Transcript Pediatric Endocarditis - Calgary Emergency Medicine

Emergency Medicine
Rounds
Dr. Edward Les
September 26, 2002
Case
16 year old girl
c/o intermittent fever and bilateral leg pain x 5
days
• unable to walk since yesterday
• feet,calves painful
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nauseated; emesis x1
L arm, R abdo pain as well
decreased energy/appetite
dry cough
• w/i clinic x 2 in past 5 days
• Rx’d tylenol and ibuprofen – relief of symptoms
with same
• CBC done @ 2nd w/i visit (3 days prior to ER):
• WBC 9.9, no shift
• Hb 142
• Platelets 121
• U/A:
• 10-20 WBC, 5-10 RBC, many epith
• PMH – noted at triage:
VSD
• scheduled for f/u echo following week
Course in ER
*Had taken Tylenol and ibuprofen 1 hour prior to
presentation
• Initial VS:
– T 37.6, P 108, BP 97/47
• Noted to be somewhat lethargic and unable to
bear weight with some L leg swelling by triage
nurse; tender RUQ
Course in ER
• Seen by ER doc 1 hour after triage:
– Continued afebrile
– Symptoms abated since arrival
– Documented exam - generally normal apart from
cardiac murmur
– Note made of low platelet count and abnormal U/A
• Discharged – dx: viral syndrome with myalgia
2 days later……
Presented to FHH with ongoing
intermittent fever, migratory arthritis,
abdo pain, N/V, sore throat
Subsequently found to have endocarditis as
demonstrated by transesophageal echo
and Group C Strep bacteremia
Complicated course in hospital
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Abdominal wall abscess – sx drained
Pleural effusions – chest tube
Coagulopathy
Pericardial effusion/tamponade – drained 300 mL
Rx with IV Pen V and gent, then Pen V alone x 4
weeks
*Noted to have very poor dental hygiene
Her cardiac anatomy
Based on echo 1 year prior to presentation
• restrictive perimembranous VSD
– ~ 4 mm
– L R flow gradient 78 mm Hg
• LV size - upper limit of normal
Infective Endocarditis
in childhood
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Background
Etiology
Epidemiology
Pathogenesis
Clinical manifestations
Diagnosis
Prognosis/complications
Treatment
Prevention
Pediatric infective endocarditis
• Acute vs subacute
• Bacterial, fungal, viral
• Acute: usually S. aureus, S. pyogenes, S pneumoniae etc
• Subacute: usually S. viridans or enterococcus
• Lots of overlap  better to classify simply by etiologic agent
• Remains significant cause of M&M despite
advances in management and prophylaxis
Why?
• Diagnosis can be difficult when delayed
• Physicians/dentists/public not sufficiently aware of
threat of IE and preventative measures available
• Special risk groups have emerged
Survivors of cardiac surgery
Patients taking immunosuppressants
Patients with chronic IV catheters/ increased PICU
complexity
IV narcotics users
Epidemiology
• 1 in 1280 pediatric admissions per year?
Am Heart J. 1984:107:1235-1240
• Probably higher now
• Most often a complication of congenital or
rheumatic heart disease
• Can also occur in children without a cardiac
malformation
– 8-10% of cases: usually S. aureus
• Rare in infancy
• following open heart sx
• NICU kiddies with central lines
Etiology
Common:
Uncommon:
Native valve or other
cardiac lesions
Native valve or other
cardiac lesions
S. viridans group
S. aureus
S. pneumoniae
Haemophilus influenzae
S. epidermidis
HACEK group
Coxiella burnetti*
Neisseria gonorrheae
Brucella*
Chlamydia spp*.
Streptobacillus
moniliformis*
Pasteurella multocida*
Campylobacter fetus
Enterococcus
Prosthetic Valve
S. epidermidis
S. aureus
S. viridans
P. aeruginosa
Serratia marcescens
Diptheroids
Legionella spp.*
HACEK group
Fungi
*fastidious organisms
Culture negative
• 5-10% of cases
– Fastidious organisms or anaerobes
– Prior antibiotic treatment
– Non-bacterial
– R-sided endocarditis
pathogenesis
Intact cardiac endothelium:
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poor stimulation of coagulation
weakly receptive to bacterial attachment
Valve surface altered to produce suitable site for bacterial attachment
and colonization
Platelets and fibrin deposition in the formation of sterile vegetation –
Nonbacterial Thrombotic Endocarditis (NBTE)
Bacteria reach this site and produce colonization
The surface is covered with platelets and fibrin  clot propogates over
deposited bacteria
Further bacterial multiplication and vegetation growth
- 107-1010 cfu/g of tissue
Localization of IE
• high pressure areas: down stream from sites
where blood flows at high velocity through a
narrow orifice
Venturi effect: maximal deposition of bacteria in low-pressure
sink
e.g.:
atrial surface of mitral valve (MR)
ventricular aspect of aortic valve (AR)
RV wall (restrictive VSD)
Transient bacteremia
Occurs whenever a mucosal surface heavily
colonized with bacteria is traumatized
If preexistent NBTE, it may result in
colonization and IE
– Surgical or dental procedures can be
implicated in approximately 65% of cases
– Poor dental hygiene particular risk factor in
kids with cyanotic CHD
Generally…
• Patients with IE and no underlying heart disease: Staph
aureus more common
• S. viridans more common after dental procedures
• Group D enterococci more often after lower bowel or
genitourinary manipulation
• Pseudomonas or Serratia – IV drug use
• Fungal organisms after open heart surgery
Sticky bugs
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Organisms more frequently associated with IE adhere
more readily to normal leaflets in vitro
e.g.
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FimA is a surface adhesin of S.viridans that serves as an important colonization
factor. Homologues of fimA genes were found in many S. viridans strains and
enterococci.
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Fibronectin is implicated as the host receptor within NBTE. Low-fibronectinbinding mutants of S. aureus have decreased ability to produce IE.
3.
Gm + coccus resistant to phagocytosis, platelet microbicidal proteins (PMP),
and complement-mediated killing
Who to worry about?
• High risk:
• Children with VSD’s, L-sided valvular disease, and systemicpulmonary arterial communications
 Most frequent structural lesions associated with IE:
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Tetralogy of Fallot
VSD (esp restrictive)
Aortic stenosis/coarctation
PDA
TGV
B-T shunts
Valve replacements/valved conduits
• Low risk:
• pulmonic stenosis, ASD
Others at risk…
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Congenital bicuspid aortic valve
Mitral valve prolapse with regurg
Hypertrophic cardiomyopathy
Ventriculo-atrial shunts
Immunopathologic factors
IE cause both humoral and cellular responses
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Rheumatoid factor:
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Antinuclear antibodies:
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titers correlate with the level of hypergammaglobulinemia and decrease with therapy)
may contribute to the musculoskeletal manifestations, low-grade fever, or pleuritic pain
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Connected with long duration of illness, extravascular manifestations,
hypocomplementemia
May cause diffuse glomerulonephritis, and some of the peripheral manifestations such as
Osler nodes
Clinical manifestations
• Relate to 4 underlying phenomena:
– Bacteremia (or fungemia)
– Valvulitis
– Immunologic response
– Emboli
Symptoms
• Fever
– Absent in 5-10% of cases
– Staph: hi spiking
– Strep: low grade
• Chills
• Chest and abdominal
pain
• Arthralgia, myalgia
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Dyspnea
Malaise
Night sweats
Weight loss
CNS manifestations
– Stroke, seizures,
headache
Presentation is a
continuum
signs
• Fever
• Tachycardia
• Embolic phenomena
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Roth spots
Petechiae
Splinter hemorrhages
Osler’s nodes
CNS lesions
• Janeway lesions
• Splenomegaly
• Arthritis
• New or ’ing murmur
• CHF
• Arrythmias
• Metastatic infection
• Arthritis
• Meningitis
• Mycotic arterial
aneurysm
• Pericarditis
• Abscesses
• Septic pulmonary emboli
• Clubbing
– Long-term
Famous but rare
janeway
Splinter
hemorrhage
Lab
• Hematology
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Anemia: normochromic, normocytic,
Thrombocytopenia (5-15%)
Leukocytosis (20-30%)
Elevated ESR, with mean value of 57mm/hr (90-100%)
Hypergammaglobulinemia (20-30%)
• Urinalysis
– Proteinuria (50-65%)
– Microscopic hematuria (30-60%)
– Red cell casts (12%)
Lab
• Serology
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Rheumatoid factor (40-50%)
Circulating immune complexes
ANA
hypocomplementemia
• Blood culture
– Most important lab test
– Positive cultures in 90-95% of cases
Sign/sx/lab
Very common
Common
Infrequent
Rare
Fever
Positive BC
 ESR or CRP
HA, myalgia,
malaise
Anemia
Hematuria
Leukocytosis
RF
New or ’ing heart
murmur
CHF
Petechiae
Peripheral emboli
Splenomegaly
Neuro ’s
Echocardiographic
vegetations
Osler’s nodes
Janeway lesion
Roth spots
Splinter
hemorrhages
Diagnosis
• Need a HIGH index of suspicion in a child with
an underlying contributory factor
• Modified Duke’s criteria
Li JS et al. Clin Infect Dis 2000: 30:633-8.
– Sensitivity >80%
– NPV 92%
• Uses pathologic criteria and major and minor
clinical criteria
Duke’s – major clinical criteria
Positive blood culture for IE
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Typical bug from 2 separate BC’s, or
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Enterococcus in absence of primary
focus, or
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Persistently + BC with bug consistent
with IE drawn >12 h apart, or
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All 3 or a majority of 4 or more
separate BC’s with 1st and last drawn at
least 1 h apart, or
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+ Q fever serology
Evidence of endocardial involvement
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+ echo for IE: oscillating intracardiac
mass, on valve or supporting
structures, or in path of regurgitant
jets, or on implanted materials, in the
absence of alternative anatomic
explanation, or
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Abscess, or
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New partial dehiscence of prosthetic
valve, or
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New valvular regurgitation
Duke’s – minor clinical criteria
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Predisposing heart condition
or IV drug use
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Fever > 38 C
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Vascular phenomena
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Major arterial emboli
Septic pulmonary infarcts
Mycotic aneurysm
Intracranial hemorrhage
Conjunctival hemorrhages
Janeway lesions
4. Immunologic phenomena
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Osler’s nodes
Roth spots
Glomerulonephritis
Rheumatoid factor
5. Microbiologic evidence
• + BC but not meeting major
criterion, or
• Serologic evidence of active
infection with organism
consistent with IE
Definite IE
Pathologic criteria
Microorganisms
• by culture or histology
in a lesion/vegetation/
intracardiac abscess
or
Lesions
• vegetation or intracardiac
abscess present,
Possible IE
At least 1 major and
1 minor,
or
3 minor
Rejected
Alternative diagnosis
for manifestations of
IE
or
Resolution of
manifestations with
abx <4 days
or
Clinical criteria
•2 major criteria, or
•1 major and 3 minor, or
•5 minor
No path evidence of
IE at surgery or
autopsy after abx for
< 4 days
Blood cultures
• Prior to antibiotics
• Prep the skin
• 70% isopropyl alcohol, then iodine – let dry
• Peripheral blood
• Timing doesn’t matter
• Need lots of blood!!
– 20 ml/draw in adults; 1-2 mL/draw in neonates, 2-3
infants, 3-5 older kids, 10-20 adolescents
– Low-grade bacteremia (1-10 cfu/mL venous blood
• Most of the bugs are buried - most of the damage is
occuring away from the surface (valve-ring abscesses and
ruptured chordae)
Blood cultures in IE
Towns, ML and LB Reller. ID Clinics NA 2002; 16(2)
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Acute IE: 2-3 cultures from several venipuncture sites w/i 5 minutes of
each other – then treat
Subacute IE: several BC’s spaced 30 minutes to an hour apart prior to
instituting empiric abx therapy
Multiple cultures:
– More blood = single most important factor for successful recovery of
bug
– Rate of positivity increases as more cultures are obtained (up to a
point)
– Need multiple BC’s to meet Duke criteria for diagnosis
• ONE BC is inadequate!!!
• Doesn’t maximize chance of isolating etiologic agent
• Cannot demonstrate presence of continuous bacteremia
• Cannot distinguish true bacteremia from contamination
Blood volume related to culture
positivity
Towns, ML and LB Reller. ID Clinics NA 2002; 16(2)
Notify the lab of suspected IE
• May need prolonged culture (> 7 days) on
enriched media to detect nutritionally
variant and fastidious bacteria or fungi
• Indicate if received abx prior to collection
Dx: procedures
• Echo
– TTE
• rapid, noninvasive
• specificity: 98%
• sensitivity: <60%
– TEE
• improved spatial
resolution
• specificity: 94%
(prosthetic valve: 88100%)
• sensitivity: 76-100%
(prosthetic valve: 8694%)
Helps predict risk of
embolism
Remember …..
Absence of vegetations does not exclude IE
Vegetations are often not visualized in the
early phases or in patients with complex
CHD
Dx: procedures
• EKG
– May show arrhythmias or conduction
disturbances
Prognosis
• Pre-antibiotic era – fatal
• With abx – mortality still 25-50%
• Serious morbidity in 50-60%
– CHF in 30%: valvular veggies, myocardial abscesses,
pericardial effusions, ruptured sinus of Valsalva, acquired VSD,
heart block
– Systemic emboli: stroke, abscesses, osteomyelitis, arthritis,
renal impairment, meningitis
– Pulmonary emboli
– Mycotic aneurysms
Veggies eat your heart out
Mycotic aneurysms
• Develop during active IE
• More common with S.viridans
• May arise by the following mechanisms:
– direct bacterial invasion of the arterial wall with
subsequent abscess formation or rupture
– septic or bland embolic occlusion of the vasa vasorum
– immune complex deposition with resultant injury to
arterial wall
• Tend to occur at bifurcation areas; middle cerebral
artery is most common
• Clinically silent until rupture
I.E. in the E.D.
Treatment
• Empiric abx:
Vanco + gent
or
Pen + gent
(?talk to ID)
• Treat CHF if present
• Admit
Treatment
• Prolonged ; usually at least 4-6 weeks abx
– hi #’s or bugs
– relatively protected locale; bacteria relatively
metabolically quiescent within the veggies
• need b/w 5 and 20 times MIC
Surgical intervention:
indications
• refractory CHF
• physiologically significant
valve dysfunction as
demonstrated by echo
• >2 serious systemic embolic
episode
• uncontrolled
infection/ineffective
antimicrobial therapy
• resection of mycotic
aneurysms
• most cases of prosthetic valve
IE (caused by more antibioticresistant pathogens)
• local suppurative
complications including
perivalvular or myocardial
abscesses
Surgical therapy:
echo features
• Persistent vegetations after a major systemic
embolic episode
• Large (>1cm diameter) anterior mitral valve
vegetation
• Increase in vegetation size 4 weeks after
antibiotic therapy
• Acute mitral insufficiency
• Valve perforation or rupture
• Periannular extension of infection
Prevention:
in at risk groups
• Antimicrobrial prophylaxis prior to
various procedures
• Proper dental care and hygiene
• Vigorous treatment of sepsis and local
infections
• Careful asepsis during heart surgery and
catheterization
I.E. prophyaxis in the E.D.
What’s the evidence?
• Nonexistent: no RCT
• Uncommon disease even in highest risk kids
• Bacteremia from dental procedures accounts for
only ~10% of cases
• Efficacy of prophylaxis only ~50%
I.E. prophyaxis in the E.D.
Which patients?
Moderate risk
• Congenital heart disease*
• Acquired valvular heart
disease
• Hypertrophic CM
• MV prolapse with regurg
*not isolated ASD, repaired VSD/PDA after 6
months, pacemaker, defibrillator
High risk
• Prev bacterial IE
• Prosthetic valve or
surgically constructed
systemic-pulmonary
shuns or conduit
• Cyanotic congenital
HD (TGV, T of F, etc)
I.E. prophyaxis in the E.D.
Which procedures?
• I&D of odontogenic abscess
• Urinary catheterization in setting of UTI
• ? I&D of cutaneous abscess
– AHA recommendation, but…..
Bibrow, BJ et al. Ann Emerg Med 1997; 29:407
100 BC’s after I&D of 50 abscesses:
0 of 100 positive
I.E. prophyaxis in the E.D.
What drugs?
retrospectroscope
The clues in our girl:
• Hx:
Restrictive VSD
Persistent/intermittent fever, malaise, arthralgia
• Exam: Murmur
Bad teeth
• Lab:
Hematuria, proteinuria
Thrombocytopenia
Summary of endocarditis
• Serious complications
• Death if untreated
• Relatively non-specific signs
• Importance of clinical suspicion
– Review of medical history, review of systems, careful exam
– Immediate admission/referral
• If you suspect it: draw appropriate cultures
Questions?