Bacterial Endocarditis • Allergan – Research Grant • Genentech – Research Grant Henry F

2/1/2017 Disclosures Bacterial Endocarditis • Allergan – research grant • Genentech – research grant Henry F. Chambers, MD Infective endocarditis: Outline • Native valve endocarditis • Prosthetic valve endocarditis • Cardiac implantable device infections • Unusual causes of endocarditis • Prophylaxis (time permitting) Circulation. 132:1435-86, 2015 1 2/1/2017 Which of the following is the most common bacterial etiology of infective endocarditis worldwide? 1. Streptococcus mutans Native Valve Endocarditis 2. Streptococcus sanguis 3. Group A β-hemolytic streptococcus 4. Enterococcus faecalis 5. Staphylococcus aureus When bacteremia is documented, which of the Which of the following is NOT a following is LEAST likely to be associated with endocarditis? HACEK Organism? 1. Haemophilus species 1.Streptococcus mutans 2. Acinetobacter species 2.Streptococcus gallolyticus 3. Cardiobacterium hominis 3.Streptococcus mitis 4. Eikenella corrodens 4.Enterococcus faecalis 5. Kingella species 5.Group A β-hemolytic streptococcus 6. Who gives a flying #%&$ anyway? 2 2/1/2017 Etiology of Native Valve Endocarditis Etiology of Native Valve Endocarditis in Injection Drug Users Organism Percent of cases Organism Right-sided Left-sided S. aureus 27-35 Streptococci 33-35 S. aureus 77% 23% Enterococci 8-10 Streptococci 5% 15% Enterococci 2% 24% Coagulase-negative staphylococci 4-9 Gram-negative bacilli 5% 12% HACEK/Gram-negative bacilli 3/4 Polymicrobial 2 Candida <1% 12% Candida 1 Culture-negative 3% 3% Culture-negative 6 Which of the following is NOT a major Definition of IE criterion in the Modified Duke Criteria for the Diagnosis of IE? • Definite IE 1. Typical organism consistent with IE from 2 – Pathological criteria: positive culture or histology separate blood culture in absence of a of vegetation, embolus, intracardiac focus primary focus – Clinical criteria: 2 major OR 1 major + 3 minor OR 2. Anti-phase 1 IgG antibody titer for Coxiella 5 minor burnetii > 1:800 • Possible IE: 1 major + 1 minor or 3 minor 3. Oscillating intracardiac mass on a valve or • Rejected: alternative diagnosis, does not supporting structure on TTE meet criteria for possible 4. Worsening or changing pre-existing regurgitation murmur 3 2/1/2017 Modified Duke Criteria for the Diagnosis of IE Major Criteria for Diagnosis of IE 1. Typical organism consistent with IE from 2 separate blood culture in absence of a • Blood cultures primary focus – At least 3 sets from different sites with first 2. Anti-phase 1 IgG antibody titer for Coxiella and last at least 1h apart burnetii > 1:800 • Echocardiography 3. Oscillating intracardiac mass on a valve or – Should be performed expeditiously in supporting structure on TTE, abscess, PVE patients suspected of IE dehiscence 4. New valvular regurgitation Typical Organisms in Blood Cultures Minor Criteria Consistent with IE • Predisposing heart condition, IDU • Organisms* – Staphylococcus aureus o • Temperature > 38 C – Viridans group streptococci • Vascular/immunologic phenomena: GN, – Strep. gallolyticus (aka bovis) Osler node, Janeway lesion, Roth spot, +RF, – Enterococcus (community-acquired) septic pulmonary emboli, systemic emboli, – HACEK mycotic aneurysm • In absence of primary focus • Positive blood culture not meeting major • Or persistently positive blood cultures criterion, positive serologic test – 2 cultures drawn > 12h apart positive • ECHO minor criteria eliminated – All 3 or majority of > 4 separate cultures with first and last drawn > 1h apart * Coag-negative staph in patients with prosthetic valve 4 2/1/2017 IE SUSPECTED What is High Risk? High risk patient or moderate • High risk patients (examples) Low risk patient to high clinical suspicion, – Prosthetic valve & low clinical suspicion Initial TTE difficult imaging candidate – Congenital heart disease TEE after TTE asap – Previous endocarditis Neg Pos – New murmur, heart failure, heart block, stigmata of IE Rx Neg Pos • High risk TTE (examples) Low High risk suspicion suspicion features on TTE – Large or mobile vegetations, anterior MV leaflet veg Look for Yes suspicion Rx – Valvular insufficiency, perivalular extension, valve No other TEE source perforation No – Ventricular dysfunction Look for other TEE source TEE “Acute” Community-acquired Native Osler node Janeway lesions Valve Endocarditis • A 63 y.o. man with no significant past medical history presents with a week of fever, rigors, and progressive dyspnea on exertion. •Exam – T 39.5, BP 160/40, P110 – Skin and conjunctiva (next slide) – JVD (+), rales ½ way up bilaterally. – Loud diastolic decrescendo murmur at the lower left sternal border. Conjunctival hemorrhage Roth spots 5 2/1/2017 Which of the following is the most appropriate empirical regimen for this patient? 1. Ampicillin + gentamicin 2. Cefazolin + gentamicin 3. Ceftriaxone + gentamicin 4. Nafcillin + vancomycin 5. Vancomycin + gentamicin Septic Pulmonary Emboli, Staph endocarditis Definitive Therapy – Native Valve Endocarditis Splinter Hemorrhage 6 2/1/2017 Native Valve S. aureus IE Treatment of Viridans Group Streptococci and Strep. gallolyticus IE Regimen Duration Comments MSSA • Pen MIC < 0.12 μg/ml Nafcillin or 6 wk 2 wk uncomplicated R- – Penicillin, ceftriaxone, vancomycin x 4 weeks oxacillin sided IE (IDU) – Penicillin or ceftriaxone + gent x 2 weeks Cefazolin 6 wk Pen-allergic naf-intolerant • Pen MIC > 0.12 μg/ml, < 0.5 μg/ml patient (equivalent to naf) – Penicillin or ceftriaxone (4 wk) + gent (2 wk) MRSA – Ceftriaxone or vancomyin (4wk) Vancomycin 6 wk MSSA if beta-lactam hypersensitivity • Pen MIC > 0.5 μg/ml Daptomycin 6 wk > 8 mg/kg/day, vanco – Penicillin or ceftriaxone + gent alternative – Vancomycin – Duration not defined (4 wk?) No gentamicin, no rifampin – both III/B Contraindications to Short Course Treatment of Endocarditis Caused by Penicillin-Susceptible Therapy of Endocarditis due to Viridans Streptococci/Strep gallolyticus “Nutritionally Variant Streptococci” • Isolate with MIC Pen > • Prosthetic valve 0.1µg/ml – (short course not effective • Abiotrophia and Granulicatella species • High level resistance gent – ↑relapses) – Susceptibility tests unreliable • VIII nerve dysfunction • Native valve with cardiac – Often penicillin tolerant, tendancy to • Reduced renal function complications relapse – Intra or extra cardiac – Cr Cl < 20 mL/min abscess/focal infection • Visual impairment • Therapy • Native valve with CNS (severe) – Pen or amp 4 wks + gentamicin 2-4 wks complications • Non-viridans streptococci, (not β-lactam alone) • Yoyo Ma or Itzak Perlman Gemella, Abiotrophia, Granulicatella species – Or vancomycin alone (?) 7 2/1/2017 Enterococcal Endocarditis Regimen Duration Comments HACEK Organisms (Strength of Rec) Pen or amp + gent 4-6 wk Pen S, Gent 1 mg/kg q8h, 6 • Haemophilus species wk for PVE, symptoms>3 mo Amp + Ceftriaxone 6 wk Pen S, Aminoglycoside • Aggregatibacter species susceptible or resistant • Cardiobacterium hominis Pen or amp + strep 4-6 wk Gent resistant, Strep synergy, ClCr > 50 • Eikenella corrodens Vanco + gent 6 wk Pen resistant or beta-lactam • Kingella species intolerant (toxic!) Linezolid or dapto > 6 wk VRE: Dapto 10-12 mg/kg & combo with amp or ceftaroline Regimens Recommended for Treatment of Culture-Negative Endocarditis IE Due to a HACEK organism • Prior antibiotics Regimen Comments • Fastidious organisms – HACEK Ampicillin Avoid: assume amp or pen resistant unless MIC test confirmed susceptible – Abiotrophia defectiva, et al – Brucella sp. Amp + gent NO GENT: nephrotoxic • “Non-cultivatable” organism – Bartonella quintana Ceftriaxone Regimen of choice – Coxiella burnetii, Chlamydophila psittaci, Ceftriaxone + gent NO GENT: nephrotoxic Trophyrema whipplei, Legionella sp, Mycoplasma • Fungi (molds) Ciprofloxacin Levo or FQ as single agent OK as • Not endocarditis alternative regimen – Libman-Sacks, myxoma, APLS, marantic, tumor 8 2/1/2017 Surgical Management NVE/PVE • Optimal timing of surgery not known • Early surgery – Heart failure due to valvular dysfuntion Prosthetic Valve Endocarditis – IE from fungi or MDR organisms (i.e., VRE) – Presence of heart block, annular or aortic abscesses – Persistent bacteremia or fever > 5-7 days not attributable to another source – Emboli, large vegetations (> 10mm) Prosthetic Valve Endocarditis While awaiting TEE, which of the following antimicrobial regimens is most appropriate • A 70 y.o. male with fever, chills, and low back in this setting? pain for 6 days. • Bioprosthetic AVR 9 months previously for critical aortic stenosis. 1. Vancomycin •Exam 2. Daptomycin – T 38, BP 104/70, P 110 3. Vancomycin + rifampin – Left conjunctival petechiae. 4. Vancomycin + gentamicin + rifampin – Rales 1/3 way up bilaterally. 5. Daptomycin + linezolid + gentamicin – Grade II/VI SEM • Blood cultures: 3/3 positive at 18 hours for Gram-positive cocci 9 2/1/2017 PVE versus NVE Causes of Prosthetic valve endocarditis • Similar presentations but ….. EARLY (≤ 2 mo post op) LATE (> 12 mo post op) • Different microbiology • Coag-neg Staph • Viridans streptococci • More invasive infection, higher rates of • S. aureus • S. aureus – Heart failure • Less common • Coag-neg Staph – Conduction disturbances – Gram Neg bacilli • Less comon – Enterococci – Enterococci – New or changing murmurs – Fungi (Candida) – Gram neg bacilli – Diphtheroids – CNS events – Fungi – Diphtheroids JAMA 2007;297:13 Therapy for PVE due to viridans streptococci or S. gallolyticus Therapy for Staphylococcal PVE 24 h dosage Weeks Regimen 24 h dose Weeks Methicillin sensitive Pen or ceftriaxone 24 mu/2g 6

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