Classification of Recommendations Quality of the evidence - - PDF document

2/18/16 1

Bacterial Endocarditis

Henry F. Chambers, MD

Disclosures

• AstraZeneca – advisory board
• Cubist/Merck – research grant
• Genentech – advisory board
• Merck – stock
• Theravance – advisory board

2/18/16 2

• 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)

2/18/16 3

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

2/18/16 4

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)

2/18/16 5

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

2/18/16 6

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

2/18/16 7

IE SUSPECTED

Initial TTE

High risk patient or moderate to high clinical suspicion, difficult imaging candidate Neg Pos

Rx

Look for

• ther

source suspicion

TEE TEE after TTE asap

Low risk patient & low clinical suspicion Neg Pos suspicion

TEE

Low suspicion Look for other source High risk features on TTE Yes No

No TEE Rx

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

2/18/16 8

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 > 38oC
• 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

2/18/16 9

Septic Pulmonary Emboli, Staph endocarditis Petechiae, Staph endocarditis

2/18/16 10

Splinter Hemorrhage Osler’s Node, Staph endocarditis

2/18/16 11

Subconjunctival Hemorrhage Roth Spots

2/18/16 12

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

2/18/16 13

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

• f native valve endocarditis caused by MSSA
• r MRSA.
• 1. True
• 2. False

2/18/16 14

Native Valve S. aureus IE

Regimen Duration Comments

MSSA Nafcillin or

• xacillin (I/C)

6 wk 2 wk uncomplicated R- 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

2/18/16 15

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

2/18/16 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 (Strength of Rec) Duration Comments Pen or amp + gent (IIa/B) 4-6 wk Pen S, Gent 1 mg/kg q8h, 6 wk for PVE, symptoms>3 mo Amp + Ceftriaxone (IIa/B) 6 wk Pen S, Aminoglycoside susceptible or resistant Pen or amp + strep (IIa/B) 4-6 wk Gent resistant, Strep synergy, ClCr > 50 Vanco + gent (IIa/B) 6 wk Pen resistant or beta-lactam intolerant (toxic!) Linezolid or dapto (IIb/C) > 6 wk VRE: Dapto 10-12 mg/kg & combo with amp or ceftaroline

2/18/16 17

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

2/18/16 18

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)

2/18/16 19

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

2/18/16 20

Surgical Management NVE/PVE

• Optimal timing of surgery not known
• Early surgery

– Heart failure due to valvular dysfuntion – 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)

Valve Surgery with Stroke

• Stroke is an independent risk factor for post-
• p mortality
• Early surgery with stroke or subclinical

cerebral emboli may be considered if intracranial hemorrhage excluded by imaging and neurological damage is not severe (IIb/B)

• For patients with major stroke of hemorrhage,

delay valve surgery 4 weeks (IIa/B)

2/18/16 21

Embolic Events in IE

• Systemic embolization in up to 50% and higher
• CNS accounts for 65%
• Highest rates in MV IE (anterior > posterios leaflet)
• 10-fold drop in rate during first 2-3 weeks of antibiotic

therapy

• ~3% of patients suffer a stroke after 1 week of

therapy (benefit of early surgery correspondingly less

• Value of CNS imaging all patients with IE unknown,

may be considered as part of pre-op evaluation

• Mr. K, a 49 y/o man, presents with fevers and chills. He

has had mechanical mitral valve for which he takes 4 mg

• f warfarin daily. He has no neurologic findings. 3/3

blood cultures are positive for Gram-positive cocci in

• clusters. Which of the following would you recommend?
• 1. Discontinue warfarin.
• 2. Continue warfarin.
• 3. Obtain CT brain scan and if negative for blood continue

warfarin.

• 4. Obtain CT brain scan or MRI, with contrast, and if

negative for blood or embolic events continue warfarin.

• 5. Discontinue warfarin if there is a vegetation on TTE or

TEE.

2/18/16 22

Anticoagulation

• Discontinue all forms of anticoagulation in patients

with a mechanical PVE and a CNS embolic event for 2 weeks (IIa/C)

– Reinstitute heparin first then carefully transition to warfarin

• Aspirin or other antiplatelet agents as adjunctive

therapy is not recommended (III/B)

• Continuation of long-term antiplatelet therapy in IE

with no bleeding complications may be considered (IIb/B)

All patients with left-sided IE should have imaging performed to identify metastatic foci of infection.

• 1. True
• 2. False

2/18/16 23

Pan-Scanning

• If done, perform prior to surgery
• No recommendations for routine evaluation of

patients with IE for metastatic foci of infection

• Cerebrovascular imaging may be considered in all

patients with L-sided IE (IIb/B)

Out-Patient Antibiotic Therapy

• Evaluate and stabilize patients in the

hospital (I/C)

• OPAT reserved for those at low risk of

complications of heart failure and systemic emboli (I/C)

2/18/16 24

End of Therapy and Follow-up

• Baseline ECHO at EOT (IIa/C)
• Educate the patient about IE (I/C)
• Dental evaluation (I/C)
• Routine EOT blood cultures not recommended (III/C)
• Audiograms for patient on aminoglycosides (IIb/C)
• Empirical antibiotics prior to obtaining 3 blood

cultures should be avoided (III/C)

• Monitor vestibular function by symptoms in

aminoglycoside-treated patients (I/C)

Dental Management

• Thorough dental evaluation of inpatients to

identify and eliminate oral diseases (I/C)

• Exam should focus on periodontal

inflammation and lesions predisposing to abscess (I/C)

• Full series of intraoral radiographs to

identify lesions not evident on oral examination (I/C)

2/18/16 25

Questions