Infective EndocarditisJohn R. Butterly, M.D.

Infective EndocarditisEssential characteristicsGeneral definitions and epidemiologyNVEI.V. drug abusePVEPathogenesis

Pathophysiology

Clinical features

Treatment

Infective EndocarditisFebrile illnessPersistent bacteremiaCharacteristic lesion of microbial infection of the endothelial surface of the heart

Variable in sizeAmorphous mass of fibrin & plateletsAbundant organismsFew inflammatory cellsthe vegetation

Infective EndocarditisTypically involves the valvesMay involve all structures of the heartChordae tendinaeSites of shuntingMural lesionsInfection of vascular shunts, by strict definition, is endarteritis, but lesion is the sameMajority of cases caused by streptococcus, staphylococcus, enterococcus, or fastidious gram negative cocco-bacillary forms

Infective EndocarditisGram negative organismsP. aeruginosa most commonHACEK - slow growing, fastidious organisms that may need 3 weeks to grow out of cultureHaemophilus sp.ActinobacillusCardiobacteriumEikenellaKingella

Infective EndocarditisAcute Toxic presentationProgressive valve destruction & metastatic infection developing in days to weeksMost commonly caused by S. aureusSubacuteMild toxicityPresentation over weeks to monthsRarely leads to metastatic infectionMost commonly S. viridans or enterococcus

Infective EndocarditisCase rate may vary between 2-3 cases /100,000 to as high as 15-30/100,000 depending on incidence of i.v. drug abuse and age of the population55-75% of patients with native valve endocarditis (NVE) have underlying valve abnormalitiesMVPRheumaticCongenitalASH or:i.v. drug abuse

Infective EndocarditisCase rates7-25% of cases involve prosthetic valves25-45% of cases predisposing condition can not be identified

Infective EndocarditisPediatric populationThe vast majority (75-90%) of cases after the neonatal period are associated with an underlying congenital abnormalityAortic valveVSDTetralogy of FallotRisk of post-op infection in children with IE is 50%MicrobiologyNeonates: S. aureus, coag staph, group B strepOlder children: 40% strep, S. aureus

Infective EndocarditisAdult populationMVP prominent predisposing factorHigh prevalence in population2-4%20% in young womenAccounts for 7 30% NVE in cases not related to drug abuse or nosocomial infectionRelative risk in MVP ~3.5 8.2, largely confined to patients with murmur, but also increased in men and patients >45 years oldMVP with murmur incidence IE 52/100/000 pt. yearsMVP w/o murmur incidence IE 4.6/100,000 pt. years

Infective EndocarditisAdult populationRheumatic Heart Disease20 25% of cases of IE in 1970s & 80s 7 18% of cases in recent reported seriesMitral site more common in womenAortic site more common in menCongenital Heart Disease10 20% of cases in young adults 8% of cases in older adultsPDA, VSD, bicuspid aortic valve (esp. in men>60)

Infective EndocarditisIntravenous Drug AbuseRisk is 2 5% per pt./yearTendency to involve right-sided valvesDistribution in clinical series46 78% tricuspid24 32% mitral 8 19% aorticUnderlying valve normal in 75 93%S. aureus predominant organism (>50%, 60-70% of tricuspid cases)

Infective EndocarditisIntravenous Drug AbuseIncreased frequency of gram negative infection such as P. aeruginosa & fungal infectionsHigh concordance of HIV positivity & IE (27-73%)HIV status does not in itself modify clinical pictureSurvival is decreased if CD4 count < 200/mm3

Infective EndocarditisProsthetic Valve Endocarditis (PVE)10 30% of all cases in developed nationsCumulative incidence 1.4 3.1% at 12 months3.2 5.7% at 5 yearsEarly PVE within 60 daysNosocomial (s. epi predominates)Late PVE after 60 daysCommunity (same organisms as NVE)

Infective EndocarditisPathologyNVE infection is largely confined to leafletsPVE infection commonly extends beyond valve ring into annulus/periannular tissueRing abscessesSeptal abscessesFistulaeProsthetic dehiscenceInvasive infection more common in aortic position and if onset is early

Infective EndocarditisPathogenesisEndothelial damagePlatelet-fibrin thrombiMicroorganism adherence

Infective EndocarditisNonbacterial Thrombotic EndocarditisEndothelial injuryHypercoagulable stateLesions seen at coaptation points of valvesAtrial surface mitral/tricuspidVentricular surface aortic/pulmonicModes of endothelial injuryHigh velocity jetFlow from high pressure to low pressure chamberFlow across narrow orifice of high velocityBacteria deposited on edges of low pressure sink or site of jet impaction Venturi EffectPlatelet-fibrin thrombi

Venturi Effect

Conversion of NBTE to IEFrequency & magnitude of bacteremiaDensity of colonizing bacteriaOral > GU > GIDisease state of surfaceInfected surface > colonized surfaceExtent of traumaResistance of organism to host defensesMost aerobic gram negatives susceptible to complement-mediated bactericidal effect of serumTendency to adhere to endotheliumDextran producing strepFibronectin receptors on staph, enterococcus, strep, Candida

PathophysiologyClinical manifestationsDirect Constitutional symptoms of infection (cytokine)Indirect Local destructive effects of infectionEmbolization septic or blandHematogenous seeding of infectionN.B. may present as local infection or persistent fever, metastatic abscesses may be small, miliaryImmune responseImmune complex or complement-mediated

PathophysiologyLocal destructive effectsValvular distortion/destructionChordal rupturePerforation/fistula formationParavalvular abscessConduction abnormalitiesPurulent pericarditisFunctional valve obstruction

PathophysiologyEmbolizationClinically evident 11 43% of patientsPathologically present 45 65%High risk for embolizationLarge > 10 mm vegetationHypermobile vegetationMitral vegetations (esp. anterior leaflet)Pulmonary (septic) 65 75% of i.v. drug abusers with tricuspid IE

Clinical FeaturesInterval between index bacteremia & onset of sxs usually < 2 weeksMay be substantially longer in early PVEFever most common signMay be absent in elderly/debilitated pt.Murmur present in 80 85%Generally indication of underlying lesionFrequently absent in tricuspid IEChanging murmur

Classical Peripheral ManifestationsLess common today

Not seen in tricuspid endocarditis

Petechiae most common

Janeway Lesions

Splinter Hemorrhage

Oslers Nodes

Subconjunctival Hemorrhages

Roths Spots

Clinical FeaturesSystemic emboliIncidence decreases with effective anti-microbial RxNeurological sequelaeEmbolic stroke 15 20% of patientsMycotic aneurysmCerebritis CHFDue to mechanical disruptionHigh mortality without surgical interventionRenal insufficiencyImmune complex mediatedImpaired hemodynamics/drug toxicity

DiagnosisPublished criteria for diagnostic purposes in obscure casesHigh index of suspicion in patients with predisposing anatomy or behaviorBlood culturesEchocardiographyTTE 60% sensitivityTEE 80 95% sensitive

Goals of TherapyEradicate infection

Definitively treat sequelae of destructive intra-cardiac and extra-cardiac lesions

Antibiotic TherapyTreatment tailored to etiologic agentImportant to note MIC/MBC relationship for each causative organism and the antibiotic usedHigh serum concentration necessary to penetrate avascular vegetation

Antibiotic TherapyTreatment before blood cultures turn positive Suspected ABEHemodynamic instabilityNeither appropriate nor necessary in patient with suspected SBE who is hemodynamically stable

Antibiotic TherapyEffective antimicrobial treatment should lead to defervescence within 7 10 daysPersistent fever in:IE due to staph, pseudomonas, culture negativeIE with microvascular complications/major emboliIntracardiac/extracardiac septic complicationsDrug reaction

Surgical Treatment of Intra-Cardiac ComplicationsNYHA Class III/IV CHF due to valve dysfunctionSurgical mortality 20-40%Medical mortality 50-90%Unstable prosthetic valveSurgical mortality 15-55%Medical mortality near 100% at 6 monthsUncontrolled infection

Surgical Treatment of Intra-Cardiac ComplicationsUnavailable effective antimicrobial therapyFungal endocarditisBrucellaS. aureus PVE with any intra-cardiac complicationRelapse of PVE after optimal therapy

Surgical Treatment of Intra-Cardiac ComplicationsRelative indicationsPerivalvular extension of infectionPoorly responsive S. aureus NVERelapse of NVECulture negative NVE/PVE with persistent fever (> 10 days)Large (> 10mm) or hypermobile vegetationEndocarditis due to highly resistant enterococcus

PreventionProphylactic regimen targeted against likely organismStrep. viridans oral, respiratory, eosphogeal Enterococcus genitourinary, gastrointestinalS. aureus infected skin, mucosal surfaces

Prevention the procedureDental procedures known to produce bleedingTonsillectomy Surgery involving GI, respiratory mucosaEsophageal dilationERCP for obstructionGallbladder surgeryCystoscopy, urethral dilationUrethral catheter if infection presentUrinary tract surgery, including prostateI&D of infected tissue

Prevention the underlying lesionHigh risk lesionsProsthetic valvesPrior IECyanotic congenital heart diseasePDAAR, AS, MR,MS with MRVSDCoarctation Surgical systemic-pulmonary shunts

Intermediate riskMVP with murmurPure MSTricuspid diseasePulmonary stenosisASHBicuspid Ao valve with no hemodynamic significanceLesions at highest risk

Prevention the underlying lesionLow/no riskMVP without murmurTrivial valvular regurg.Isolated ASDImplanted device (pacer, ICD)CADCABG

This wallet card is to be given to patients by their physician. Healthcare professionals, please see back of card for reference to the complete statement.

Name: ____________________________________________ needs protection from BACTERIAL ENDOCARDITIS because of an existing HEART CONDITION Diagnosis: __________________________________________ Prescribed by: _______________________________________ Date: ______________________________________________

ChemoprophylaxisAdult Prophylaxis: Dental, Oral, Respiratory, Esophageal Standard Regimen

Amoxicillin 2g PO 1h before procedure or Ampicillin 2g IM/IV 30m before procedure Penicillin Allergic Clindamycin 600 mg PO 1h before procedure or 600 mg IV 30m before Cephalexin OR Cefadroxil 2g PO 1 hour before Cefazolin 1.0g IM/IV 30 min before procedure Azithromycin or Clarithromycin 500mg PO 1h before

Adult Genitourinary or Gastrointestinal Procedures High Risk Patients Standard Regimen Before procedure (30 minutes): Ampicillin 2g IV/IM AND Gentamicin 1.5 mg/kg (MAX 120 mg) IM/IV After procedure (6 hours later) Ampicillin 1g IM/IV OR Amoxicillin 1g PO Penicillin Allergic Complete infusion 30 minutes before procedure Vancomycin 1g IV over 1-2h AND Gentamicin 1.5 mg/kg IV/IM (MAX 120 mg)

Moderate Risk Patients Standard Regimen Amoxicillin 2g PO 1h before OR Ampicillin 2g IM/IV 30m before Penicillin Allergic Vancomycin 1g IV over 1-2h, complete 30m before

SummaryYou need to go to medical school (and graduate) in order to take care of patients with endocarditis.