Infective EndocarditisIrsad Andi ArsoFaculty of Medicine Gadjah Mada University

ObjectivesDescribe the incidence of IE in various heart conditions.Review the Duke criteria of infective endocarditisReview the indications for prophylaxis and current recommendations for antimicrobial therapy.Review the efficacy and controversies in IE prophylaxis.

BackgroundRelatively rare in childrenPre-antibiotic era: mortality was nearly 100%Mortality approaches 15-25%

Epidemiology

Increasing incidence beginning in the 80sIncreasing number of surgical patientsIncreasing number of complex congenital heart diseaseIncreased use of prosthetic materialsNICUs and PICUs

Pathogenesis, Part 1Damaged endotheliumundamaged endothelium not conducive to bacterial colonizationendothelium can be damaged by high-velocity flowstrauma to endothelium can induce thrombogenesis, leading to nonbacterial thrombotic endocarditis (NBTE). NBTE is more receptive to colonization

Heart disease and IEBerkowitz, FE: Infective endocarditis. IN Nichols EG, Cameron DE, Greeley WJ, et al (eds):Critical Heart Disease in Infants and Children. St. Louis, Mosby-Year Book, 1995.

Disease

No.

%

Acyanotic Heart Disease

VSD

194

21.8

Aortic stenosis

89

10.0

PDA

25

2.8

Coarctation of the aorta

25

2.8

Pulmonary stenosis

21

2.4

VSD with other defects

18

2.0

Atrioventricular septal defect

16

1.8

Mitral valve abnormality

16

1.8

Atrial septal defect

11

1.2

Mitral valve prolapse

8

0.9

Cyanotic Heart Disease

Tetralogy of Fallot

143

16.0

Transposition of Great Vessels

35

3.9

Tricuspid Atresia

9

1.0

Rheumatic Heart Disease

86

9.7

No Heart Disease

75

8.4

Pathogenesis, Part 2Berkowitz, FE: Infective endocarditis. IN Nichols EG, Cameron DE, Greeley WJ, et al (eds):Critical Heart Disease in Infants and Children. St. Louis, Mosby-Year Book, 1995.

Microorganism

No.

%

Streptococcus viridans

289

31.3

Staphylococcus aureus

225

24.4

Negative cultures

152

16.4

Other streptoccal species (e.g. enterococci)

55

5.9

HACEK and diphtheroids

50

5.4

Gram negative bacilli

45

4.8

Strept pneumoniae

18

1.9

Fungi

14

1.5

Others

28

3.0

MicrobiologyS. ViridansMost common causative organismGram negative bacilliNeonates and immunocompromised patientsProsthetic valvesWithin first year of surgery: Coag-negative staphAfter first year: similar to native valve endocarditisHACEK organismsHemophilus, Actinobacillus, Cardiobacterium, Eikenella, KingellaFrequently affect damaged valves and can cause emboli

DiagnosisTraditionally based upon positive blood cultures in the presence of a new or changing heart murmur, or persistent fever in the presence of heart disease.Shortcomings include culture-negative endocarditis, lack of typical echocardiographic findings, etc.

Duke CriteriaBased on pathological and clinical criteria.Utilizes microbiological data, evidence of endocardial involvement, and other phenomenon associated with infective endocarditis to estimate the probability of infective endocarditis in a given patient.Has been shown to be valid and reproducible in childrenDurack DT, Lukes AS, Bright DK. New criteria for diagnosis of infective endocarditis: utilization of specific echocardiographic findings. AM J Med 96:200, 1994

Stockheim JA, Chadwick EG, Kessler S, et al. Are the Duke Criteria superior to the Beth Israel criteria for the diagnosis of infective endocarditis in children? Clin Infect Dis 27:1451, 1998

Duke criteriaDefinitivePathological criteriaMicroorganisms, orPathologic lesionsClinical criteria2 major criteria, or1 major and 3 minor criteria, or5 minorPossible Findings consistent with infective endocarditis that fall short of definitive but are not rejectedRejectedFirm alternative diagnosis, orResolution of manifestations of endocarditis with antibiotic therapy of 4 days or less, orNo pathological evidence of endocarditis at surgery or autopsy with antibiotic therapy of 4 days or less

Duke criteria: Major criteriaPositive blood cultureTypical microorganism consistent with IE, from two separate blood culturesS. viridans, S. bovis, HACEKcommunity-acquired S. aureus or enterocci (no primary focus)Persistently positive culturesat least two positive cultures, drawn 12 hours apartall of three, or a majority of four or more cultures (with first and last sample drawn at least one hour apartEvidence of endocardial involvementPositive echocardiogramoscillating intracardiac mass on valve or supporting structures, ormyocardial abscess, ornew partial dehiscence of prosthetic valveNew valvar regurgitation

The echocardiogram in IE

Duke criteria: Minor criteriaPredispositionPredisposing heart condition or IV drug abuserFever> 38.0 C Vascular phenomenaarterial emboli, septic pulmonary infarct, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhage, Janeways lesionImmunologic phenomenaglomerulonephritis, Oslers nodes, Roths spots, rheumatoid factors Microbiologic evidencepositive blood culture but does not meet major criteria as noted Echocardiographic evidenceconsistent with IE but does not meet major criteria as noted

SequelaeNeurologic manifestations, 20%Cerebral emboli, mycotic aneurysms, cerebritis, brain abscess, hemorrhage, etc.Peripheral embolizationIschemia, infarction, mycotic aneurysms, etcPulmonary infarctionRenal insufficiencyCongestive heart failure

Treatment of infective endocarditis GENERAL CONSIDERATIONSAntimicrobial therapy should be administered in a dose designed to give sustained bactericidal serum concentrations throughout much or all of the dosing intervalIn vitro determination of the minimum inhibitory concentration of the etiologic cause of the endocarditis should be performed in all patients

Treatment of infective endocarditisGENERAL CONSIDERATIONS The duration of therapy has to be sufficient to eradicate microorganisms growing within the valvular vegetationsThe need for prolonged therapy in treating endocarditis has stimulated interest in using combination therapy to treat endocarditis

Antibiotic Dosage and routeDuration Comments

Aqueous crystalline12-18 million U/24 h 4 wkspreferred in most patients older than 65 yrspenicillin G sodiumIV either continuouslyand in those with impairment of the eighthor in 6 = divided doses nerve or renal functionorCeftriaxone sodium2g once daily IV or IM 2 wks

Aqueous crystalline12-18 million U/24 h 2 wkswhen obtained 1h after a 20-30 min. penicillin G sodium IV either continuouslyIV infusion or IM injection, serum or in six equallyconcentration of gentamicin of divided dosesapproximately 3 mcg/mL is desirable; with gentamicin1 g IM or IV every 8 h 2 wkstrough concentration should be < 1 pg/mLsulfate

Vancomycin30 mg/kg per 24 h IV 4 wksvancomycin therapy is recommended forhydrochloridein two equally dividedpatients allergic to beta lactams; peak doses, not to exceed 2serum concentrations of vancomycin shouldgram/24h unless serumbe obtained one h after completion of thelevels are monitoredinfusion and should be in the range of 30-45 mcg/mL for twice-daily dosingVIRIDANS STREPTOCOCCI AND STREP. BOVISJAMA 1995; 274:1706

ENTEROCOCCI

STAPH. ENDOCARDITIS IN NATIVE VALVES

STAPH. ENDOCARDITIS IN PROSTHETIC VALVES

HACEK ORGANISMS

Indications for surgery in IE The indications for surgery in patients with native-valve IE and prosthetic-valve IE are essentially the same Surgery is warranted for patients with active IE who have one or more of the following complications:CHF that is directly related to valve dysfunctionPersistent or uncontrolled infection while receiving appropriate antimicrobial therapy, including evidence of perivalvular extensionRecurrent emboli, particularly in the presence of large vegetations

Indications for surgery in IERelative indications for surgeryEvidence of perivalvular infection, such as intracardiac abscess or fistula formationRupture of a sinus of Valsalva aneurysmFungal endocarditisEndocarditis due to highly resistant microorganismRelapse after a course of adequate antimicrobial therapy, particularly in prosthetic valve endocarditisCulture-negative IE with fever more than 10 days after starting empirical therapy

Indications for surgery in prosthetic valve IESame as native valve endocarditisPerivalvular infectionValve Dehiscenceexcessively mobile prosthesis on echoresults in hemodynamic instability

OUTCOME OF SURGERYThe outcome of surgery in patients with IE has been good, particularly when surgical treatment is radical with the removal of all infected and necrotic tissueIn a recent study of 138 patients who underwent valve surgery in the presence of active infection, the early mortality, due to heart failure or septic multiorgan failure, was 11.5 %Risk factors for early mortality were NYHA class IV or cardiogenic shock, advanced age, preoperative acute renal failure, and staphylococcal infectionOperation for infective endocarditis: Results after implantation of mechanical valves. Ann Thorac Surg 1998; 65:359.

ACC/AHA recommendation for surgery in patients with native valve endocarditis

ACC/AHA recommendation for surgery in patients with prosthetic valve endocarditis

ACC/AHA recommendation for valve replacement with mechanical prosthesis

ACC/AHA recommendation forvalve replacement with bioprosthesis

Prevention of IENo randomized controlled human trials which definitively establishes the efficacy of antibiotic prophylaxis.Most cases of endocarditis are NOT attributable to an invasive procedureCurrent recommendations are based upon literature analysis of procedure-related endocarditis, prophylaxis studies in experimental animal models, and retrospective analysis of human endocarditisDajani AS, Taubert KA, Wilson W, et al. Prevention of bacterial endocarditis: Recommendations by the American Heart Association. JAMA 277;1794: 1997

Endocarditis prophylaxis recommendedHigh-riskProsthestic cardiac valvesPrevious bacterial endocarditisComplex cyanotic heart diseaseSurgically constructed systemic-pulmonary shunts or conduitsModerate-riskMost other congenital heart diseaseAcquired valvar dysfunctionHypertrophic cardiomyopathyMitral valve prolapse WITH regurgitation and/or thickened leaflets

Endocarditis prophylaxis NOT recommendedIsolated secundum ASDSurgically repaired VSD, ASD, or PDA after 6 months (no residua)s/p CABGMVP without MRPrevious Kawasaki disease w/o valvar dysfunctionPrevious rheumatic fever w/o valvar dysfunctionPacemakers and AICDsFlow murmurs

Dental procedures and IE prophylaxis: RecommendedDental extractionsPeriodontal proceduresDental implants and reimplantation of avulsed teethEndodontic proceduresSubgingival placement of antibiotic fibers and stripsInitial placement of orthodontic bands (not brackets)intraligamentary local anesthetic injectionsProphylactic cleaning

Dental procedures and IE prophylaxis: Not recommendedRestorative dentistryNon-intraligamentary local anesthetic injectionsTaking oral impressionsFluoride treatmentsOral radiographsOrthodontic appliance adjustmentShedding primary teeth

Other procedures and IE prophylaxis: RecommendedRespiratoryT&ASurgical procedures involving respiratory mucosaRigid bronchoscopyGastrointestinalSclerotherapyEsophageal stricture dilationERCP with biliary obstructionSurgery involving biliary tract or intestinal mucosaGenitourinary tractProstatic surgery, cystoscopyUrethral dilation

Other procedures and IE prophylaxis: Not RecommendedRespiratoryEndotracheal intubationPE tubesFlexible bronchoscopyGastrointestinalTransesophageal echocardiographyEndoscopy (with or without biopsy)Genitourinary tractVaginal hysterectomy, and vaginal or Caesarean deliveriesIn uninfected tissues: urethral catheterization, uterine D&C, therapeutic abortions, sterilization procedures, insertion or removal of IUDsCircumcision

How about Tattoos and Body piercing?Ear piercing43% of respondents had ear piercingOnly 6% took antibiotics23% reported infections but no IE reportedTattoos5% of respondents had tattoosNo antibiotics or infections reported

PhysiciansMajority of physicians did not approve of piercing or tattoos60% felt that IE prophylaxis use was appropriateCetta F, Graham LC, Lichtenberg RC, Warnes CA. Piercing and tattooing in patients with congenital heart disease. J Adolesc Health 1999;24:160