Infective endocarditis

Epidemiology

• Most commonly mitral valve, then aortic, tricuspid and pulmonic
• Most cases have a risk factor e.g. congenital or acquired cardiac abnormality OR IVDU, indwelling lines, poor dental hygiene or HIV
• Unrecognised disease carries nearly 100% mortality

• In developed countries, native valve endocarditis is often in the setting of mitral valve prolapse
• In developing countries, rheumatic heart disease is the greatest risk factor
• Native valve endocarditis is predominantly left-sided with mortality of 16-27% with treatment
• Risk factors for mortality include comorbidities, ALOC, CCF, bacteria other than Strep viridans or Staph aureus and medical therapy without valve surgery
• IVDU
  • 2-5% of IVDU per year develop IE
  • Predilection for tricuspid valve, 40% recurrence and 56% mortality if HIV+ and CD4 < 200
  • Large vegetation size and fungal organism predict poor outcome in IVDU

• Prosthetic valve endocarditis
  • 1-4% of recipients in first year then 1% per year thereafter
  • No difference between mechanical and bioprosthetic
  • Early = <60 days and usually hospital-acquired
    • Mortality 30-80%
  • Late = >60 days and usually community-acquired
    • Mortality 20-40%

Pathophysiology

• Normal endothelium denuded by turbulent flow or particulate matter in IVDU
• Cocaine use in particular can lead to vasospasm and endothelial damage with high risk of IE
• Results in sterile vegetations (nonbacterial thrombotic endocarditis – same as seen in Libman-Sacks endocarditis [SLE] or marantic endocarditis [malignancy] or around prosthetic valves
• Transient bacteraemia then causes colonisation of thrombus
  • Typically through skin or mucosal (oropharyngeal, GI, GU) or severe periodontal disease
• Adherent organisms then cause further thrombus formation and sequestration of organisms within the clot itself, preventing phagocyte penetration
• Vegetation then fragments with microemboli and sustained bacteraemia

Organisms

• S. aureus
  • >30% of cases in non-IVDU vs. >50% in IVDU
  • Rapid destruction of valves, multiple distal abscesses, myocardial abscess, conduction defects, pericarditis
• Streptococcus viridans group
  • Strep. Mitis/sanguinis/salivarius/bovis/angionsus/mutans
  • Oral commensals
  • Far more indolent
  • Invades abnormal valves primarily vs. normal valves

• S. epidermidis
  • Seen in prosthetic valve endocarditis due to contamination in peri-operative period
  • Aspergillus and C. albicans account for majority of mycotic prosthetic valve endocarditis and cause large vegetations and emboli

• Enterococcus
  • Typically underlying valvular disease and risk factors such as diabetes mellitus or instrumentation of GU/GI tract
• HACEK (fastidious, gram-negative normal oral flora)
  • Blood cultures negative in 5% of cases (half of these due to prior antibiotics but the other half due to HACEK)
  • Haemophilus aprophilus, parainfluenzae and paraphrophilus
  • Actinobacillus actinomycetemcomitans (now Aggregatibacter)
  • Cardiobacterium hominis
  • Eikenella corrodens
  • Kingella kingae
• Fungi

Culture-negative organisms

• Brucella
• Bartonella
• Coxiella burnetii
• Chlamydia
• Legionella
• Mycoplasma
• Trophyerma whipplei

Risk factors

• Cardiac
  • Congenital heart disease
  • Rheumatic heart disease
  • Mitral valve prolapse
  • Valve regurgitation
  • Degenerative valve disease
  • Prosthetic valve
• Predisposing factors
  • IVDU
  • Haemodialysis
  • High-risk surgery (e.g. dental, respiratory, infected)
  • Long lines
  • BM transplant recipients
  • Immunosuppressed

Clinical features

• Asymptomatic through to floridly septic
• Early bacteraemia causes non-specific illness with fever, chills, nausea, vomiting, fatigue and malaise (by far the most common presentation)
• Fever is almost universal in IVDU. May be absent in elderly, severe CCF, renal failure, immunosuppression
• Murmurs are often regurgitant if present (found in 85% of cases overall but <50% of right-sided)
• Acute or progressive CCF in 70% of cases
• Heart blocks and arrhythmias due to conduction system involvement
• Mental status change seen in 10-15%
• Always consider in fever of unknown origin and patients with risk factors and fever

• Embolic
  • Stroke, ICH (MCA territory most common)
  • Retinal artery embolism can cause acute monocular blindness
  • Septic pulmonary emboli
  • Coronary artery emboli can cause MI or myocarditis
  • Embolic splenic infarcts with LUQ pain and radiation to left shoulder
  • Renal emboli cause flank pain and haematuria
  • Mesenteric embolism leading to ischaemic bowel
  • Acute limb ischaemia
  • Mycotic aneurysms (can rupture to produce SAH)
  • Conjunctival haemorrhages
  • Janeway lesions (palm) (<10%)
  • Splinter haemorrhages (15%)

• Examination
  • Above + 
  • Immunologic criteria: Osler’s nodes (10-23%), Roth spots, Rheumatoid factor
  • Splenomegaly
  • New neurological signs
  • New murmur
  • LV failure
  • Haematuria

Diagnosis

• Who to admit for workup
  • Febrile IVDU (hot shot can be observed)
  • Unexplained fever in patient with prosthetic heart valve
  • Prolonged constitutional symptoms of unclear cause should raise suspicion
  • New murmur with evidence of vasculitis or embolisation
  • >2 weeks unexplained fever

• ECG: 
  • Prolonged PR, new LBBB or new RBBB with left anterior fascicular block suggests spread from aortic valve into conducting system
  • Junctional tachycardia, Wenckebach or complete heart block suggests spread from mitral valve into AV node and Bundle of His
• Lab
  • BC (90% positive)
    • Need at least 3 sets drawn 12 hours apart in total
    • Minimum of 3 out of 4 sets positive with first and last set >1 hour apart
    • Need 10mL in each bottle to identify low-grade bacteraemia
    • Do not withold antibiotics if in septic shock or systemic complications to obtain full set of BC
    • Advise lab if high-risk of culture-negative IE for specific testing
  • Serology
  • Rheumatoid factor

• Echo
  • TTE is first-line for native valves
    • Specificity for vegetations is 98% but sensitivity varies (highest in IVDU 88-94%) as often right-sided, thin patients and large vegetations. Sensitivity far lower in obesity, COAD or chest wall deformities
  • TOE: 90-99% sensitive
    • Recommended for prosthetic valves, inadequate TTE images or high-risk clinical features with negative TTE
  • Oscillating intracardiac mass
  • Abscess
  • New partial dehiscence of prosthetic valve

• Anaemia (70-90% of cases)
• CRP raised in most

Modified Duke Criteria

• Definite IE
  • Pathological criteria
    • Microorganism on vegetation or confirmed pathological diagnosis of endocarditis
  • Clinical
    • 2 major; 1 major and 3 minor; 5 minor
• Possible endocarditis
  • 1 major and 1 minor or 3 minor
• Rejected
  • Firm alternative diagnosis
  • Resolution of manifestations of IE within 4 days of antibiotic therapy
  • No pathological evidence at surgery or autopsy after antibiotic therapy for 4 days
  • Does not meet possible endocarditis criteria

• Major criteria
  • Positive blood culture
    • Typical microorganism from 2 separate BC
      • Viridans strep or HACEK or CA-S. aureus or enterococci in absence of primary focus
    • Microorganisms consistent with IE* from persistently positive BC
      • 2 positives drawn >12 hours apart
      • All of 3 or a majority of 4 separate cultures (with first and last >1 hr apart)
  • Evidence of endocardial involvement
    • Positive echo: Oscillating mass, abscess or new partial dehiscence OR
    • New valvular regurgitation (murmur)

• Minor criteria
  • Predisposition: IVDU or heart condition
  • Fever >38
  • Vascular: Major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, ICH, conjunctival haemorrhages and Janeway lesions
  • Immunologic: Osler nodes, RF, Roth spots, GN
  • Microbiologica: BC not meeting major criteria or serological evident*
  • Echo: Consistent with IE but not meeting major criteria
  • *Not including coag-negative Staph, diphtheroids or uncommon causes

Treatment

• Initial haemodynamics
  • Rapid resus
  • Left-sided valve rupture leads to APO and is managed with reduction of afterload to promote forward flow
    IABP indicated for acute mitral valve rupture but CI for aortic valve rupture (worsens retrograde flow in diastole)
  • Manage stroke as per usual protocol + directed therapy for endocarditis
  • Anticoagulation for native valve endocarditis is not beneficial and increases bleeding risk (incl. ICH)
  • Maintain usual anticoagulation if prosthetic valve

• Empirical native valve
  • Gent 5-7mg/kg IV + BenPen 1.8g IV q4h + Fluclox 2g IV q4h
  • Fluclox > Vanc for MSSA
  • If MRSA suspected (IVDU, healthcare-associated infection) replace BenPen with Vancomycin 25-30mg/kg load IV then 15mg/kg IV BD
• Empirical prosthetic valve or pacemaker lead
  • Gent + Fluclox + Vanc
• Definitive treatment
  • Definitive antibiotic therapy based on culture and sensitivities
  • Usually 4-6 weeks IV therapy
  • Prompt surgical consult for below indications

• Surgery
  • Haemodynamic instability
  • Severe valvular dysfunction
  • Relapsing prosthetic valve endocarditis
  • Major embolic complications
  • New conduction defects
  • Persistent bacteraemia
  • Abscess enlargement
  • Abscess (root, paravalvular, intracardiac)
  • Recurrent emboli
  • Organisms: S. aureus, Q fever, fungal
  • Early surgery <48 hours reduces embolic complications but not mortality

Prevention

• Need highest risk patient and procedure
  • Patient
    • Prosthetic valve
    • Previous IE
    • Congenital HD only if:
      • Unrepaired cyanotic defects
      • Competely repaired defects with prosthetic material in last 6 months
      • Repaired defects with residual prosthetic exposure
      • Rheumatic heart disease in high-risk patients (ATSI)
  • Procedure
    • All dental except simple fillings without gingival involvement, local anaesthetic, examination, removal of sutures, supragingival plaque removal
    • Invasive ENT or respiratory procedure to treat established infection
    • Tonsillectomy/adenoidectomy
    • GI/GU infections need enterococci cover
      GI/GU procedures need usual surgical prophylaxis if indicated that covers enterococci

Last Updated on December 20, 2021 by Andrew Crofton