Endocarditis Khalid Ibrahim, PharmDUniversity of MinnesotaImage adapted from U Copenhagen Dept. Oral Surgery!Overview endocarditis though definitions and epidemiology !Describe the pathophysiology, list implicated pathogens, and identify disease characteristics related to the specific types of endocarditis!Identify the characteristic clinical, physical, and laboratory findings associated with endocarditis!List workup considerations!Identify empiric and definitive treatment modalities for each type of endocarditisObjectivesIntroduction!Endocarditis: inflammation of the endocardium! Implies bacterial presence in the lesion! Can be within septal defects or mural endocardium! Classification!Native Valve Endocarditis!Prosthetic Valve Endocarditis (PVE)!Endocarditis due to intravenous drug abuse (IVDA)! “Infective Endocarditis” vs “Bacterial Endocarditis”!SBE!ABEDefinitions!Acute Bacterial Endocarditis (ABE):! Fulminating infection! High fever! Systemic toxicity! Death in < 6 weeks!Subacute Bacterial Endocarditis (SBE):! Indolent infection! Prior to valvular disease! Death in 6 weeks – 3 months!“Left-sided” endocarditis! Mitral valveDefinitions (cont.)!“Right-sided” endocarditis! Involvement of the tricuspid valve! Related to IVDA and indwelling pacemakers!“Native-valve” endocarditis!“Prosthetic-valve” endocarditis!“Culture-Negative” endocarditis! Bad isolation/identification technique! Fastidious isolate! Non-bacterial culprit! Antibiotics administration pre-cultureEpidemiology!Less than 5 cases per 100,000! Approximately 1 case per 1000 admissions! Unchanged for 30 years!Greater than 50% patients over age 50! Unusual in children!Overall mortality 16-27%! Age! Aortic valve involvement! CHF! CNS complicationsEpidemiology (cont.)!> 75% IE patients have evidence of endocarditis risk factors! History of IV drug abuse! History of rheumatic heart disease ! Congenital heart disease or malformations! Mitral valve prolapse or valvular insufficiency! Ventral septal defect! Valvular stenosis! Prosthetic valveRehm SJ IDCNA 12:879-901,1998 (Adapted)Graphic adapted from Heartpoint.comSurface alterationNBTEBacterial attachmentSheath coveringPathophysiology!Surface Alteration!Non-Bacterial Thrombotic Embolism! Fibrin/Platelet deposition!Bacterial attachment! Transient bacteremia!Sheath covering! Fibrin/Platelets ! Protective environment ! Vegetation growth!109-1010org per gram of tissue!Valvular tissue destructionEtiologyStreptococci 60-80Viridans streptococci 30-40 Enterococci 5-18 Other streptococci 15-25 Staphylococci 20-35 Coagulase-positive 10-27 Coagulase-negative 1-3 Gram-negative aerobic bacilli 1.5-13 Fungi 2-4 Miscellaneous bacteria <5 Mixed infections 1-2 Culture-negative <5-24 Percentage of casesClinical presentation!Variable – ABE with sepsis-like presentation!Vague symptoms! Fever! Anorexia and weight loss! Malaise/weakness! Chills! Diaphoresis! Dyspnea! Cough! Focal neurologic complaints (20% cases)!Embolic phenomenonPhysical findings!Low grade fever (90% cases)!Cardiac examination (85% cases)! Murmur! Change in murmur (10%): Likely 2º CHF!Classic symptoms (>1 in IE)! Petechiae! Splinter hemorrhages! Osler nodes! Janeway lesions! Roth SpotsGraphic adapted from Loyola University Chicago School of MedicineGraphic adapted from pharmacology2000.comLaboratory findings!Hematologic! Often abnormal but not diagnostic! Anemia/pancytopenias ! ESR / CRP! Rh-factor / circulating immune complexes!Blood culture! Single most important lab test! Continuous / low grade bacteremia! Minimum of 3 sets (different sites) in first 24 h! May require >3 if previous abx administered! Hold Cx’s for 3 weeksLaboratory findings (cont.)!Echocardiography! Transthorasic echocardiography (TTE)!Rapid!Non-invasive!98% specificity, 60 % sensitivity!Views obstructed by obesity, COPD, chest-wall deformities! Transesophageal echocardiography (TEE)!Higher ultrasonic frequency!88-100% specificity, 86-94% sensitivityNote: Negative TTE or TEE do not rule out vegatative IEDiagnosis!Straightforward if oslerian manifestations present! Bacteremia/fungemia ! Evidence of active valvulitis! Peripheral emboli**! Immunologic phenomenon****Typically evident for acute (not R. sided)!Duke CriteriaDuke criteria!Definite Case of Endocarditis! Pathologic (on open heart surg or autopsy)!M/o demonstrated by Cx or histology from vegetation or abscess!Pathologic lesion (vegetation/abscess)! Clinical (Duke Criteria)!2 major criteria!1 major criteria & 3 minor criteria!5 minor criteria!Possible Case of Endocarditis! Findings consistent with IE, but not qualified as “definite” or “rejected” according to Duke criteria(Am J Med 96:200-209,1995)Duke criteria (cont.)!Rejected Possibility of Endocarditis!Pathologic ! No evidence of IE at surgery/autopsy after antibiotic therapy < 4 days!Clinical! Firm alternate diagnosis!Resolution of manifestations (with therapy) < 4 daysDuke Major criteria! Positive blood cultures!Typical pathogen frequently associated with endocarditis!Multiple positive cultures (75-100% of cultures positive)!Positive cultures obtained throughout the day! Evidence of endocardial involvement!New evidence of valve regurgitation!Echocardiogram positive !Vegetation present!Evidence of intra-cardiac abscess!Dehiscence of prosthetic valveDuke Minor criteria! Fever >38 C (100.4 F)! History of IVDA or predisposing heart disease! Positive Blood culture but not typical pathogen! Echo not meeting major criterion! Immune!+RF, Osler Node, Roth Spot, or Glomerulonephritis ! Vascular !PE, mycotic aneurysm, Janeway lesion, arterial emboli, intracranial hemorrhage, Flame hemorrhageWorkup!CBC with differential, U/A, ESR! > 3 sets of blood cultures drawn at different sites and times !EKG & Echo! CXR + V/Q if R. sided involvement suspected!Antibiotic sensitivity studies if BCxs positive!Peak / trough serum inhibitory titer (SIT) & serum bactericidal titer (SBT)!Physical for classic findings of endocarditis!Also consider: rh-factor and serologyGeneral approach to treatment !High dose, prolonged therapy!Bactericidal!Bacteriostatic agents combinationTreatment issues!Hold antibiotics before Cx?! Abx reduce recovery by 35-40%! If patient does not have 1) toxic appearance 2) clinical or EEG evidence of severeor progressive valve regurgitation or CHF! If initial BCx (-), delay 2-4 days!Use of aminoglycosides (AG)! Oto- and Nephro-toxic! Duration of therapy! Desired