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Tetracycline S
Tetracycline S
OfficialreprintfromUpToDate
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Tetracyclines
Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.
Literaturereviewcurrentthrough:Sep2015.|Thistopiclastupdated:Jul23,2014.
INTRODUCTIONChlortetracyclinewasthefirsttetracyclinediscovered,in1948.Sincethenfiveadditional
tetracyclineshavebeenisolatedorderived(oxytetracycline,tetracycline,demeclocycline,doxycyclineand
minocycline),butonlythelastfourareavailableforsystemicuseintheUnitedStates.Ofthesefouragents,
doxycyclineandminocyclinearethemostfrequentlyprescribed.Researchtofindtetracyclineanalogueslead
tothedevelopmentoftheglycylcyclines.Tigecyclineisthefirstofthisnewclassofagentsandexhibitsbroad
spectrumantibacterialactivitysimilartothetetracyclines[1].
Doxycyclineisoneofthemostactivetetracyclinesandisthemostoftenusedclinicallysinceitpossesses
manyadvantagesovertraditionaltetracyclineandminocycline.Doxycyclinecanbeadministeredtwicedaily,
hasbothintravenous(IV)andoral(PO)formulations,achievesreasonableconcentrationsevenifadministered
withfood,andislesslikelytocausephotosensitivity[2].Doxycyclinemaybeanalternativeforuseinchildren
sinceitbindscalciumtoalesserextentthantetracycline,whichcancausetoothdiscolorationandbony
growthretardation.
MECHANISMOFACTIONThetetracyclinesenterthebacterialcellwallintwoways:passivediffusion
andanenergydependentactivetransportsystem,whichisprobablymediatedinapHdependentfashion.
Onceinsidethecell,tetracyclinesbindreversiblytothe30Sribosomalsubunitatapositionthatblocksthe
bindingoftheaminoacyltRNAtotheacceptorsiteonthemRNAribosomecomplex.Proteinsynthesisis
ultimatelyinhibited,leadingtoabacteriostaticeffect[3].
RESISTANCEIncontrasttomanyotherantibiotics,tetracyclinesareinfrequentlyinactivatedbiologicallyor
alteredchemicallybyresistantbacteria.Resistancetotheseagentsdevelopsprimarilybypreventing
accumulationofthedruginsidethecelleitherbydecreasinginfluxorincreasingefflux.Onceresistance
developstooneofthedrugsinthisclass,itistypicallyconferredtoalltetracyclines.
However,therearedifferencesinresistanceamongspeciesofbacteria.Resistancegenestotetracyclines
oftenoccuronplasmidsorothertransferableelementssuchastransposons[4].Bacteriacarryingaribosome
protectiontypeofresistancegeneproduceacytoplasmicproteinthatinteractswiththeribosomesandallows
theribosomestoproceedwithproteinsynthesiseveninthepresenceofhighintracellularlevelsofthedrug
[4,5].
Tigecyclinehasareducedpotentialforresistance,asitisnotaffectedbythetwomajormechanismsof
tetracyclineresistance:ribosomalprotectionproteinsandeffluxpumps[6].Thus,tigecyclinemayhaveactivity
againsttetracyclineresistantorganisms[7,8].
SPECTRUMOFACTIVITYTheantimicrobialactivityofallthetetracyclinesisessentiallythesame
althoughsomedifferencesintherelativedegreeofactivityagainstcertainpathogensdoexistamongthe
variousagents(table1).Asanexample,minocyclineappearstobethemostactiveofthecompoundsdueto
itsslightincreaseinlipidsolubility.Doxycyclinefollowscloselybehind.
Thetetracyclinesareconsideredbroadspectrumbacteriostaticantibioticsthatareusedtotreatinfection
causedbymanyaerobicgrampositiveandgramnegativebacteria.However,theyalsohaveactivityagainst
manyatypicalpathogens,includingRickettsiaspp.,Borreliaspp.,Coxiellaburnetii,Treponemaspp.,
Chlamydiaspp.,Mycoplasmapneumoniae,Plasmodiumspp.,Vibriocholerae,Vibriovulnificus,Brucellaspp.,
Calymmatobacteriumgranulomatis,Leptospira,Borreliaburgdorferi,Borreliarecurrentis,Burkholderia
pseudomallei,Mycobacteriummarinum,andEntamoebahistolytica.Thesedrugshavelittleactivityagainst
fungiandviruses[9].
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AgainstN.gonorrhoeae,the2006GonococcalIsolateSurveillanceProject(GISP)reportshowsthat25.6
percentofisolatescollectedin2006wereresistanttopenicillin,tetracycline,ciprofloxacin,orsome
combinationofthoseantibiotics[10].Therefore,useoftetracyclinesforthetreatmentofN.gonorrhoeaeinthe
USisNOTrecommendedbytheCDC.
DoxycyclineiseffectiveforpatientswithnongonococcalurethritiscausedbyChlamydiatrachomatishowever,
recurrenturethritisinpatientspreviouslytreatedwithdoxycyclinemaybetheresultoftetracyclineresistantU.
urealyticum.DoxycyclineisanalternativeagentinthetreatmentofgenitalChlamydialinfections[11].
Tigecyclinehasabroaderspectrumofactivitywhencomparedtothetetracyclines.Tigecyclinehasactivity
againstgrampositivepathogensincluding:Enterococcusspp.,vancomycinresistantenterococci(VRE),
Listeria,Streptococcusspp.,bothmethicillinsusceptibleandresistantS.aureus,andS.epidermidis.Its
gramnegativeactivityincludes:Acinetobacterbaumannii,Citrobacterspp.,Enterobacterspp.,Escherichia
coli,Klebsiellaspp.,Pasteurellamultocida,Serratiamarcescens,andStenotrophomonasmaltophilia[6,7].
PHARMACODYNAMICS/PHARMACOKINETICSInanimalstudies,the
pharmacokinetic/pharmacodynamicparameterthatmostcloselycorrelateswiththeefficacyoftetracyclinesis
the24hourratiooftheareaundertheconcentrationversustimecurve(AUC)totheminimuminhibitory
concentration(MIC).AfterexposureofStaphylococcusaureustothetetracyclinesatfivetimestheMICfor
twohours,apostantibioticeffectlastingforthreehourshasbeenobserved[12].
CombinationoftetracyclinesandpenicillinsAdeleteriouseffectwasobservedforthecombinationofa
staticandcidalantibioticwhenchlortetracyclineandpenicillinwereusedtogetherforthetreatmentof
pneumococcalmeningitis.Thecombinationofthetwodrugswasinferiortopenicillinalone.Tetracycline
administeredwithampicillinoramoxicillinmayresultindiminishedbactericidalactivityofthepenicillin.Thus,
combinationsoftetracyclinesandpenicillinsshouldbeavoided,ifpossible.
AbsorptionofthetetracyclinesAbsorptionoftetracyclinesoccursprimarilyintheproximalsmallintestine
andthestomach.Thebioavailabilityoforaldoxycyclineapproaches95percent(withorwithoutfood),with
peakserumconcentrationsseenonetothreehoursafterthedose.Bycontrast,thebioavailabilityoforal
tetracyclineisreducedby50percentifitistakenwithfood.Theabsorptionofalltetracyclinescanbe
decreasedwiththeconcomitantadministrationofmultivalentcations(ie,aluminum,calcium,iron,magnesium).
Thesecationschelatewiththetetracyclinesimpairingtheirabsorption.Concurrentadministrationofproducts
containingdivalentortrivalentcationsshouldbeavoidedwithalltetracyclineswiththepossibleexceptionof
doxycycline[13].
SerumconcentrationsThemaximumserumconcentrationafteranintravenousdoseofdoxycyclineoccurs
within30minutesaftertigecycline,withinonehour.Peakconcentrationsofdoxycyclinerangefrom1.5to2.5
mcg/mLafteradoseof200mgorallyand4to10mcg/mLforthesamedoseadministeredintravenously.
Doxycyclinehasanapparentvolumeofdistributionof50litersandis90percentproteinbound.
DistributionIngeneral,tetracyclinespenetrateintotissuesandbodyfluidsfairlywell.Amongthefollowing
agents,thedegreeoftissuepenetrationcorrelatestolipidsolubility:minocycline>doxycycline>
tetracycline[14].
Fordoxycycline,therapeuticconcentrationshavebeenfoundintheaqueoushumour,CSF(11to56percentof
serumconcentrations),peritonealfluid,tears,lungs,sinuses,digestiveandbiliarytracts,kidney,liver,and
prostate[1416].Doxycyclinealsodistributesintothebone,fat,andmuscleatconcentrationsbelowplasma
levels[15].
Tetracyclinedistributeswellintoasciticfluid,bile,CNS(10to26percent),sinuses,pleuralandsynovialfluid
[14].
Minocyclinehasbeenfoundintherapeuticconcentrationsintheaqueoushumor,bile,duodenum,fallopian
tubes/ovaries,liver,lung,sinuses,saliva,sputum,tears,andthyroidgland.Minocyclinedistributesinlower
concentrationstothebladder,breast,lymphnodes,prostate,andskin[14,15].
Tigecyclinedistributeswellintothebile,CSF,andlung.Animaldatademonstratethattigecyclinedistributes
wellintobone,bonemarrow,spleen,andthyroid[15,17].
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Inaddition,allthetetracyclinescrosstheplacentaandaccumulateintheboneandteethofthefetus.The
tetracyclinesarealsoexcretedinbreastmilk,althoughcomplexationwithcalciuminbreastmilklimits
availabilitytothebreastfedinfant[14].
RoutesofeliminationTheroutesofeliminationdifferamongthetetracyclines.Theprimaryrouteof
eliminationfortetracyclineisthekidneyviaglomerularfiltration.Doxycyclineisprimarilyeliminatedinthe
intestinaltract,withupto90percentofthedoseexcretedinthefeces.Approximately20percentofa
doxycyclinedoseiseliminatedbyglomerularfiltration.Tigecyclineiseliminatedthroughthefecesas
unchangeddrug.
Doseadjustmentisnotnecessaryfordoxycyclineortigecyclineinpatientswithrenaldysfunction,andthus,
thesearethepreferredtetracyclinesinthispopulation[13].Doseadjustmentisonlyrequiredinseverehepatic
dysfunctionfordoxycyclineandtigecycline(maintenancedose25mgIVevery12hours)[6].Minocyclineis
metabolizedinthelivertoatleastsixinactivemetabolites.Only4to9percentofminocyclineisexcretedvia
thekidneys,andfecalconcentrationsarealsominimal.Noaccumulationofminocyclineisseenwithhepatic
failure.Similartodoxycycline,foodhaslittleeffectontheabsorptionofminocycline.Thetetracyclinesare
minimallyremovedbyhemodialysis,peritonealdialysis,orhemofiltrationtherefore,doseadjustmentsarenot
necessaryinthesesituations[13].
SPECIALPOPULATIONS
PregnantorbreastfeedingwomenTetracyclinescancausefetaltoxicitywhengiventopregnantwomen.
Forcertaininfections,thepotentialrisksmaybeoffsetbythebenefits.However,tetracyclinesshould
generallynotbeusedinpregnantwomenorchildrenundertheageofeightyearsunlessotherappropriate
drugsareineffectiveorcontraindicated.
Tetracyclinescrosstheplacentaandachieveconcentrationsinumbilicalcordplasmaandamnioticfluidof60
and20percent,respectively,oflevelsinthematernalcirculation.Thiscancauseaccumulationinfetalbone
andteeth.Tetracyclinesarefoundinhighconcentrationsinhumanbreastmilk,butconcentrationsareverylow
inbreastfedinfants,whichisprobablyareflectionofchelationbycalciuminbreastmilk[13].
RenalfailureTheseagents,withthepossibleexceptionofdoxycyclineandtigecycline,shouldgenerally
notbeusedinpatientswithendstagerenaldisease(table2)[2].
ADVERSEREACTIONSTetracyclinesaregenerallysafedrugs,butsomeadverseeffectscanoccur.
Thefollowingprovidesabriefsummaryofsomeofthemajoradverseeffectsassociatedwithtetracyclines.
Theseissuesarediscussedindetailseparately.SeeTetracyclinedruginformation,Doxycyclinedrug
information,Minocyclinedruginformation,Tigecyclinedruginformation,andDemeclocyclinedruginformation.
GastrointestinalDoserelatedgastrointestinalsideeffectsarethemostcommoncomplaintinpatients
takingoraltetracyclinesandintravenoustigecycline[1].Theseincludeabdominaldiscomfort,epigastricpain,
nausea,vomitingandanorexia.Foodmaydecreasethesesymptomsbutalsomaydecreasetheabsorptionof
tetracyclineby50percent.Fooddoesnotaffecttheabsorptionofdoxycycline.
Tetracyclinesmayaltergutfloratocauselargebulkystoolsanddiarrhea.Diarrheausuallysubsidesoncethe
agentisstopped.Apatientwithcontinueddiarrhea,fever,andarisingwhitebloodcountshouldbeevaluated
forantibioticassociateddiarrheacausedbyClostridiumdifficile.Esophagealulcerationsandstrictureshave
beenreportedwithtetracyclinesbutcanbepreventedbytakingthedrugswithplentyofwaterandnotbefore
bedtime.(See"Clostridiumdifficileinfectioninadults:Clinicalmanifestationsanddiagnosis".)
AllergicandskinreactionsHypersensitivityreactionscanoccurwithtetracyclinesbutareuncommon.Ifa
patientisallergictoonetetracycline,theyshouldbeconsideredallergictoall.Photosensitivityreactionscan
occur,rangingfromaredrashtoblisteringonareasexposedtothesun.Thesereactionsaremostcommon
withdemeclocyclinebutcanoccurwithallanalogues.Photosensitivitycanbedecreasedbyavoidingdirect
sunlightorwearingprotectiveclothingwithsunscreen[2].
TeethandboneTetracyclinescancauseabrowntoyellowdiscolorationoftheteethinchildrenunderthe
ageofeightthatissometimesassociatedwithhypoplasiaoftheenamel.Thedarkeningeffectonthe
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permanentteethappearstobedoserelatedanddoesnotoccurinadults.Theseagentsgenerallyshouldbe
avoidedinchildrenundertheageofeighthoweveriftheymustbeused,doxycyclinemaybethepreferred
agent.Tetracyclinesmayalsodepositinthebonelikelyduetochelateformationwithcalcium,thusadding
anotherreasontoavoidtheseagentsinchildrenwithdevelopingboneformation[2].
LiverandrenalHepatotoxicitywithtetracyclinesisrarebutcanbefatal.Thisoccursmorecommonlywith
tetracyclineandminocyclineandlessoftenwithdoxycycline[18].
Tetracyclinesinhibitproteinsynthesisandmayexacerbatepreexistingrenalfailurebyincreasingtheazotemia
fromaminoacidmetabolism.Demeclocyclinecancauseanephrogenicdiabetesinsipidus,asideeffectthatis
usedtherapeuticallytotreatthesyndromeofinappropriateantidiuretichormonesecretion(SIADH).Theuseof
outdatedtetracyclineshasbeenassociatedwithareversibleFanconilikesyndromeandrenaltubularacidosis
however,currentformulations,whichdonotcontaincitricacidasanexcipient,havevirtuallyeliminatedthis
possibility[2].(See"Treatmentofhyponatremia:Syndromeofinappropriateantidiuretichormonesecretion
(SIADH)andresetosmostat".)
MortalityTigecyclinehasbeenassociatedwithincreasedmortalitywhencomparedwithotherantibacterial
drugs.InSeptember2010,theUSFoodandDrugAdministration(FDA)issuedasafetyannouncement
regardingincreasedmortalitywiththeuseoftigecyclineinpatientswithhospitalacquiredpneumonia(HAP)
[19].A2013analysisof10clinicaltrialsshowedanincreasedriskofdeathinpatientsreceivingtigecyclinefor
FDAapproveduses,includingcommunityacquiredbacterialpneumonia,complicatedskinandskinstructure
infections,andcomplicatedintraabdominalinfections(2.5versus1.8percent,adjustedriskdifference0.6
percent)[2].TheFDAhassubsequentlyaddedaboxedwarningstatingthattigecyclineshouldbereservedfor
useinsituationswhenalternativeagentsarenotsuitable[20].(See"Treatmentofcommunityacquired
pneumoniainadultswhorequirehospitalization",sectionon'Tigecycline'and"Treatmentofhospitalacquired,
ventilatorassociated,andhealthcareassociatedpneumoniainadults",sectionon'Otheragents'.)
MiscellaneousAJarischHerxheimertypereaction(JHR)hasoccurredinpatientsbeingtreatedfor
spirochetalinfections.Effectsincludefever,chills,headache,malaise,muscleaches,leukocytosis,and
exacerbationofcutaneouslesions.TheJHRoccursin75to80percentofthosetreatedforsyphilis,54percent
ofthosetreatedfortickbornerelapsingfever,and82percentofthosetreatedforlousebornerelapsingfever.
PreventionoftheJHRinpatientsisoflimitedvaluethebestresultsarewiththeuseoftumornecrosisfactor
(TNF)antibodiesandsteroids.Pretreatmentwithacetaminophenormeptazinolmayreducethesymptomsand
duration[21].
Vertigohasbeenassociatedwithminocyclineandappearstobedoserelated.Morecommoninwomenthan
men,thismayappearduringthesecondorthirddayoftherapyandusuallyresolvesinonetotwodaysafter
discontinuingthedrug.Complaintsconsistofdizziness,ataxia,nausea,vomiting,andtinnitus.
Hematologiceffectsareveryuncommonbutmayincludehemolyticanemia,thrombocytopenia,neutropenia,
andeosinophilia.Other,lesscommonreactions,includeminocyclineinducedlupus[2224]andpericardial
effusions[25].
Nauseaandvomitinghavebeenreportedwithincreasedfrequencywithtigecycline(30and20percent)
comparedtotetracyclines[6].
DRUGINTERACTIONSTheabsorptionoftetracyclinescanbeimpairedbycoadministeredmineralsand
antacids(eg,calcium,magnesium,iron),lanthanum,anddairyincludingmilk.Tetracyclinescaninteractwith
oralisotretinoin,betalactams,andavarietyofotherdrugs.Specificdruginteractionsofthetetracyclinesand
managementsuggestionsmaybedeterminedbyusingLexiInteract,thedruginteractionsprogramincluded
withUpToDate.
SUMMARYANDRECOMMENDATIONS
Tetracyclinesinhibitbacterialproteinsynthesisbybindingreversiblytothe30Sribosomalsubunit.(See
'Mechanismofaction'above.)
Decreasedaccumulationofdrugwithinbacterialeadstoresistancedruguptakeisaffectedby
decreasinginfluxorincreasingefflux.(See'Resistance'above.)
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Thetetracyclinesareconsideredbroadspectrumbacteriostaticantibioticswithactivityagainstmany
aerobicgrampositiveandgramnegativebacteriaandatypicalpathogens,suchasmycoplasmaand
chlamydia.(See'Spectrumofactivity'above.)
Absorptionoftetracyclinesoccursprimarilyintheproximalsmallintestineandthestomachwithgood
distributionintotissuesandbodyfluids.(See'Pharmacodynamics/pharmacokinetics'above.)
Tetracyclinesshouldgenerallynotbeusedinpregnantwomenorchildrenundertheageofeightyears
unlessotherappropriatedrugsareineffectiveorcontraindicated.(See'Specialpopulations'above.)
Tetracyclinesaregenerallysafethemostcommonadverseeventsarerelatedtogastrointestinal
symptoms(eg,epigastricdiscomfortandnausea).(See'Adversereactions'above.)
UseofUpToDateissubjecttotheSubscriptionandLicenseAgreement.
REFERENCES
1. SteinGE,CraigWA.Tigecycline:acriticalanalysis.ClinInfectDis200643:518.
2. Perdue,BE,Standiford,HC.Tetracyclines.In:AntimicrobialTherapyandVaccines,Yu,VL,Merigan,
TC,Barriere,SL(Eds),WilliamsandWilkins,Baltimore1999.p.981.
3. SchnappingerD,HillenW.Tetracyclines:antibioticaction,uptake,andresistancemechanisms.Arch
Microbiol1996165:359.
4. SpeerBS,ShoemakerNB,SalyersAA.Bacterialresistancetotetracycline:mechanisms,transfer,and
clinicalsignificance.ClinMicrobiolRev19925:387.
5. RobertsMC.Tetracyclinetherapy:update.ClinInfectDis200336:462.
6. Tigecycline(tygacil).MedLettDrugsTher200547:73.
7. ZhanelGG,HomenuikK,NicholK,etal.Theglycylcyclines:acomparativereviewwiththe
tetracyclines.Drugs200464:63.
8. WyethantibioticTygacilapprovedforbroadspectrum,earlyuse."ThePinkSheet"200567:12.
9. KleinNC,CunhaBA.Tetracyclines.MedClinNorthAm199579:789.
10. CentersforDiseaseControlandPrevention.SexuallyTransmittedDiseaseSurveillance,2006.Atlanta,
GA:U.S.DepartmentofHealthandHumanServices,November2007.
11. CentersforDiseaseControlandPrevention(CDC).Nonfatal,unintentionalmedicationexposuresamong
youngchildrenUnitedStates,20012003.MMWRMorbMortalWklyRep200655:1.
12. CraigWA.Pharmacokinetic/pharmacodynamicparameters:rationaleforantibacterialdosingofmiceand
men.ClinInfectDis199826:1.
13. SaivinS,HouinG.Clinicalpharmacokineticsofdoxycyclineandminocycline.ClinPharmacokinet1988
15:355.
14. Mandell,GL,Bennett,JE,Dolin,R,etal.PrinciplesandPracticesofInfectiousDiseases,6thed,
ChurchillLivingstone,Philadelphia2005.
15. AgwuhKN,MacGowanA.Pharmacokineticsandpharmacodynamicsofthetetracyclinesincluding
glycylcyclines.JAntimicrobChemother200658:256.
16. YimCW,FlynnNM,FitzgeraldFT.Penetrationoforaldoxycyclineintothecerebrospinalfluidofpatients
withlatentorneurosyphilis.AntimicrobAgentsChemother198528:347.
17. MacGowanAP.Tigecyclinepharmacokinetic/pharmacodynamicupdate.JAntimicrobChemother2008
62Suppl1:i11.
18. HeatonPC,FenwickSR,BrewerDE.Associationbetweentetracyclineordoxycyclineand
hepatotoxicity:apopulationbasedcasecontrolstudy.JClinPharmTher200732:483.
19. USFoodandDrugAdministration(FDA).FDAdrugsafetycommunication:Increasedriskofdeathwith
Tygacil(tigecycline)comparedtootherantibioticsusedtotreatsimilarinfections.
http://www.fda.gov/Drugs/DrugSafety/ucm224370.htm(AccessedonSeptember02,2010).
20. USFoodandDrugAdministration(FDA).FDAdrugsafetycommunication:FDAwarnsofincreasedrisk
ofdeathwithIVantibacterialTygacil(tigecycline)andapprovesnewboxedwarning.
http://www.fda.gov/Drugs/DrugSafety/ucm369580.htm(AccessedonMay05,2015).
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21. PoundMW,MayDB.ProposedmechanismsandpreventativeoptionsofJarischHerxheimerreactions.
JClinPharmTher200530:291.
22. SchliengerRG,BircherAJ,MeierCR.Minocyclineinducedlupus.Asystematicreview.Dermatology
2000200:223.
23. ColmegnaI,PerandonesCE,ChavesJG.Minocyclineinducedlupusandautoimmunehepatitis.J
Rheumatol200027:1567.
24. LawsonTM,AmosN,BulgenD,WilliamsBD.Minocyclineinducedlupus:clinicalfeaturesandresponse
torechallenge.Rheumatology(Oxford)200140:329.
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Topic494Version8.0
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GRAPHICS
Spectrumofactivityofthetetracyclines
Pathogens/syndromes
Rickettsialinfections(doxycycline)
Chlamydialinfections(doxycycline)
Traveler'sdiarrhea(doxycycline)
EarlyLymedisease(doxycycline)
Chloroquineresistantmalaria(doxycycline)
Acne
Amebiasis
Actinomycosis
Brucellosis
Borreliarecurrentis
Legionnaire'sdisease
Leptospirosis
Mycobacteriummarinum
Melioidosis
Mycoplasmapneumoniae
Meningococcalprophylaxis(minocycline)
MRSA(minocyclineortigecycline)
Nocardiosis
Pelvicinflammatorydisease
Staphylococcusaureus(minocyclineortigecycline)
Syphilis
Tularemia
Vibriovulnificus
VRE(susceptiblestrains)
Whipple'sdisease
Graphic58190Version2.0
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Dosingandadministrationoftetracyclines
Drug
Doxycycline 100mgIV/POevery12hoursNoadjustmentinrenaldysfunction
Tetracycline 250500mgPOevery6hourswithnormalrenalfunction.
250500mgPOevery12to24hourswithCrCl1050mL/min.
NotrecommendedwhenCrCl<10mL/min
Minocycline 100mgPOevery12hoursNoadjustmentinrenaldysfunction
Demeclocycline 150300mgPOevery12to24hoursAvoiduseinrenaldysfunction
Tigecycline 100mginitialdosethen50mgIVevery12hoursNoadjustmentinrenal
dysfunction
Graphic80309Version2.0
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Disclosures
Disclosures:DByronMay,PharmD,BCPSNothingtodisclose.DavidCHooper,MDConsultant/AdvisoryBoards:Bacterioscan
[Antimicrobials(Urinediagnosticunderdevelopment)]Cubist[Antimicrobials(Daptomycin,fidaxomycin,tedizolid,ceftolozane
tazobactam)]Shionogi[Antimicrobials(Antigramnegativebetalactamunderdevelopment)]Melinta[Antimicrobials(Antimicrobials
underdevelopment)]Cepheid[Antimicrobials(rapidgeneticdiagnostics)]FabPharma[Antimicrobials(Antimicrobialunder
development)].JenniferMitty,MD,MPHNothingtodisclose.
Contributordisclosuresarereviewedforconflictsofinterestbytheeditorialgroup.Whenfound,theseareaddressedbyvetting
throughamultilevelreviewprocess,andthroughrequirementsforreferencestobeprovidedtosupportthecontent.Appropriately
referencedcontentisrequiredofallauthorsandmustconformtoUpToDatestandardsofevidence.
Conflictofinterestpolicy
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