Infective Endocarditis

OVERVIEW

• endocarditis is a disease characterised by inflammation of the endocardium, typically affecting the heart valves and usually caused by infection and can be acute, subacute or chronic
• most commonly affecting the aortic valve (previously mitral valve)
• most cases of fulminant endocarditis are caused by S. aureus
• always suspect endocarditis in S. aureus septicaemia (perform TOE)

CAUSE

Organisms

• Staphylococcus aureus (MSSA or MRSA)
• Coagulase negative Staphylococci: S. epidermidis, S. lugdenensis 
• Streptococcus viridans
• Streptococcus bovis
• Enterococcus
• HACEK organisms

-> Haemophillus aphrophilus, parainfluenzae and paraphrophilus
-> Actinobacillus actinomycetemcomitans
-> Cardiobacterium hominis
-> Eikenella corrodens
-> Kingella kingae

• Fungi

Culture negative endocarditis

• Brucella
• Bartonella
• Coxiella burnetti (Q fever)
• Chlamydia
• Legionella
• Mycoplasma
• Whipples disease (Trophyerma whipplei)

RISK FACTORS

Cardiac lesions

• congenital heart disease
• rheumatic heart disease
• mitral valve prolapse
• valve regurgitation
• degenerative valve disease
• prosthetic valve (1-5%) – early (<60 days) or late (>60 days)

Predisposition to infection

• IV drug use – tricuspid, aortic and mitral valve
• haemodialysis
• high risk surgery (e.g. dental, respiratory and infective)
• long lines
• bone marrow transplant recipients
• immunosuppressed (e.g. HIV)

CLINICAL FEATURES

History

• 50% occur in patients with normal valves!
• spectrum:
  — asymptomatic
  — malaise, night sweats, anaemia, weight loss
  — crashing cardiogenic shock and sepsis
• haematuria (glomerulonephritis)
• embolic complications
  — stroke (esp if PFO), intracranial haemorrhage
  — septic pulmonary emboli
  — splenic infarction, and other end organs, etc
• presence of risk factors

EXAMINATION

• Skin rash
• Splinter haemorrhages and conjunctival haemorrhages
• Oslers nodes – tender nodules on pulps of fingers and toes
• Janeway lesions – non-tender haemorrhagic pulps on fingers and toes
• Roth spots – retinal hemorrhages with a pale centre
• Splenomegaly
• New neurological signs
• New murmur, e.g. aortic regurgitation and associated systemic features
• Left ventricular failure – basal crackles and effusions
• Emboli — major arteries, pulmonary, spleen
• Haematuria

INVESTIGATIONS

Bedside

• ECG: look for widening PR interval, p mitrale, TWI, dysrhythmia

Laboratory

• Blood cultures (90% of the time positive)
  — need at least 2 sets drawn 12 hours apart, or
  — minimum of 3 out 4 sets postive with first and last positive set >1 hour apart
• Serology for causative organisms
• Rheumatoid factor
• PCR for microbial 16S ribosomal RNA genes from valve tissue (if culture negative)

ECHO

• TTE = 60% sensitive, TOE = 90-99% sensitive, specificity of 90%
• oscillating intracardiac mass on valve or supporting structures, in the path of regurgitant jets, or on implanted material in the absence of an alternative anatomic explanation
• abscess, or
• new partial dehiscence of prosthetic valve

DIAGNOSIS

Use the Modified Duke Criteria (see MedCalc)

• Two major criteria, or
• One major and three minor criteria, or
• Five minor criteria

Major criteria

• Positive blood culture for Infective Endocarditis 
  Typical microorganism consistent with IE from 2 separate blood cultures, as noted below:
  — viridans streptococci, Streptococcus bovis, or HACEK group, or
  —community-acquired Staphylococcus aureus or enterococci, in the absence of a primary focus
  or Microorganisms consistent with IE from persistently positive blood cultures defined as:
  — 2 positive cultures of blood samples drawn >12 hours apart, or
  — all of 3 or a majority of 4 separate cultures of blood (with first and last sample drawn 1 hour apart)
• Evidence of endocardial involvement
  Positive echocardiogram for IE defined as :
  — oscillating intracardiac mass on valve or supporting structures, in the path of regurgitant jets, or on implanted material in the absence of an alternative anatomic explanation, or
  — abscess, or
  —new partial dehiscence of prosthetic valve
• New valvular regurgitation (worsening or changing of preexisting murmur not sufficient)

Minor criteria

• Predisposition: predisposing heart condition or intravenous drug use
• Fever: T> 38.0° C (100.4° F)
• Vascular phenomena: major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhages, and Janeway lesions
• Immunologic phenomena: glomerulonephritis, Osler nodes, Roth spots, and rheumatoid factor
• Microbiological evidence: positive blood culture but does not meet a major criterion as noted below¹ or serological evidence of active infection with organism consistent with IE
• Echocardiographic findings: consistent with IE but do not meet a major criterion as noted above

¹ Excludes single positive cultures for coagulase-negative staphylococci, diphtheroids, and organisms that do not commonly cause endocarditis.

MANAGEMENT

Overview

• resuscitation
• specific therapy: IV antibiotics +/- surgery
• supportive care and monitoring
• treat underlying cause and complications
• consults: infectious diseases, cardiology, cardiothoracic surgery

IV antibiotics

• Empiric treatment for community acquired disease with a native valve:
  benzylpenicillin 1.8 g (child: 45 mg/kg up to 1.8 g) IV, 4-hourly
  + flucloxacillin 2 g (child: 50 mg/kg up to 2 g) IV, 4-hourly
  + gentamicin 4 to 6 mg/kg (child <10y: 7.5 mg/kg; 10y+: 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)
• Empiric treatment for hospital acquired disease OR a prosthetic valve OR penicilin hypersensitity OR suspected CA-MRSA:
  vancomycin 1.5 g (child <12y: 30 mg/kg up to 1.5 g) IV, 12-hourly
  + gentamicin 4 to 6 mg/kg (child <10y: 7.5 mg/kg; 10y+: 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)
• duration: usually for at least 1 to 2 weeks (low risk patients may qualify for home-based therapy)
• gentamicin is is given q24h and is usually stopped after 3 doses unless proven streptococcal or enterococcal endocarditis (give q8h and continue)
• avoid clindamycin and lincomycin due to high failure rates
• directed therapy varies according to the underlying causative organism and the valve affected

Surgery (valve replacement)

• indications

(1) haemodynamic instability
(2) abscess enlargement
(3) abscess (root, paravalvular, intracardiac)
(4) recurrent emboli
(5) organisms: Staphylococcus aureus, Q fever, fungal endocarditis

• early surgery (<48h) reduces long-term embolic complications, no effect on mortality (Kang et al, NEJM 2012)

PREVENTION

Overview

• more conservative approach as risks of adverse effects from antibiotics higher than risks of developing IE from dental, GI or GU tract procedure
• must have high risk patient AND high risk surgery

Risk assessment

• high risk patients:

1. any prosthetic material in used in valve repair
2. previous infectious endocarditis
3. congenital heart disease (unrepaired cyanotic, partially repaired, or completely repaired <6 months previously)
4. cardiac transplant patients with valvulopathy

• high risk surgery

1. all dental procedures that involve manipulation of gingival tissue or periapical region of teeth or perforation of oral mucosa
— thus only check ups and simple fillings that don’t involve gingiva don’t need antibiotic prophylaxis
2. respiratory tract surgery
— incision and biopsy, tonsillectomy, adenoidectomy

Antibiotics

• give a single dose of antibiotic prior to procedure (or within 2 hours of procedure)

1. amoxicillin 50mg/kg PO
2. cephazolin 50mg/kg IV/IM
3. cephalexin 50mg/kg PO (penicillin allergic)
4. clindamycin 20mg/kg PO (penicillin allergic)

• if currently infected with a bug AND operation is taking place on that area AND the organism is likely to cause infectious endocarditis
  -> consult infectious diseases specialist
  -> give prophylactic treatment perioperatively

COMPLICATIONS

• embolic (major arteries, brain, limbs, lungs, organs such as spleen)
• sepsis (local and metastatic abscess formation)
• valve incompetence and heart failure / cardiogenic shock
• arrhythmias
• death

References and Links

LITFL

• CCC — Infectious Endocarditis Echocardiography

Journal articles

• Kang DH, et al. Early surgery versus conventional treatment for infective endocarditis. N Engl J Med. 2012 Jun 28;366(26):2466-73. doi: 10.1056/NEJMoa1112843. PubMed PMID: 22738096. [Review in Crit Care]
• Prendergast BD, Tornos P. Surgery for infective endocarditis:who and when? Circulation 2010;121:1141-1152 PMID: 20212293
• Sharma V, Candililo L, Hausenloy DJ. Infective endocarditis: An intensive care perspective. Trends Anaes Crit Care 2010;2 (1) 36-41 [Free Full Text]
• Sonneville R, Mourvillier B, Bouadma L, Wolff M. Management of neurological complications of infective endocarditis in ICU patients. Ann Intensive Care. 2011 Apr 20;1(1):10. PMC3224466.
• Thury F, Grisoli D, Collart F, Habib G, Raoult D. Management of infective endocarditis: challenges and perspectives. The Lancet 2012;379:965-975 PMID: 22317840