeandceftriaxoneagainstpneumococci(includingpenicillinintermediate
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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].
ClinicaltrialdataontheseagentsforuseinMRSAinfectionsaredetailedseparately.(See"Methicillinresistant
Staphylococcusaureus(MRSA)inadults:Treatmentofbacteremiaandosteomyelitis",sectionon'Ceftobiprole'
and"MethicillinresistantStaphylococcusaureus(MRSA)inadults:Treatmentofbacteremiaandosteomyelitis",
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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
Firstgenerationcephalosporins,includingcefazolin,areactiveagainstmostgrampositivecocciexceptfor
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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.)
UseofUpToDateissubjecttotheSubscriptionandLicenseAgreement.
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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.
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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(normal
renalfunction)

1050

<10

Removalby
dialysis

Cefazolin

12gQ8h

0.51gQ12h

0.51gQ24h

Yes(HD),No(PD)

Cefuroxime

0.751.5gQ68

0.751.5gQ8

0.75gQ24h

Yes(HD,PD)

12h

Cefoxitin

12gQ46h

12gQ812h

0.51gQ24h

Yes(HD),No(PD)

Cefotetan

12gQ12h

12gQ24h

12gQ48h

Yes(HD)

Cefotaxime

12gQ6h

12gQ812h

12gQ1224h

Yes(HD),No(PD)

Ceftizoxime

12gQ68h

0.251gQ812
h

0.251gQ24h

Yes(HD),No(PD)

Ceftriaxone

12gQ1224h

NC

NC

No(HD)

Ceftazidime

12gQ8h

12gQ1224h

0.51gQ2448
h

Yes(HD,PD)

Cefepime

12gQ812h

0.52gQ1224

0.251gQ24h

Yes(HD)

200400mgQ
12h

Yes(HD)

h
Ceftaroline

600mgQ12h

300400mgQ
12h

HD:hemodialysisPD:peritonealdialysisNC:nochange.
*Usualadultdosingandrenaladjustmentsshownareformoderatetosevereinfections.Forspecific
dosingrecommendations,seerelateddiseasetreatmenttopicsandLexiCompdruginformationincluded
withUpToDate.
NotavailableintheUnitedStatesorCanada.
1hourinfusion.
Graphic58411Version8.0

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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,MDPatentHolder:VaccineTechnologiesInc[Vaccines(Choleravaccines)].Equity
Ownership/StockOptions:Pulmatrix[Infectiousdiseases(Inhaledantimicrobials)]PharmAthene[Anthrax(Antibodytherapies)].DavidC
Hooper,MDNothingtodisclose.AllysonBloom,MDNothingtodisclose.
Contributordisclosuresarereviewedforconflictsofinterestbytheeditorialgroup.Whenfound,theseareaddressedbyvettingthrougha
multilevelreviewprocess,andthroughrequirementsforreferencestobeprovidedtosupportthecontent.Appropriatelyreferenced
contentisrequiredofallauthorsandmustconformtoUpToDatestandardsofevidence.
Conflictofinterestpolicy

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