Infective endocarditis

Mohamed Salih Aziz

definitionLife-threatening infection involving the

endocardium and the cardiac valves.May also involve septal defects.Infective preferred to bacterial.

Epidemiology10-20,000 cases per year in the USMale:Female ratio 1.7:1New trends

Mean age was 30 in 1926, now > 50% of patients are over 60

Decline in incidence of rheumatic feverMore prosthetic valvesMore nosocomial cases, injected drug useMore staphylococcal infection

EpidemiologyMitral valve alone 28-45%Aortic valve alone 5-36% (bicuspid valve in

20% of all native valve IE)Both mitral and aortic valves 0-36%Tricuspid valve 0-6%Pulmonic valve <1%Right and left sided 0-4%

ClassificationOld:

Subacute Bacterial Endocarditis Death in 3-6 months

Acute Bacterial Endocarditis Death in < 6 weeks

New:Native Valve EndocarditisProsthetic Valve Endocarditis

PathogenesisAlteration of the valvular endothelial

surface leading to deposition of platelets and fibrin

Bacteremia with seeding of non-bacterial thrombotic vegetation (NBTE)

Adherence and growth, further platelet and fibrin deposition

Extension to adjacent structuresPapillary muscle, aortic valve ring abscess,

conduction system

PathogenesisLow pressure (downstream) side of structural

lesionAtrial side of mitral valve (MR)Ventricular side of aortic valve (AR, AS with R)Congenital abnormality (MV prolapse, bicuspid

AV)Scarring from rheumatic heart disease or

sclerosis as a consequence of agingProsthetic valves

Other turbulence, high-velocity jetsVentricular septal defectStenotic valve

Direct mechanical damage from catheters, pacemaker leads

PathogenesisTransient bacteremia

Traumatization of mucosal surface colonized with bacteria (oral, GI)

Low grade, cleared in 15-30 minutesSusceptibility to complement-mediated

bacterial killingLeads to concept of prophylaxis

MicrobiologyStaphylococcus aureus (30-40%)Viridans group streptococci (18%)Enterococci (11%)Coagulase-negative staphylococci (11%)Streptococcus bovis (7%)Other streptococci (5%)Non-HACEK Gram negatives (2%)HACEK Organisms (2%)Fungi (2%)“Culture negative” (2-20%)

Streptococcus ViridansOral origin90% cure rate 30% complications

Strep. Gallolyticus (Bovis)GI lesions CA colon colonoscopy or barium enema should be

performed

Strept. PneumoniaeRareTypically has fulminant courseAssociated e perivalvular abscessAssociated e pericarditisAortic valve typically involvedH/O alcohol abuseConcurrent meningitis in ~ 70%

Group B strep ( agalactiae)Risk factors ( DM, liver failure, elective

abortion, carcinoma, alcoholism and drug abuse)

Associated with villous adenoma of the colonMortality is 50%

EnterococcusAffects older men after GU manipulationsAffects younger women after obst.

Manipulations40% no obvious underlying heart disease.95% develop a heart murmur.Peripheral stigmata are uncommon.

Staph aureusFulminant course.Wide spread metastatic infections e.g myocardial

abscesses, purulent pericarditis, valve ring abscesses, and peripheral abscesses in brain, kidneys, spleen.

40% chance of death.1/3 neurological manifestations e.g hemiplegia.The most common causative organism in drug

addicts.Less severe in addicts than non-addicts.Coagulase –ve staph. Common in prosthetic valve

endocarditis.

Gram –ve endocarditisE.g gram –ve bacilli ( HACEK,

enterobactericae).Increased risk in drug addicts, elderly,

prosthetic valves and cirrhotic.CHF is commonPrognosis is poorMortality ~ 80%

Salmonella speciesValvular perforationsAtrial thrombiMyocarditispericarditis

Serrata marcescensesNoted mainly in drug abusersTypically involve mitral and aortic valveLarge vegetation and near total occlusion of

the valvular orifice Absence of significant underlying valvular

destruction

PseudomonasDrug addictsAffects normal valvesMajor embolic phenomenaInability to sterilize valvesNeurologic complicationsRing and annular abscessesSplenic abscessesProgressive CHFAssociated with the use of Pentazocine and

Triplelennamine

Fungal endocarditisIncreased risk in drug addicts, immunocomromised, broad

spectrum antibiotics, CV catheters.Candida parpsilosis and candida tropicalis

predominate in injecting drug abusers.Candida albicans and aspergillus non-drug addictsPoor prognosis due toLarge, bulky vegetations, invasion of myocardiumWide spread septic emboliPoor penetration of antifungal agents into vegetations-ve blood culuresMortality >80% for molds and > 40% for yeasts

Q fever ( Coxiella burnetii)Most patients have underlying heart disease.Chronic presentation.Exposure to animals and its products.H/O influenza-like illness 6-12 months

previously.majority of cases occur in prosthetic valvesCommonly affects aortic valveAssociated with hepatosplenomegaly,

thrombocytopenia, hypergammaglobulenemia and immune complex glomerulonephritis.

Culture –ve endocarditis<5 %Recent administration of antibiotics.Slow growth e.g HACEKFungal endocarditis.Non-culturable intracellular micro-organisms

(e.g Bartonella species, chlamydia, T. whipplei).

Marantic endocarditis.

Characteristics of Causative Organisms

Adherence factors critical for growth in the vegetationCan adhere to damaged valves (Staph, Strep and

Enterococci have adhesins that mediate attachment)

Staph adhesin binds fibrinogen and fibronectinBacteria trigger tissue-factor production from

local monocytes and induce platelet aggregation so the organisms become enveloped in the vegetation

Protection from immune clearance leads to large numbers of bacteria (109-1010 per g of tissue)

Risk FactorsStructural heart disease

Rheumatic, congenital, agingProsthetic heart valves

Injected drug useInvasive procedures (?)Indwelling vascular devicesOther infection with bacteremia (e.g.

pneumonia, meningitis)History of infective endocarditis

Clinical ManifestationsSymptoms

Fever, sweats, chillsAnorexia, malaise, weight loss

SignsAnemia (normochromic, normocytic)SplenomegalyMicroscopic hematuria, proteinuriaNew or changing heart murmur, CHFEmbolic or immunologic dermatologic signsHypergammaglobulinemia, elevated ESR,

CRP, RF

Cardiac Pathologic ChangesVegetations on valve closure linesDestruction and perforation of valve leafletRupture of chordae tendinae,

intraventricular septum, papillary musclesValve ring abscessMyocardial abscessConduction abnormalities

S. Aureus mitral valve vegetation, anterior leaflet

Pathologic ChangesKidney

Immune complex glomerulonephritisEmboli with infarction, abscess

Aortic mycotic aneurysmsCerebral embolism

Infarction, abscess, mycotic aneurysmsPurulent meningitis is rare

Pathologic ChangesSplenic enlargement, infarctionSeptic or bland pulmonary embolismSkin

PetechiaeOsler nodes: diffuse infiltrate of neutrophils,

and monocytes in the dermal vessels with immune complex deposition. Tender and erythematous

Janeway lesions: septic emboli with bacteria, neutrophils and S.C hemorrhage and necrosis. Blanching and non-tender. Palms and soles

Case Definition1977 Pelletier and Petersdorf criteria 1981 von Reyn criteria1994 Duke criteria2000 Modified Duke criteria

Modified Duke CriteriaMajor Criteria

Positive blood cultures with typical organisms

Persistently positive blood culturesEvidence of Endocardial involvementPositive Echocardiogram

Oscillating intracardiac massAbscessDehiscence of prosthetic valve

New Valvular regurgitation

Modified Duke CriteriaMinor Criteria

Predisposition (valvular disease or IDU)FeverVascular phenomena (Arterial emboli, septic

pulmonary infarcts, intracranial hemorrhage, Osler, Janeway)

Immunologic phenomena (GN, Osler, Roth spots, Rheumatoid Factor)

Modified Duke CriteriaDefinite IE

Pathologic criteriaClinical criteria

2 Major Criteria OR 1 Major and 3 minor Criteria OR 5 Minor Criteria

Possible IE 1 Major and 1 Minor OR 3 Minor

Rejected IE

Blood CulturesMULTIPLE BLOOD CULTURES BEFORE

EMPIRIC THERAPYIf not critically ill

3 blood cultures over 12-24 hour period? Delay therapy until diagnosis confirmed

If critically ill3 blood cultures over one hour

No more than 2 from same venipunctureRelatively constant bacteremia

“Culture Negative” IELess common with improved blood culture

methodsSpecial media required

Brucella, Mycoplasma, Chlamydia, Histoplasma, Legionella, Bartonella

Longer incubation may be requiredHACEK

Coxiella burnetii (Q Fever), Trophyrema whipplei will not grow in cell-free media

HACEKHaemophilus aphrophilus, H. paraphrophilus,

parainfluenzaeActinobacillus actinomycetemcomitansCardiobacterium hominisEikenella corrodensKingella kingae

Other microbiologic methods

PCRCoxiella burnetiiTropheryma whippleiBartonella henselae

SerologyCoxiella burnetiiBartonellaBrucellaLegionellaChlamydophila psittaci

EchocardiographyTransthoracic

Relatively low sensitivityGood specificity

TransesophagealDetection of valve ring abscess (87% vs. 28%

sensitivity for TTE)Detection of prosthetic valve IE

When to go to TEE first?Limited thoracic windows = TTE low

sensitivityProsthetic valvesPrior valvular abnormalityS. aureus bacteremia and suspected IEBacteremia with organisms likely to cause

IE= high prior probability of IE

Other testsElectrocardiogram

Conduction delaysIschemia or infarction

Chest X-raySeptic emboli in right-sided IEValve calcificationCHF

Treatment of IENative vs. Prosthetic ValveBactericidal therapy is necessaryEradication of bacteria in the vegetation

May be metabolically inactive (stationary phase)

May need higher concentrations of antimicrobial agents

Antimicrobial TherapyMost patients are afebrile in 3-5 daysLong duration of therapy (4-6 weeks or more)Combination therapy most important for

Shorter course regimensEnterococcal endocarditisProsthetic valve infections

Native Valve IEViridans Streptococci and S. bovis

Aqueous Penicillin G 12-20 million units/day continuously or divided q4 or q6 for 4 weeks

If intermediate susceptibility to penicillin, aqueous penicillin G 24 million units or ceftriaxone 2 g q24

PLUS aminoglycoside for the first 2 weeks

Native Valve IEAminoglycosides for synergy

Low concentrations are adequate (1-3 mcg/ml)Gentamicin 3 mg/kg divided q12 or q8Little data for q24 dosing

Native Valve IEEnterococci, ampicillin sensitive

High rates of failureβ-lactams are bacteriostatic, must combine with

aminoglycoside for optimal therapyHigh-level gentamicin resistance occurs in 35%

High-dose ampicillin for 8-12 weeksEnterococci, ampicillin resistant

Vancomycin plus gentamicinEnterococci, vancomycin resistant

Linezolid or daptomycinPenicillin + vancomycin + gentamicin ?

Native Valve IES. aureus

Penicillinase-resistant semi-synthetic penicillin (oxacillin or nafcillin) 1.5-2 g IV q4 or cephalosporin (cefazolin 1-2 g IV q8) for 4-6 weeks

Aminoglycoside synergistic but does not affect survival, not recommended

Short course in right-sided IE 2 weeks of semi-synthetic penicillin and

aminoglycoside

Native Valve IEMethicillin-resistant S. aureus

Vancomycin is bacteriostaticVancomycin plus aminoglycoside or rifampinDaptomycinLinezolid

Native Valve IEHACEK

Ceftriaxone 2 g IV q 24 x 4-6 weeksFungal

AmphotericinFluconazoleCaspofungin, little dataSurgery usually necessary 1-2 weeks into

treatment

Native Valve IEIndications for surgery

Refractory CHFMore than one systemic embolic eventUncontrolled infectionPhysiologically significant valvular

dysfunctionIneffective antimicrobial therapy (e.g.

fungal)Local suppurative complicationsMycotic aneurysm

Prosthetic Valve IEStaphylococci most common

Coagulase negative staphylococciEnterococcusNutritonally variant streptococciFungi

Prosthetic Valve IERisk is greatest in the first 3 months and first

year (early PV IE)Coagulase-negative staphylococci in early

endocarditis, S. aureusLate-onset more similar to native valve disease

in microbiology but more coagulase-negative staphylococci. Valve is endothelialized

Prosthetic Valve IETEE should be used firstStaphylococci

Vancomycin or oxacillin plus rifampicin for at least six weeks, gentamicin for the first two weeks (3 mg/kg q24)

Rifampicin started at least 2 days after 2 other agents to avoid resistance

Prophylaxis of IEUncertainty and controversyNo randomized trialsIndirect evidence (uncontrolled clinical

series, case-control studies)Decision analysis

Clinical Case43 yrs man ESRD, Cadaveric Renal

Transplant 2004Recurrent UTIs, placement of nephrostomy

tubeFevers, chills, altered mental status, sepsis

syndromeBradycardia to 35 and increased PR

Urine with MRSA, 4/4 blood cultures with MRSA

Initial TTE: EF 35-45%, thickened AV with moderate AS, thickened or calcified MV mild MR“Compared with last previous echo, there is no

significant change. In the presence of valvular thickening, cannot rule out endocarditis.

Next day TEE thickened AV, mild to moderate AS, no AR. 2

vegetations ~1 cm on ventricular sideMarkedly thickened MV, large mobile vegetation

>4cm on atrial side anterior leaflet, possible second vegetation on posterior leaflet, mild MR

Renal allograft removed the following day with abscess

Replacement of AV and MV and resection of left ventricular abscess cavity two days later