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Endocarditis & Endovascular Infections. Thomas Hawn, July 2009. Vegetation. Tricuspid valve. Medic.med.uth.tmc.edu. Case. 45 yo female S/P MVA ARDS in the ICU x 15 d with new onset fever. PE IJ central line along with 2 peripheral ivs. Question:

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Endocarditis endovascular infections

Endocarditis & Endovascular Infections

Thomas Hawn, July 2009





Endocarditis endovascular infections


45 yo female S/P MVA

ARDS in the ICU x 15 d with new onset fever.


IJ central line along with 2 peripheral ivs.


How do you diagnose a CVC infection?

Central venous catheter infections

Central Venous Catheter Infections

Criteria for positivity

Paired quantitative: catheter:vein cfu ratio >3

Unpaired quantitative: catheter cx >100 cfu/ml

Differential time: >120 minutes


Paired quantitative7994Siegman-Igra, meta-analysis (cath:vein ratio>3-10:1)

Unpaired quantitative7896Siegman-Igra, meta-analysis (CFU/ml>15-100)

Differential time to positivity89100Gaur et al, n=33 (time>120 minutes)

96100Blot et al (1998), n=64, (time > 120 minutes)

94 91Blot et al (1999), n=28, (time > 120 minutes)

Central venous catheter infections1

Central Venous Catheter Infections

Diagnostic Recommendations

If CVC infection is suspected,

1. Draw 2 sets of bld cxs (one percutaneously)

2. Check paired quantitative or qualitative with time to positivity monitoring

3. If catheter is removed, send tip for culture.

Criteria for positivity:

>15 CFU by semi-quantitative method (roll-plate)

>100 CFU by quantitative method (sonication)

Central venous catheter infections2

Central Venous Catheter Infections


Blood culture grow Staphylococcus aureus in 2 out of 2 sets (4 bottles).

Catheter 100 CFU/ml

Vein15 CFU/ml


What is your management recommendation?

Should the line be removed?

Duration of Rx?

Should a TTE or TEE be obtained?

Endocarditis endovascular infections

Short Term CVC Management

Mermel et al CID 2009 IDSA Catheter Rx Recs

Endocarditis endovascular infections

Long Term CVC Management

Mermel et al CID 2009 IDSA Catheter Rx Recs

Uncomplicated cvc bacteremia

Uncomplicated CVC Bacteremia

1) No septic emboli

2) Negative surveillance cultures 2-4 d after starting therapy

3) Removable focus of infection

4) Not immunocompromised

5) Rapid clinical resolutions of sxs within 72h of starting abx and removing focus of infection

6) No indwelling prosthetic devices or underlying heart disease

Should the line be removed in s aureus bacteremia

Should the line be removed in S. aureus bacteremia?

S. aureus bacteremia, n=244

Management recommended: remove focus of infection, check surveillance cultures, TEE, start therapy (decide duration based on whether endocarditis present)

Cure rate:

Recommendations followed:79.5%

Recommendations not followed: 64.4%

Foreign body removed:83.7%

Foreign body not removed:43.5%

Fowler et al (1998) CID 27: 478-86

Endocarditis endovascular infections


40 yo M with mitral valve prolapse.

Dentist plans to place orthodontic brackets.

50 yo F with a history of endocarditis will undergo cystoscopy

What do you recommend for IE prophylaxis?

What is the highest risk of bacteremia exposure

What is the highest risk of bacteremia exposure?

Cumulative exposure measures CFU per minute per ml per year of bacteria

Tooth extraction

Dental Exam

Mucoperiosteal surgery

Daily life


Brushing teeth


NT tube


(Relative to tooth extraction)









2007 guidelines: Emphasize that daily activities incur highest risk, rather than procedures.

Endocarditis endovascular infections


Lockhart et al Circulation 117: 3118 (2008)

What are risk factors for ie

What are risk factors for IE?

IE incidence

#/100,000 person years

General population 4.9

Prior endocarditis

Rheumatic heart disease

Congenital heart disease:


VSD with medical Rx

VSD with surgical Rx

Aortic stenosis

Pulmonic stenosis

Prosthetic valve

MVP with murmur

MVP without murmer

Steckelberg & Wilson 1999











2007 aha guidelines

2007 AHA Guidelines

  • Cardiac Conditions with recommended prophylaxis:

  • 1. Prosthetic cardiac valve

  • 2. Previous IE

  • 3. Congenital Heart Disease:

  • A. Unrepaired cyanotic CHD, including palliative shunts & conduits

  • B. Completely repaired CHD with prosthetic material or device, during the first 6 months after the procedure

  • C. Repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or device

  • 4. Cardiac transplant recipients who develop cardiac valvulopathy

  • Compared to 1997: Simplified list with emphasis on risk of adverse outcome from IE rather than risk of acquisition.

  • (no longer recommended for MVP or RHD)

2007 aha guidelines1

2007 AHA Guidelines

Procedures for which endocarditis is recommended for the above categories of patients:

1. All dental procedures that involve manipulation of gingival tissue or the periapical region of teeth or perforation of the oral mucosa.

2. Respiratory tract or infected skin/soft tissue procedures

3. NOT recommended for GU or GI procedures solely to prevent IE

Compared to 1997:

Simplified list of which procedures qualify

(no GU/GI, criteria for dental procedure straightforward)



HPI: 14 yo M

2 m h/o of fever, HA, myalgias.

RLQ pain led to appendectomy

w/ necrotizing lymphadenitis.

Left calf pain resolved with Abx.

After Abx, fever returned

Then, R wrist swollen & tender

R thigh pain developed.

PE: T 39.3, P 108, BP 128/35

II/VI systolic murmur

splinter hemorrhages in 3 nails

petechial rash on legs


Bld Cx 6/6 bottles Viridans strep

45 yo M h/o ESLD, HCV, EtOH

Fever x 3d.

Also with SOB and abdominal pain.

PE: Tm 38.5



?splinter hemorrhages 2 nails


Bld Cx: 1/6 bottles with Viridans strep



  • What is your DDx?

  • How many modified Duke criteria does this patient have?

  • How useful are the modified Duke criteria?

  • What work-up is needed?

Ddx of endocarditis

DDx of Endocarditis

A. associated with neoplasms: atrial myxoma, marantic (adenoCa), carcinoid

B. associated with autoimmune: rheumatic heart disease, SLE (Libman-Sacks endocarditis), anti-phospholipid syndrome, polyarteritis nodosa, Behcet’s disease

C. Postvalvular operation: thrombus, sutures

D. Other: eosinophilic heart disease, ruptured mitral chordae, myxomatous degeneration

Modified duke clinical criteria

Modified Duke Clinical Criteria

  • Definite IE

  • Pathological criteria:

    • Microorganisms: demonstrated by culture or histology in a vegetation, in a vegetation that has embolized, or in an intracardiac abscess, or

    • Pathologic lesions: vegetation or intracardiac abscess present, confirmed by histology showing active endocarditis.

  • Clinical criteria

  • 2 major criteria, or

  • 1 major and 3 minor criteria

  • 5 minor criteria

Modified duke clinical criteria1

Modified Duke Clinical Criteria

Possible IE

1 major and 1 minor

3 minor


Firm alternate diagnosis for manifestations of endocarditis

Resolution of manifestations of endocarditis with antibiotic therapy for ≤ 4 days, or

No pathological evidence of IE at surgery or autopsy, after antibiotic therapy for ≤ 4 days.

Major criteria

Major Criteria

1. Positive blood culture for IE

A. Typical microorganism consistent with IE from 2 separate blood cultures as noted below:

viridans streptococci, Streptococcus bovis, HACEK group, Staphylococcus aureus, or community-acquired enterococci,

in the absence of a primary focus

B. Microorganisms consistent with IE from persistently positive blood cultures as defined as

(i) ≥2 positive cultures of blood samples drawn >12 hours apart

(ii) all of 3 or a majority of ≥4 separate cultures of blood

(with the first and last samples drawn ≥1 hour apart)

iii. Coxiella: + Bld cx or anti-phase I Ab titer>1:800

Bacteremia ie likelihood

Bacteremia & IE Likelihood

PathogenIE:non IE Ratio

S. mutans

S. bovis

S. sanguis

S. mitior

E. faecalis

S. anginosus

Grp G Streptococcus

Grp B Streptococcus

Grp A Streptococcus

14.2 : 1

5.9 : 1

3.0 : 1

1.8 : 1

1.0 : 1.2

1.0 : 2.6

1.0 : 2.9

1.0 : 7.4

1.0 : 32.0

Major criteria1

Major Criteria

2. Evidence of endocardial involvement

A. Positive echocardiogram for IE defined as

(i) oscillating intracardiac mass on valve or supporting structures, in the path of regurgitant jets, or on implanted material in the absence of an alternative anatomic explanation, or

(ii) abscess, or

(iii) new partial dehiscence of prosthetic valve, or

B. New valvular regurgitation (worsening or changing or pre-existing murmur not sufficient)

Minor criteria

Minor Criteria

1. Predisposition: predisposing heart condition or intravenous drug use

2. Fever: temperature ≥ 38.0 C

3. Vascular phenomena: major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhage, and Janeway lesions

4. Immunologic phenomena: glomerulonephritis, Osler’s nodes, Roth spots, and rheumatoid factor

5. Microbiological evidence: positive blood culture but does not meet a major criteria as noted above or serologic evidence of active infection with organism consistent with IE (excludes single positive cultures for coagulase-negative Staphylococci and organisms that do not cause endocarditis).

Endocarditis endovascular infections

Clinical Manifestations

Osler’s nodes

Splinter hemorrhages

Janeway’s lesions



Mylonakis, NEJM, 2001

Endocarditis endovascular infections

Clinical Manifestations: Complications

Mycotic aneurysm


Endocarditis endovascular infections

Clinical Manifestations

Septic pulmonary emboli


Assessment of duke criteria

Assessment of Duke Criteria

  • Sensitivity: 80% for definite IE

  • 100% for definite + possible IE

  • Negative predictive value >98% for rejected category

  • Adopted modifications from Li et al (2000)

    • a. S. aureus bacteremia should be a major criteria regardless of the source (community or nosocomial)

    • b. Eliminate the ECHO minor criteria since TEE’s are more widely used now

    • c. Add Coxiella to list of major criteria (a single positive blood culture or antiphase I IgG antibody titer > 1:800).

    • d. To increase specificity, change the category “possible IE” to cases with 1 major and 1 minor criteria or 3 minor criteria.



  • When do you recommend a TEE?

  • Should all pts with a CVC-associated S. aureus bacteremia get a TEE?

Role of transesophageal echo in diagnosing ie

Role of Transesophageal ECHO in diagnosing IE

1. Prosthetic valves

2. Suspected complication

(such as perivalvular abscess)

3. Those in “Possible Endocarditis” category

4. ? Negative TTE & S. aureus bacteremia

Should all patients with s aureus bacteremia have a tee

Should all patients with S. aureus bacteremia have a TEE?

Arguing in favor:

1) Increased sensitivity leads to more diagnoses & better Rx

TTE sensitivity=32%

TEE sensitivity=100%

2) ? Cost effective (save costs of lengthy treatment)

Arguing against:

3) TEE more labour intensive

4) Small vegetations may be adequately treated with short course treatment.

Case rx s

Case: Rx ?s

3. 65 yo female with 4 weeks of fever, myalgias, nausea and decreased appetitie.

ECHO: MV vegetation with severe MR.

4. 30 year old male with h/o IVDU and dental caries with fever for 1 day after recent injection.

ECHO: AV vegetation with severe AI.


What empiric treatment do you recommend before the results of blood cultures are known?

What antibiotics do you recommend for viridans strep?

Who can be treated for 2 wks?

Empiric antibiotic selection

Empiric Antibiotic Selection

Empiric Therapy for IE

Main goal is to treat acute IE, most often caused by S. aureus



Vancomycin + gentamicin (if MRSA rates significant)


Nafcillin + gentamicin

(if MRSA not significant, less commonly used now)

Subacute IE: more difficult and less important to Rx empirically.

Vancomycin + ceftriaxone covers many of the important organisms.

Aha rx of viridans strep ie

AHA: Rx of Viridans Strep IE

Viridans streptococci & S. bovis,

PCN susceptible (MIC ≤0.12 mg/ml)

i. PCN G 12-18 mU iv/day x 4 wks,

ii. ceftriaxone 2g iv or im qd x 4 wks,

iii. PCN G 12-18 mU iv qd + x 2 wks,

gentamicin 1 mg/kg iv q8h

iv. vancomycin 1g iv bid x 4 wks (for b-lactam allergic pts)

Aha rx of viridans strep ie1

AHA: Rx of Viridans Strep IE

  • Viridans streptococci & S. bovis,

  • relatively resistant to PCN (MIC > 0.12 mg/ml & < 0.5 mg/ml)

  • i. PCN G 24 mU iv/day x 4 wks

  • + gentamicin 3 mg/kg iv qdx 2 wks

  • Ceftriaxone 2g iv qdx 4 wks

  • + gentamicin 3 mg/kg iv qdx 2 wks

  • iii. vancomycin 1g iv bid x 4 wks (for b-lactam allergic pts)

Aha rx of enterococcus abiotrophia grunulicatella ie

AHA: Rx of Enterococcus, Abiotrophia, & Grunulicatella IE

i. PCN G 18-30 mU iv/dayx 4-6 wks

+ gentamicin 1 mg/kg iv q8hx 4-6 wks

ii. ampicillin 12 g/day ivx 4-6 wks

+ gentamicin 1 mg/kg iv q8hx 4-6 wks

iii. vancomycin 1g iv bid x 6 wks

+ gentamicin 1 mg/kg iv q8hx 6 wks

(for b-lactam allergic pts)

Aha rx of hacek ie


i. ceftriaxone 2g iv/im qdx 4 wks

(or other 3rd or 4th gen. cephalosporin)

ii. Ampicillin-sulbactam 12g iv/dayx 4 wks

iii. Ciprofloxacin 500 mg po bid or 400 mg iv bidx 4 wks

(less experience with quinolones & HACEK)

Endocarditis endovascular infections


30 yo M with h/o IDU with fever

Diagnosed with MV IE 2° MRSA

Started on vancomycin/gentamicin

Daily cultures positive x 8 d


Should a vancomycin MIC be obtained?

Should vancomycin troughs be obtained?

Should a different drug be used?

Does this patient need cardiac surgery?

Endocarditis endovascular infections

Randomized trial

Inclusion: positive SA blood cx

Randomize to: daptomcyin (n=124)

vs. standard therapy ( b-lactam or vancomycin/gentamicin 1 mg/kg x 4d)


Overall success ITT: daptomycin 42.7%

standard Rx: 39.3%

Conclusion: Daptomycin is non-inferior to standard Rx

Median duration of bacteremia:

DaptoStd RxP



Fowler et al NEJM 2006

Vancomycin dose mics

Vancomycin Dose & MICs

Do high troughs help?

Hidayat et al Arch Int Med 2008

Are high MICs associated with poor outcomes?

Soriano et al CID 2008

Prospective observational study

Inclusion: MRSA bacteremia, n=414

If vancomycin MIC = 2

OR for mortality: 6.39 (1.68-24.3)

Prospective cohort study

Inclusion: MRSA sputum, blood, wound

Measure vancomycin MIC

Compare high (≥2) vs low (<2) MIC

Compare achievement of trough goal target of 15 ucg/ml

Endocarditis endovascular infections


16 yo male with a 1 week history of fever to 103 F.

Developed confusion, blurrred vision and abdominal pain. Head CT showed hypodense lesions bilaterally in the parietal lobe, abdominal CT showed a 2 cm splenic infarct, and an ophthalmologic exam showed bilateral emboli.

4 out of 4 cultures grew MRSA. ECHO showed mild MR and a vegetation on the anterior leaflet.

Does this patient need cardiac surgery?

Indications for cardiac surgery

Indications for Cardiac Surgery

Valvular dysfunction

-Acute aortic or mitral insufficiency with signs of ventricular failure

-Heart failure unresponsive to medical therapy

-Valve perforation or rupture

Perivalvular extension

-Valvular dehiscence, rupture, or fistula

-New heart block

-Large abscess, or extension of abscess despite appropriate antimicrobial therapy.

Indications for cardiac surgery1

Indications for Cardiac Surgery

  • Vegetation

  • Persistent vegetation after systemic embolization:

  • -Anterior mitral leaflet vegetation, particularly >1 cm

    • -One or more embolic events during the 1st 2 wks of therapy

  • -2 or more embolic events during or after antimicrobial therapy

  • Increase in vegetation size after 4 weeks of antimicrobial therapy

  • Endocarditis endovascular infections


    Fever with right sided weakness

    HPI: 29 yo M w/ 6 wk h/o fever, chills, sweats, anorexia, and lower back pain.

    Syncopal episode & R weakness and aphasia.

    T 38.9, 100/70, 90

    GEN WDWN, expressive aphasia

    CV NL S1, S2 IV/VI SEM

    Chest: Bibasilar crackles

    Ext: subungal hemorrhage of the R 3rd finger & L 4th toe

    Labs: Cr 1.3, WBC 14.3, HCT 27

    Q: Does this patient need cardiac surgery?

    How do you manage embolic complications?

    Complications from ie

    Complications from IE

    1. Embolization: Difficult to predict who will embolize

     emboli with: AV & MV anterior leaflet,

    S. aureus, Candida, HACEK, & Abiotrophia organisms,

    ? Size > 1 cm

    2. CHF: Poor prognosis with medical Rx alone

    Delaying surgery until decompensation will  mortality

    3. Extracranial Mycotic Aneurysms

    Surgical intervention advised

    4. Intracranial Mycotic Aneurysms

    Debates @ merits of screening & surgery.

    Very little data to guide decision.

    Endocarditis endovascular infections


    CC: fever and rash

    HPI: 45 year old male from St. Paul Island in Alaska

    R thumb stung by the barb of a yellow-fin Irish Lord fish.

    Pain, swelling, and erythema of the thumb x 2d, spread to R arm.

    Prescribed TMP-SMX for cellulitis.

    Erythema progressed

    After 1 week, annular, flat, erythematous macules developed on all extremities.

    Pt developed fever, chills, sweats, nausea, vomiting, and myalgias over the next month.

    Culture negative endocarditis

    Culture Negative Endocarditis

    ExposureCommon pathogensDiagnostic methods

    BirdsC. psittaciComplement fixation, ELISA

    EtOHism, Bartonella quintana“Fastidious” organism bld cx,

    homelesssubCx to chocolate agar

    AnimalsCoxiella burnettiCFA titers to phase I & II Ags

    Brucella species“Fastidious” organism bld cx Serology

    Nosocomial, FungiExtended incubation of blood immuosuppression cultures

    STD, Neisseria gonorrheaBld cx. Commercial systems sexually active may inhibit Neisseria.

    EpidemicLegionellaSpecial culture for fastidious pneumophilia organisms, consider urinary antigen for Legionella

    Culture negative endocarditis1

    Culture Negative Endocarditis

    Houpikian & Raoult Medicine 84: 162-173 (2005)

    n=348 subjects, France 1983-2001

    blood culture negative IE

    PathogenN (%)

    C. burnetti167 (48)

    Bartonella 99 (28)

    Rare fastidious 5 (1)

    Tropheryma whipplei

    Abiotrophia elegans

    Mycoplasma hominis

    Legionella pneumophila

    No etiology: on abx 58 (16.7)

    not on abx 15 (4.3)

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