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Infective Endocarditis: Prevention,
Diagnosis, and Treatment
RISK FACTORS:
Once infective endocarditis is properly diagnosed, the
overall cure rate for is over 80% and major complications can be avoided.
The major risk factors for endocarditis are a history of endocarditis,
prosthetic valvular heart disease or regurgitant heart murmur. 1% to 3% of
patients who undergo valvular heart surgery contract endocarditis within
60 days after the operation. Intravenous drug use continues to be a risk
factor for endocarditis.
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Primary Risk Factors For
Infective Endocarditis
History of infective endocarditis
Prosthetic valvular heart disease
Complex cyanotic heart disease
Surgically constructed pulmonary shunts
Acquired valvular heart disease
Hypertrophic cardiomyopathy
Mitral valve prolapse with regurgitation |
DIAGNOSIS:
The clinical clues to the diagnosis of infective
endocarditis are:
Fever
Regurgitant Heart Murmur
Vascular Skin Lesions (found primarily on the palms or
soles, under the nail beds and in the subconjuctivial sacs or on the
soft palate.)
Less Specific (Possible) Clues:
Heart Disease
Weight Loss
Splenomegaly
When fever, a regurgitant heart murmur, vascular skin
lesions, weight loss, and splenomegaly are present in a patient what has
risk factors for endocarditis, the physician should consider the diagnosis
and collect three blood cultures within 24 hours. Patients with sustained
bacteremia due to typical organisms are likely to have endocarditis.
Transesophageal echocardiography can confirm the diagnosis by showing
cardiac lesions compatible with vegetations or abscess.
Negative blood cultures (culture-negative endocarditis)
or cultures that produce an organism not usually associated with
endocarditis pose a diagnostic problem. If the clinical picture suggests
infective endocarditis and transesophageal echocardiography shows
compatible lesions, the patient should be treated.
The frequent cause of culture-negative endocarditis is sub optimal
antibiotic therapy before the diagnosis is considered, i.e. oral
antibiotics prescribed for a vague fever. Even minute concentrations of
antibiotic in the blood may inhibit culture growth, especially
streptococci that may be exquisitely susceptible to the penicillins.
Ideally, one should wait at least 24 hours after the last dose of
antibiotic before collecting blood cultures. In some cases, if necessary,
tow or more blood cultures beyond the usual tow or three sets should be
obtained, spaced several days apart.
If these strategies fail, one should consider empiric
therapy directed at the usual causes of endocarditis, (i.e. streptococci
in the patient with native heart valves, or staphylococci in patients with
prosthetic heart valves). About 50% of patients will respond clinically to
empiric therapy.
If a patient remains ill after 7 to 10 days of
therapy, further diagnostic studies should be pursued. For example, the
epidemiologic setting may suggest a diagnosis of Q-fever (due to
Bartonella henselae).
At least 50% of patients with fungal endocarditis have
negative blood cultures. Consider it in patients who have undergone
prolonged antibiotic therapy, parental nutrition through central vascular
catheters, or immunosuppressive therapy. Fungi such as Candida and
Aspergillus can produce large valvular vegetations. Surgical intervention
with debridement and valve replacement is usually required. The diagnosis
may only be established by stains, smears and cultures or resected valves
or other embolic lesions found during surgery.
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Empiric Antibiotic Therapy
For Endocarditis In Adults With Normal Renal
Function |
CLINICAL SETTING
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LIKELY PATHOGENS |
ANTIBIOTIC REGIME (IV) |
Patient has native valve
Not acutely ill |
Viridans streptococci
HACEK organisms+ |
Ampicillin 2 g every 4 hours, plus
Gentamicin 1.5 mg/kg every 12 hours |
Acutely ill
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Staphylococcus aureus
Streptococcus pneumonia |
Vancomycin 1.0 g every 12 hours, plus
Gentamicin 1.5 mg/kg every 12 hours |
Intravenous drug abuser
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Staphylococcus aureus
Pseudomonas aeruginosa |
Vancomycin 1.0 g every 12 hours, plus Gentamicin
3.0 mg/kg every 12 hours |
Patient has prosthetic valve
Onset within 60 days
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Staphylococcus epidermis
Staphylococcus aureus |
Vancomycin 1.0 every 12 hours, plus
Gentamicin 1.5 mg/kg every 12 hours |
Onset after 60 days
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Viridans streptococci
Staphylococcus epidermis
Staphylococcus aureus |
Ampicillin* 2 g every 4 hours, plus
Vancomycin 1.0g every 12 hours, plus
Gentamicin 1.5 mg/kg every 12 hours |
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+ Haemophilus sp, Catinobacillus actinomycetemcomitans,
Cardiobacterium hominis, Eikenella corrodens, Kingella sp
* Vancomycin may be substituted for Ampicillin in patients
allergic to penicillin |
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Antibiotic therapy for infective endocarditis due
to streptococci and
Enterococci in adults with normal renal function |
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ORGANISM TYPE |
ANTIBIOTIC REGIME (IV) |
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Penicillin-sensitive streptococcus
(Penicillin MIC+ < 0.1 micrograms/ml |
Penicillin G* 18 million units daily for 4 weeks,
or
Ceftriaxone 2.0 g every 24 hours for 4 weeks |
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Penicillin-insensitive streptococcus
(penicillin MIC > 0.1 and < 0.5
micrograms/ml) |
Penicillin G 18 million units daily for 4 weeks,
or
Gentamicin 1.5 mg/kg every 12 hours for 2 weeks |
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Enterococcus species or streptococcus
(penicillin MIC>0.5 micrograms/ml
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Penicillin G 30 million units daily for 4-6 weeks
plus either Gentamicin 1.5 mg/kg every 12 hours for 4-6 weeks (if
Gentamicin MIC is <500 micrograms/ml) or
Streptomycin 7.5 mg/kg every 12 hours for 4-6
weeks
(if Streptomycin MIC is < 2,000 micrograms/ml) |
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Vancomycin-resistant enterococcus
(Vancomycin MIC > 8 micrograms/ml) |
Quinupristin-dalfopristin 7.5 mg/kg every 8 hours
for 6 weeks |
+ Minimal inhibitory concentration of the
isolate to an antibiotic
* Vancomycin 1.0 g intravenously every 12 hours
can be substituted if the patient is allergic to penicillin
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Antibiotic therapy for infective endocarditis due
to staphylococci and HACEK group organisms in adults with normal
renal function |
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SETTING AND PATHOGEN |
ANTIBIOTIC REGIME (IV) |
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Patient with native valve
Methicillin-susceptible
Staphylococcus aureus or S epidermis
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Oxacillin* 2.0 g every 4 hours for 6 weeks |
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Methicillin-resistant S aureus or
S. epidermis |
Vancomycin 1.0 g every 12 hours for 6 weeks |
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HACEK group organisms+ |
Ceftriaxone 2.0 g every 24 hours for 4 weeks |
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Patient with prosthetic valve
Methicillin-resistant S aureus
Or S epidermis |
Oxacillin 2.0 g every 4 hours for 6 weeks, plus
Rifampin 300 mg by mouth every 8 hours for 6
weeks, plus
Gentamicin 1.5 mg/kg every 12 hours for 2 weeks |
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Methicillin-resistant S aureus
or S epidermis |
Vancomycin 1.0 g every 12 hours for 6 weeks, plus
Rifampin 300 mg by mouth every 8 hours for 6 weeks, plus
Gentamicin 1.5 mg/kg every 12 hours for 2 weeks |
* Vancomycin 1.0 g intravenously every 12 hours
can be substituted if the patient is allergic to penicillin
+ HACEK group includes Haemophilus
parainfluenzae, Haemophilus aphrophilus, Actinobacillus
actinomycetemcomitans, Cardiobacterium hominis, Eikenella
corrodens and Kingella kingae
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MEDICAL MANAGEMENT OF INFECTIVE ENDOCARDITIS
Before the advent of antibiotics, death was the
near-universal outcome for patients with infective endocarditis. Today,
with antibiotic and surgical therapy, the death rate is 15% to 20%. Once a
working diagnosis of infective endocarditis is established, begin
aggressive intravenous antibiotic therapy directed at a likely pathogen.
Most patients with native valve or late-onset prosthetic valve
endocarditis have infection due to streptococcal species. Therapy is
guided by the minimal inhibitory concentration (MIC) of the isolate to
penicillin. Patients with an isolate MIC equal to or less than 0.1 to 0.5
micrograms/ml should receive intravenous penicillin with Gentamicin for 6
weeks. Higher doses of penicillin are recommended when the MIC is greater
than 0,5 micrograms/ml or the organism is an enterococcus.
Vancomycin-resistant enterococci are a growing concern.
One study reported success with quinupristin-dalfopristin plus doxycycline
and rifampin but at present, options are limited and often treatment is
unsuccessful.
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Algorithm for the diagnosis and management of
infective endocarditis |
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Suspect infective endocarditis
If patient has fever, heart murmur, classic
vascular skin lesions, weight loss, splenomegaly |
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Check for key risk factors: history
of endocarditis, presence of prosthetic heart valve, invasive
procedures such as dental extractions, nosocomial bacteremia or
fungemia, intravenous drug abuse |
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Clinical picture compatible with infective
endocarditis?
YES
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NO Pursue other diagnosis
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Discontinue antibiotic therapy, collect two to
three blood cultures
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Cultures positive for bacteria typically
associated with infective endocarditis (streptococci, staphylococci,
HACEK organisms)? |
NO Refer for transesophageal
echocardiography and or serologic studies
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YES
Start antibiotic therapy, adjusting for
susceptibility. Monitor closely for signs of congestive heart
failure, valve dysfunction, persistent fever, conduction defects,
major embolic events. |
YES Positive results
NO
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If valve dysfunction or abscess is found, refer
for surgical debridement or valve repair or replacement
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Pursue other diagnosis
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While most patients with infective endocarditis respond
to antibiotic therapy and have a smooth course and favorable outcome, some
require more intensive evaluations and treatment. For example, in patients
with congestive heart failure, the heart failure may or may not be
associated with valvular or cardiac dysfunction due to the endocarditis,
and serial transesophageal echocardiographic studies are needed to asses
valve functions during medical therapy.
Surgical intervention must be available immediately when
medical management fails. In the past, surgeons were reluctant to operate
on patients with active infection, but we know now that restoration of
cardiac function by surgery clearly improves outcomes. The persistence of
fever beyond several days of therapy of the development and evolutions of
first-degree atrioventricular block on the electrocardiogram may indicate
an annular or myocardial abscess, which will likely require surgery. Even
after antibiotic therapy has been completed, patients are at a risk for
mechanical valve dysfunction, and a significant number require corrective
surgery some time in the near future.
NEUROLOGICAL COMPLICATIONS OF ENDOCARDITIS
While major neurological complications resulting from
endocarditis are rare, they are associated with significant morbidity and
mortality. This is especially true with the organism is S aureus. Embolic
strokes and encephalopathy are usually seen during the initial
presentation of the illness. Brain abscesses and mycotic aneurysms are
more worrisome but are rare. Mycotic aneurysms in the cerebral circulation
are usually peripheral and small and resolve with antibiotic treatment.
Aneurysms that are more central may bleed into the subarachnoid space or
ventricles, and neurosurgical intervention is usually required. Large
brain abscesses may need to be drained surgically.
In general, anticoagulation therapy should be
discontinued because of the increased risk of intracranial bleeding from
such neurological complications. However, the decision depends on the type
of valve, cardiac rhythm, and prior valve-related embolic events.
PROPHYLAXIS GUIDELINES FOR INFECTIVE ENDOCARDITIS
Although antibiotic prophylaxis to prevent endocarditis
has become standard practice before many dental and surgical procedures,
there is little published evidence to suggest that it really works. A
controversial case-control study of dental and cardiac risk factors in 273
patients concluded that dental treatment does not seem to increase the
risk for infective endocarditis and "few cases of infective
endocarditis would be preventable with antibiotic prophylaxis, even with
100% effectiveness assumed," and it called for a reconsideration of
current prophylaxis policies. However, the study did confirm that cardiac
valvular abnormalities are clearly associated with risk for endocarditis.
These abnormalities include mitral valve prolapse, congenital heart
disease, rheumatic valvular heart disease, previous cardiac surgery and a
history of infective endocarditis. A known cardiac murmur was associated
with a six fold increase in risk.
The American Heart Association has recently updated
guidelines for prophylaxis. Diseases associated with risk for endocarditis
are listed and prophylactic regimes for dental and other invasive
procedures are described. Patients who undergo cardiac valve surgery
should receive perioperative antibiotic prophylaxis with a
first-generation or second-generation cephalosporin. For surgical centers
with a high prevalence of methicillin-resistant staphylococci, Vancomycin
should be used instead. The antibiotic infusion must be given shortly
before the skin incision, preferably within 30 minutes. The antibiotic
should not be continued longer than 24 hours after the operation. Some
surgeons give a preoperative dose and another dose during surgery if the
operation is longer than 4 hours, and no more is given afterward.
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Antibiotic prophylaxis for invasive procedures |
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PROCEDURE |
PROPHYLACTIC REGIMEN |
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Oral, respiratory, esophageal
Dental extraction
Periodontal procedures
Dental implants
Prophylactic cleaning
Tonsillectomy, adenoidectomy
Rigid bronchoscopy
Esophageal dilation
Sclerotherapy
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Amoxicillin* 2 g by mouth 1 hour before the
procedure, or 2 g intramuscularly or intravenously ½ hour before
the procedure |
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Gastrointestinal, genitourinary
Endoscopic retrograde cholangiopancreatography for
biliary obstruction
Biliary tract surgery
Operations on intestinal mucosa
Prostate surgery
Cystoscopy
Urethral dilation
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Ampicillin * 2 g intramuscularly or intravenously,
plus Gentamicin 1.5 mg/kg intramuscularly or intravenously ½ hour
before the procedure |
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* Substitute clindamycin 600 mg by mouth or
intravenously if patient is allergic to penicillin |
From The Cleveland Clinic Journal of Medicine, Volume
67, Number 5, May 2000
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