Infective Endocarditis

1. MICROORGANISMS’ WONDERLAND
Update not Nostalgia
Dr Diya Saleh
(Medical Registrar)
General Medicine A

2. CASE 1
32 years old male
• PC:
• Fever and generalized body stiffness for 12 days
• Bed ridden for this period
• Passing Cola-colored urine on day 5 of fever
• PHx:
• Hepatitis C
• Psoriasis
• Ex-IVDU: last used 6 years ago, now on Methadone
• 2004: L arm abscess
• 2005: R arm cellulitis (Group A, B hemolytic Strep on BC)

3. •
FHx:
•
•
•
SLE
Epilepsy
Social Hx:
•
•
Smoker
•
•
Lives with girlfriend and son
Denied heavy alcohol drinking
O/E:
•
GCS: 15/15
•
T 38.7, HR 108, BP 122/65, PO2sat 94% RA, RR 16
•
Generalized Lymphadenopathy
•
No rash
•
Chest: clear (CXR: hilars LN enlargements)
•
Heart: no murmur
•
Abdo: generalized tenderness, hepatosplenomegaly (confirmed
by US), ?ascites
•
CNS: neck stiffness, ?papilodema

4. •
Inestigations:
• VBG: PH 7.48, PO2 41, PCO2 40, HCO3 29, Lactate 1.4
• Hb 11.3, WCC 13.8, Neutro 11.9, Platlets 125
• CRP 156
• Na 125, K 4.3, Cr 54, Urea 5.6
• Bil 16, ALT 15, AST 25, GGT 133, ALP 221
• Urine:Leuc 2+, Blood 5+, Prot 3+, Urobilinogen 1+

6. DIAGNOSIS?

10. •CTB: NAD
•LP: NAD

14. WHAT DO YOU WANT TO DO NEXT?

18. CASE 2
• 45 years old male presented with
• fever, productive cough and SOB,
• Hx of IVDU.
• O/E: Temp 39 C, HR 100, BP 105/65
• Chest: R basal crepitation

19. • First Differentia?

20. EASILY MISSED!
INFECTIVE ENDOCARDITIS

21. ROADMAP
1. Epidemiology
2. Pathology
3. Diagnosis
1.
2.
3.
4.
5.
6.
7.
Duke criteria
Blood cultures
Echocardiography
Treatment basics
Complications
Prophylaxis
Summary

22. EPIDEMIOLOGY
• Incidence: 2.6 - 7.0 cases / 100,000 population / year.
• New Trends:
• Mean age was 30 in 1926, now > 50% of patients are
over 60
• Decline in incidence of rheumatic fever
• More prosthetic valves
• More nosocomial cases, injected drug use
• More staphylococcal infection
• Mitral valve alone 28-45% (MV > AV > TV)

23. PATHOLOGY
•
Staphylococcus (40%) , NOT Streptococcus (34%) is now the leading
pathogen*, in the developed world.
•
IVDU: may get unusual pathogen. Polymicrobial infection is common
•
Risk of prosthetic (Mechanical = tissue) valve endocarditis is 4% first
year then decline to 1% per year.
•
Regurgitation valve lesions are more susceptible than stenotic ones.
•
Transvenous pacemaker lead and/or implanted defibrillator
associated endocarditis is usually nosocomial. Onset within weeks
of implantation.
•
100% fatal if undiagnosed and untreated vs 20% fatal if diagnosed and
treated.
*Karchmer, Scientific American Medicine, 1999

25. CLASSIFICATIONS
•
Acute vs Subacute: causative microorganism is primarily responsible for the
temporal course.
•
S.aureus Acute
•
Viridans Strep, Enterococcus Faecalis Subacute IE: classic PUO
•
Bartonella species and the agent of Q fever, C. burnetii, is exceptionally
indolent
•
Right vs Left sided heart: IVDU. May present as pneumonia
•
Native vs Prostatic valve: IVDU
•
Negative (5 - 15%) vs Positive blood culture
•
Bad isolation/identification technique
•
Fastidious isolate:
• HACEK organisms: Haemophilusaphrophilus, H. paraphrophilus,
parainfluenzaeActinobacillusactinomycetemcomitansCardiobacteriumho
minisEikenellacorrodens, Kingellakingae
• Bartonella species have now been established as an important cause
•
Non-bacterial
•
Antibiotics administration pre-culture: 1/3 - 1/2 of cases

27. DIAGNOSIS
• In 1994 investigators from Duke University modified
the von Reyn criteria (1981) to include:
• Role of echocardiography
• IVDU as risk factor
• In 2000, further modification to include:
• Role of TOE
• Q fever (Coxiella brunetti)

28. MODIFIED DUKE CRITERIA
Major Criteria
•Isolation of causative organism by two separate blood cultures at least
12hrs apart, or Three or more positive cultures taken at least one hour
apart
•Endocardial involvement evidence by echo. Oscillating mass, prosthetic
valve dehiscence, abscess, new regurgitation.
Minor criteria
•Predisposing lesion or IVDU
•Fever >38C
•Signs of embolization: Janeway lesion, Intracranial infarct/ bleeding.
•Immunologic phenomena: Glomerulonephritis, Oslers nodes,
Rheumatoid factor, Roths spots.
•Positive blood culture not meeting major criteria.
•Echo finding, but not meeting major criteria.

29. MODIFIED DUKE CRITERIA
Definite Infective Endocarditis
Pathologic criteria:
Microorganisms demonstrated by culture or histology in a vegetation or
embolus.
Clinical criteria:
2 major or
1 major + 3 minor or
5 minor
Possible endocarditis
Findings that are suggestive of IE but fall short of definite, but not rejected.
Rejected Infective Endocarditis
Firm, alternative diagnosis explaining the evidence suggesting infective
endocarditis.
Resolution of syndrome with antibiotic therapy in 4 days or less.
No pathologic evidence at surgery with Abx therapy of four days or less.

30. painful, nodules found in the
pulp of fingers and toes and
are seen more often in
subacute IE
Macular, blanching, nonpainful, e
rythematous lesions on the
palms and soles

32. Septic Retinal Embolus
Roth’s spots 5%
retinal haemorrhages with pale
centres

34. THE CAUSATIVE ORGANISMS CAN BE AS
MANY AS THIS

35. BLOOD CULTURE
ENDOCARDITIS VS NON-ENDOCARDITIS

36. TRANSTHORACIC (TTE) VSTRANSOESOPHAGEAL
(TOE) ECHOCARDIOGRAPHY
• TTE does not detect vegetations <2 mm in
diameter
• TOE is 90% sensitive (vs 60% in TTE) in
detecting vegetations and is particularly
useful for identifying valve ring abscesses as
well as prosthetic valve endocarditis
• However, TTE may be used in pts with a low
pretest likelihood of endocarditis (<5%).

37. TTE VS TEE (TOE)

38. ECHOCARDIOGRAPHIC FINDINGS
• Vegetation
• Abscess
• Pseudoaneurysm
• Perforation
• Fistula
• Valve aneurysm
• Dishence of prosthetic valve

39. “ECHO SHOULD BE DONE IN ALL
CASES OF SUSPECTED
ENDOCARDITIS.”
(This is not all patients with fever or positive blood cultures).
Circulation 1997; 95: 1686-1784

40. COMPLICATIONS
• CARDIAC COMPLICATIONS:
• Heart failure- acute or insidious
• Paravalvular abscesses- esp aortic,
increased in IVDU
• Heart block
• Other extravalvular complicationspericarditis, fistulas

41. •
EMBOLIZATION: Vegetations >10 mm in diameter and those
located on the mitral valve are more likely to embolize:
• Stroke
• Blindness
• Painful ischemic or frankly gangrenous extremities
• Unusual pain syndromes (eg, due to splenic or renal
infarction)
• Hypoxia (due to pulmonary emboli in right-sided
endocarditis)
• Paralysis (due to embolic infarction of either the brain or
spinal cord)
• Effect of antibiotic therapy on embolic risk- decreases,
but can occur wks after initiation
• Predictors of embolization- strep bovis, saureus, L sided,
seen on TTE, not just TOE

42. •
NEUROLOGIC COMPLICATIONS
• Acute encephalopathy
• Meningoencephalitis
• Purulent or aseptic meningitis
• Embolic stroke
• Cerebral hemorrhage (due to stroke or a
ruptured mycotic aneurysm)
• Brain abscess or cerebritis
• Seizures (secondary to abscess or embolic
infarction)

45. •
MYCOTIC ANEURYSMS (most feared)
• cerebral and systemic
•
RENAL DISEASE
• renal infarction due to emboli
• drug induced acute interstitial nephritis
• glomerulonephritis due to deposition of immunoglobulins
and complement in the glomerular membrane- pre
commencement of antibiotics
•
METASTATIC ABSCESSES
• rare- kidneys, spleen, brains, soft tissues
•
MUSCULOSKELETAL COMPLICATIONS
• osteomyelitis- esp vertebral (staph aureus)
•
COMPLICATIONS OF MEDICAL OR SURGICAL THERAPY
• Aminoglycoside-induced ototoxicity or nephrotoxicity

46. POOR PROGNOSTIC MARKERS:
• Low serum albumin
• Infection with S. aureus
• Heart failure
• Diabetes mellitus
• Apache II score
• Embolic events
• Paravalvular abscess
• Vegetation size
• Female sex

48. TREATMENT

49. EMPIRICAL TREATMENT IN
FULMINANT INFECTION
At least three blood cultures (no more than one
from each venipuncture) must be obtained
before therapy is commenced:
• benzylpenicillin 1.8 g IV, 4-hourly
PLUS
• di/flucloxacillin 2 g IV, 4-hourly
PLUS
• gentamicin 4 to 6 mg/kg IV, for 1 dose, then
determine dosing interval for a maximum of
either 1 or 2 further doses based on renal
function

50. ALTERNATIVE EMPIRICAL
TREATMENT
• vancomycin 1.5 IV, 12-hourly (adjust initial dosage for
renal function and monitor blood concentrations
PLUS
•
gentamicin 4 to 6 mg/kg IV, for 1 dose, then determine
dosing interval for a maximum of either 1 or 2 further
doses based on renal function
• Indications:
• prosthetic cardiac valve, pacemaker or intra-cardiac device
• health care–associated infection
• penicillin hypersensitivity
• MRSA is suspected

51. NON FULMINANT INFECTION
WAIT FOR BLOOD CULTURE RESULT
• methicillin-susceptible staphylococci
• di/flucloxacillin 2 g IV, 4-hourly for 4 to 6
weeks
• methicillin-resistant staphylococci
• vancomycin 1.5 g IV, 12-hourly for 6 weeks
+/- Rifampicin & Fusidic Acid

52. • Viridans streptococci susceptible to benzylpenicillin
• benzylpenicillin 1.8 g IV, 4-hourly for
• 2 weeks (uncomplicated endocarditis)
• 4 weeks (complicated endocarditis)
PLUS
• gentamicin 1 mg/kg IV, 8-hourly for 2 weeks
• Viridans streptococci resistant to benzylpenicillin
• vancomycin 1.5 g IV, 12-hourly for 4 - 6 weeks
PLUS
• gentamicin 1 mg/kg IV, 8-hourly for for 4 - 6 weeks

54. HITH CRITERIA
(MUST FULFILL ALL)
• afebrile for at least 72 hours with negative blood cultures
• no evidence of cardiac failure (or if cardiac failure
present, stable and well controlled with medical therapy)
• vegetations less than 10 mm and no intracardiac abscess on
transoesophageal echocardiogram
• no new cardiac conduction abnormalities
• no neurological findings that may result from cerebral embolism
or mycotic aneurysm
• continuing supervision by a cardiologist, and an infectious
diseases physician or clinical microbiologist

55. ANTICOAGULANT??

56. • Anticoagulation is contraindicated in native
valve endocarditis because increases the risk of
intracerebral bleed.
• “If anticoagulation is indicated for another
reason, it should be continued, with INR at low
therapeutic range.
• Anticoagulation does not prevent embolization
due to IE.”
ACC guidelines on Diagnosis and Management of Infective Endocarditis .

60. RELAPSES
• Mostly occur within 1-2 months after completion
of therapy.
• Obtaining one or two blood cultures during this
period is prudent .

61. TIME TO OPERATE?
severe valve regurgitation that
impairs cardiac function

66. PROPHYLAXIS
• No randomised controlled trial has been
performed to decide the role of antibiotic prophylaxis
and there are no human studies showing that it can
prevent endocarditis.
• Guidelines produced in different parts of the world
rely on expert consensus and consequently can
differ in their recommendations.
• Australian guidelines follow the lead of the
American Heart Association

67. Antibiotic prophylaxis is recommended in patients with the
following cardiac conditions if undergoing a specified dental or other
procedure
•
prosthetic cardiac valve or prosthetic material used for cardiac valve
repair
•
previous infective endocarditis
•
congenital heart disease but only if it involves:
• unrepaired cyanotic defects, including palliative shunts and
conduits
• completely repaired defects with prosthetic material or
devices, whether placed by surgery or catheter
intervention, during the first 6 months after the procedure (after
which the prosthetic material is likely to have been
endothelialised)
• repaired defects with residual defects at or adjacent to the site
of a prosthetic patch or device (which inhibit endothelialisation)
•
cardiac transplantation with the subsequent development of cardiac
valvulopathy
•
rheumatic heart disease in Indigenous Australians only

68. Prevention of Infective Endocarditis. Guidelines (2007)

70. ARE DENTISTS INNOCENT?
• “Toothbrushing for 1 year has a greater risk of producing
bacteraemia than a single extraction”
Roberts GJ 1999 Pediatr Cardiol 20:317-325
Dentists are innocent!
• First and most important – proper oral hygiene & Regular
dental review

73. STANDARD PROPHYLAXIS
•
amoxycillin 2 g orally, 1 hour before the procedure oramoxy/ampicillin 2
g IV, just before the procedure oramoxy/ampicillin 2 g IM, 30 minutes
before the procedure.
•
hypersensitive to penicillin
•
clindamycin 600 mg orally, 1 hour before the
procedure orclindamycin 600 mg IV over at least 20 minutes, just
before the procedure
OR
•
lincomycin 600 mg IV over at least 1 hour, just before the procedure
OR
•
vancomycin 25 mg/kg up to 1.5 g IV, ending the infusion just before
the procedure

74. MCQ1
• A 60 year old male has a previous rash whist talking
flucoxacillin. He presents with aortic valve endocarditis with
Staphylococcus Aureus sensitive to flucoxacillin. He is treated
with IV Cephazolin 2g every 8 hours for the past week. He
develops pulmonary oedema and a new early diastolic murmur
in the aortic area.
What is the best management ?
A. Add Gentamycin to Cephazolin
B. B. Start flucoxacillin after rapid desensitisation
C. Change to Vancomycin and Rifampin
D. Transfer to ICU for Intra-aortic balloon pump insertion
E. Urgent aortic valve repair.

75. MCQ2
• 60 years old man presents with a Streptococcus Bovis
endocarditis which is adequately diagnosed and treated.
which of the following is the next most appropriate
investigation?
A. Iron Studies
B. Small bowel series
C.
Gallium scan
D.
Colonoscopy
E. HIV antibody test

76. ANSWER MCQ2
D – colonoscopy
Strep bovis typically comes from the gut
and is associated with bowel polyps and
carcinoma

77. WHAT DO WE NEED TO KNOW?
• IE is rare but serious disease, with high mortality rate
• IVDU and the elderly are at greatest risk of developing IE.
• Every case of PUO should be suspected for IE
• The signs and symptoms of IE are nonspecific and
varied.
• A thorough but timely evaluation (including serial blood
cultures, adjunct labs, and an echo) is crucial to
accurately diagnose and treat IE.
• Beware of life-threatening complications.
• Antibiotics prophylaxis is reserved for high risk patients

78. MANY THANKS
• For your attendance and attention
• To Department of Medicine for the support:
• Dr Bassi
• Dr Vidyarantna
• Debbie Hobbs & Kim Adams
• And all others
• Frankston Hospital Library staff
• Finally not to forget our hard working interns,
Linda and Victor

79. QUESTIONS?