Infective endocarditis

1. Infectious diseases Pharmacotherapy
Lesson 5
Infective Endocarditis [IE]Infective Endocarditis [IE]
tsegayemlk@yahoo.com or tsegaye.melaku@ju.edu.etJuly, 2018 +251913765609+251913765609
By: Tsegaye Melaku [MSc]

2.  Session hitsSession hits
Causes and development
Clinical Pictures & lab/diagnostic criteria/evaluation
Most likely causative pathogens(patient specificpatient specific)Most likely causative pathogens(patient specificpatient specific)
Appropriate management/recommendations
Prophylactic issue(candidatescandidates)
Monitoring & evaluation plan
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3.  A 62-year-old woman with a hx of ESRD on HD presents to the ER with
complaints of weakness, HG fever, and chills. Her current weight is 105
kg. On interviewing the patient, you determine she has had T2DM for
25 yrs and has been receiving dialysis Monday, Wednesday, and
Friday for the past 6 months. She denies any use of alcohol, illicit drugs,Friday for the past 6 months. She denies any use of alcohol, illicit drugs,
or tobacco. Cardiac exam: new murmur
 What information would make you suspect IE?
 Does she have any risk factors for IE?
 What additional information you need before Rx?
 Identify your empirical Rx recommendations.
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4. Infective endocarditis (IE): serious infection affecting the lining
and valves of the heart.
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8. Two categories: acute or sub acute [olderolder classificationclassification]
Acute disease
– Often : virulent organisms (S.(S.
aureusaureus).
– More aggressive/Toxic
presentation
Sub-acute disease
– Less virulent organisms(viridansviridans
group streptococcigroup streptococci)
– Produce a slower and more
subtle presentation.
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presentation
– Progressive valve destruction &
metastatic infection developing
in days to weeks
– High fevers, leukocytosis, and
systemic toxicity
– Mortality: few days to weeks.
subtle presentation.
– Weakness, fatigue, low-grade
fever, night sweats, weight
loss.
– Death occurring in several
months.
– Metastasis less common

9. Can also classified as: [newer classification]
Native Valve IE
Prosthetic Valve IE
Additional ConsiderationAdditional Consideration
Intravenous drug abuse (IVDA) IE
Nosocomial IE
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10.  Fairly uncommon infection.
 10,000 to 20,000 new cases annually in US.
 5-7 cases/100,000 persons-years.
 4th cause of serious infectious diseases syndromes [UTI, pneumonia,
and intra-abdominal sepsis].and intra-abdominal sepsis].
 50% of cases occur in patients older than 50 years.
 IVDUs: increased risk for IE [150 to 2000 cases/100,000150 to 2000 cases/100,000 persons yr]
 Ethiopia: 16% death
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11.  Congenital Heart Disease
10 – 20% of cases in young adults
8% of cases in older adults
PDA, VSD, bicuspid aortic valve (esp. in men>60)
 Intravenous Drug Abuse
Risk is 2 – 5% per pt./yearRisk is 2 – 5% per pt./year
Tendency to involve right-sided valves
– Distribution in clinical series
• 46 – 78% tricuspid
• 24 – 32% mitral
• 8 – 19% aortic
Underlying valve normal in 75 – 93%
S. aureus predominant organism (>50%, 60-70% of tricuspid
cases)
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15. Prosthetic Valve Endocarditis (PVE)
10 – 30% of all cases in developed nations
Cumulative incidence
– 1.4 – 3.1% at 12 months
– 3.2 – 5.7% at 5 years
Early PVE –IE occurring within 1 year of surgery
–– Nosocomial (S. epidermidis predominates)Nosocomial (S. epidermidis predominates)
Late PVE – IE occurring beyond 1 year of surgery
–– Community (same organisms as NVE)Community (same organisms as NVE)
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16.  Congenital or structural cardiac defects,
 Valvular disease, long-term hemodialysis,
 diabetes mellitus; poor oral hygiene,
 Major dental treatment, previous endocarditis,
 Hypertrophic cardiomyopathy,
 Mitral valve prolapse with regurgitation
Any structural cardiac defect turbulence of blood flow  
predisposes to the development of IE
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17. Any type of microorganism
In majority of cases: streptococci, staphylococci, & enterococci.streptococci, staphylococci, & enterococci.
Less common: Gm(-), fungal, and atypical organisms[HACEK*]
*Culture-negative endocarditis
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19.  For IE to develop, the occurrence of several factors is required.
 Primary mxm: alteration of the endothelial surfacesalteration of the endothelial surfaces of the heart
valves to allow for organism attachment and colonizationattachment and colonization.
Due to inflammatory process [RHD or by injury from turbulentRHD or by injury from turbulent
blood flowblood flow]blood flowblood flow]
 Native-valve IE
Platelets & fibrin deposit on the damaged valves forming
a non-bacterial thrombotic endocarditis (NBTE).
Then, hematogenous spread bacteria (i.e, bacteremia), adhere to
and colonize nidus   Vegetation.
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20. Further deposits of platelets and fibrin cover the bacteria:
Providing a protective coatingprotective coating that allows for development
of a suitable environment for continued organism and
vegetation progression.
Acquisition of PVE : direct inoculation (not hematogenous)during
surgery causative organisms are typically Nosocomial
[Drug resistant]
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22.  Quite variable and often non-specific.
 Fever: most frequent and persistent symptom; rarely exceeds 39.4°C
Absent (if previous antibiotic use, CHF, chronic liver or renal
failure, or if less virulent organism (i.e., sub-acute disease).
 Heart murmurs (>85% of cases) Heart murmurs (>85% of cases)
 Splenomegaly and mycotic aneurysms
 Petechiae: pinpoint, flat red spots on the buccal mucosa, Conjunctivae,
and extremities
 Splinter hemorrhages: small dark streaks beneath finger/toes nails
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(.wav)

23.  Osler nodes: painful, tender subcutaneous nodules located on the pads
of the fingers and toes.
 Janeway lesions: small, painless, hemorrhagic macular plaqueshemorrhagic macular plaques on the
palms of the hands or soles of the feet due to septic emboli (in ~5% of
patients)patients)
Associated with acute [S. aureus] IE
 Clubbing of the finger tips: in long-standing illness
 Roth spots: rarely (<5%); oval-shaped retinal hemorrhages with a
pale center near the optic disc
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25. 25

26. A. Janeway lesions on toe (left) and plantar
surface (right) of the foot
B. Septic emboli with hemorrhage and infarction
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1. More specific
2. Erythematous, blanching macules
3. Non-painful
4. Located on palms and soles

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30. 30
1. Non-specific
2. Non-blanching
3. Linear reddish-brown lesions found under the nail bed
4. Usually do NOT extend the entire length of the nail

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Acute S. aureus IE with perforation of the
aortic valve and aortic valve vegetation.
Acute S. aureus IE with mitral valve ring
abscess extending into myocardium.

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36.  Clinical signs and symptoms
 Laboratory/procedures:
Biopsy or Blood cultures: definitive dx
CBC, ESR
CxR
Look for multiple focal infiltratesLook for multiple focal infiltrates
and calcification of heart valves
**A mass of platelets, fibrin, microcolonies of microorganisms,and scant inflammatory cells.36
Echocardiogram[TTE,TEE]
Visualize Vegetations**(arrow)
Assess the need for surgical intervention
Determine the possible source of emboli

37.  Blood Cultures
Minimum of three blood cultures (ideally spread over 24 hrs)
Three separate venipuncture sites ideally
Obtain correct volume of blood for culture bottles
 Positive Result
1 set gives 90% sensitivity, remaining 2 sets add 8%1 set gives 90% sensitivity, remaining 2 sets add 8%
Multiple same cultures are important in confirming significance,
especially for less typical organisms
 Negative Result
Prior antibiotic therapy
‘Culture negative endocarditis’ – fastidous orgs / non-culturable
May support a non-endocarditis patient diagnosis
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38. Be cautious when you send
multiple samples
Bacteraemia is continuous in
IE rather than intermittent, so
positive results from only one
set out of several blood
cultures should be regarded
with caution.
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39. Due to prior administration of Antibiotics
May also be due to infection caused by fastidious or slow-
growing microorganisms.
Diagnostic methods should include
Serological investigations
A systematic approach is advised, based on the clinical
history of the patient and their exposure to possible risk
factors.
09-07-2018 Dr.T.V.Rao MD 39

40. Dx of IE is established with certainty
Only when vegetations are examined histologically
and microbiologically.
But, there is highly sensitive and specific diagnostic schema
Modified Duke criteria [clinical, laboratory,& echo
findings]
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45.  Therapeutic Considerations
Penetrate into the vegetation,
Achieve adequate drug concentrations,
Achieve adequate kill rates.
Parenteral at high doses
Bactericidal and synergistic activity
Extended treatment course of 4 to 6 weeks
 Goal:
Eradicate the infection and minimize/prevent any complications
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46.  Evaluate for risk factors [hint for most likely causative organism].
 If no risk factors: cover gram-positive organisms primarily.
 Streptococci: penicillin plus gentamicin
 Staphylococci or enterococci: vancomycin plus gentamicin
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47.  DOC: penicillin G
Ceftriaxone: alternative
Length of therapy: 4 weeks
If the shorter length of therapy is chosen, add gentamicin (ie, 2
weeks).weeks).
Vancomycin: allergic or intolerant to β-lactams
Patients with PVE: 6 weeks with penicillin G or ceftriaxone with
or without gentamicin during the initial 2 wks of therapy.
Less susceptible: penicillin G or ceftriaxone + gentamicin for
the entire 6 weeks.
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50. American Heart Association, Circulation , 2005
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51.  First determine
a) Whether the isolate is methicillin susceptible versus
methicillin resistant and
b) Patient has a native versus prosthetic valve.
Native valve [methicillin-susceptible]: penicillinase-resistantNative valve [methicillin-susceptible]: penicillinase-resistant
penicillin (eg, nafcillin or oxacillin) or cefazolin with or without
gentamicin,
Methicillin resistant: add vancomycin
Add ( 1st days of 3-5 days) of aminoglycosides
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52. Vancomycin + gentamicin for first 2 weeks/ rifampin for the
entire length of treatment.
Alternatives: Daptomycin, Ceftaroline, linezolid,
quinupristin/dalfopristin, or tigecycline alone or in combination.
Staphylococcal PVE: treat for minimum of 6 weeks
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57. High-dose penicillin G, ampicillin, or vancomycin + gentamicin
Treatment length is usually 4 to 6 weeks, with the aminoglycoside
used over the entire course.
Vancomycin: Alternative
VREVRE
Daptomycin, linezolid or quinupristin/dalfopristin for a
minimum of 8 weeks.
Imipenem/cilastatin + ampicillin or ceftriaxone + ampicillin for the
treatment of E. faecalis, [8 weeks of therapy]
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61. Gm(-) Organisms
Pseudomonas spp.
Antipseudomonal β-lactam (eg, piperacillin/tazobactam,
cefepime, imipenem/cilastatin)+ high-dose aminoglycoside
(tobramycin 8 mg/kg/day).
Length of treatment: minimum of 6 weeks.
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62. HACEK Group
Are difficult to isolate, often taking weeks for identification.
Ceftriaxone (or 3rd /4th generation cephalosporin): DOC
Ampicillin-sulbactam/ciprofloxacin: alternative
Length of treatment: 4 weeks
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63. Fungi
Requires early valve replacement[often considered]
Treatment of fungal IE is exceptionally difficult.
IV Amphotericin B(0.6–1 mg/kg/day): DOC.IV Amphotericin B(0.6–1 mg/kg/day): DOC.
with or without 5-flucytosine (25 mg/kg orally 4x/daily)
Duration Rx: minimum of 8 weeks of treatment.
Oral azoles (eg, fluconazole): as long-term suppressive
therapy to prevent relapse.
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64. Surgery: in
Unresolved infection, ineffective antimicrobial therapy,
More than one episode of serious emboli,
Refractory congestive heart failure,
Significant valvular dysfunction,
Mycotic aneurysm requiring resection,
Local complications (perivalvular or myocardial abscesses), or
Prosthetic-valve infection associated with a pathogen
demonstrating higher antimicrobial resistance.
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66. Harrison 19th edition
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69. To prevent the development of IE,…appropriate for these at-risk
patients:
Presence of prosthetic valves or material,
Prior IE, congenital cardiac disease and cardiac transplantPrior IE, congenital cardiac disease and cardiac transplant
Dental procedures involving manipulation of gingival tissue or
periapical region of teeth or perforation of the oral mucosa.
Prophylaxis for GI or genitourinary surgeries primarily targets
enterococci
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70. From American Heart association & European society of cardiology
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72. Efficacy and safety
Routine assessment of
Clinical signs and symptoms,
Laboratory tests (i.e, repeat blood cultures), microbiologicLaboratory tests (i.e, repeat blood cultures), microbiologic
testing, and
Serum drug concentrations (if appropriate)
Blood culture negative within 3 to 7 days.
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73. 1. Antimicrobial for cardiac device-related IE (CDRIE)
2. Infective endocarditis during pregnancy
3. Non-bacterial thrombotic endocarditis (NBTE)
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