Endocarditis & Endovascular Infections. Thomas Hawn, July 2010. 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
Thomas Hawn, July 2010
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?
Criteria for positivity
Paired quantitative: catheter:vein cfu ratio >3
Unpaired quantitative: catheter cx >100 cfu/ml
Differential time: >120 minutes
Paired quantitative 79 94 Siegman-Igra, meta-analysis (cath:vein ratio>3-10:1)
Unpaired quantitative 78 96 Siegman-Igra, meta-analysis (CFU/ml>15-100)
Differential time to positivity 89 100 Gaur et al, n=33 (time>120 minutes)
96 100 Blot et al (1998), n=64, (time > 120 minutes)
94 91 Blot et al (1999), n=28, (time > 120 minutes)
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)
Blood culture grow Staphylococcus aureus in 2 out of 2 sets (4 bottles).
Catheter 100 CFU/ml
Vein 15 CFU/ml
What is your management recommendation?
Should the line be removed?
Duration of Rx?
Should a TTE or TEE be obtained?
Mermel et al CID 2009 IDSA Catheter Rx Recs
Mermel et al CID 2009 IDSA Catheter Rx Recs
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
S. aureus bacteremia, n=244
Management recommended: remove focus of infection, check surveillance cultures, TEE, start therapy (decide duration based on whether endocarditis present)
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
Pappas et al (2009) CID 48: 503-35
Anidulafungin non-inferior to fluconazole,
But, … possibly more efficacious
of Candidemia and Other Forms of Invasive
Pappas et al (2007) CID 45: 883-93
Rx Success associated with Catheter Removal
RDBPCT, n=595 candidemic pts
Catheter removed 77.9%
Catheter not removed 63.2%
Drug choice & need to check sensitivities
C. albicans: sensis not routine, based on risks
C. glabrata: echinocandin preferred (B-III) or check fluc sensi
C. krusei: no fluc
C. parapsilosis: fluc preferred (B-III)
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?
Cumulative exposure measures CFU per minute per ml per year of bacteria
(Relative to tooth extraction)
2007 guidelines: Emphasize that daily activities incur highest risk, rather than procedures.
Lockhart et al Circulation 117: 3118 (2008)
#/100,000 person years
General population 4.9
Rheumatic heart disease
Congenital heart disease:
VSD with medical Rx
VSD with surgical Rx
MVP with murmur
MVP without murmer
Steckelberg & Wilson 1999
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
CV III/VI SEM over LUSB,
?splinter hemorrhages 2 nails
Bld Cx: 1/6 bottles with Viridans strep
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
1 major and 1 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.
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
PathogenIE:non IE Ratio
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
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)
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).
Mylonakis, NEJM, 2001
Septic pulmonary emboli
High rate of lesions in neurologically asymptomatic cases
1. Prosthetic valves
2. Suspected complication
(such as perivalvular abscess)
3. Those in “Possible Endocarditis” category
4. ? Negative TTE & S. aureus bacteremia
Arguing in favor:
1) Increased sensitivity leads to more diagnoses & better Rx
2) ? Cost effective (save costs of lengthy treatment)
3) TEE more labour intensive
4) Small vegetations may be adequately treated with short course treatment.
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 Therapy for IE
Main goal is to treat acute IE, most often caused by S. aureus
Vancomycin +/- gentamicin
more difficult and less important to Rx empirically.
Vancomycin + ceftriaxone covers many of the important organisms.
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)
i. PCN G 18-30 mU iv/day x 4-6 wks
+ gentamicin 1 mg/kg iv q8h x 4-6 wks
ii. ampicillin 12 g/day iv x 4-6 wks
+ gentamicin 1 mg/kg iv q8h x 4-6 wks
iii. vancomycin 1g iv bid x 6 wks
+ gentamicin 1 mg/kg iv q8h x 6 wks
(for b-lactam allergic pts)
i. ceftriaxone 2g iv/im qd x 4 wks
(or other 3rd or 4th gen. cephalosporin)
ii. Ampicillin-sulbactam 12g iv/day x 4 wks
iii. Ciprofloxacin 500 mg po bid or 400 mg iv bid x 4 wks
(less experience with quinolones & HACEK)
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?
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:
Dapto Std Rx P
MRSA 8d 9d 0.28
MSSA 4d 3d 0.25
Fowler et al NEJM 2006
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
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?
-Acute aortic or mitral insufficiency with signs of ventricular failure
-Heart failure unresponsive to medical therapy
-Valve perforation or rupture
-Valvular dehiscence, rupture, or fistula
-New heart block
-Large abscess, or extension of abscess despite appropriate antimicrobial therapy.
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.
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.
After 1 week, annular, flat, erythematous macules developed on all extremities.
Pt developed fever, chills, sweats, nausea, vomiting, and myalgias over the next month.
Exposure Common pathogens Diagnostic methods
Birds C. psittaci Complement fixation, ELISA
EtOHism, Bartonella quintana “Fastidious” organism bld cx,
homeless subCx to chocolate agar
Animals Coxiella burnetti CFA titers to phase I & II Ags
Brucella species “Fastidious” organism bld cx Serology
Nosocomial, Fungi Extended incubation of blood immuosuppression cultures
STD, Neisseria gonorrhea Bld cx. Commercial systems sexually active may inhibit Neisseria.
Epidemic Legionella Special culture for fastidious pneumophilia organisms, consider urinary antigen for Legionella
Houpikian & Raoult Medicine 84: 162-173 (2005)
n=348 subjects, France 1983-2001
blood culture negative IE
Pathogen N (%)
C. burnetti 167 (48)
Bartonella 99 (28)
Rare fastidious 5 (1)
No etiology: on abx 58 (16.7)
not on abx 15 (4.3)
Baddour et al Infective Endocarditis: Treatment, Diagnosis, & Management. Circulation 111: e394-433 (2005).
Mermel et al Guidelines for the Management of Intravascular Catheter-Related Infections. CID 49: 1-45 (2009).
Pappas et al Guidelines for the management of Candidiasis CID 48: 503-35 (2009).
Wilson et al Prevention of Infective Endocarditis. Circulation 115: (2007).