• Presentation of infective endocarditis (IE) is highly variable and can affect almost any organ system
• A high index of suspicion is required in the febrile patient with significant risk factors
• Clinical presentation of IE is changing and classic findings, such as haemorrhagic lesions, are becoming less common.
• Consider a diagnosis of endocarditis in all patients presenting with bacteraemia without an obvious source, especially if the patient has one of the risk factors outlined below

Symptoms and signs

• Non-specific and of insidious onset
• Lethargy
• Nausea, vomiting
• Anorexia, weight loss
• Fever, night sweats
• Shortness of breath
• Musculoskeletal pain
• Haemorrhagic lesions:
• mucocutaneous petechiae
• Janeway lesions (painless, haemorrhagic, macular plaques most frequently seen on palms and soles of feet)
• Roth spots (small, retinal haemorrhages with pale centres, seen near optic nerve)
• splinter haemorrhages
• Anaemia
• Clubbing (if prolonged disease)
• Splenomegaly
• New murmur
• New embolic event which is unexplained
• Discitis

Risk factors

• Previous IE
• Known Valvular heart disease such as:
  • aortic regurgitation/stenosis/bicuspid aortic valve
  • mitral regurgitation/stenosis/ Rheumatic heart disease
• Prosthetic heart valve
• Intra cardiac device such as pacemaker
• Known congenital heart disease
  • patent ductus arteriosus
  • atrial and ventricular septal defect
  • coarctation of aorta
  • complex congenital heart disease
• IV drug use (right sided valve lesions more common)
• Immunosuppressed patients
• Patients with renal failure/dialysis
• Indwelling IV catheter

Blood Cultures

• Aseptic technique is vital. Follow Collection of blood culture specimens guideline
• Draw each sample by separate venepuncture and not from an indwelling catheter
• If patient is IV drug user, or has prosthetic heart valve or central venous catheter, consider fungal cultures. State suspicion of endocarditis on form; blood culture will then be incubated for 3 weeks
• Inform microbiologist of suspected IE

Patient has severe sepsis or septic shock

• Take 2 separate sets of blood cultures and administer empirical antimicrobials within 1 hr of diagnosis

Patient acutely ill

• Take 3 sets of blood cultures at >1 hr intervals within first 24 hr before starting antimicrobial therapy with at least 1 hr interval between each set (one aerobic and one anaerobic bottle per set)
  
  • do not delay antimicrobial therapy in acutely ill patients

Patient not acutely ill

• Take 3 separate sets of blood cultures at >1 hr intervals within first 48 hr
• If patient not acutely ill but antimicrobials have already been commenced, discontinue antimicrobial therapy and take 2 sets of blood cultures daily for 3 days (6 sets)

Other investigations

• FBC and differential WCC:
• look for leucocytosis, usually with neutrophilia
• look for anaemia, usually normochromic normocytic
• ESR
• CRP
• Complement C3, C4, CH50
• ECG, look for conduction defects such as first or second degree block
• Urinalysis, look for protein and microscopic haematuria
• Consider echocardiography in patients on the basis of a balanced clinical assessment by a suitable experienced senior clinician

Diagnostic criteria

• See Duke classification

Table 1: Duke classification in the diagnosis of IE

Table 2: Definitions of Duke major clinical criteria

Table 3: Definitions of Duke minor clinical criteria

• Once diagnosis confirmed or highly likely based on the Duke classification, refer to the on-call cardiology team to review
• In an ill patient, after blood cultures taken, do not wait for blood culture report or echocardiographic confirmation. Start empirical treatment

Empirical anti-microbial treatment

Penicillin Allergy

• Ask the patient and record what happened when they were given penicillin
• True penicillin allergy is rare
• In IE, alternative antimicrobials are less effective with greater risks attached
• If any doubt about whether patient is truly allergic to penicillin, seek advice from a microbiologist or consultant in infectious diseases

Infection Control alerts

• Check for IC alert
• If IC alert not available, check previous 12 months of microbiology reports
• If MRSA present, treat as tagged for MRSA. See MRSA management
• if ESBL, MGNB, CARB present, treat as tagged for ESBL. See ESBL/MGNB/CARG management

Select antimicrobial treatment for types of endocarditis

See original table

• Monitor serum concentrations of vancomycin and gentamicin to avoid toxicity
• Monitor for signs of deafness and balance problems which may occur at normal levels

Culture positive

• Direct choice of antimicrobials by results of blood culture and sensitivity with guidance of a microbiologist and/or infectious diseases consultant
• Treat prosthetic valve endocarditis for at least 6 weeks

Culture negative

• Up to 30% of all cases of IE are blood culture negative
• Failure to culture may be explained by:
  • pre-treatment with antimicrobials
  • inadequate number/poor quality of samples
  • infection with atypical pathogen, (e.g. Chlamydia, Coxiella burnetii, Brucella spp., Bartonella spp, Legionella spp, Tropheryma whipplei)
  • infection with a fastidious organism (e.g. members of the HACEK group)
• Continue antimicrobials in definite or probable IE
• In case of cardiac surgery, surgeon to send a tissue from valvular biopsy to microbiology requesting ‘PCR to identify causative organism’
• Take 3 sets of blood cultures at >1 hr intervals within 24 hr with at least 1 hr interval between each set (one aerobic and one anaerobic bottle per set) for indicating on request for prolonged incubation
• In case of previous cardiac surgery, surgeon to send tissue from a valvular biopsy to microbiology requesting 'PCR to identify causative organism including Coxiella burnetii, and Bartonella spp'
• Request antinuclear, anti-phospholipid and anti-pork antibodies
• In patients with negative blood cultures, vegetations, metastatic infection, perivalvular invasion or embolism, consider candida or aspergillus. Consult microbiologist
• Seek opinion of cardiologist and microbiologist for advice on need for serology, culture with special media and subsequent treatment

• ESR can remain raised for up to four weeks
• Temperature usually settles within first 2–4 days, and a subsequent rise may indicate uncontrolled infection but may also indicate antimicrobial resistance, or superinfection with another pathogen
• In cases of aortic valve endocarditis, repeat ECG twice weekly - looking for development of conduction defect (prolonged PR interval) as may signify developing aortic root abscess
• Repeat echocardiogram weekly on cardiology advice

Complications

• Heart failure
• Vegetation embolisation, threatening limbs/organs and/or leading to metastatic abscess (pneumonia/lung abscess in right-sided disease)
• Abscess in aortic valve ring – can produce heart block
• Immune complex disease – vasculitic rash, arthritis, glomerulonephritis

Early surgical intervention indicated

• Decision to undertake valve surgery as part of treatment of infective endocarditis can be extremely challenging. Early consultation will help the timing of surgery – consider an early referral where there is:
• development of heart failure from acute, severe, valvular regurgitation
• evidence of annular or aortic abscess (prolongation of PR interval on daily ECG)
• evidence of significant valve dysfunction and persistent infection after 7–10 days of appropriate antimicrobial treatment
• early prosthetic valve endocarditis (within 2 months of surgery)
• Staph. aureus prosthetic valve endocarditis
• resistant infection, especially associated with prosthetic valve
• fungal endocarditis
• large vegetations (>10 mm)

Endocarditis MDT

A clinician from the team responsible for the patient must:

• Refer patients with suspected or proven infective endocarditis to the on-call cardiology team
• Attend and present patient at the endocarditis MDT

Decisions at MDT

• Diagnosis and further investigations for patients with possible endocarditis or valvular heart disease
• Optimisation/adjustment of antibiotics and other medication
• Follow-up (both in hospital and in primary care)
• Referral for surgery
• Referral for advanced therapies
• Ceilings of care and referral to palliative care
• Referral to other specialities

• Arrange discharge in consultation with cardiology, infectious diseases and microbiology teams involved. Decision will be based on:
• settling of physical signs
• improvement in appetite
• patient’s sense of wellbeing
• improvement in inflammatory marker (even if still raised)
• Arrange out-patient follow-up in cardiology clinic. Arrange to repeat inflammatory markers and, if possible, echocardiogram before this appointment
• Discuss follow-up with patient. Emphasise need for antimicrobial prophylaxis for future dental and surgical procedures