Endocarditis & Endovascular Infections
Thomas Hawn, ID Fellows Course, July 2009
I. Diagnosis
A. Differential Diagnosis of Infective Endocarditis (Berbari et al., 1997):
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
B. Microbiology
1. Etiologic agents:
Streptococci 60-80%: viridans 30-40%, enterococi 5-18%, other 15-25%
Staphylococci 20-35%: coag positive 10-27%, coag negative 1-3%
Gram-negative aerobic bacilli: 1.5-13%
Fungi 2-4%, Culture negative <5-24%
2. Ratio of infective endocarditis cases to non-endocarditis bacteremia for various pathogens:
S. mutans 14.2:1, S. bovis 5.9:1, S. sanguis 3:1, S. mitior 1.8:1, E. faecalis 1:1.2, S. anginosus 1:2.6, Grp G strep 1:2.9, Grp
B strep 1:7.4, Grp A strep 1:32.
C. Diagnostic criteria of Infective Endocarditis
Table I: Modified Duke Clinical Criteria for Diagnosis of IE (Baddour et al., 2005; Durack et al., 1994)
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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, using specific definitions in Table 2
2 major criteria, or
1 major and 3 minor criteria
5 minor criteria
Possible IE
1 major and 1 minor criteria
3 minor criteria
Rejected
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.
Does not meet criteria for possible IE
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Table II: Definitions of terms used in the Modified Duke criteria for the diagnosis of IE
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Major criteria
1. Positive blood culture for IE
A. Typical microorganism consistent with IE from 2 separate blood cultures as noted below:
Viridans streptococci (including nutritionally variant strains (Abiotrophia species), 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) single positive blood culture for Coxiella burnetti or anti-phase 1 IgG antibody titer >1:800
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)
* TEE recommended for pts with prosthetic valve, those rated “possible IE” by clinical criteria, and those with complicated
IE (i.e. paravalvular abscess). TTE recommended for remainder.
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 (nontender, erythematous or hemorrhagic, macular or nodular lesions on pads
of fingers/toes or palm/sole).
4. Immunologic phenomena: glomerulonephritis, Osler’s nodes (painful, nodular lesions often on pads of fingers/toes), Roth
spots (oval, pale retinal lesions surrounded by hemorrhage), 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).
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D. Comments on the diagnosis of IE
1. Compared to the older von Reyn criteria from 1981 (Beth Israel criteria), the Duke criteria have improved sensitivity.
Major changes included the addition of echocardiographic findings to the diagnosis, inclusion of IVDU as a risk factor,
emphasis on blood cultures from organisms that are typical for IE (viridans strep, S. bovis, HACEK), or community acquired
Staph aureus or enterococci, and the absence of a primary focus. (Heiro et al., 1998)
2. For 69 cases of pathologically proven IE, the sensitivity of the von Reyn criteria was 51% while it was 80% for the Duke
criteria (for the the diagnosis of Definite IE). If both “Definite and Possible” endocarditis are included, then the sensitivity is
100%. The negative predictive value for the rejected category is >98%. Hard to assess specificity since the number of cases
who do not have endocarditis is difficult to accurately determine (Durack et al., 1994).
2. Fever present in 87% of Durack’s cases—although a helpful criteria, its absence does not rule out IE.
3. Vascular phenomena—splinter hemorrhages and petechiae are not part of the criteria since they are thought to be nonspecific.
4. Li et al (2000) proposed modifications to the Duke criteria that were incorporated by the AHA in 2005 (Baddour et al.,
2005; Li et al., 2000). These recent changes included:
a. To increase specificity, the category “possible IE” was changed to cases with 1 major and 1 minor criteria or 3 minor
criteria.
b. S. aureus bacteremia became a major criteria regardless of the source (community or nosocomial)
c. Eliminate the ECHO minor criteria since TEE’s are more widely used now
d. Add Coxiella to list of major criteria (a single positive blood culture or antiphase I IgG antibody titer > 1:800).
e. Use TEEs as initial test in pts with prosthetic valves, a suspected complicated IE (such as perivalvular abscess), and
those in the “possible IE” category. TTE as initial test for all others.
F. Diagnosis of unusual pathogens & work-up for culture-negative endocarditis (Berbari et al., 1997)
Table III
Exposure
Epidemic
Birds
Nosocomial,
immuosuppression
EtOHism,
homeless
Animals
STD, sexually
active
Common pathogens
Legionella
C. psittaci
Fungi
Bartonella quintana
Coxiella burnetti
Brucella species
Neisseria gonorrhea
Diagnostic methods
Special instructions to lab to culture for fastidious
organisms—subculture to BCYE media, consider urinary
antigen for L. pneumophilia
Complement fixation, ELISA
Extended incubation of blood cultures
Fastidious organism bld cx with subculture to chocolate
agar
CFA titers to phase I & II antigens
Bld cx with lysis centrifugation, serology
Bld cx. Commercial systems may contain
polyanetholesulfonate which inhibits Neisseria.
A recent series of 348 subjects with blood culture negative endocarditis from France: 167 (48%) were Coxiella burnetti, 99
(28%) were Bartonella (Houpikian and Raoult, 2005).
II. Risk Factors & Prevention
1. What are risk factors for IE? (Steckelberg and Wilson, 1993)
Baseline incidence in general population is 4.9/100,000 person years.
Conditions with increased risk: prior endocarditis 740/100,000; congenital heart disease: overall 120, VSD 220 with
medical management, VSD with surgical management 60, aortic stenosis 180, pulmonic stenosis 20, prosthetic cardiac valve
308-383, rheumatic heart disease 440, mitral valve prolapse with murmur 52, MVP without murmer 4.6.
For prevention of endocarditis during procedures, see AHA recommendations (Dajani et al., 1997).
2. Are recent dental procedures a risk factor? Controversial. Historically, dental procedures have been implicated as a risk
factor for endocarditis. New AHA guidelines include re-evaluation of the data and argues that dental treatment is not a major
risk factor for IE. In one case-control study with 546 subjects. Dental treatment was no more frequent than controls in the
preceding 3 months (Strom et al., 1998).
Estimates of the cumulative exposure to bacteremia indicates that daily activities lead to a much greater burden of bacteremia
than dental procedures. Cumulative exposure of annual bacteremia (CE)=PxIxTxF, where P=prevalence of bacteremia
expressed as a percentage prevalence related to the procedure, I=intensity of bacteremia in cfu/ml; T=length of bacteremia in
minutes; f=frequency of bacteremia events in one year.
Risk of cumulative exposure to bacteremia in one year (CFU minutes per ml per year) compared to tooth extraction (Roberts,
1999):
Table IV
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Risk relative to a tooth extraction
Tooth extraction (permanent tooth)
1
Flossing
365,000
Dental exam
222
Brushing teeth 702,556
Mucoperiosteal surgery
~5555
Chewing
136,778
Baseline activities of daily life
1,693,556
NT tube
166
2. Prevention of endocarditis (Wilson et al., 2007)
New 2007 guidelines have dramatically altered the 1997 recommendations.
1997 guidelines stratified individuals into risk categories by host risks and procedural risks and then made recommendations.
The 2007 guidelines emphasize that most IE occurs as a result of sporadic, transient bacteremias associated with daily living
rather than procedures. Hence, the benefits of prophylaxis for medical procedures is unlikely to be significant.
Summary of major changes: 1. more limited set of cardiac conditions are recommended for prophylaxis (no longer
recommended for MVP with regurgitation, RHD, and more limited #of CHD.
2. simplified list of which procedures qualify (no GU/GI, criteria for dental procedure straightforward)
Table V
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Cardiac conditions associated with highest risk from IE & for which prophylaxis is recommended:
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
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
Oral Regimens for a dental procedure:
Amoxicillin 2g po 30-60 min prior to procedure
If allergic to PCN or ampicillin: Cephalexin 2g or Clindamycin 600 mg or azithromycin/clarithromycin 500 mg
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III. Treatment
Table VI: Treatment of Endocarditis (Baddour et al., 2005)
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A.
i.
ii.
iii.
iv.
Viridans streptococci & S. bovis, PCN susceptible (MIC ≤0.12 g/ml)
PCN G 12-18 mU iv/day
x 4 wks,
ceftriaxone 2g iv or im qd
x 4 wks,
PCN G 12-18 mU iv qd + gentamicin 3 mg/kg iv qd
x 2 wks,
vancomycin 1g iv bid
x 4 wks
(for -lactam allergic pts)
B. Viridans Streptococci & S. bovis, relatively resistant to PCN (MIC > 0.12 g/ml & ≤ 0.5 g/ml)
i. PCN G 24 mU iv/day
x 4 wks
+ gentamicin 3 mg/kg iv qd
x 2 wks
ii. ceftriaxone 2g iv/day
x 4 wks
+ gentamicin 3 mg/kg iv qd
x 2 wks
ii. vancomycin 1g iv bid
x 4 wks
(for -lactam allergic pts)
C. Enterococci, Abiotrophia defective, Granulicatella species, & Viridans strep with PCN MIC >5 g/ml
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 divided in 6 doses
x 4-6 wks
+ gentamicin 1 mg/kg iv q8h
x 4-6 wks
iii. vancomycin 1g iv bid
x 6 wks
(for -lactam allergic pts)
+ gentamicin 1 mg/kg iv q8h
x 6 wks
D. Staphylococcus in the absence of prosthetic material
MSSA:
i. nafcillin or oxacillin 2g iv q4h
+ option of adding gentamicin 1 mg/kg iv q8h
ii. cefazolin 2g iv q8h
+ option of adding gentamicin 1 mg/kg iv q8h
iii. vancomycin 1g iv bid
x 6 wks
x 3-5 days
x 6 wks
x 3-5 days
x 6 wks
(for -lactam allergic pts)
MRSA:
vancomycin 1g iv bid
x
(for -lactam allergic pts)
E. Staphylococcus in the presence of prosthetic material
MSSA:
nafcillin or oxacillin 2g iv q4h
+ rifampin 300 mg iv/po q8h
+ gentamicin 1 mg/kg iv q8h
MRSA:
vancomycin 1g iv bid
+ rifampin 300 mg po q8h
+ gentamicin 1 mg/kg iv q8h
6 wks
x > 6 wks
x > 6 wks
x 2 wks
x 4-6 wks
x > 6 wks
x 2 wks
F. HACEK organisms
i. ceftriaxone 2g iv/im qd
x 4 wks (or other 3rd or 4th gen. ceph.)
ii. ampicillin-sulbactam 12g iv/day divided in 4 doses x 4 wks
iii. ciprofloxacin 500 mg po bid or 400 mg iv bid
x 4 wks
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IV. Management of Complications
A. Prognostication: How accurately can mortality be predicted based on presenting features?
Hasbun et al (2003) (Hasbun et al., 2003)
Retrospective observational cohort study. N=513 with left-sided native valve endocarditis.
Relative risk of unadjusted association of variables and 6 –month mortality:
Immunocompromosed: relative risk=1.86 (95% CI= 1.23-2.59), fever 1.62 (1.04-2.30), mental status 2.26 (1.49-3.06), CHF
2.09 (1.39-2.92), aortic valve vs. other 1.41 (0.92-2.02), vegetation absent vs. present 1.02, disabling emboli 1.25 (0.711.97), 0-1 vs. >2 emboli 0.79, blood culture with pathogen other than Viridans strep 4.26, pathogen other than S. aureus 1.59
(1.04-2.25), pathogen other than Enterococcus 1.87 (1.12-2.71), medical treatment only 2.12 (1.29-3.16)
Adjusted analysis revealed 5 independent variables:
Mental status 1.98 (1.14-2.93), comorbidity score 1.76, CHF 1.91, medical Rx 2.45,
Microbiology: Staph aureus 3.56; bug other than Viridans strep 4.87.
B. Embolization
1. Embolization Risks: Occurs in 22-50% of cases. Highest risk occurs with aortic and mitral valve infections, IE due to S.
aureus, Candida, HACEK, and Abiotrophia organisms. Greatest risk is during the 1st 2 wks (13 events per 1000 patient
days compared to <1.2)
2. Prediction of embolization: Very difficult to predict which individuals will have emboli. Size of vegetation on Echo has
not been uniformaly helpful in predicting embolization. Some studies suggest that vegetations > 1 cm have a higher risk
of embolization, but others have not confirmed this. The highest rate of emboli was seen with vegetations on the anterior
leaflet of the mitral valve. An increase in size of vegetations after 4-8 weeks of therapy increased the risk of emboli in
one study.
C. Congestive Heart Failure: CHF indicates a poor prognosis if medical therapy alone is employed and is also a powerful
predictor of poor surgical outcome. Delaying surgery to the point of decompensation increases mortality (from 6-11% to
17-33%).
D. Indications for valve surgery:
Table VII: Features suggesting potential need for surgical intervention
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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 (not cutaneous)
Increase in vegetation size after 4 weeks of antimicrobial therapy
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.
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E. Mycotic Aneurysms
Extracranial
Most are asymptomatic. Surgical intervention is strongly advised.
Intracranial
See below.
F. Management of Neurologic Complications of Infective Endocarditis
Questions:
-Should neurologic complications from IE affect the timing of cardiovascular surgery?
-Should patients with IE be screened for cerebral mycotic aneurysms?
1. Background
Central nervous system complications occur in 20-40% of patients with infective endocarditis. The types of complications
compiled from 1014 patients from several different studies include: embolus (13.4%), meningitis (7.0%), encephalopathy
(6.4%), headache (3.7%), hemorrhage (3.6%), seizure (3.5%), abscess (1.9%), mycotic aneurysm (1.5%) (Tunkel, 1993).
2. When should cardiac surgery be performed in patients with neurologic complications from IE?
There is general agreement that cerebral hemorrhage is associated with a higher risk of peri-operative mortality and
post-operative stroke. However, for other types of CNS complications the data is not as clear. Four studies have addressed
the question with 2 studies favoring waiting at least 2 weeks and 2 others finding no difference in immediate versus delayed
surgery.
The best data on this question is from Eishi et al who found that a delay in cardiac surgery resulted in a lower complication
rate (Eishi, 1995). Eishi retrospectively evaluated 181 patients with cerebral complications of IE. For pts with cerebral
infarction (n=68), the mortality rate and cerebral complication rate decreased when surgery was delayed: 66.3% & 45.3% for
surgery at less than 24h, 31.3% & 43.8% at 2-7 days, 16.7% &16.7% at 8-14 days, 10% &10% at 15-21 days, 26.3% &10.5%
at 22-28 days, and 7.0% &2.3% for those operated after 4 weeks. For patients with hemorrhagic infarction, the complication
rate remained high at 4 weeks (19% with complications).
Ting et al found that only preoperative hemorrhage was associated with mortality and postoperative stroke (Ting, 1991).
However, a large percentage of these patients were asymptomatic. By comparison, all of the subjects in Eishi’s study were
symptomatic.
Summary: While there are no prospective randomized trials to assess this question, there is some data to suggest that
waiting 2 weeks for cardiac surgery improves the outcome of pts with cerebral infarcts associated with septic emboli.
3. Should patients with IE be screened for cerebral mycotic aneurysms?
Intracranial mycotic aneurysms (ICMA) occur in around 1.2 to 5% of pts with IE. The incidence of ICMA in
asymptomatic versus symptomatic patients is not known. Mortality varies from 30% for unruptured to 80% for ruptured
ICMAs.
Expert opinion suggests that (Baddour et al., 2005):
1) In the absence of clinical signs or symptoms of ICMAs, routine screening with imaging studies is not warranted.
2) Imaging procedures to detect ICMAs are indicated for those with sxs (localized or severe HA, sterile meningitis, or focal
neurological signs). Conventional angiography remains the gold standard although the sensitivity of MRAs is good for
aneurysms greater than 5mm.
3) Treatment of detected aneurysms:
37% will heal on antibiotics alone (Bingham, 1977). There are no data which can prospectively identify pts at risk for
imminent rupture.
Some guidelines for deciding on surgical intervention include:
a) a single ICMA distal to the first bifurcation of a major artery (i.e. MCA) should be monitored with serial angiograms and
excised promptly if it enlarges or bleeds.
b) ICMAs proximal to the first bifurcation are less amenable to surgery.
c) If cardiac valve replacement is indicated, a bioprosthetic valve may be preferred to avoid anti-coagulation.
Due to the paucity of data in this area, it is difficult to assess the wisdom of these recommendations. Data clearly
shows that some aneurysms will resolve with medical therapy alone. Based on this, it seems reasonable to not screen
asymptomatic individuals with the intent to perform immediate surgery. However, it may be worthwhile to do so for
establishing a baseline and influencing the length of treatment (i.e., treat with antibiotics until the aneurysm resolves).
V. Endovascular Catheter-Related Infections
A. Diagnosis (Mermel et al., 2009)
If an intravascular central venous catheter (CVC)-related infection is suspected:
1. 2 sets of blood cultures, with one drawn percutaneously, should be obtained (AII)
2. Paired quantitative blood cultures or paired qualitative blood cultures with a continuously monitored differential time to
positivity are recommended for the diagnosis, especially if the long term catheter cannot be removed (AII) (Siegman-Igra et
al., 1997).
3. If the catheter is removed, quantitative or semi-quantitative cultures of the catheter are recommended (AII) (criteria for
positivity >15 CFU per catheter by semi-quantitative method, >100 CFU by quantitative method). Culture of catheters
should only be done when an infection is suspected
For paired quantitative blood cultures, if the colony count is at least 3-fold greater from the catheter compared to the vein,
then it is predictive of a catheter related infection.
For unpaired quantitative blood cultures, >100 CFU/ml is predictive of a catheter infection.
For differential time to positivity, a 2 hour time difference predicts a catheter infection.
Data (Blot et al., 1999; Blot et al., 1998; Gaur et al., 2003; Mermel et al., 2001; O'Grady et al., 2002; Siegman-Igra et al.,
1997)
Paired quantitative
Unpaired quantitative
Sens
79
78
Spec
94
96
Reference and notes
Siegman-Igra, meta-analysis (cath:vein ratio>3-10:1)
Siegman-Igra, meta-analysis (CFU/ml>15-100)
Differential time to positivity
89
96
94
100
100
91
Gaur et al, n=33 (time>120 minutes)
Blot et al (1998), n=64, (time > 120 minutes)
Blot et al (1999), n=28, (time > 120 minutes)
B. Management (see IDSA guidelines) (Mermel et al., 2001; O'Grady et al., 2002):
Removable CVC
1. For extraluminal infections (tunnel infections, port abscess), remove line and treat with antibiotics for 10-14 days.
For intraluminal infections:
2. Is if a complicated or uncomplicated infection? Complicated infections might have persistent bacteremia, septic emboli,
endocarditis. If complicated, remove line and treat for extended period (depending on complications and organism, generally
at least 4-6 weeks).
2. For uncomplicated luminal infections:
a. S. aureus: remove CVC, Rx for 14 days, strongly consider TEE.
b. Gram negative: Remove CVC, Rx for 14 days.
c. Candida: remove CVC, Rx for 14 days
d. Coagulase-negative staphylococcus: consider retaining catheter and treating with systemic antibiotic + antibiotic lock
therapy for 10-14 days. If catheter is removed, treat for 5-7 days.
Tunneled CVC or implantable device
1. For extraluminal infections (tunnel infections, port abscess), remove line and treat with antibiotics for 10-14 days.
For intraluminal infections:
2. Complicated: same as above.
3. For uncomplicated luminal infections:
The guidelines are similar to those for removable lines. The difference lies in the strength of the recommendation and
degree of insistence on CVC removal. There is acknowledgement that some clinicians will strongly prefer to attempt to
salvage the CVC without removal.
a. S. aureus: Primary rec: remove CVC, Rx for 14 days, strongly consider TEE.
If salvage Rx chosen & TEE negative, Rx for 4-6 wks with systemic abx and antibiotic lock therapy.
b. Gram negative: Primary rec: remove CVC, Rx for 14 days.
If salvage Rx chosen, Rx for 14 days with systemic abx and antibiotic lock therapy.
c. Candida: Remove CVC, Rx for 14 days. Salvage treatment should not be attempted.
d. Coagulase-negative staphylococcus: may retain CVC and treat with systemic antibiotic x 7d + antibiotic lock therapy for
10-14 days. If catheter is removed, treat for 5-7 days (most clinicians would attempt to salvage the line).
VI. Common questions to the ID consult service:
1. Does every patient with S. aureus bacteremia need prolonged iv abx? a transesophageal ECHO? should the line be
removed?
Recommendations for the treatment of S. aureus bacteremia (SAB) continue to evolve. There are no randomized
trials evaluating the optimal length of treatment for uncomplicated SAB (normal ECHO, negative surveillance cultures 2-4 d
after starting therapy, removable focus of infection, not immunocompromised, rapid clinical resolutions of sxs within 72h of
starting abx and removing focus of infection, and no indwelling prosthetic devices or underlying heart disease). For
uncomplicated SAB, many would treat for 14 days. In one study of pts with SAB, TTE had a sensitivity of only 32% for IE
while TEE (used as a gold standard) had a sensitivity of 100% (Fowler et al., 1997). Even if SAB is nosocomially acquired,
there is a high risk of IE (46% of pts with S. aureus IE in one study had nosocomial SAB (Fowler et al., 1999)). TEEs may
actually be cost-effective compared to empiric treatment of 2-4 wks (Rosen et al., 1999). Due to the high rates of IE
complicating SAB, evidence is accumulating to perform a TEE before deciding to treat as uncomplicated bacteremia for 14
days. Removal of lines is strongly advised. In one study, 56.5% of pts who did not have their line removed had a relapse
(compared to a 22.3% failure rate for those who had their line removed (Fowler et al., 1998). For an excellent review of the
management of line infections, see Mermel et al (2001) (Mermel et al., 2001).
In summary: 1) 2 wks of treatment is probably adequate for uncomplicated SAB, 2) remove all lines if possible,
3) there is some evidence that TEEs should be strongly considered in all patients before deciding to treat as uncomplicated
SAB. The standard of care is not settled on the role of TEEs.
2. Which patients with IE can be treated for only 2 weeks? Are there any oral options for treating endocarditis?
A. Patients with PCN susceptible viridans streptococci & S. bovis (MIC ≤0.1 g/ml) can be treated with 2 weeks of
penicillin and gentamicin (left or right-sided lesions).
B. Uncomplicated right-sided endocarditis caused by S. aureus in injection drug users can also be treated with 2 weeks of
therapy (DiNubile, 1994; Heldman et al., 1996). Some patients with a h/o IDU leave the hospital against medical advice
before completing a full course of therapy which has raised interest in designing effective shorter-course regimens. For
uncomplicated, right-sided IE due to MSSA (no metastatic foci of infection), 2 week regimens of nafcillin + aminoglycoside
have efficacy rates of greater than 95% and are considered appropriate treatment.
For oral regimens, the only data concerns IDUs with right-sided S. aureus. One study (Heldman et al) compared 28
days of iv treatment (oxacillin or vancomycin + gentamicin for the 1 st 5 days) versus 5 days of iv treatment (oxacillin or
vancomycin + gentamicin) followed by 23 days of oral ciprofloxacin and rifampin (Heldman et al., 1996). The oral and iv
regimens were similarly effective. A previous, uncontrolled study had found a cipro-rifampin oral regimen to be effective in
10 patients (Dworkin et al., 1989). While this oral regimen is rarely used and is not appropriate for standard care, it may
provide an alternative for patients who refuse iv therapy.
3. Given the inconvenient dosing of nafcillin (q4h), is it truly better than a 1 st generation cephalosporin (i.e. cefazolin at q8h)
for treating S. aureus endocarditis? Is it OK to use ceftriaxone with qd dosing for S. aureus?
The standard of care for treating MSSA has evolved to include a penicillinase-resistant penicillin (nafcillin or oxacillin).
There have been no prospective randomized trials in humans comparing nafcillin with cefazolin. The data rests on a few case
reports of significant failure rates of cefazolin and IE. The data arguing in favor of nafcillin over 1 st generation
cephalosporins are:
A. In vitro data: Nafcillin has a lower MIC (0.25 g/ml) for S. aureus than cephalosporins (cefazolin 1 g/ml, ceftriaxone 2
g/ml). While this is true, the peak drug level/MIC ratio is extremely high for all of them (nafcillin 320, cefazolin 188,
ceftriaxone 112). A level of 10-12 is thought to represent a saturated peak/MIC level for most infections (especially since
beta-lactams have time-dependent or concentration-independent killing properties).
B. The inoculum effect: Argument: The MIC of nafcillin remains low even at the high concentration of bacteria found in
vegetations. In contrast, the MIC is raised for cefazolin and the MBC is so high that there is no bactericidal activity. While
some data supports this, other studies contradict it.
C. Animal model: Argument: nafcillin sterilizes vegetations more quickly and is thus more effective in animal models of
endocarditis. The data does not uniformly support this point either.
Overall, the data is inconclusive comparing nafcillin and cefazolin or any other cephalosporin. Due to the standard
of care that has evolved, nafcillin continues to be the drug of choice for MSSA IE even though the data do not correspond to
the strength of the preference. With continuous infusion pumps, nafcillin has become much easier to give as home therapy
and this option will be available for most patients.
References:
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