Foundation Volume 3, Chapter 39, Bacterial Conjunctivitis

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FoundationVolume3,Chapter39.TopicalOphthalmicAntibioticsintheManagementofBacterialConjunctivitisandKeratitis
Chapter39
TopicalOphthalmicAntibioticsintheManagementof
BacterialConjunctivitisandKeratitis
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RENESOLOMONandERICDONNENFELD
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BACTERIALCONJUNCTIVITIS
BACTERIALKERATITIS
PROPERTIESOFTOPICALOPHTHALMICANTIBACTERIALAGENTS
REFERENCES
Bacterialconjunctivitisiscommon,1generallymildtomoderateinseverity,
andusuallyselflimiting.Treatmentwithtopicalophthalmicantibiotics
speedsresolutionofthedisease,decreasesmorbidity,preventsrecurrence
andspreadofthediseasetosocialcontacts,decreasestheincidenceof
permanentconjunctivalchanges,decreasestheriskofcornealorintraocular
infectionwhensurgeryisanticipated,andpreventsthedevelopmentof
chronicconjunctivitiswithitsgreatertreatmentchallengesandriskof
progressiontocornealdamageordisease.24Themostfrequentlyisolated
pathogensinacutebacterialconjunctivitisareStreptococcuspneumoniaeand
HaemophilusinfluenzaeinpediatricpatientsandStaphylococcusepidermidis
inadultpatients.5,6
Chronicconjunctivitisisdefinedasanycaseofconjunctivitisthatlastslonger
than2weeks.Themostcommonpathogensassociatedwiththiscondition
areStaphylococcusaureusandS.epidermidis,themostcommonorganisms
foundinnormallidandconjunctivalflora.Thesepathogensproducetoxins
thatcandamagetheconjunctivaandcorneaproducingthesuperficial
punctatekeratopathythatiscommonlyseen.Thepunctatekeratopathy
characteristicallyinvolvestheinferiorcorneaandconjunctiva.These
organismsalsocommonlyspreadtootherocularstructures,suchasthe
meibomianorifices,lashfollicles,andthelacrimalcanaliculi,andmayeven
breachthecornealepithelium.2,3
Other,moreserioustypesofinfectiousconjunctivitisincludehyperacute
bacterialconjunctivitis,usuallycausedbyNeisseriagonorrhoeaeandS.
pneumoniae.N.gonorrhoeaeisoftenassociatedwithoropharyngeal
infectionsandrequiressystemicandtopicaltherapy.2,3
Inthetreatmentofacutebacterialconjunctivitis,mostphysiciansdonot
performculturesandthereforeprescribebroadspectrumantibioticagents.
Becausebacterialconjunctivitisisusuallyselflimiting,agentsassociated
withahigherincidenceofoculartoxicityorhypersensitivityreactionsare
bestavoided.Combinationproductswithgrampositiveandgramnegative
coveragearepopularfortheirbroadspectrumofactivity,butsomecontain
agentsthatcanbeirritatingorcauseallergicreactions.Patientcomplianceis
acommontreatmentchallenge,particularlyinpediatricpatientsbecause
theyarereluctanttoletanyoneinstillanythingintotheireyesandare
sensitivetoirritatingagents.
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BACTERIALKERATITIS
Bacterialkeratitisisanophthalmicemergencythathasthepotentialtocause
significantvisionlosssecondarytocornealscarringandperforation.Rapid
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diagnosisandimmediatetreatmentwithappropriateantimicrobialtherapy
arenecessarytolimittheextentoftissuedamageandtoimprovethevisual
prognosis.3,7Approximately30,000casesofmicrobialkeratitisare
diagnosedeachyearintheUnitedStates.8Themostlikelycausative
organismsdependongeographiclocation,preexistingcornealdisease,urban
orruralenvironment,historyofcontactlenswear,andclimate.913
Approximately87%ofallcasesofbacterialkeratitisintheUnitedStates
resultfrominfectionbyoneofthefollowingorganisms:Grampositive
infectionsaremostcommonlysecondarytostreptococciorstaphylococci,
whereasthegramnegativeorganismsincludePseudomonasspeciesor
Enterobacteriaceae(especiallySerratiamarcescensbutalsoCitrobacter,
Klebsiella,Enterobacter,andProteusspecies).1416Currently,themost
commoncausesofmicrobialkeratitisareS.aureusinthenorthernUnited
StatesandPseudomonasandStreptococcusspeciesinthesouthernUnited
States.3,11,17S.pneumoniaeisthemostcommonpathogeninmany
developingcountries.Staphylococcusspeciesarethemostcommon
organismassociatedwithphotorefractivekeratectomyorLASIK.18
Pseudomonasspeciesarefrequentlyassociatedwithovernightcontactlens
wearbutmayalsobeseenwithdailywearcontactlenses.1927Infact,
Pseudomonasspecieshavebecomeamorecommoncauseofbacterial
keratitisinthesouthernUnitedStatesthanS.aureus.28,29Inchildren
youngerthan3yearsofage,Pseudomonasspecieshavebeenidentifiedas
themostcommonbacterialcauseofkeratitis.30,31
Manyophthalmologistsdiagnoseandtreatbacterialkeratitisbasedontheir
empiricalobservationsandonlyperformamicrobialanalysisonparticularly
severeulcers(e.g.,thoseencroachingonorinvolvingthevisualaxis).Most
physicianschoosewhattheythinktobeabroadspectrumantibioticand
begintreatmentimmediately,3,32,33butthechoiceofagentmayalsobe
influencedbywhichpathogenissuggestedbythediseasepresentationand
thephysicians'knowledgeofpathogenprevalenceinthelocalenvironment
andpatientpopulation.28,3436Caremustbetakeninthechoiceofabroad
spectrumantibioticbecausecertaincommerciallyavailableagentsmayhave
significantgapsinthespectraoftheirantimicrobialefficacy,maypoorly
penetratethecornea,ormaybebacteriostaticratherthanbactericidal.Any
ofthesecharacteristicswouldmakethemunsuitableforthetreatmentof
bacterialkeratitis.
Forapproximately25years,themainstayforthetreatmentofthese
infectionshasbeendualtherapyusingtopicallyadministeredfortified
antibiotics.37Theseantibioticsarenotcommerciallyavailableandare
speciallyformulatedbyhospitalpharmaciesorphysicianswhenneeded.
Traditionally,oneantibioticprovidedcoverageagainstgramnegative
pathogens(anaminoglycosidesuchastobramycinorgentamicin[13.6
mg/ml]),andthesecondantibioticcoveredthespectrumofgrampositive
bacteria(vancomycin[25mg/mL],cefazolin[50mg/mL],orbacitracin
[10,000U/mL]).Together,theyprovidedaninitialempiricalregimenforthe
treatmentofbacterialkeratitis.Duringthepastseveralyears,the
fluoroquinolonefamilyofantibioticshasofferedanalternativetofortified
antibioticsasthemainstayoftreatmentforbacterialulcerations.Two
doublemasked,controlled,clinicaltrialshavesupportedtheclinicalefficacy
ofusingthecommerciallyavailablefluoroquinolones(ofloxacin0.3%or
ciprofloxacin0.3%)ascomparedwithfortifiedtobramycinand
cefazolin.38,39
Therearevariousroutesforadministeringantibioticsinthetreatmentof
ocularinfectionsandincludetopical,subconjunctival,oral,intravenous,and
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intramuscular.Topicalapplicationofantibioticsisthepreferredrouteof
administrationforbacterialconjunctivitisandkeratitisbecausethedrops
providetherapeuticallyeffectiveconcentrationsthedropswashaway
bacteriaandbacterialantigensadversesystemiceffectsofthedrugsare
decreasedoreliminatedandinreliablepatients,theycanbeadministered
onanoutpatientbasis.4043Thefactorsthatcontributetoachievingeffective
therapeuticconcentrationsofthedruginthecorneaincludethefrequencyof
administration,theconcentrationofthedrug,thelipophilicnatureofthe
drugwheretheepitheliumisintact,thelengthofcontacttimeofthedrug
withthecornea,andthelackofanintactcornealepithelium.44,45Thenext
sectiondealswiththeindividualcharacteristicsofthevarioustopical
ophthalmicantibioticsusedtotreatbacterialconjunctivitisandkeratitis.
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PROPERTIESOFTOPICALOPHTHALMICANTIBACTERIAL
AGENTS
FLUOROQUINOLONES
Chemistry,OphthalmicPreparation,andPharmacologicAction
Thefluoroquinolones,thenewestclassofagentstobedeveloped,arebased
ontheprototype,nalidixicacid(1,8naphthyridine),whichwassynthesizedin
1962.46
Inthe1980s,thefluoroquinoloneswerecreatedfromnalidixicacidbyadding
afluorineatomtoposition6ofthemolecule(Fig.1).Thisadditionwidened
theantibacterialspectrumofactivityandresultedindecreaseddevelopment
ofresistantorganisms.Threefluoroquinolonesavailableforophthalmicuse
areofloxacin(Ocuflox,Allergan,Inc,Irvine,CA),ciprofloxacin(Ciloxan,
AlconLaboratories,Inc,FortWorth,TX),andnorfloxacin(Chibroxin,Merck&
Co,Inc,WestPoint,PA).Theyareformulatedas0.3%solutionsandtheir
structuralformulasareshowninFigure1.
Fig.1.Chemicalstructureofthenalidixicacid
(A)fromwhichthefluoroquinolones,including
ciprofloxacin(B)andofloxacin(C),were
derived.
ThefluoroquinolonesarebactericidalandworkbyinhibitingbacterialDNA
gyrase(bacterialtopoisomeraseII),theenzymeresponsibleformaintaining
thesuperficialtwistsinbacterialDNA.47Theyprovidebroadspectrum
activityagainstgrampositiveandgramnegativebacteriainvivoandin
vitro.Theyhavelesspredictableactivityagainstanaerobesand
streptococci.48
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Thefluoroquinolonesarealsoavailableforsystemicuse,butclinicalprofiles
oftheophthalmicandsystemicformulationsaredistinctlydifferent.For
example,topicalophthalmicofloxacinandciprofloxacinareindicatedforuse
inchildrenasyoungas1yearofage,whereassystemicformulationsare
approvedonlyforuseinolderchildrenandadultsbecauseofconcernsabout
thepotentialriskofdrugdepositionincartilageandarthropathy.Inaddition,
theprevalenceoffluoroquinoloneresistantbacteriaismuchhigheramong
systemicpathogensthanamongtheocularpathogenscommonlyassociated
withconjunctivitisandkeratitis.Moreover,althoughtheuseofsystemic
fluoroquinolonesmustbecarefullyconsideredtopreventfurtherinductionof
resistantstrains,thisisofmuchlessconcerninophthalmicuse,becausethe
strainsofbacteriaaffectedaremuchlower.49Althoughresistancehasbeen
lessofaconcerninophthalmicuse,resistancetofluoroquinoloneantibiotics
hasbeenincreasing,andforthisreason,theiruseisgenerallyreservedfor
visionthreateninginfectionsandinfectionsnotrespondingtoconventional
therapy.50
ClinicalExperienceandOphthalmicUsesfortheIndividual
OphthalmicPreparationsoftheFluoroquinolones
OFLOXACIN0.3%SOLUTION
Ofloxacinhasbeentestedagainstmanypreviouslyestablishedantibioticsin
thetreatmentofexternalocularinfectionandhasbeenfoundtohaveawide
spectrumofactivity.5153TheOfloxacinStudyGroupcomparedthe
effectivenessandsafetyofofloxacin0.3%withgentamicin0.3%inthe
treatmentofbacterialexternaloculardisease.Clinicalimprovementrates
were98%(51of52)intheofloxacingroupversus92%(48of52)inthe
gentamicingroup.Ofloxacineradicatedorcontrolledasimilarproportionof
culturedorganismsasdidgentamicin.Therewasnostatisticallysignificant
differenceinactivitybetweenthetwodrugs.Theincidenceofadverse
effectsattributabletoofloxacintreatmentwas3.2%comparedwith7.1%for
gentamicin.54
TheOfloxacinStudyGroupalsocomparedtheefficacyofa10daycourseof
topicalofloxacintotopicaltobramycininthetreatmentofexternalocular
infection.Initially,theclinical,microbiologic,andoverallimprovementrates
werenotstatisticallysignificantlydifferentbetweenthetwogroups.The
ofloxacintreatedpatients'examinationsignsandsymptomsondays3to5
weresignificantlymorereducedthanthoseofthetobramycintreated
patients.55,56
Ofloxacinhasalsobeenproventobecomparablewithchloramphenicolinthe
treatmentofexternalocularinfection57whileavoidingtheriskofpossibly
fatalsystemiccomplicationsthathavebeenassociatedwithtopical
chloramphenicol.
Ofloxacinhasbeencomparedwiththetraditionaltreatmentregimenofa
fortifiedaminoglycosidecombinedwithafortifiedcephalosporininthe
treatmentofbacterialkeratitis.O'Brienandcoworkerscomparedofloxacin
0.3%monotherapywithtobramycin1.5%pluscefazolin10%therapy.The
proportionofhealedulcersinbothculturepositivetreatmentgroupswas
similar(89%ofloxacinhealedby28daysand86%ofcombinationtherapy
healedby28days).Adverseeffectswerehigherinthefortifiedantibiotics
groupfiveofthesixculturepositivepatientswhodiscontinuedstudy
medicationswereinthefortifiedantibioticsgroup.38TheOfloxacinStudy
Groupcomparedofloxacinmonotherapytotraditionaldualtherapyof
fortifiedgentamicin1.5%andcefuroxime5%.Thisgroupfoundboth
treatmentstobeequallyeffectiveinthe49culturepositivecasesstudied.51
OfloxacinismoreefficaciousagainstmethicillinresistantS.aureusthan
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ciprofloxacinis.58
Ofthecurrentlyavailablefluoroquinolones,ofloxacinhasthehighestintrinsic
solubility,59iswelltoleratedbecauseofitsnearneutralpH(6.4),andhas
thehighestrateofpenetrationintooculartissues.60,61Thishighrateof
tissuepenetrationmayalsobesignificantinthosecasesinwhichphysicians
wishtouseatopicalantibioticforprophylaxisinintraocularsurgery.
CIPROFLOXACIN0.3%SOLUTION
Intworandomizedmulticenterstudies,ciprofloxacin0.3%wascompared
withaplaceboandwithtobramycin0.3%inthetreatmentofculturepositive
bacterialconjunctivitis.Ciprofloxacinwasstatisticallysignificantlymore
effectivethanplacebowithreductionoreradicationofpathogensin93.6%of
ciprofloxacintreatedpatientsversus59.5%oftheplacebogroup.
Ciprofloxacinandtobramycinwereequallyeffective,withimprovedcultures
in94.5%and91.9%ofpatients,respectively.62
Topicalciprofloxacin0.3%hasalsobeenprovenassafeandeffectiveas
tobramycin0.3%andfusidicacidgel1%inthetreatmentofbacterial
conjunctivitisinastudyof257pediatricpatients.Theinvestigators
determined87.0%oftheciprofloxacintreatedpatientsand89.9%ofthe
tobramycintreatedpatientstobeclinicallycuredafter7daysoftreatment.
Noadverseeffectsoccurredineitherofthetreatmentgroups.6365
Monotherapywithciprofloxacin0.3%hasbeencomparedwithcombination
therapyinthetreatmentofbacterialkeratitis.Hyundikandcoworkers
studied176culturepositivecasesofbacterialkeratitisrandomizedto
treatmentwithciprofloxacin0.3%orwithtobramycin0.3%andcefazolin
5%.Therewerenostatisticallysignificantdifferencesbetweenthetreatment
regimensintermsofoverallclinicalefficacy(91.5%versus86.2%),timeto
cure,orreductioninsignsandsymptoms.Theincidenceoftreatment
failureswaslesswithciprofloxacinthanwithcombinationfortifiedtherapy.
Severalotherstudieshaveexaminedtheeffectivenessofciprofloxacinin
treatingocularbacterialinfections.6673Therewasatrendtowardresistance
ofS.pneumoniaetociprofloxacin,39butciprofloxacinismoreactiveagainst
Streptococcusviridans,Pseudomonasaeruginosa,H.influenzae,andS.
marcescensthanofloxacinis.58
CiprofloxacinhasshownpotentinvitroactivityagainstP.aeruginosa,
includingtheaminoglycosideresistantstrains.47,74Theoverallinvivo
effectivenessofciprofloxacinagainstpathogens,thoughhighat
approximately92percent,hasdeclinedinthepastfewyears,75andthereis
concernabouttheemergenceofresistantstrainsofStaphylococcusand
Pneumococcusspecies.Therealsoexistsanointmentformofciprofloxacin
0.3%andoneclinicaltrialhasshownitseffectivenessintreatingbacterial
keratitis.76
NORFLOXACIN0.3%SOLUTION
Norfloxacinistheleastpotentofthetopicalfluoroquinolones.48,77,78Ithas
beenshowntobeeffectiveinthetreatmentofbacterialconjunctivitis79but
not,withtheexceptionofonesmallstudy,bacterialkeratitis.80In
conjunctivitis,itiscomparableinefficacytotobramycin0.3%81and
ciprofloxacin0.3%.64Norfloxacinhasalsobeenshowntobeaseffectiveas
gentamicin0.3%inthetreatmentofblepharitisandconjunctivitis.82Inthe
studybyMillerandcoworkers,norfloxacinsuppressedoreliminated89%of
allorganisms,basedonpretreatmentandposttreatmentcultures.
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Norfloxacinhasthehighestrateofresistantbacteriaamongthe
fluoroquinolonesbasedoninvitrotestingwithocularisolates.59,83,84
GeneralizationsontheGroupofOphthalmicFluoroquinolones
Multiplearticleshavesupportedtheeffectivenessofthefluoroquinolonesin
treatingocularbacterialinfections.8588
Whataretheadvantagesanddisadvantagesofthefluoroquinolonesas
comparedwithother,socalledfortifiedantibiotics?Theaforementioned
clinicalstudiesconclusivelyshowthatciprofloxacinandofloxacinare
statisticallyequaltofortifiedantibioticsintimetohealandcurerateof
infectiouscornealulcers.However,otherparametersshouldbeanalyzed.
Theacutemanagementofbacterialcornealulcersrequiresrapidaccessto
therapy.Inaddition,thecostandtoxicityofantibiotictherapymustbe
considered.Fortifiedantibioticsarenotcommerciallyavailableandmustbe
preparedonrequest.Thefluoroquinolonesaresuperiorwithrespectto
accessibility,cost,andlowtoxicity.Thefluoroquinolonesperformatleastas
wellas,andoftenbetterthan,theaminoglycosidesinthetreatmentof
gramnegativecornealulcers.
Oneofthemainadvantagesofthefluoroquinolonesistheirhighintrinsic
solubility.60,89,90Althoughofloxacinismoresolublethanciprofloxacin,both
achievehighintracorneallevelsinpatientswithanintactepithelium.71Ina
rabbitmodelwiththeepitheliumintact,itwasshownthatciprofloxacin
achieves10.47g/mLinthedeepcorneaofloxacinachieved21.50g/mL.60
Ofloxacinismorelipophilicthanciprofloxacin,whichmaymakeitmore
effectiveinpenetratinganintactepithelium.91Inmostcasesofbacterial
keratitis,theepitheliumispartiallydenudedandlipidsolubilityisnotas
importantanissuebecauseofthelossofthebarrierfunctionofthe
epithelium.92However,whenthemoreintacttheoverlyingepitheliumis,
suchasinthecasesofsutureabscessesafterpenetratingkeratoplasty,the
morelikelyciprofloxacinandofloxacinaretoofferanadvantage.Thehigh
stromallevelsofciprofloxacinandofloxacinmayexplaintheexcellent
clinicalresponsebypatientswithulcersdespiteintermediateorresistant
laboratorysusceptibilitypatternsinvitro.
Theonespeciesforwhichciprofloxacinandofloxacinarenotofequal
efficacytofortifiedantibioticsolutionsisstreptococci.Neitherinvitronor
clinicallydotheyprovideasgoodgrampositivecoverageascefazolin,
vancomycin,orbacitracin.Inamulticenterprospective,butnonblinded
evaluationofciprofloxacin0.3%versusfortifiedantibioticsperformedby
Leibowitz,6223.1%ofS.pneumoniaecornealulcersdidnotrespondto
ciprofloxacin.Basedonpreviousinvitrodata,casereports,andthetwo
prospectiveevaluations,streptococciseemtobeaweakpointinthe
spectrumofactivityofthefluoroquinolones.Therefore,anypatientat
increasedriskofdevelopingaS.pneumoniaeinfectionshouldbetreated
withanantibiotic,suchasbacitracin,vancomycin,orcefazolin,inadditionto
afluoroquinolone.Thereisaknownincreasedincidenceofstreptococcal
infectionsinsutureabscessesafterpenetratingkeratoplastyand
pseudophakicbullouskeratopathy.S.pneumoniaeisalsocommonlyseenin
cornealulcersrelatedtodacryocystitisandfilteringblebinfections.
Anaerobicstreptococcalinfections,suchasthosecausingacrystalline
keratopathy,areunlikelytorespondtofluoroquinolonemonotherapy.
Finally,patientswithhospitalacquiredcornealulcers,inwhichthereisan
increasedriskofmethicillinresistantS.aureus,shouldbetreatedatleastin
partwithfortifiedvancomycindrops.
AdverseEffects
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Thefluoroquinoloneshavelowratesofadverseeffects.93Thatofofloxacin
(consistingprimarilyoftransientlocalirritation)islessthan0.6%,38,5457,94
andtherehasneverbeenanyreportofcornealepithelialtoxicitywith
ofloxacin.95TheOfloxacinStudyGroup51notedthatfortifiedantibiotics
showeddrugtoxicitytotheocularsurface(definedaspunctatecorneal
staining,papillaryconjunctivalreaction,orconjunctivalfluoresecinstaining)
in50.8%ofpatientsreceivingcombinationtherapyversusonly10.2%of
ofloxacintreatedpatients.
Aswithofloxacin,fewerpatientstreatedwithciprofloxacinthantreatedwith
fortifiedantibiotics,reportedoculardiscomfort.39Themostcommonly
reportedadverseeffectfromtopicalciprofloxacintreatmentistheformation
ofawhitecrystallineprecipitateinapproximately17%oftreatedeyes.39,63
65Thisresultsfromprecipitationofthedrug(formulatedatpH4.5),whichis
poorlysolubleatthenearneutralpHofthetearfilm.Therelationship
betweenthisprecipitateandantibacterialefficacyisunknown.The
precipitateresolvesspontaneouslywithoutsequelaeaftercessationofthe
medication.Afewpatientsmayalsoexperiencesomelocalburningor
irritation.Therehavebeenafewcasereportsofcornealprecipitateswith
norfloxacinuseinbacterialkeratitis,96buttheoverallincidenceofadverse
effectsseemstobelow.
Likethe0.3%solution,theciprofloxacinointmenthasalsobeenshownto
causeawhiteprecipitatethatresolvesspontaneouslywithoutsequelaeafter
discontinuingit.Otheradverseeffectsfromtheointmentincludeburning,
puntateepitheliopathy,blurredvision,andtearing.76
EXTEMPORANEOUSLYCOMPOUNDEDFORTIFIEDANTIBIOTICS
Extemporaneouslycompoundedfortifiedantibioticeyedroppreparations
containhighconcentrationsthatareusuallypreparedfromproducts
formulatedforintravenoususe.Atypicaltreatmentregimenmightconsistof
acombinationofacephalosporin(e.g.,50mg/mLcefazolin)forgram
positivebacteriacoverageandanaminoglycoside(e.g.,13mg/mL
tobramycinorgentamicin)forgramnegativebacteriacoverage.However,
theseagentsarenotcompatiblewhencombinedinthesamesolutionand
mustbeformulatedseparatelyandadministeredfromdifferentbottles.
Anothercommonextemporaneouslyfortifiedantibioticisvancomycin50
mg/mL.97Mostneedtoberefrigeratedafterdispensingtothepatient,
because,beingderivedfromintravenousproducts,theydonotcontaina
preservative.Instillationofthetwoagentsmustbeseparatedbyintervalsof
severalminutesormore(e.g.,15minutesmightbeideal)toprevent
washoutofthefirstagentbythesecond.Thehighconcentrationsusedin
thesepreparationsexacerbatetheirepithelialtoxicpotential.Thisisa
specialconcernfortheaminoglycosides.
Inthetreatmentofbacterialkeratitis,fortifiedcefazolinaminoglycoside
preparationsareaseffectiveasthefluoroquinolonesofloxacinand
ciprofloxacin,butaremoredifficulttoobtainanduse.Notallpharmaciesare
equippedtoformulateextemporaneouslycompoundedagentsandnotall
pharmacistsarefamiliarwiththeprocedures.
Therehasbeensomedebateintheliteratureastotheefficacyofusinga
collagenshieldasavehicletoabsorbanddeliverdrugs.Advocatesargue
thatcollagenshieldssoakupantibioticsandcontinuouslydeliverthemtothe
corneaforseveralhours,enablinghigherconcentrationstobedeliveredfor
longerperiodsoftime.However,somestudieshavefoundthatcollagen
shieldsarenotmoreefficaciousthanusingfortifiedantibioticsalone.98,99
Accordingtoseveralotherstudies,collagenshieldsarelaborintensiveyetas
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effectiveintreatingbacterialkeratitis,asfrequentdosagesofdrops.100104
AMINOGLYCOSIDES
Thetwomostcommonlyusedaminoglycosidesaretobramycinsulfate
availableasa0.3%solutionorointment(AKTOB[Acorn,Inc,BuffaloGrove,
IL],Defy,Tobrex[AlconLaboratories,FortWorth,TX])andgentamicin
sulfate(Fig.2)availableasa0.3%solution(Garamycin,Genoptic[Allergan,
Inc,Irvine,CA],Gentacidin,Gentak[Akorn,Inc,BuffaloGrove,IL],Ocu
mycin)andointment(Garamycin,Genoptic).Neomycin[Bausch&Lomb
Pharmaceutical,Inc,Tampa,FL]isalsoused,butisonlyavailableasa
componentofcombinationproducts,notasasingleagent.Thebasic
structureofaminoglycosidesconsistsoftwoormoreaminosugars
connectedbyglycosidicbondstoahexosenucleus.Theindividual
characteristicsofanaminoglycosidearedeterminedbydifferencesinthe
aminosugarsattachedtothenucleus.
Fig.2.Theaminoglycosides,withsomeofthe
morecommonlyusedophthalmicformulations
pictured,tobramycin(A),andgentamicin(B),
whichcontainthecharacteristictwoormore
aminosugarsconnectedbyglycosidicbondsto
ahexosenucleus.
Theaminoglycosidescausebacterialcelldeathbyirreversiblybindingto30S
ribosomesandcausingmisreadingofthegeneticcodeanddecreasedor
abnormalproteinsynthesis.105Aminoglycosidesarevaluedinthetreatment
ofexternalocularinfectionsbecausetheyareactiveagainstaerobicgram
negativeorganisms,includingPseudomonasspecies,Proteusspecies,
Klebsiellaspecies,Escherichiacoli,Salmonellaspecies,Shigellaspecies,S.
marcescens,Haemophilusspeciesandmanygrampositivestaphylococci.106
Invitro,tobramycinisthreetimesaseffectiveasgentamicinagainst
Pseudomonas.107Theaminoglycosideshavelimiteduseasbroadspectrum
agentsbecauseofresistancecausedbyaminoglycosidemodifyingenzymes.
Thisoccursatanunacceptablyhighfrequency(29%41%).108Ofparticular
concernistheirlackofrelativeefficacyagainstS.epidermidisandS.
pneumoniae.
ClinicalExperienceandOphthalmicUses
Gentamicinandtobramycinhavebeenshowntobeeffectiveinthetreatment
ofconjunctivitis,blepharoconjunctivitis,andbacterialkeratitis.105,109111
Thecommerciallyavailableconcentrationsareacceptableforthetreatment
ofbacterialconjunctivitis,butthehighlyconcentrated,fortifiedpreparations
arepreferredforbacterialkeratitisandarebestusedinconjunctionwithan
antibioticmoreactiveagainstgrampositivebacteria.
AdverseEffects
Gentamicinandtobramycinhavebeenshowntobesafe,buttobramycinmay
havefeweradverseeffects.112Themostsignificantsafetyconcernwith
aminoglycosidesiscornealepithelialtoxicity.108,113,114Thisisespeciallyso
forneomycinandgentamicin.113Lassetal.evaluatedtheconcentration
dependenttoxicitiesofneomycin,amikacin,gentamicin,andtobramycin
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usingarabbitepithelialcellculturemodel.113Subfortifiedconcentrationsof
neomycinandgentamicinsignificantlyinhibitedepithelialcellmetabolism
after5minutesofexposurealltheaminoglycosidessignificantlyinhibited
cellmetabolismatalltestedconcentrationsafter30and60minutesof
exposure.Fortifieddosesmaycauseareversiblepunctateepithelialkeratitis
orpseudomembranousconjunctivitis.115,116Severalcasesofconjunctival
defectsornecrosishavebeenreportedwiththeuseoffortified
gentamicin,114,117andatleastonecaseofconjunctivalnecrosishasbeen
attributedtofortifiedtobramycinuse.114Twocasesofpseudomembranous
conjunctivitissecondarytotopicalgentamicinhavebeenreported:onecase
afteruseofcommercialstrengthgentamicinandoneinresponsetofortified
1.36%gentamicin.118Neomycinhasahighrateofassociatedallergic
reactionsinonestudy,18.5%of27patientswithchronicconjunctivitishad
patchtestsensitivitytoneomycin.119Otherneomycintoxicmanifestations
areconjunctivitis,eyelidedema,punctatecornealerosions,andinhigh
concentrations,reducedcornealsensation.120
BACITRACIN
Bacitracinisapolypeptideantibioticthatcontainsathiazolidinering
structure(Fig.3).Bacitracinisbactericidalbybindingtocellmembranes121
andiscommerciallyproducedasatopicalophthalmicointment(AKTracin,
Akorn,Inc,BuffaloGrove,IL)orincombinationwithpolymyxinB(AKpoly
bac[Akorn,Inc,BuffaloGrove,IL],Polysporin,Polytracin[Medical
Ophthalmics,TarponSprings,FL])orwithpolymyxinBandneomycin(AK
Spore[Akorn,Inc,BuffaloGrove,IL],Neosporin[MonarchPharmaceuticals,
Bristol,TN],OcusporB).Allthesepreparationscontainbacitracinina
concentrationof500Upergramofointment.Unlikemostoftheother
antibacterialagentsdiscussedinthischapter,bacitracinisonlyavailablefor
topicalusebecauseofitssystemictoxicityandpoorsolubility.
Fig.3.Structuralformulaofbacitracin,the
polypeptideantibioticthatcontainsa
thiazolidinering.
Bacitracinisefficaciousagainstmostgrampositiveorganismsandselect
gramnegativeorganisms,includingpenicillinaseproducingstaphylococci,
Neisseriaspecies,Haemophilusspecies,andActinomycesspecies.Bacitracin
penetratesanintactcorneapoorly,butitspenetrationmaybeincreasedbya
cornealepithelialdefect.122
AdverseEffects
Commerciallyavailablepreparationsandfortifieddosagesofbacitracin
generallydonotirritatetheocularsurfaces.Hypersensitivityreactions,
namelyskineruptions,havebeenreported.Thereisonereportofanacute
anaphylacticreactionassociatedwithtopicalapplicationofbacitracin.123
BETALACTAMANTIBIOTICS
Thisclassofantibioticsincludesthepenicillinsandcephalosporins.Penicillins
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(Fig.4)arecomposedofathiazolidineringconnectedtoabetalactamring
towhichasidechainisconnected.Thesidechainisresponsibleforthe
individualcharacteristicsofthepenicillins.Likethepenicillins,the
cephalosporins(Fig.5)containabetalactamring,arebactericidal,and
inhibitcellwallsynthesis.Bypreventingthesynthesisofpolysaccharides
neededforbacterialcellwallstructure,theycausebacterialdeath.They
tendtobemoreactiveagainstgrampositiveorganisms,withincreased
gramnegativeactivityintheextendedspectrumpenicillinsandthesecond
andthirdgenerationcephalosporins.Bacteriabecomeresistanttopenicillins
byproducingbetalactamasecephalosporinstendtoberesistantto
degradationbybetalactamase.AllmethicillinresistantS.aureusand
enterococciarealsoresistanttocephalosporins.Approximately10%of
patientsallergictopenicillinwillalsobeallergictocephalosporins.
Fig.4.Chemicalformulasofthepenicillin
agents,whichcontainbetalactamrings
attachedtothiazolidinerings(e.g.,penicillin
[A]andmethicillin[B]).
Fig.5.Illustrationsofthecephalosporins,
whichcontainmodificationstopositionsofthe
betalactamringofcephalosporin(A),to
createcefazolin(B),andceftazidime(C).
Thebetalactamantibioticsarenotavailableinpharmaceutically
manufacturedtopicalophthalmicpreparationsbecauseoftheirpoorstability.
Themostcommonlyusedtopicalagentinthisclassisafirstgeneration
cephalosporin,cefazolin50mg/mL,andismadefromaparenteral
preparation.Asmentioned,cefazolinisusedwithatopicalaminoglycosidein
thetreatmentofbacterialkeratitis.However,ceftazidimealoneorin
combinationwithanaminoglycosideorvancomycinhasalsobeenexplored
asaninitialagentfortopicaltherapyofbacterialkeratitis.124Athird
generationcephalosporin,ceftazidime,wasfoundtobeaseffectiveas
cefazolinintreatingrabbitcornealulcerscausedbyS.aureusandS.
pneumoniaeandaseffectiveastobramycinagainstP.aeruginosa.125,126
Thecefazolinaminoglycosidecombinationhasbeenproventobeequivalent
tomonotherapywithofloxacinandciprofloxacininbacterialkeratitis.Topical
cefazolinmayalsohaveanimportantroleincombinationwith
fluoroquinolones.Bowerandcoworkers127havepredictedthat98.7%of
theirlaboratory'socularbacterialisolateswouldbesusceptibletoa
fluoroquinolonecefazolincombinationversus88.2%,82.3%,and80.4%,
respectively,withofloxacin,ciprofloxacin,andnorfloxacin.Thus,insevere
casesofbacterialkeratitis,cefazolinmaybeadesirableadditionto
fluoroquinolonetherapywhilecultureresultsarependingandmaysupplant
theneedforfortifiedaminoglycosides.128
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AdverseEffects
Themostcommonadverseeffectsareallergicreactionstothepenicillins
withsomecrossallergenicitywiththecephalosporins.Topicalpenicillincan
resultinanaphylaxis,andlesssignificantly,thereisahighincidenceof
contactallergicblepharitis.129Thecephalosporinshaverelativelyfewside
effects,129andapproximatelyonly5%ofpatientsmanifestallergic
reactions.
CHLORAMPHENICOL
Chloramphenicol,anitrobenzenederivative(Fig.6),availableasa1%
ointmentora0.5%solution(AKChlor,Chlormycetin[Monarch
Pharmaceuticals,Bristol,TN],Chloroptic[Allergan,Inc,Irvine,CA],Ocu
Chlor),wasthefirstbroadspectrumantibioticwithgrampositiveandgram
negativecoverage.Ithasbeenwidelyusedinointmentformforthe
treatmentofexternalocularinfection.130
Fig.6.Structureofchloramphenicol,a
derivativeofnitrobenzene.
Chloramphenicolinhibitsbacterialproteinsynthesisbybindingtothe50S
ribosomalsubunit.Itisprimarilybacteriostaticbutmaybebactericidalto
someorganisms(e.g.,H.influenzae).
Chloramphenicolhasgoodantimicrobialactivityagainstmostgrampositive
ocularisolatesandlimitedgramnegativecoverage.Chloramphenicolshould
notbeusedtotreatinfectionsinwhichgramnegativebacteria,especially
PseudomonasorSerratiaspecies131aresuspected.Becauseitisusually
bacteriostatic,notbacteriocidal,andbecauseofitslimitedspectrum,
chloramphenicolshouldnotbeusedinvisionthreateningcircumstances.
Insomestudies,chloramphenicolhasbeenshowntobeaseffectiveas
ciprofloxacin,norfloxacin,andtrimethoprimpolymyxinBinthetreatmentof
bacterialconjunctivitis.79,132,133
AdverseEffects
Muchhasbeenwrittenaboutapossiblelinkbetweentopicalophthalmicuse
ofchloramphenicolandaplasticanemia.Oralchloramphenicolcanaffectthe
bonemarrowintwowaysoneisadoserelated,reversiblebonemarrow
suppressionandtheotherisanidiopathic,usuallylethaleffect.Topical
chloramphenicolhasbeenassociatedwithdoserelatedandidiopathicbone
marrowsuppressions.134140Chloramphenicolshouldbestnotbeusedin
patientswhohaveafamilyhistoryofdrugrelatedbonemarrow
failure.141,142Concernabouttheriskofaplasticanemiaandthe
developmentofmoreeffectiveantibioticshavebeensufficienttodrastically
reducetheuseofchloramphenicolintheUnitedStates,althoughitisstill
widelyusedinothercountries.
Burningmayoccurwithtopicalinstillationofchloramphenicol,butitis
relativelynonirritatingtoocularstructuresandallergicreactionsare
uncommon.
ERYTHROMYCIN
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Erythromycin0.5%isamacrolideantibiotic(Fig.7)thatinhibitsbacterial
proteinsynthesisbyirreversiblybindingtothe50Sribosomalsubunit.143It
isbacteriostaticinlowconcentrationsbutcanbebactericidalinhigh
concentrations.Otherdeterminantsofitsbactericidalactivityinclude
organismsusceptibility,growthrateofthebacteria,andpH.144Erythromycin
isavailableinointmentform(0.5%)fortopicalophthalmicuse(Akmycin,
Ilotycin).
Fig.7.Chemicalstructureofthemacrolide
antibiotic,erythromycin.
Erythromycinisusedasprophylaxisagainstneonatalconjunctivitiscaused
byC.trachomatisandN.gonorrhoeae.Itisalsousedtotreatmildbacterial
conjunctivitis.Ithasabroadspectrumofantibacterialactivity145andiswell
toleratedbytheocularsurface,butmanyresistantstrainshavedeveloped.
Forexample,severalstrainsofH.influenzae,oneofthemostcommon
pathogensinpediatricconjunctivitis,areresistanttoerythromycin.
Therefore,itsusefulnessinthetreatmentofexternalocularinfectionsis
limited.
AdverseEffects
Topicalapplicationoferythromycinisnotusuallyirritatingtooculartissues.
POLYMYXINANDCOMBINATIONPRODUCTS
ManyofthecombinationproductscurrentlyavailableintheUnitedStates
containpolymyxinBsulfate(Fig.8).Itprovidesefficacyagainstcommonly
encounteredgramnegativepathogenssuchasH.influenzae.Polymyxinisa
bactericidalpolypeptideantibioticthatinterfereswithcellwallsynthesisand
formsfalseporesinbacterialcellmembranes.Itislesseffectiveagainst
Proteus,Providencia,Serratia,andBrucellaspecies.Itcameintousein
ophthalmologyinthe1950s,whenitwasshownthatpolymyxinwaseffective
intreatingPseudomonascornealulcersinrabbits.146Theeffectivenessof
thisagentwasthenshownintreatinghumancornealulcersinfectedwith
Pseudomonasspecies.147,148
Fig.8.PolymyxinBsulfate,apolypeptide
antibiotic,whichisthemostcommon
polymyxininclinicaluse.
CombinationsofpolymyxinBwithneomycinandgramicidinortrimethoprim
areavailableassolutions,andcombinationswithbacitracin,neomycin,and
bacitracin,oroxytetracyclineareavailableasointmentsonly.Theointments
contain10,000UpergramofpolymyxinB.
Twoantibioticscommonlycombinedwithpolymyxinaregramicidinand
trimethoprim.Gramicidinaltersbacterialcellwallpermeability.Like
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bacitracin,itisonlyusedtopicallybecauseofsystemictoxicity.
Trimethoprimisacompetitiveinhibitorofbacterialdihydrofolatereductase,
anenzymethatisnecessaryforpurinesynthesis.149Theothercompounds
thatpolymyxinBarecombinedwithareaddressedelsewhereinthischapter.
Allpolymyxincombinationproductshaveshownefficacyagainstbacterial
conjunctivitis,150,151butnoclinicalstudiesoftheiruseinthetreatmentof
bacterialkeratitishavebeenconducted.Clinicalstudieshaveshownthat
polymyxinBtrimethoprimandpolymyxinBneomycingramicidinareas
effectiveaseachother152153andgentamicinsulfate,154sodium
sulfacetamide,154andchloramphenicol138,150inthetreatmentofbacterial
conjunctivitis.
AdverseEffects
Thosecombinationantibioticproductsthatdonotcontainthehighly
allergenicagentneomycinarecommonlyrecommendedinthe
literature.4,149,150PolymyxinBrarelycausesahypersensitivityreaction.
ChronicuseofpolymyxinBmayresultintoxicconjunctivitis.
SULFACETAMIDE
Sulfacetamide(Fig.9)10%ointment(AKSulf,Cetamide,SulamydSodium)
andsulfacetamide10%to30%solutions(10%AKSulf[Akorn,Inc,Buffalo
Grove,IL],Bleph10[Allergan,Inc,Irvine,CA],Ophthacet,Ocusulf,Sulf10
[CIBAVision,Duluth,GA],SulamydSodium,andIsoptoCetamide)actby
preventingtheincorporationofparaaminobenzoicacidintofolicacid,thus
inhibitingbacterialpurinebiosynthesis.Sulphonamidesarebacteriostatic.
Fig.9.Chemicalstructureofsulfacetamideone
ofthemorecommonlyusedsulfonamidesin
ophthalmicpreparations.
Sulphonamideswereusedinthetreatmentofexternalocularinfections
beforetheneedtoperformefficacystudies.Itisdifficulttofind
documentationoftheirvalueinthemedicalliterature.Inastudyof158
casesofculturepositivepediatricconjunctivitis,topicalsulfacetamidewas
foundtobeequivalentinefficacytotrimethoprimpolymyxinBand
gentamicinsulfatesolutions.154Likeerythromycin,sulfacetamideshavea
broadspectrumofantibacterialactivity,butmanystrainsofresistant
bacteriahavedeveloped.SulfacetamideisstilleffectiveagainstH.
influenzaebutisineffectiveagainstmanystaphylococcalisolates,S.
marcescens,andP.aeruginosa,whichmakesitapoorchoiceasafirstline
treatmentforbacterialkeratitis.155Itremainsadrugofchoiceforthe
treatmentofNocardiaspecies.156
AdverseEffects
Topicalsulfacetamideisgenerallywelltolerated.However,thereisasmall
butsignificantriskofStevensJohnsonsyndromeassociatedwiththeuseof
topicalsulfacetamide.157159
TETRACYCLINES
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Tetracycline(Fig.10)inhibitsbacterialproteinsynthesisbybindingtothe
30Sribosome,anditisamongthebroadestspectrumagentsavailable.For
mostorganisms,tetracyclineisbacteriostatic.
Fig.10.Thebasisofthetetracyclines,shown
above,isafourring
naphthacencecarboxamide.
Systemicandtopical(ointment)tetracyclineareusedconcurrentlytotreat
C.trachomatisconjunctivitis.Tetracyclinecanalsobeusedforprophylaxis
againstophthalmianeonatorumfromN.gonorrhoeaeorchlamydial
infections.160,161Innewbornsdevelopingophthalmianeonatorum,coexisting
oropharyngealinvolvementusuallyrequiresmorethantopicaldruguse.
AdverseEffects
Adversereactionsfromtetracyclines,includingdepositionintheteethand
bones,maybeseenwithbothsystemicuseandtopicalapplication.
VANCOMYCIN
Vancomycinisacomplexbactericidaltricyclicglycopeptide(Fig.11)that
inhibitsbacterialcellwallsynthesis.162,163Itisactiveprimarilyagainst
grampositivebacteria,includingmethicillinresistantS.aureus,S.
epidermidis,andEnterococcusspecies.
Fig.11.Vancomycinisacomplexbactericidal
tricyclicglycopeptide.
Topicalvancomycinhasbeenusedsuccessfullytotreatchronicmethicillin
resistantS.aureusininstitutionalizedpatients.164Vancomycinhasnotbeen
testedagainstotherantibioticsinthetreatmentofbacterialkeratitis,but
therearenumerousreportedcasesofkeratitiscausedbyresistant
organismsthatresolvedwithtopicalvancomycintherapy.165,166Vancomycin
50mg/mLhasbeentestedagainstciprofloxacin0.3%inarabbitmodelof
methicillinresistantS.aureuskeratitisciprofloxacinwasfoundtobemore
effectiveinthatstudy.167Theseresultshavenotbeenverifiedinclinical
studies.Vancomycinshouldbeconsideredasafirstlinetherapyinsevere
casesofkeratitisinpatientsathighriskforinfectionbymethicillinresistant
organisms,suchashealthcareworkersorinstitutionalizedpatients.
AdverseEffects
Vancomycinisrarelyusedinroutineocularinfectionsbecauseitisnot
commerciallyavailableinatopicalophthalmicform.Itsuseshouldbe
limitedbecauseoftheriskofthedevelopmentofbacterialresistance.
TopicalapplicationofvancomycinproducesdiscomfortbecauseofitslowpH
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insolution.Adverseeffectsincludeconjunctivalinjection,chemosis,papillary
conjunctivitis,andsuperficialpunctatekeratopathy.Inrabbits,topical
applicationwasnotedtoretardcornealepithelialwoundhealing.168
SELECTINGTHEOPTIMALOPHTHALMICANTIBIOTIC
TheGoalsofTreatment
Inallbacterialinfections,thegoaloftreatmentistorapidlyeradicatethe
specificpathogenwhileminimizingadversesideeffectsandtreatmentcosts.
Anidealagentdoesnotexistandthechoiceofthemostappropriateagent
mustbebasedonarationalcompromise.Thenatureofthiscompromise
mustbepatientanddiseasespecific.
CLINICALJUDGMENTINCHOOSINGANOPHTHALMICANTIBIOTIC
Inuncomplicatedacutebacterialconjunctivitis,theneedfortreatment
efficacy,thoughstillimportanttolimittherateofrecurrenceandspreadto
personalcontacts,mustbebalancedbyastrongassuranceoftreatment
safetyandcomfort,particularlyinchildren,andareasonableconcernfor
treatmentcost.Afurtherconsiderationistolimittheuseofantibiotics
neededforsystemicinfectionssothatwidespreadresistancedoesnotoccur.
Thepreparationchosenisusuallycommerciallyavailableinatopical
ophthalmicformandhasabroadspectrumofefficacyagainstthemost
commonlyimplicatedpathogens.Theophthalmologistandthepatientcan
usuallyrestassuredthattheyaredealingwithaselflimitedandusually
benignprocess.Inthetreatmentofacutebacterialconjunctivitis,nosafety
riskscanbejustified,andagentswithknowntoxicityorahighincidenceof
hypersensitivityreactionsshouldnotbeconsidered.However,inchronicor
recurrentbacterialconjunctivitis,theidealagentisthemosteffectivebroad
spectrumantibioticavailablethatthepatientwilltolerate,unlessantibiotic
susceptibilitytestingsuggeststhataspecificnarrowspectrumagentmaybe
moreeffective.
Thesightthreateningnatureofbacterialkeratitismeansthattreatment
speedandefficacymusttakeonmoreimportance.Guidanceinthechoiceof
anantibioticbyknowingthespecificorganismanditssensitivitycanbe
crucialtotheoutcome.Thecostoftreatmentshouldonlybetakeninto
accountiftwoormoretreatmentoptionsareequalinefficacyandsafety.153
CommonPrescribingPractices
Physiciansvarywidelyintheirprescribingpractices.Mostcasesofacute
bacterialconjunctivitisaretreatedbynonophthalmologistphysicians.
Identificationofthecausativeorganism(e.g.,bygramstainorculture)is
rare.Theuseofamild,broadspectrumantibioticpreparation,suchasone
ofthepolymyxinBcombinationproducts(e.g.,polymixinBtrimethoprimor
polymixinBzincbacitracin)canberecommended.Sodiumsulfacetamideis
alsocommonlyused,despiteitsbacteriostaticnatureandlimitedspectrum
becauseofitslowcostandlongclinicalhistory.Theuseofchloramphenicol,
becauseofthefearofaplasticanemia,andtheuseofneomycin,becauseof
itsrelativelyhighrateofallergicreactions,areonthedecline.Erythromycin
cannotberecommendedbecauseofitslackofbroadspectrumandthe
emergenceofresistantH.influenzae.Inmoreseriouscases,a
fluoroquinolonemaybeindicatedbecauseofitsbroadspectrumandefficacy
againstH.influenzae,asmentionedearlier,acommonpathogeninpediatric
conjunctivitis.
Whenbacterialconjunctivitisbecomeschronicorrecurrentculturingand
sensitivityofthecausativeagentisrecommended.Insuchcases,more
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aggressivetreatmentwithatopicalfluoroquinoloneisrecommended.Ofthe
fluoroquinolones,ofloxacinfollowedbyciprofloxacinhasthebestcoverage,
andthelowestincidenceofresistance.Theirexcellenttissuepenetration
capabilitieswillallowthemtoeradicateanybacteriathathavebreachedthe
cornealepitheliumandmayalsohelpreduceselfreinfectionfrompathogens
sequesteredinthemeibomianorificesorlacrimalcanaliculi.
BACTERIALKERATITIS
CommonPrescribingPractices
Themedicalliteraturedocumentsthevalueoffortifiedantibioticsandthe
commerciallyavailabletopicalfluoroquinolonepreparationsinthetreatment
ofbacterialkeratitis.Ina1996surveyof124ophthalmologistsfromFlorida,
NewYork,andIllinois,16982%reportedthattheywouldusea
fluoroquinoloneforinitialtreatmentoflessseverecornealulcers,and6%
saidthattheywouldusefortifiedantibiotics.Formoresevereulcers,
prescribingpracticesshiftedslightlytowardfortifiedantibiotics,with62%
reportingthattheywouldusefluoroquinolonesforthesecasesand23%
statingthattheywouldusefortifiedantibiotics.Onecommoncombinationof
extemporaneouslycompoundedfortifiedantibioticsiscefazolin10%and
tobramycin1.5%administeredasseparatesolutions.Vancomycin50mg/mL
shouldbesubstitutedforcefazolinforthosecasesinwhichantibiotic
susceptibilitytestingsuggeststhatitwillbethemosteffectiveagentorthere
isasignificantriskofmethicillinresistantS.aureus.Invitrosusceptibility
testinghasshownthattheuseofafluoroquinoloneincombinationwith
fortifiedcefazoliniseffectiveagainstmoreocularisolatesthanofloxacin,
ciprofloxacin,ornorfloxacinusedalone.Therefore,fortifiedtobramycinmay
bereplacedwithcommerciallyavailableofloxacinorciprofloxacin.127Itis
notknownwhethertheprecipitationofciprofloxacinhasanydetrimental
effectonefficacy.Norfloxacinistheleasteffectiveoftheavailable
fluoroquinolonesandhasnotbeenshowneffectiveinthetreatmentof
bacterialkeratitis.
BacktoTop
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