Emergency Medicine Rounds

Dr. Edward LesSeptember 26, 2002

Case

16 year old girlc/o intermittent fever and bilateral leg pain x

5 days• unable to walk since yesterday• feet,calves painful

• 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– 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 Endocarditisin childhood

• 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 emergedSurvivors of cardiac surgeryPatients taking immunosuppressantsPatients with chronic IV catheters/ increased PICU complexityIV 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

EtiologyCommon:Native valve or other cardiac lesions

Uncommon:Native valve or other cardiac lesions

Prosthetic Valve

S. viridans groupS. aureus

Enterococcus

S. pneumoniaeHaemophilus influenzaeS. epidermidisHACEK groupCoxiella burnetti*Neisseria gonorrheaeBrucella*Chlamydia spp*.Streptobacillus moniliformis*Pasteurella multocida*Campylobacter fetus

S. epidermidisS. aureusS. viridansP. aeruginosaSerratia marcescensDiptheroidsLegionella spp.*HACEK groupFungi

*fastidious organisms

Culture negative

• 5-10% of cases– Fastidious organisms or anaerobes– Prior antibiotic treatment– Non-bacterial– R-sided endocarditis

pathogenesis

Intact cardiac endothelium: poor stimulation of coagulationweakly 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

• Organisms more frequently associated with IE adhere more readily to normal leaflets in vitro

e.g.

1. 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.

2. Fibronectin is implicated as the host receptor within NBTE. Low-fibronectin-binding 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 systemic-pulmonary arterial communications

Most frequent structural lesions associated with IE:» 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…

• Congenital bicuspid aortic valve• Mitral valve prolapse with regurg• Hypertrophic cardiomyopathy• Ventriculo-atrial shunts

Immunopathologic factors

IE cause both humoral and cellular responses

• Rheumatoid factor:– titers correlate with the level of hypergammaglobulinemia and decrease with therapy)

• Antinuclear antibodies:– may contribute to the musculoskeletal manifestations, low-grade fever, or pleuritic

pain

• Circulating immune complexes:– 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

• Dyspnea • Malaise • Night sweats• Weight loss• CNS manifestations

– Stroke, seizures, headache

Presentation is a continuum

signs

• Fever• Tachycardia• Embolic phenomena

• 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 rarejaneway

Splinter hemorrhage

Lab

• Hematology– 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– 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

FeverPositive BC ESR or CRP

Common

HA, myalgia, malaiseAnemiaHematuriaLeukocytosisRF

Infrequent

New or ’ing heart murmurCHFPetechiaePeripheral emboliSplenomegalyNeuro ’sEchocardiographic vegetations

Rare

Osler’s nodesJaneway lesionRoth spotsSplinter hemorrhages

Diagnosis• Need a HIGH index of suspicion in a

child with an underlying contributory factor

• Modified Duke’s criteriaLi 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

• Typical bug from 2 separate BC’s, or

• Enterococcus in absence of primary focus, or

• Persistently + BC with bug consistent with IE drawn >12 h apart, or

• All 3 or a majority of 4 or more separate BC’s with 1st and last drawn at least 1 h apart, or

• + Q fever serology

• + 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

• Abscess, or

• New partial dehiscence of prosthetic valve, or

• New valvular regurgitation

Positive blood culture for IE

Evidence of endocardial involvement

Duke’s – minor clinical criteria

1. Predisposing heart condition or IV drug use

2. Fever > 38 C

3. Vascular phenomena• Major arterial emboli• Septic pulmonary infarcts• Mycotic aneurysm• Intracranial hemorrhage• Conjunctival

hemorrhages• Janeway lesions

4. Immunologic phenomena• 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

Pathologic criteria

Microorganisms• by culture or histology in a lesion/vegetation/ intracardiac abscess orLesions• vegetation or intracardiac abscess present,

Clinical criteria

•2 major criteria, or•1 major and 3 minor, or•5 minor

At least 1 major and 1 minor, or3 minor

Alternative diagnosis for manifestations of IE or

Resolution of manifestations with abx <4 days

or

No path evidence of IE at surgery or autopsy after abx for < 4 days

Definite IE Possible IE

Rejected

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)

• 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: 88-100%)• sensitivity: 76-100%

(prosthetic valve: 86-94%)

Helps predict risk of embolism

– > 1 cm or fungating– Location on AV or anterior MV

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 antibiotic-resistant 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?