Classification of Recommendations Quality of the evidence - PDF document

2/18/16 Bacterial Endocarditis Henry F. Chambers, MD Disclosures • AstraZeneca – advisory board • Cubist/Merck – research grant • Genentech – advisory board • Merck – stock • Theravance – advisory board 1

2/18/16 Circulation. 132:1435-86, 2015 Classification of Recommendations • Quality of the evidence (precision) – Level A: Multiple randomized trials or meta- analyses (multiple populations) – Level B: Single randomized trial or nonrandomized studies (limited populations) – Level C: Expert opinion, case reports, standard of care (very limited populations) 2

2/18/16 Classification of Recommendations • Estimated treatment effect – Class I: Benefit>>>Risk: should do it – Class IIa: Benefit >> Risk: reasonable to do it – Class IIb: Benefit > Risk: may consider doing it – Class III: No benefit or harm: don’t do it Overall Strength of Evidence and Data Quality • Class I of any quality < 40% • Level C > 50% • Only 3 Class I, level A – At least 3 blood cultures – Get an ECHO in patients with suspected IE – Test enterococci for susceptibility to penicillin, vancomycin, gentamicin synergy 3

2/18/16 Of the following subspecialties which is the most recommended in AHA guidelines for its consultative expertise? 1. Cardiology 2. Cardiothoracic surgery 3. Clinical Pharmacy 4. Infectious Diseases Of the following subspecialties which is the most recommended for its consultative expertise in AHA guidelines? 1. Cardiology = 3 2. Cardiothoracic surgery = 3 3. Clinical Pharmacy = 3 4. Infectious Diseases = 25 (Class I, level C) 4

2/18/16 Which of the following is NOT a major criterion in the Modified Duke Criteria for the Diagnosis of IE? 1. Typical organism consistent with IE from 2 separate blood culture in absence of a primary focus 2. Anti-phase 1 IgG antibody titer for Coxiella burnetii > 1:800 3. Oscillating intracardiac mass on a valve or supporting structure on TTE 4. Worsening or changing pre-existing regurgitation murmur Modified Duke Criteria for the Diagnosis of IE 1. Typical organism consistent with IE from 2 separate blood culture in absence of a primary focus 2. Anti-phase 1 IgG antibody titer for Coxiella burnetii > 1:800 3. Oscillating intracardiac mass on a valve or supporting structure on TTE, abscess, PVE dehiscence 4. New valvular regurgitation 5

2/18/16 Major Criteria for Diagnosis of IE • Blood cultures – At least 3 sets from different sites with first and last at least 1h apart (Class I, Level A) • Echocardiography – Should be performed expeditiously in patients suspected of IE (Class I, Level A) Typical Organisms in Blood Cultures Consistent with IE • Organisms* – Staphylococcus aureus – Viridans group streptococci – Strep. bovis – Enterococcus (community-acquired) – HACEK • In absence of primary focus • Or persistently positive blood cultures – 2 cultures drawn > 12h apart positive – All 3 or majority of > 4 separate cultures with first and last drawn > 1h apart * Coag-negative staph in patients with prosthetic valve 6

2/18/16 IE SUSPECTED High risk patient or moderate Low risk patient to high clinical suspicion, & low clinical suspicion Initial TTE difficult imaging candidate TEE after TTE asap Neg Pos Rx Neg Pos Low High risk suspicion suspicion features on TTE Look for Rx Yes suspicion other No source TEE No Look for other TEE TEE source What is High Risk? • High risk patients (examples) – Prosthetic valve – Congenital heart disease – Previous endocarditis – New murmur, heart failure, heart block, stigmata of IE • High risk TTE (examples) – Large or mobile vegetations, anterior MV leaflet veg – Valvular insufficiency, perivalular extension, valve perforation – Ventricular dysfunction 7

2/18/16 ECHO at Completion of Rx? TTE at the time of antimicrobial therapy completion to establish baseline features is reasonable (Class IIa, Level C) Minor Criteria • Predisposing heart condition, IDU • Temperature > 38 o C • Vascular/immunologic phenomena: GN, Osler node, Janeway lesion, Roth spot, +RF, septic pulmonary emboli, systemic emboli, mycotic aneurysm • Positive blood culture not meeting major criterion, positive serologic test • ECHO minor criteria eliminated 8

2/18/16 Septic Pulmonary Emboli, Staph endocarditis Petechiae, Staph endocarditis 9

2/18/16 Splinter Hemorrhage Osler’s Node, Staph endocarditis 10

2/18/16 Subconjunctival Hemorrhage Roth Spots 11

2/18/16 Definition of IE • Definite IE – Pathological criteria: positive culture or histology of vegetation, embolus, intracardiac focus – Clinical criteria: 2 major OR 1 major + 3 minor OR 5 minor • Possible IE: 1 major + 1 minor or 3 minor • Rejected: alternative diagnosis, does not meet criteria for possible Treatment 12

2/18/16 Which one of the following regimens is NOT recommended for treatment of IE caused by a penicillin-susceptible strain of S. aureus (MSSA)? 1. Cefazolin 2. Daptomycin 3. Nafcillin or oxacillin 4. Penicillin G 5. Vancomycin Gentamicin should not be used for treatment of native valve endocarditis caused by MSSA or MRSA. 1. True 2. False 13

2/18/16 Native Valve S. aureus IE Regimen Duration Comments MSSA Nafcillin or 6 wk 2 wk uncomplicated R- oxacillin (I/C) sided IE (IDU) Cefazolin (I/B) 6 wk Pen-allergic naf-intolerant patient (equivalent to naf) MRSA Vancomycin (I/C) 6 wk For MSSA if beta-lactam hypersensitivity Daptomycin (IIb/B) 6 wk > 8 mg/kg/day, vanco alternative No gentamicin, no rifampin – both III/B Which one of the following regimens is NOT recommended for treatment of IE caused by penicillin-nonsusceptible viridans group streptococci (VGS) (pen MIC > 0.5 µg/ml) , Abiotrophia defectiva, or Granulicatella sp. 1. Ceftriaxone + gentamicin 2. Ampicillin + gentamicin 3. Penicillin + gentamicin 4. Vancomycin + gentamicin 5. Vancomycin 14

2/18/16 Treatment of VGS and Strep. bovis IE • Pen MIC < 0.12 µg/ml – Penicillin, ceftriaxone, vancomycin x 4 weeks • Pen MIC > 0.12 µg/ml, < 0.5 µg/ml – Penicillin or ceftriaxone (4 wk) + gent (2 wk) – Ceftriaxone or vancomyin (4wk) • Pen MIC > 0.5 µg/ml (and nutritionally deficient species) – Penicillin or ceftriaxone + gent – Vancomycin – Duration not defined (4 wk?) – ID consult Case • 65 y/o diabetic man with fever and dysuria • Urinalysis: 50-100 WBCs • Urine culture and 2/2 blood cultures: • Enterococcus faecalis , penicillin susceptible (MIC < 8 µg)/ml), synergy with gentamicin (MIC < 500) and streptomycin (MIC < 500) • TEE: 5 mm AV vegetation • Serum creatinine: 1.65 mg/dL, clearance = 42 ml/min 15

2/18/16 Which one of the following regimens would you prescribe for this patient? 1. Ampicillin 2. Ampicillin + gentamicin 3. Ampicillin + ceftriaxone 4. Vancomycin + gentamicin 5. Ampicillin + streptomycin Enterococcal Endocarditis Regimen Duration Comments (Strength of Rec) Pen or amp + gent 4-6 wk Pen S, Gent 1 mg/kg q8h, 6 (IIa/B) wk for PVE, symptoms>3 mo Amp + Ceftriaxone 6 wk Pen S, Aminoglycoside (IIa/B) susceptible or resistant Pen or amp + strep 4-6 wk Gent resistant, Strep (IIa/B) synergy, ClCr > 50 Vanco + gent 6 wk Pen resistant or beta-lactam (IIa/B) intolerant (toxic!) Linezolid or dapto > 6 wk VRE: Dapto 10-12 mg/kg & (IIb/C) combo with amp or ceftaroline 16

2/18/16 Which of the following is NOT a HACEK Organism? 1. Haemophilus species 2. Acinetobacter 3. Cardiobacterium hominis 4. Eikenella corrodens 5. Kingella species 6. Who gives a flying #%&$ anyway? HACEK Organisms • Haemophilus species • Aggregatibacter species • Cardiobacterium hominis • Eikenella corrodens • Kingella species 17

2/18/16 Which one of the following regimens would you prescribe for a patient with IE due to a HACEK organism? 1. Ampicillin 2. Ampicillin + gentamicin 3. Ceftriaxone 4. Ceftriaxone + gentamicin 5. Levofloxacin + gentamicin Which one of the following regimens would you prescribe for a patient with IE due to a HACEK organism? Regimen Strength Comments Ampicillin III/C Avoid: assume amp or pen resistant if no reliable MIC Amp + gent III/C NO GENT: nephrotoxic Ceftriaxone IIa/B Regimen of choice Ceftriaxone + gent III/C NO GENT: nephrotoxic Levo + gent III/C NO GENT: nephrotoxic, Levo or FQ as single agent OK as alternative regimen (IIb/C) 18

2/18/16 Culture-Negative Endocarditis • Prior antibiotics • Fastidious organisms – HACEK – Abiotrophia defectiva, et al • “ Non-cultivatable ” organism – Bartonella quintana – Coxiella burnetii , Chlamydophila psittaci , Trophyrema whippelii , Legionella sp • Fungi (molds) • Not endocarditis – Libman-Sacks, myxoma, APLS, marantic Fever during Therapy of Endocarditis • Very common, lasts into the second week • Persistent fever a concern in PVE • Causes – Abscess: valve ring or elsewhere – Septic pulmonary emboli, pleural effusion – Another infection (e.g., IV site, fungal superinfection) – Polymicrobial endocarditis – Drug fever – No cause • Work-up – Repeat blood cultures – Imaging studies: TEE, abdominal CT 19