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Infective Endocarditis Department of Cardiology Terminology • Infective endocarditis - bacterial or fungal infection of the interior of the heart • Acute IE - severe febrile illness, rapidly damages hematogenously seeding to extracardiac site and progress to death without treatment • Subacute IE - indolent course, gradual progression during several weeks to months • Prosthetic valve IE - infection with foreign valve materials - early PVE (within 2 mo. of op), late PVE (more than after 12 mo. of op) Epidemiology • Incidence - 1.7 to 6.2 per 100,000 person-years - male-to female ratio 1.7 : 1 - the median age 47 to 69 years - injection drug use 150 to 2000 per 100,000 person-years - mitral valve prolapse 100 per 100,000 person-years • In developing countries - rheumatic heart disease - young age • Prosthetic valve - 7-25% • Nosocomial infective endocarditis - 7-29% GU, GI tract procedures, surgical wound Etiology Modified Duke Criteria Major Criteria I. Positive blood culture Typical microorganism for IE from 2 separated blood culture Viridans streptococci, Streptococcus bovis, S. aureus or Community-aquired enterococci in the absence of primary focus Microorganism consistent with IE persistently positive blood cultures Single positive blood culture for Coxiella burnetii II. Evidence of endocardial involvement Positive echocardiogram Oscillating intracardiac mass on valvular surface or structure Abscess New valvular regurgitation Increase or change in preexisting murmur not sufficient Minor Criteria I. Predisposing heart condition or injection drug use II. Fever > 38℃ III. Vascular phenomena : major arterial emboli, mycotic aneurysm, conjunctival hemorrhage, intracranial hemorrhage IV. Immunologic phenomena : GN, Osler’s node, Roth’s spot, RF V. Microbiologic evidence : positive blood culture but not meeting major criteria ¶ Definite infective endocarditis 2 major criteria or 1 major criteria + 3 minor criteria or 5 minor criteria ¶ Possible infective endocarditis 1 major criteria + 1 minor criteria 3 minor criteria Predisposing condition More common Less common Mitral valve prolapse Rheumatic heart disease Degenerative valvuar disease Idiopathic Hypertropic AS IV drug use Pulmonary system shunts Prosthetic valve Coarctation of the aorta Congenital anomaly Previous endocarditis Clinical Manifestation • Fever : most common symptom - highly suspicious in a febrile patients with valvular abnormalities, IV drug abuser, or bacteremia with organisms frequently causing IE - Subacute IE : low-grade fever (< 39.4) - Acute IE : often high fever (39.4~40) • Absence or blunting of fever - elderly, severe debilitated congestive heart failure renal or liver failure previous use of antibiotics • Other common Sx of subacute IE - anorexia, malaise, night sweat, weight loss Cardiac manifestation • Heart murmur - predisposing pathologic factor or newly regurgitant murmur - detected in 85% of IE involving normal valve • Congetive heart failure : 30~40% of patients - due to consequence of valve dysfunction - more rapid progression in aotic valve involvement • Perivalvular abscess - due to extension of infection beyond valve leaflet into valvular annulus - cardiac fistulae with new murmur - conduction blockade • MI due to emboli to a coronary artery Noncardiac manifestation • Classic nonsuppurative peripheral lesion - Janeway lesion, Osler’s node, splinter hemorrhage • Hematogenous metastastic focal infection - skin, spleen, kidney, skeletal systems, meninges • Arterial emboli : often with infarction - more likely in large vegetation (>10mm) or mitral vegetation • Neurologic symptoms - most often due to embolic stroke intracranial hemorrhage, ruptured mycotic aneurysm, seizure Petechiae Conjuctival Hemorrhage Osler’s Node Roth’s Spot Splinter Hemorrhage Janeway Lesion Treatment • Acute endocarditis, especially IV drug user - coverage for MRSA & enterococci Vancomycin + Gentamicin, immediately after blood culture • Native valve, community-acquisition of infection, MRSA-unlikely Nafcillin + Penicillin + gentamicin • Culture – negative episode in subacute IE - in subacute endocarditis with native valve : Ceftriaxone + Gentamicin - in subacute endocarditis with prosthetic valve : Ceftriaxone + Gentamicin + Vancomycin • 2 or 3 additional culture in the case of culturenegative after 48~72hr Treatment Organism Drug, Dose, Duration Comments Streptococci Penicillin-susceptible Penicillin G 2~3 million units IV q 4h for 4wks Penicillin G + Gentamicin 1mg/kg IM or IV q 8hr for 2wks Penicillin G 6wks + Gentamicin 2wks prosthetic valve Ceftriaxone 2g/d IV for 4wks For nonimmediate penicillin allergy Vancomycin 15mg/kg IV q 12hr for 4wks For severe or immediate penicillin allergy Relatively Penicillinresistant Streptococci Penicillin G 3 million unit for 46 wks + Gentamicin for 2 wks Penicillin G 6wks + Gentamicin 4wks prosthetic Moderately Penicillinresistant Streptococci Penicillin G 3-4 million unit IV + Gentamicin for 4-6 wks Penicillin G 6wks + Gentamicin 6wks prosthetic ** Relatively penicillin-resistant : MIC > 0.1 µg/ml and < 0.5 µg/ml Moderately penicillin-resistant : MIC > 0.5 µg/ml and < 0.8 µg/ml Enterococci / Penicillin-resistant Streptococci (MIC>1µg/ml) Penicillin G 3-4 million unit IV q4h + Gentamicin for 4-6 wks Vancomycin 15mg/kg IV q12h + Gentamicin for 4-6 wks For penicillin-allergic patient Nafcillin or Oxacillin 2g IV q4h for 4-6 wks + Gentamicin for 3-5 day May use Penicillin G in the case of penicillin-susceptible Staphylococci Methicillin-susceptible infecting Native valves Cefazolin 2g IV q8h for 4-6wks + Gentamicin for 3-5 day Vancomycin 15mg/kg IV q 12h for 4-6 wks Methicillin-resistant infecting native valves Vancomycin 15mg/kg IV q 12h for 4-6 wks Methicillin-susceptible infecting Prosthetic valves Nafcillin/Oxacillin + Gentamicin+ Rifampin 300mg PO q8h for 6-8wks Methicillin-resistnat infecting Prosthetic valves Vancomycin + rifampin 6wks + Gentamicin 2 wks HACEK organism Ceftriaxone 2g/d IV for 4wks For immediate or severe penicillin allergy Use gentamicin during initial 2 wks before initiating rifampin for determine susceptibility Haemophilus species Treatment Monitoring • Daily EKG for evaluation of conduction abnormality - herald of perivalvular extension of infection • Careful cardiac exam basis to assess for new regurgitant murmur - Widening of pulse pressure – suggestive of aortic insufficiency • Renal function monitoring - especially in the case of use of aminoglycoside • Follow up blood culture : - at least 1h , If negative 48-72hrs - should be repeated daily until sterile - recheck in the case of fever - perform again after 4~6 wks of therapy for document of cure • Duration of Fever - resolution of fever within 5~7 days in almost patients - defervescence within 3 days in half of patients - defervescence in 75% of patients within 1 wk/ 90% in 2 wks - more slow defervescence in S. aureus, G(-) organisms • Pronged fever over 1 week with appropriate therapy possible another new events other than treatment failure - perivalvular extension of infection - myocardial abscess - focal metastatic infection - drug fever - nosocomial infection - other complication of hospitalization ; eg) pulmonary embolism Blood culture F/U TEE, abdomen CT, urine culture Examination of intravascular devices Surgical Intervention I. Surgery required for optimal outcome Moderate to severe congestive heart failure due to valve dysfunction Partially dehisced unstable prosthetic valve Persistent bacteremia despite optimal antimicrobial therapy Lack of effective microbicidal therapy (e.g., fungal or Brucella endocarditis) S. aureus prosthetic valve endocarditis with an intracardiac complication Relapse of prosthetic valve endocarditis after optimal antimicrobial therapy II. Surgery to be strongly considered for improved outcome Perivalvular extension of infection Poorly responsive S. aureus endocarditis involving the aortic or mitral valve Large (>10-mm diameter) hypermobile vegetations and increased embolic risk Persistent unexplained fever ( 10 days) in culture-negative native valve endocarditis Poorly responsive or relapsed endocarditis due to highly antibiotic-resistant enterococci or gram-negative bacilli