Transcript Infective Endocarditis

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Endocarditis is an inflammation of the
endocardium, the membrane lining the
chambers of the heart and covering the cusps
of the heart valves.
Endocarditis refers to infection of the heart
valves by various microorganisms.
Typically affects native valves, but also
nonvalvular areas or implanted mechanical
devices (e.g., mechanical heart valves).
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Bacteria primarily cause endocarditis
Fungi and other atypical microorganisms can
lead to the disease; hence, the more
encompassing term infective endocarditis is
preferred.
Severity
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Acute or subacute depending on the pace and
severity of the clinical presentation.
Acute: Fulminating form associated with
◦ high fevers and systemic toxicity.
◦ Virulent bacteria, such as Staphylococcus aureus,
frequently cause this syndrome,
◦ if untreated, death may occur within days to weeks.
Severity
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Subacute
◦ more indolent and caused by less-invasive
organisms, such as viridans streptococci,
◦ usually occurring in preexisting valvular heart
disease.
Etiology
Best classified based on
 The etiologic organism,
 The anatomic site of infection,
 Pathogenic risk factors.
 Infection also may follow surgical insertion
of a prosthetic heart valve, resulting in
prosthetic-valve endocarditis (PVE).3
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Infective endocarditis is an uncommon, but
not rare.
The mean male-to-female ratio is 1.7:1.
Most cases occur in individuals >50 years of
age
It is uncommon in children.
PVE accounts for 10% to 30% of cases of
infective endocarditis.
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Most persons with IE have risk factors, such
as preexisting cardiac valvular abnormalities.
Many types of structural heart disease result
in turbulent blood flow that increases the risk
for IE.
A predisposing risk factor, however, may be
absent in up to 25% of cases
Other conditions associated with a higher
incidence include diabetes, long-term
hemodialysis, and poor dental hygeine.
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Presence of a prosthetic valve (highest risk)
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Previous endocarditis (highest risk)
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Complex cyanotic congenital heart disease (e.g., single-
ventricle states)
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Surgically constructed systemic pulmonary shunts or conduits
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Acquired valvular dysfunction (e.g., rheumatic heart disease)
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Hypertrophic cardiomyopathy
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Mitral valve prolapse with regurgitation
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IVDA
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Every organism causing human disease has
been reported to cause IE.
Three groups of organisms result in a
majority of cases: streptococci, staphylococci,
and enterococci
The incidence of staphylococci, particularly S.
aureus, continues to increase
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Streptococci cause IE in patients with
underlying cardiac abnormalities, such as
mitral valve prolapse or rheumatic heart
disease.
Staphylococci (S. aureus and coagulasenegative staphylococci) are the most common
cause of PVE within the first year after valve
surgery, and S. aureus is common in those
with a history of IVDA.
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Polymicrobial IE is uncommon, most often
associated with IVDA.
Enterococcal IE follows GU manipulations
(older men) or obstetric procedures (younger
women).
isolation of the causative pathogen and
determination of its antimicrobial
susceptibilities offer the best chance for
successful therapy
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Table 115-1 Etiologic Organisms in Infective Endocarditis
Agent
Percentage of Cases (%)
Streptococci
60–80
Viridans streptococci
30–40
Other streptococci
15–25
Staphylococci
20–35
Coagulase positive
10–27
Coagulase negative
1–3
Enterococci
5–18
Gram-negative aerobic bacilli
1.5–13
Fungi
2–4
Miscellaneous bacteria
<5
Mixed infections
1–2
"Culture negative"
<5–24
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The mitral and aortic valves are affected most
commonly in cases involving a single valve.
Subacute endocarditis involves mitral valve.
Acute disease involves aortic valve.
35% of cases involve concomitant infections
of aortic and mitral valves.
Infection of tricuspid valve is less common,
and related to IVDA.
pulmonary valve is rarley infected.
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IE occurs via hematogenous spread
It requires the sequential occurrence of several
factors.
◦ The endothelial surface of the heart is damaged.
◦ Platelet and fibrin deposition occurs on the
abnormal epithelial surface (nonbacterial
thrombotic endocarditis) .
◦ Bacteremia gives organisms access to and results in
colonization of the endocardial surface
◦ Bacteremia is the result of trauma to a mucosal
surface with a high concentration of resident
bacteria, such as the oral cavity and
gastrointestinal tract.
◦ After colonization of the endothelial surface, a
"vegetation" of fibrin, platelets, and bacteria
forms. This allows unimpeded bacterial growth to
concentrations as high as 109 to 1010 org/g tissue
Surgery may directly inoculate the valve with
bacteria from the patient's skin or operating
room personnel.
 The recently placed nonendothelialized valve
is more susceptible to bacterial colonization
than are native valves.
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Bacteria also may colonize the new valve from
contaminated bypass pumps, cannulas, and
pacemakers, or from a nosocomial bacteremia
subsequent to an intravascular catheter.
Vegetations in IE may be single or multiple
and vary in size from a few mls to cms.
 Bacteria within the vegetation grow slowly
and are protected from antibiotics and host
defenses.
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Adverse effects of IE and the resulting lesions
include
 (a) local perivalvular damage
 (b) embolization of septic fragments with
potential hematogenous seeding of remote
sites.
 (c) formation of antibody complexes.
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Formation of vegetations may destroy valvular
tissue
 Continued destruction can lead to acute HF
 Valvular stenosis may occur.
 Abscesses can develop in the valve ring or in
myocardial tissue
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Vegetations may be friable, and fragments
may be released downstream.
 Infected particles(septic emboli)can result in
organ abscess or infarction.
 Septic emboli from RT-side endocarditis lodge
in the lungs, causing pulmonary abscesses.
Emboli from LT-side affect organs with high
blood flow, such as the kidneys, spleen, and
brain
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Circulating immune complexes consisting of
Ag, Ab, and complement may deposit in
organs, producing local inflammation and
damage (e.g., glomerulonephritis in the
kidneys).
 Development of "mycotic" aneurysms,
cerebral infarction, splenic infarction and
abscess, and skin manifestations such as
petechiae, Osler nodes, and Janeway lesions
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Highly variable and nonspecific.
 Fever is most common (Table 115–2).
◦ low grade, particularly in subacute cases.
 Heart murmurs inmajority of patients
 IE begins insidiously and worsens gradually.
 Patients present with nonspecific Sx
◦ fever, chills, weakness, dyspnea, night
sweats, weight loss, or malaise.
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Patients with acute disease, such as those
with a history of IVDA and S. aureus infective
endocarditis, may appear with classic signs of
sepsis.
 Splenomegaly is a frequent finding in patients
with prolonged endocarditis
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Table 115-2 Clinical Presentation of Infective Endocarditis
General
The clinical presentation of infective endocarditis is highly variable and nonspecific.
Symptoms
The patient may complain of fever, chills, weakness, dyspnea, night sweats, weight loss,
and/or malaise.
Signs
Fever is common, as is a heart murmur (sometimes new or changing). The patient may
or may not have embolic phenomenon, splenomegaly, or skin manifestations (e.g., Osler
nodes, Janeway lesions).
Laboratory tests
The patient's white blood cell count may be normal or only slightly elevated.
Nonspecific findings include anemia (normocytic, normochromic), thrombocytopenia, an
elevated erythrocyte sedimentation rate or C-reactive protein, and altered urinary
analysis (proteinuria/microscopic hematuria).
The hallmark laboratory finding is continuous bacteremia; three sets of blood cultures
should be collected over 24 hours.
Other diagnostic tests
An electrocardiogram, chest radiograph, and echocardiogram are commonly performed.
Echocardiography to determine the presence of valvular vegetations plays a key role in
the diagnosis of infective endocarditis; it should be performed in all suspected cases.
Osler nodes—Purplish or erythematous
subcutaneous nodules on pads of fingers and
toes. Painful and tender. Not specific for
infective endocarditis.
 Janeway lesions—Hemorrhagic, painless
plaques on palms of hands or soles of feet.
Embolic in origin
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Splinter hemorrhages—Thin, linear
hemorrhages found under the nail beds of the
fingers or toes. not specific for infective
endocarditis.
 Petechiae—Small erythematous, painless,
hemorrhagic lesions anywhere on the skin but
frequently on the anterior trunk, buccal
mucosa and palate, and conjunctivae.
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Clubbing of the fingers
 Roth spots—Retinal infarct with central pallor
and surrounding hemorrhage.
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Emboli—in 1/3of cases and may result in
significant complications.
 Lt-side endocarditis can result in
◦ renal artery emboli causing flank pain with
hematuria,
◦ splenic artery emboli causing abdominal
pain,
◦ cerebral emboli, which may result in
hemiplegia or alteration in mental status.
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Emboli— Rt-side endocarditis may result in
pulmonary emboli, causing pleuritic pain with
hemoptysis
Anemia (normocytic, normochromic), and
thrombocytopenia
 WBC is NL or only slightly elevated,
sometimes with a mild left shift.
 Acute bacterial endocarditis, may present
with an elevated WBC, consistent with a
fulminant infection.
 ESR is elevated in 90% to 100% of patients.
 C-reactive protein also may be elevated.
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Urinary analysis: proteinuria and microscopic
hematuria occurring in approximately 50% of
individuals.
 The hallmark is continuous bacteremia from
shedding from vegetation into the blood.
 95% of patients have +ve blood cultures.
 3 sets of blood cultures, each from separate
sites, should be collected over 24 hours, and
antibiotics should be withheld until adequate
blood cultures are obtained.
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Culture negative" endocarditis
◦ clinical diagnosis of IE is likely but blood
culture is –ve.
◦ often the consequence of
 previous antibiotic therapy
 improperly collected blood cultures,
 unusual organisms.
 When blood cultures from these patients
are –ve after 48 to 72 hours, cultures
should be held for a month to detect
growth of fastidious organisms.
ECG rarely shows important diagnostic
findings but may reveal heart block,
suggesting extension of the infection.
 CXR may provide more diagnostic information
in patient with Rt-side IE.
 Echocardiogram should be performed in all
patients suspected of Septic pulmonary
emboli.
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Echocardiography
◦ Transthoracic echocardiography (TTE) OR
◦ Transesophageal echocardiography (TEE),
depends on the clinical setting.
TEE
more sensitive for detecting
vegetations (90% to 100%)
maintains good specificity (85%
to 95%)
TEE is preferred in high-risk
patients such as those with
prosthetic heart valves, many
congenital heart diseases,
previous endocarditis, new
murmur, heart failure, or other
stigmata of endocarditis
TTE
Rate of detecting vegetations
(58% to 63%)
TTE appears reasonable in the
evaluation of children or adults
in whom the clinical suspicion
of infective endocarditis is
relatively low.
The identification of IE requires the
integration of clinical, laboratory, and
echocardiographic findings.
 The Duke diagnostic criteria include major and
minor variables (Table 115–3).
 Based on the number of major and minor
criteria, patients suspected of IE are
categorized into: definite, possible or infective
endocarditis rejected
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Table 115-3 Diagnosis of Infective Endocarditis According to the
Modified Duke Criteria
Major Criteria
Blood culture positive for infective endocarditis
Typical microorganisms consistent with infective endocarditis from two separate blood
cultures:
Viridans streptococci, Streptococcus bovis, HACEK group, Staphylococcus aureus; or
Community-acquired enterococci, in the absence of a primary focus; or
Microorganisms consistent with infective endocarditis from persistently positive blood
cultures, defined as follows:
At least two positive cultures of blood samples drawn greater than 12 h apart; or
All of three or a majority of four or more separate cultures of blood (with first and last
sample drawn at least 1 h apart)
Single positive blood culture for Coxiella burnetii or antiphase I immunoglobulin G
antibody titer greater than 1:800
Evidence of endocardial involvement
Echocardiogram positive for infective endocarditis (transesophageal echocardiography
recommended in patients with prosthetic valves, rated at least "possible infective
endocarditis" by clinical criteria, or complicated infective endocarditis [paravalvular
abscess]; transthoracic echocardiography as first test in other patients), defined as
follows:
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
Abscess; or
New partial dehiscence of prosthetic valve
New valvular regurgitation (worsening or changing of preexisting murmur not sufficient)
Minor Criteria
Predisposition, predisposing heart condition or injection drug use
Fever, temperature greater than 38°C (100.4°F)
Vascular phenomena, major arterial emboli, septic pulmonary infarcts, mycotic aneurysm,
intracranial hemorrhage, conjunctival hemorrhages, and Janeway lesions
Immunologic phenomena: glomerulonephritis, Osler nodes, Roth spots, and rheumatoid
factor
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The outcome for endocarditis is improved
with
◦ rapid diagnosis
◦ appropriate treatment (i.e., antimicrobial therapy,
surgery, or both)
◦ prompt recognition of complications should they
arise
Factors associated with increased mortality
include
(a) Heart failure
(b) Culture-negative endocarditis
(c) Endocarditis caused by resistant organisms
such as fungi or gram-negative bacteria
(d) left-sided endocarditis caused by S. aureus,
(e) prosthetic-valve endocarditis
The presence of heart failure has the greatest
negative impact on the short-term prognosis.
 For native-valve IE, mortality range from 20%
to 25%;
 lower rates with viridans streptococci (4%
to6%)
 higher rates with lt-side IE caused by
enterococci (15% to 25%) and staphylococci
(25% to 47%).
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higher rates of mortality with unusuall
organisms (e.g., >50% for Pseudomonas
aeruginosa).
 mortality rate for Rt-side IE associated with
IVDA is low (e.g., 10%).
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Relapse after treatment will mostly occur
within 1st 2 months after D/C of AB.
 Relapse for viridans are low (2%),
 Relapse more likely with enterococcal
infection (8% to 20%) and PVE (10% to 15%).
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After appropriate treatment and recovery, risk
of morbidity and mortality following IE persist
for years, although it gradually declines
annually.
 Morbidity remains elevated because of a
greater likelihood of recurrent IE, heart
failure, and embolism
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The desired outcomes for treatment and prophylaxis
of IE
◦ Relieve the signs and symptoms of the disease.
◦ Decrease morbidity and mortality
◦ Eradicate the causative organism with minimal
drug exposure.
◦ Provide cost-effective antimicrobial therapy
◦ Prevent infective endocarditis from occurring or
recurring in high-risk patients with appropriate
prophylactic antimicrobials.
isolation of the infecting pathogen and
determination of antimicrobial
susceptibilities,
 high-dose, parenteral, bactericidal antibiotics
for extended
 Treatment started in the hospital, but can be
completed as outpatient if defervescence has
occurred and follow up blood cultures show
no growth.
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Large doses of parenteral antimicrobials are
necessary to achieve bactericidal
concentrations within vegetations.
 An extended duration of therapy is required,
even for susceptible pathogens, because
microorganisms are enclosed within valvular
vegetations and fibrin deposits.
 For most patients, 4 to 6 weeks of therapy is
required
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Surgery is an important adjunct in the management
of endocarditis.
Valvectomy and valve replacement are performed to
remove infected tissue and restore hemodynamic
function. Echocardiographic features that suggest
the need for surgery include
◦ persistent vegetation
◦ an increase in vegetation size after prolonged
antibiotic treatment
◦ Valve dysfunction,
◦ perivalvular extension (e.g., abscess)
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Surgery also may be considered in cases of
PVE endocarditis
◦ caused by resistant organisms (e.g., fungi or
gram-negative bacteria),
◦ if there is persistent bacteremia or other
evidence of failure despite appropriate
antimicrobial therapy.
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Treatment recommendations from the AHA
provide guidance for the management of IE.
 Guidelines use an evidence-based scoring
system where recommendations are given a
classification as well as level of evidence.
 Class I recommendations are conditions for
which there is evidence, general agreement,
or both that a given procedure or treatment is
useful and effective.
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Class II recommendations are conditions for
which there is conflicting evidence, a
divergence of opinion, or both about the
usefulness/efficacy of a procedure or
treatment (IIa implies the weight of
evidence/opinion is in favor of
usefulness/efficacy whereas IIb implies
usefulness/efficacy is less-well established by
evidence/opinion).
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Class III recommendations are conditions for
which there is evidence, general agreement,
or both that the procedure/treatment is not
useful/effective and in some cases may be
harmful.
Level of evidence is listed as A (data derived
from multiple randomized clinical trials)
 Level B (data derived from a single
randomized trial or nonrandomized studies)
 Level C (consensus opinion of experts).
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B-Lactam antibiotics, such as penicillin G (or
ceftriaxone), nafcillin, and ampicillin, remain
the drugs of choice for streptococcal,
staphylococcal, and enterococcal endocarditis,
respectively
For some pathogens, as enterococci,
synergistic antimicrobial combinations
(including an aminoglycoside) is essential to
obtain a bactericidal effect.
 Combinations may decrease the emergence of
resistant organisms during treatment (e.g.,
PVE caused by coagulase-negative
staphylococci) and hasten clinical and
microbiologic response (e.g., some
streptococcal and staphylococcal infections).
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Occasionally, combination treatment will
result in a shorter treatment course
Streptococci are a common cause of infective
endocarditis, with most isolates being viridans
streptococci
 These bacteria are common inhabitants of the
human mouth and gingiva
 During dental surgery, and even when
brushing the teeth, these organisms can cause
a transient bacteremia. In susceptible
individuals, this may result in infective
endocarditis.
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Streptococcal endocarditis is usually subacute,
and the response to medical treatment is
good
 in uncomplicated cases, response rates as high
as 98% can be expected.
 Viridans streptococci are penicillin-susceptible
 10% to 20% are moderately susceptible.
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This difference in in vitro susceptibility led to
recommendations that the MIC be
determined for all viridans streptococci and
that the results be used to guide therapy.
 Some streptococci are deemed tolerant to the
killing effects of penicillin,
 A tolerant organism is inhibited but not killed
by an antibiotic normally considered
bactericidal.
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Tolerant strains do not respond as readily to
B-lactam therapy as nontolerant ones
 This phenomenon is primarily a laboratory
finding with little clinical significance.
 Treatment for tolerant strains is identical to
that for nontolerant organisms.
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An assortment of regimens can be used to
treat uncomplicated, native-valve endocarditis
caused by fully susceptible viridans
streptococci (Table 115–4).
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Conditions to be present to consider a 2-week
treatment regimen for penicillin-sensitive
streptococcal endocarditis:
Penicillin-sensitive viridans streptococcus or S. bovis (penicillin MIC <0.1
mcg/mL)
No cardiovascular risk factors such as heart failure, aortic insufficiency, or
conduction abnormalities
No evidence of thromboembolic disease
Native-valve infection
No vegetation of greater than 5 mm diameter on echocardiogram
Clinical response within 7 days (the temperature should return to normal, the
patient should feel well, and the patient's appetite should return to normal)
If patient has immediate-type hypersensitivity
to penicillin, vancomycin is chosen for IE
caused by viridans streptococci.
 addition of gentamicin is not recommended.
 A thorough allergy history must be obtained
before a second-line therapy is administered.
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In patients with complicated infections or
when the strep has an MIC of 0.12 to less than
or equal to 0.5 mcg/mL, combination therapy
with an AG and penicillin (higher dose) or
ceftriaxone for the first 2 weeks is
recommended, followed by penicillin or
ceftriaxone alone for an additional 2 weeks
(Table 115–5).
The rationale for combination therapy of
penicillin-susceptible viridans streptococci is
that enhanced activity
 The combined treatment, however, is not
superior to penicillin alone.
 Few human data suggest that patients with
endocarditis caused by these organisms
respond less well to penicillin alone.
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In patients with endocarditis of prosthetic
valves caused by viridans streptococci, choices
of treatment are similar.
 treatment courses are extended to 6 weeks
(Table 115–6).
 If the organism is relatively resistant,
gentamicin is recommended for 6 weeks.
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Data support extended-interval dosing for the
treatment of streptococcal infective
endocarditis, and as compared with three
times-daily dosing this approach may have
greater efficacy
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Endocarditis caused by staph. has become
more prevalent because of
◦ Increased IVDA
◦ More frequent use of peripheral & CVC
◦ Increased frequency of valve-replacement surgery.
S. aureus is the most common among IVDA
and persons with venous catheters.
 Coagulase-negative staphylococci (usually
Staph. epidermidis) are prominent causes of
PVE.
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Any patient who develops staphylococcal
bacteremia is at risk for endocarditis.
 Parameters that predict higher risk of IE in
patients with S. aureus bacteremia
(a) the absence of a primary site of infection
(b) metastatic signs of infection
(c) valvular vegetations detected by
echocardiography
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Therapy for patients with left-sided, nativevalve IE caused by MSSA is 6 weeks of nafcillin
or oxacillin, often combined with a short
course of gentamicin (Table 115–7).
 For uncomplicated infections 4 weeks of
monotherapy with nafcillin or oxacillin may be
sufficient.
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Addition of AG to nafcillin hastens the
resolution of fever and bacteremia, but it does
not affect survival or relapse rates and can
increase renal toxicity
 Twice or thee times-daily dosing of AG
recommended.
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In mild, delayed allergy to penicillin, firstgeneration cephalosporins (such as cefazolin)
are effective alternatives, (see Table 115–7).
The potential for a true immediate-type
allergy should be assessed carefully
 A penicillin skin test should be conducted
before giving antibiotic treatment to any
patient with IE caused by MSSA if there is a
questionable penicillin allergy.
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In a patient with a positive skin test or a
history of immediate hypersensitivity to
penicillin, vancomycin is chosen.
 Patients who fail to respond to vancomycin
should be considered for penicillin
desensitization.
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Duration and Prognosis.
 Antibiotic therapy should be continued for 6
weeks.
 Left-sided IE caused by S. aureus continues to
have a poor prognosis, with a mortality rate of
25% to 47%.
 IE associated with IVDA have a more favorable
response to therapy
Vancomycin is used in MRSA and coagulasenegative staphylococci (see Table 115–7)
 Reports of S. aureus strains resistant to
vancomycin are emerging.
 There are currently no standard treatment
regimens to treat S. aureus IE if it is resistant
to methicillin and vancomycin.
 There is emerging literature documenting
success with daptomycin or linezolid in these
patients.
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The presence or lack of a prosthetic heart
valve in patients with a methicillin-resistant
organism guides therapy and determines
whether vancomycin should be used alone or,
combination therapy is necessary
 (Table 115–8).
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In IVDA the cause is frequently (60% to 70%)
S. aureus,
 the tricuspid valve is frequently infected,
resulting in right-sided IE.
 Most patients have no history of valve
abnormalities, are usually otherwise healthy,
and have a good response to treatment.
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Treatment
 Right-sided MSSA is treated effectively (85%)
with a 2-week course of nafcillin or oxacillin
plus an aminoglycoside.
 Short-course vancomycin is ineffective.
 Concerns with resistance (e.g., ciprofloxacin)
and limited published data preclude routine
use of oral antibacterial regimens for the
treatment of IE in the IVDA.
PVE occurring within 2 months of surgery
strongly suggests that the cause is
staphylococci implanted during the
procedure.
 The risk of staphylococcal endocarditis
remains elevated for up to 12 months after
valve replacement.
 Methicillin-resistant organisms are common,
and vancomycin is the cornerstone of therapy.
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Treatment
 Methicillin-resistant organisms are common,
and vancomycin is the cornerstone of therapy.
 Combination are recommended because of t
high morbidity and mortality.
 Rifampin may have unique activity against
infection that involves prosthetic material.
 Vancomycin is recommended with rifampin
for 6 weeks or more (see Table 115–8)
Treatment
 Vancomycin is recommended with rifampin
for 6 weeks or more (see Table 115–8)
 An aminoglycoside is added for the first 2
weeks if the organism is aminoglycosidesusceptible.
Treatment
MSSA
 penicillinase-resistant penicillin is
administered in place of vancomycin.
Treatment
 Infections after > 12 months parallels that of
native-valve endocarditis.
 antimicrobial therapy is based on the
identified organism and in vitro susceptibility.
 If other than staphylococci, treatment should
be at least 6 weeks
 A concomitant aminoglycoside is
recommended if streptococci or enterococci
E. faecalis and E. faecium
 Normal inhabitants of the GIT.
 Usually of low virulence but can become
pathogens in predisposed patients following
genitourinary manipulations (older men) or
obstetric procedures (younger women).
 E. faecalis is the most common (90%)
 Enterococci cause 5% to 18% of cases.
 They are more resistant to therapy
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Issues with therapy
 No single antibiotic is bactericidal
 MICs to penicillin are relatively high (1 to 25)
 Intrinsic resistance occurs to all
cephalosporins and relative resistance to AG.
 combinations of a cell wall active agent
(penicillin or vancomycin and an AG) are
necessary for killing
 Resistance to all available drugs is increasing
Issues with therapy
 relapse rates of monotherapy with penicillin
is 50% to 80%.
 relapse rate of penicillin-gentamicin or
susceptible strains is <15%.
Issues with therapy
 AG cannot penetrate the bacterial cell in the
absence of the penicillin, so enterococci
usually appear rsistant to AG by susceptibility
testing (low-level resistance).
 In the presence of an agent that disrupts the
cell wall AG can gain entry, attach to bacterial
ribosomes, and cause rapid cell death.
Issues with therapy
 An aminoglycoside-vancomycin combination
is also synergistic against enterococci and is
appropriate therapy for the penicillin-allergy.
 Gentamicin is favored.
 Tobramycin and amikacin, cannot be
substituted routinely.
 Low serum concentrations of AG appear
adequate, (gentamicin peak of 3 to 4 mcg/mL)
Duration
 4 to 6 weeks of ampicillin or high-dose
penicillin G plus an AG for cure (Table 115–9).
 Ampicillin has greater activity than penicillin
G.
 A 6-week course is recommended for patients
with symptoms lasting longer than 3 months
and those with PVE.
Resistance
 the only way to distinguish high-level from
low-level resistance is by performing special
susceptibility tests using 500 to 2,000 mcg/mL
of the aminoglycoside.
 High-level streptomycin-resistant = 60%
 high-level resistance to gentamicin =10% 50%.
Resistance
 Use of vancomycin or ampicillin-sulbactam
with gentamicin should be considered Blactamase–producing enterococci (esp. E.
faecium)
 VRE are reported increasingly (E. faecium)
 Because of the difficulty of treating MDR
enterococci, surgery and replacement of the
infected cardiac valve may be the only cure.
Endocarditis caused by organisms such as
Bartonella; Coxiella burnetii; Brucella,
Candida, and Aspergillus spp.; Legionella; and
gram-negative bacilli (e.g., Pseudomonas) is
relatively uncommon.
 Medical therapy is usually unsuccessful
 Cardiac surgery with extended course
antibacterial therapy is the recommended
course


Fungi cause 2% - 4% of cases
◦ Undergone recent cardiovascular surgery
◦ Intravenous drug abusers
◦ Received prolonged treatment with intravenous
catheters or antibiotics,
◦ Immunocompromised.

Combined medical–surgical approach is
recommended using Amphotericin B



Sterile blood cultures are reported in 5% to 20% of
patients
may occur as a result of
◦ Unidentified subacute right-sided IE
◦ Previous antibiotic therapy
◦ Slow-growing fastidious organisms
◦ Nonbacterial etiologies (e.g., fungi)
◦ Improperly collected blood cultures.
The AHA guidelines provide general
recommendations for culture-negative infective
endocarditis (Table 115–11)
Signs and Symptoms
 Fever usually subsides within 1 week of
therapy.
 Persistence of fever may indicate
◦ Ineffective antimicrobial therapy
◦ Emboli, infections of intravascular catheters
◦ Drug reactions.

Low-grade fever may persist even with
appropriate antimicrobial therapy.
Signs and Symptoms
 With defervescence, the patient should begin
to feel better, and other symptoms, such as
lethargy or weakness, should subside.
 Echocardiography should be performed when
antibiotic therapy has been completed to
determine new baseline cardiac function (i.e.,
ventricular size and function).
 A TTE is usually sufficient
Blood Cultures
 Should be –ve within a few days,
 Response to vancomycin may be slower.
 If +ve beyond the first few days, may indicate
inactive antimicrobials OR doses are not
producing adequate concentrations at the site
of infection.
Blood Cultures
 Cultures should be rechecked until negative.
 During the remainder of therapy, frequent
blood culturing is not necessary.
 Additional blood cultures after successful
treatment (e.g., once or twice within the 8
weeks after treatment) to ensure cure.
Microbiologic Tests
 MICs should be determined
 The agent used should be tested, as well as
alternatives.
Serum Drug Concentrations
 Few data, however, support attaining any specific
serum concentrations in patients with infective
endocarditis.
 serum concentrations of the antimicrobial should
exceed the MBC of the organisms.
 Aminoglycoside concentrations rarely exceed the
MBC for certain organisms, such as streptococci and
enterococci, and concentrations have not been
correlated with response, such as aminoglycosides
and vancomycin for staphylococci
Serum Drug Concentrations
 AG peak serum concentrations are
recommended to be on the low side (3 to 4
mcg/mL for gentamicin).
 Vancomycin: ensure adequate trough
concentrations are achieved
Antimicrobial prophylaxis to prevent infective
endocarditis in patients who are at the highest
risk.
 The objective is to diminish the likelihood of IE
in high-risk individuals from procedures that
result in bacteremia.

Key points
 Only a small number of cases of might be
prevented with prophylaxis for dental
procedures
 prophylaxis for dental procedures should be
recommended only for patients with
underlying cardiac conditions associated with
the highest risk
To determine whether a patient needs
prophylactic
 Assess the patient's risk (Table 115–12)
 Assess if procedure results in bacteremia
(Table 115–13).
 A single 2-g dose of amoxicillin is for adults,
given 30 to 60 minutes before procedures
(Table 115–14).
.
Key points
 in those with high-risk underlying cardiac
conditions, prophylaxis is recommended for
all dental procedures involving manipulation
of gingival tissue or the periapical region of
teeth or perforation of the oral mucosa
 administration of antibiotics is not
recommended for patients who undergo a GU
or GIT procedure