Andersons pediatric cardiology 1491

extraction,andsetuptechniquesarecriticaltoperformance
ofthesebroad-rangetechniques
■Singlegenetargetsthatcanidentifygenusorspecieslevelare
moresensitivethanbroad-range16SrDNAPCR.Theyare
morelikelytobesuccessfulinacutesepsisandendocarditis,
wherecirculatingbacterialnumbersmaybemuchhigher
thaninsubacuteIE.However,multipleprimerssetsare
requiredtoamplifytherangeofpathogensthatcouldbe
present,increasingcomplexityandexpense.
■Inadditiontospeciesidentification,geneticdeterminantsof
antimicrobialresistance,suchasmecA(conferringresistance
tomajorityofβ-lactamantibiotics)inS.aureus,canalsobe
rapidlydetected.
■Inthefuture,high-throughputsequencing(ornext-generation
sequencing)willberoutinelyavailable,whichcan
theoreticallyprovidewhole-genomeanalysisoforganismsin
situ.
2.Proteomictechnology
■Themajorityofcurrentlyavailabletechniquesutilize
MALDI-TOF.
■Canidentifycausativeagentbothrapidlyandaccuratelyonce
aBCispositive.97
■Directidentificationofbacteriainblood(withoutaculture
step)byMALDI-TOFispossible,althoughnotyet
developedenoughtobeusefulinclinicalpractice.
■Accuratedeterminationofminimuminhibitoryconcentration
tokeyantibioticsusedindefinitivetherapyoftenstill
requiresisolationandcultureoftheorganism.
■Futuredevelopmentsincludeuseofsophisticatedmass
spectrometryandproteomictechniquesthatnotonlydetect
thepathogenbutalsoresistanceandvirulencedeterminants.

3.Investigationofresectedmaterial,bybothbroad-rangeandpathogenspecificPCRsandmassspectrometrytechniques,canbeparticularly
informativeinidentifyingtheetiologicagent.98,99Thiscanbeusefulto
confirmacausativeagentwhereblood(ortissue)culturesmayhavenot
beenconclusiveormayhavebeenmixed,100orinbloodculture
negative–endocarditis(BCNE).


BloodCulture–NegativeEndocarditis
BCNEcanoccurdueto:
1.Priorantibioticadministration
2.Suboptimalculturetechniques
3.Fastidious,intracellularorfactitivelyintracellular,orrequirespecialized
culturetechniquesorrarelycultivablefromBCs,including:
■Coxiellaburnetii
■Bartonellaspp.
■Brucellaspp.
■Nutritionalvariantgram-positive(formerlyStreptococci)
organismsAbiotrophiasp.,Granulicatellaspp.
■Mycobacteriaspp.
■Mycoplasmaspp.
■Legionellaspp.
■Tropherymawhipplei
■Filamentousfungi
Insuchcases,acombinedapproach,usingserologicassays,directPCRon
blood,andmoleculartestingonresectedmaterialcanestablishthecausative
agent,whichallowsforreasonableaccuracyofdetectionrates.101,102
TheproportionofBCNEvariesquitewidelybetweenstudies:26.6%ina
mixedadultandpediatriccohort,10330.2%inapediatriccohort.16Thesemight
becomeidentifiedonmolecularstudiesonresectedmaterial.Itisclearthat
furtherdevelopmentofsensitiveandaccuratediagnostictests,including

molecularandproteomictechniques,arewarranted.

AntimicrobialTherapy
Principles
1.EffectivemanagementofIErequiresatleastonebactericidal
antimicrobialtobeusedinhighdosesthatiscorrectedforage,weight,
andadjustedforrenalfunction.
2.TreatmentofIEisnecessarilyprolongedbecauseinfectionisestablished


inabiofilmmatrix.Organismscontainedthereinareeithertolerantto
bactericidalkillingorcanexistas“persisters.”Thisisespecially
relevantforprostheticmaterialIE;thereforedurationoftreatmentis
long(6weeksorlonger).Inaddition,biofilmandvegetationprotect
microorganismsfromhost-mediatedclearancemechanisms.
3.CurrentAmericanHeartAssociation(AHA)andESCguidelinesprovide
comprehensiveprotocolsforpathogen-specifictherapy,butthereare
importantdifferences,whicharedetailedinTable56.6.Thesuggested
antibiotictreatmentforstreptococcalIEisshowninTable56.7andfor
staphylococcalIEisshowninTable56.8.Thetherapyshouldalwaysbe
advisedbyaclinicalmicrobiologist/infectiousdiseasesspecialist.
Table56.6
DifferencesandSimilaritiesBetween2015ESCandPediatricAHAGuidelinesin
AntimicrobialTherapyforInfectiveEndocarditis
AHA2
Fortreatmentof
streptococcalIE:
■Short-course(2weeks)
standardregimenfortreatment
ofuncomplicatedIEduetooral

streptococciinchildrennot
recommendedduetolackof
effectivenessdata
■MICsforhighlypenicillin
susceptibility≤0.1mg/L
■MICsforrelativelyresistant
strains≥0.2mg/L
Treatmentof
Staphylococcusspp.:
■TreatnativevalveIEwith
oxacillin(methicillin)-sensitive
strains;gentamicincanbeused
forfirst3–5daysofinitial
treatment,butthismay
increaselikelihoodof
ototoxicityorrenaltoxicity
■Nomentionofdelayof
rifampicintoeither
flucloxacillinorvancomycinin
treatmentofprostheticvalve
endocarditis
■Daptomycinisnow
recommendedasanalternative
agentfortreatmentof

ESC1
FortreatmentofstreptococcalIE:
■Short-course(2weeks)standardregimenfortreatmentof
uncomplicatedIEnotexplicitlyruledout
■MICsforhighlypenicillinsusceptibility≤0.0125mg/L

■MICsforrelativelyresistantstrains0.250–2.0mg/L

TreatmentofStaphylococcusspp.:
■TreatnativevalveIEwithoxacillin(methicillin)-sensitive
strains;gentamicinnotrecommendedduetolackof
evidenceofefficacyandtoxicityconcerns
■Forprostheticvalveendocarditis,additionofrifampicinto
eitherflucloxacillinorvancomycincanbedelayeduntil3–
5daysofeffectivetherapywitheitheroftheseagents.The
rationalesupportingthisrecommendationisbasedonthe
antagonisticeffectoftheantibioticcombinationswith
rifampinagainstplanktonic/replicatingbacteriaandthe
synergyseenagainstdormantbacteriawithinthebiofilm.
■Daptomycinisnowrecommendedasanalternativeagent
fortreatmentofstaphylococcalIEforpenicillin-allergic
(anaphylaxis)patientsandintreatmentofmethicillinresistantstaphylococciwhenvancomycincannotbeused.
Daptomycinmaybesuperiortovancomycinfortreatment
ofeitherMSSA(ifpenicillinallergic)orMRSAIEwhen