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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