Bacterial Endocarditis Henry F. Chambers, MD No disclosures 1 2/ - - PDF document

2/ 6/ 2020 1

Bacterial Endocarditis

Henry F. Chambers, MD

No disclosures

2/ 6/ 2020 2

Topics for Discussion

• Pathophysiology
• Epidemiology
• Diagnosis
• Treatment and Management

Pathophysiology

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Primary Lesion: Valvular Vegetation

Valvular Endothelium Trauma, turbulent blood flow, etc Platelet-fibrin deposition at site of injury Non-bacterial thrombotic endocarditis Bacteremia Adherence, colonization Infected vegetation Valve destruction Continuous bacteremia, metastatic infections Embolization Immune complexes

Mitral Valve Vegetation

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Vegetation Histopathology

Osteomyelitis

Metastatic Infection

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Systemic Embolization

Renal Infarct CNS

Septic Pulmonary Emboli

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Microvascular Emboli

Petec hiae Splinter hemor r hages Osler ’s node R

• th spots

Immune-complex Glomerulonephritis

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Epidemiology

Which one of the following statements is correct?

• 1. Staphylococcus aureus is the most common cause of

bacterial endocarditis

• 2. Dental procedures carry a substantial risk for streptococcal

endocarditis for patients with predisposing cardiac lesions

• 3. Three-quarters of patients with endocarditis have a known

underlying cardiac predisposing condition

• 4. Fever and a new cardiac murmur are present in the majority
• f patients with endocarditis

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Epidemiology

Cahill, Lancet 2016; 387: 882 3-15/ 100,000 pe rso n-ye ars

Microbiology

Organisms Approximate % of Total

Staphylococci 40-50

• S. aureus

30-40 Coag-neg 10 Streptococci 25-30 Viridans group 20

• S. gallolyticus

5 Groups B, C, D 5

Enterococcus 10 HACEK 1-2 Culture-negative 3-5

Arch Intern Med. 2009;169:463; Antimicrob Agents Chemother. 2015;60:1411; Clin Infect Dis. 2018;66:104; Lancet 2016; 387: 882

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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

Risk Factors

• Community-acquired or hospital associated
• Previous endocarditis
• Injection drug use
• Hemodialysis
• Prosthetic valve, implanted intracardiac device
• Underlying congenital or valvular heart disease
• Poor dental hygiene or dental procedures?

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Clinical Signs and Symptoms

Finding Approximate Prevalence, % Fever 90 Murmur 70-85 New murmur 50 Worsening old murmur 20 Peripheral stigmata (e.g., Osler’s) 20% or less Heart failure, cardiac complications 20-50 CNS complications 20-40

Risk of Endocarditis Following an At-Risk Dental Procedure

Predisposing condition Prophylaxis Risk of Endocarditis Prosthetic valve No 1/10,700 Native valve No 1/46,000 PV or NV Yes 1/149,000

Duval, Clinical Infectious Diseases 2006; 42:e102–7

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AHA Guidelines: Prevention of Endocarditis

• Prosthetic valve
• Previous infective endocarditis
• Congenital heart disease

– Unrepaired – Within 6 mo of repair – Incomplete repair

• Transplant cardiac valvulopathy
• Circulation. 2007;116:1736-1754

Diagnosis

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Which one of the following is a major criterion for the diagnosis of endocarditis?

• 1. Worsening or changing regurgitant murmur
• 2. Two separate blood cultures positive for S. aureus,

viridans strep, or HACEK organism

• 3. “Shaggy” appearance of the valve on

transesophageal echocardiogram

• 4. Presence of Osler’s node

Modified Duke Criteria

• Pathologic criteria

– Histopathologic evidence of endocarditis – Microorganisms on the valve or culture of it

• Major clinical criteria

– Positive blood cultures*: a) typical organisms or b) persistently positive cultures if not typical ones – Evidence of endocardial involvement: a) positive echocardiogram or b) new regurgitant murmur

• Minor clinical criteria:

– Temp > 38, IVDU, predisposing cardiac lesion, vascular phenomena, immunologic phenomena, blood culture or serological evidence of infection not meeting major criteria * Coxiella burnetti antiphase 1 IgG titer > 1:800 also counts

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Endocarditis

• Definite endocarditis

– Pathologic criteria or – Clinical criteria

• Two major clinical criteria ( i.e., ECHO + culture) or
• One major and three minor criteria or
• Five minor criteria
• Possible endocarditis

– One major + one minor criteria or – Three minor criteria

Sensitivity of ~80%, higher if “possible” are included, lower for PVE, culture-negative, cardiac device infection, R-sided endocarditis

Not Endocarditis

• Alternative diagnosis made
• Clinical resolution with < 4 days of antibiotic therapy
• No pathological evidence found at surgery or autopsy

after < 4 days of antibiotic therapy

• Clinical criteria for possible or definite endocarditis not

met

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SUSPECTED ENDOCARDITIS

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

Role of Echocardiograpy

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

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Harmonic TTE vs TEE for Diagnosis of IE

Bai, J Am Soc Echocardiogr 2017; 30:639-646.e8

• Conclusively negative harmonic

TTE useful to r/o native valve IE

• TTE less sensitive than TEE for

detecting prosthetic IE vegetations, dehiscence, abscess

• Indeterminant TTE not useful to r/o

endocarditis

• TTE insensitive for abscess, IE of

implantable cardiac device

• Specificity of TTE is ~95%

Other Diagnostic Modalities

• 18F-fluorodeoxyglucose-PET/CT

– May be useful in PVE when TEE is non-diagnostic – May be useful for detecting metastatic infection – There are issues with specificity

• Cardiac CT angiography

– Less imaging artifact than TEE in PVE – Improved resolution of paravalvular complications – May be useful in PVE when TEE is non-diagnostic

• Cardiac MRI?

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Tools for Diagnosis of Culture-Negative Endocarditis

Organism Clinical clues Serology Specific PCR Universal 16s/18s rRNA PCR

HACEK, strep, etc Prior antibiotics X Legionella Immunocompromise X X

• T. whipplei

Chronic illness X X Brucella Travel X X Bartonella sp. Cats, homeless, lice X (>1:800) X X Mycoplasma X X Q fever Animal contact, lab X (>1:800) X X Chlamydia Bird exposure X X

Treatment

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• Circulation. 132:1435-86, 2015

Which of the following statements is correct concerning the use of gentamicin for treatment of bacterial endocarditis?

• 1. It should be used in combination with nafcillin for treatment of

MSSA endocarditis

• 2. It should be used in combination with ampicillin or ceftriaxone

for treatment of HACEK endocarditis

• 3. It should be used in combination with penicillin for treatment
• f penicillin-nonsuscepitble viridans strep endocarditis
• 4. It should be used to achieve satisfactory cure rates of

enterococcal endocarditis

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Native Valve S. aureus IE

Regimen Duration Comments

MSSA Nafcillin or

• xacillin

6 wk 2 wk uncomplicated R- sided IE (IDU) Cefazolin 6 wk Pen-allergic naf-intolerant patient (equivalent to naf) MRSA Vancomycin 6 wk For MSSA if beta-lactam hypersensitivity Daptomycin 6 wk > 8 mg/kg/day, vanco alternative No gentamicin, no rifampin

Treatment of VGS and Strep. gallolyticus 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

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Enterococcal Endocarditis

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

HACEK Organisms

• Haemophilus species
• Aggregatibacter species
• Cardiobacterium hominis
• Eikenella corrodens
• Kingella species

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Antimicrobial Therapy of HACEK Endocarditis

Regimen Comments Ceftriaxone Regimen of choice NO GENT: nephrotoxic Levofloxacin Levo or FQ as single agent OK as alternative regimen NO GENT: nephrotoxic Ampicillin Avoid: assume amp or pen resistant if no reliable MIC NO GENT: nephrotoxic

Oral Step-Down

• RCT of IV vs IV/PO, > 10 days IV, L-sided (PVE ok,

26%), 10% NI margin

• 400 eligible of 1954 screened
• Strep (48%), MSSA (21%), CoNS (6%), E. faecalis

(24%)

• 1o outcome: all cause mortality, relapse, embolic

event, unplanned cardiac surgery (IV: 12%, IV/PO: 8%)

Poet Study: NEJM 380:415, 2019

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Other Management Stuff

Fever during Therapy of Endocarditis

• Very common, lasts into the second week, a concern in PVE
• Cause (if one is found, when often it is not

– Abscess: valve ring or elsewhere – Septic pulmonary emboli, pleural effusion) – Another infection (e.g., IV site, fungal superinfection) – Polymicrobial endocarditis – Drug fever

• Work-up:

– Repeat blood cultures – Imaging studies: TEE, abdominal CT, MRI of the spine, etc

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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-op mortality
• Early surgery with stroke or subclinical cerebral emboli may be

considered if intracranial hemorrhage excluded by imaging and neurological damage is not severe

• For patients with major stroke or hemorrhage,

recommendation is to delay valve surgery 4 weeks, although more recent studies have called this into question.

Venn, Am Heart J 2019;216:102-112

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Embolic Events in IE

• Systemic embolization in up to 50% and higher
• CNS accounts for 65%
• Highest rates in MV IE (anterior > posterior 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

• Systemic anticoagulation, antiplatelet therapy is contraindicated.
• Mr. K, a 49 y/o man, presents with fevers and chills. He has had

mechanical mitral valve for which he takes 4 mg of 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.

Anticoagulation

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Anticoagulation

• Discontinue all forms of anticoagulation in patients with a

mechanical PVE and a CNS embolic event for 2 weeks

– Reinstitute heparin first then carefully transition to warfarin

• Aspirin or other antiplatelet agents as adjunctive therapy is not

recommended

• Continuation of long-term antiplatelet therapy in IE with no

bleeding complications may be considered

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

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Cardiac Implantable Device Infections

(permanent pacemakers, defibrillators)

J Am Coll Cardiol 2008;49:1851; Circulation 2010;121:458; NEJM 2012;367:842; JAMA 2012;307:1727

Pacemaker Infection

• A 71 y.o. male, permanent pacemaker was implanted 2 months

ago for sick sinus syndrome/syncope, presents subjective fever

• Exam:

– T37.8C, P78 (paced), R18, BP 122/80. – Generator pocket is slightly tender, swollen, with moderate warmth and erythema; otherwise WNL.

• Cultures

– Pus aspirated from the pocket: MSSA – Blood cultures: negative

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Which of the following is the best management?

1. Cefazolin + rif x 6 wks 2. Remove generator, then cefazolin + rif x10 days 3. Remove generator, then cefazolin + rif 6 wks 4. Remove entire device, then cefazolin + rif 6 wks 5. Remove entire device, then cefazolin x 10 days

rif = rifampin

Cardiac Implantable Device Infection Types

• Pocket site/generator only : ~ 60%

– Blood culture positive <50% – Pocket infection or generator/lead erosion

• Occult bacteremia/fungemia: ~7-30%
• Lead infection +/- endocarditis: ~10-25%

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Survival with and without Device Removal

Athan, JAMA. 2012; 307:1727-1735 Algorithm for Management of an Infected Cardiac Implantable Device (CIED) Infection

Baddour LM et al. N Engl J Med 2012;367:842-849

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Algorithm for Management of an Infected Cardiac Implantable Device (CIED) Infection

Baddour LM et al. N Engl J Med 2012;367:842-849

Re mo ve E ntire De vic e

Suspe c te d CI E D I nfe c tio n Blo o d Culture Po sitive Ne g ative Po sitive

AHA Guidelines for Management of Cardiac Implantable Device Infections

• Blood cultures before antibiotics

– If positive, then TEE

• Gram stain, culture of pocket tissue, lead tips
• Device removal for all infections and occult staphylococcal bacteremia

(consider for GNR bacteremia)

• Therapy (antibiotic based on susceptibility)

– Pocket infection: 10-14 days – Bloodstream infection: > 14 days – Lead or valve vegetations: 4-6 weeks Circulation 2010;121:458-77

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AHA Guidelines for Reimplantation

• Determine if reimplantation necessary
• New device on contralateral side
• >72h negative BC before reimplantation
• If IE: reimplant > 14d after original removal
• Antibiotic prophylaxis: 1h before implantation, none thereafter

Questions