Lucan · Conditions

Infective endocarditis

Australian guidance: eTG Antibiotic — Endocarditis

1. Definition and epidemiology

Infective endocarditis (IE) is a microbial infection of the endocardial surface of the heart, most commonly affecting cardiac valves. In Australia, incidence is estimated at 3 to 9 cases per 100,000 population annually, with higher rates among people who inject drugs, those with prosthetic valves, and patients with cardiac implantable electronic devices. In-hospital mortality remains approximately 15 to 25% even with optimal management, making IE one of the most lethal infections encountered in clinical practice.

2. Pathophysiology

IE begins when turbulent blood flow, congenital or acquired valve abnormality, or endothelial damage creates a nidus for bacterial adhesion. Damaged endothelium exposes subendothelial collagen and tissue factor, triggering platelet aggregation and fibrin deposition to form a sterile thrombotic vegetation. Transient bacteraemia, arising from dental procedures, skin breaches, intravenous drug use, or gastrointestinal manipulation, seeds these vegetations. Organisms with surface adhesins (particularly Staphylococcus aureus and viridans streptococci) bind avidly to fibrin and platelet matrices. The resulting vegetation is avascular and forms a protected biofilm environment that impairs phagocytosis and antibiotic penetration, necessitating prolonged high-dose bactericidal therapy. Ongoing microbial replication causes progressive valve destruction, perivalvular abscess, and haematogenous seeding of distant organs including the brain, kidneys, and spleen. Right-sided IE, most common in people who inject drugs, characteristically seeds the pulmonary vasculature causing septic pulmonary emboli. (Robbins Ch 12)

3. Clinical presentation and diagnostic criteria

Classic features are fever, new or changing cardiac murmur, and evidence of embolic phenomena or metastatic infection. Examination may reveal Janeway lesions (painless haemorrhagic macules on the palms and soles, representing septic emboli), Osler nodes (painful nodules on finger or toe pads, immune complex mediated), Roth spots (retinal haemorrhages with pale centres), and splinter haemorrhages. Splenomegaly occurs in subacute disease. Diagnosis is made using the modified Duke criteria, which incorporate major criteria (positive blood cultures with typical organisms and echocardiographic evidence of IE or new valvular regurgitation) and minor criteria (predisposing cardiac conditions, fever, vascular phenomena, immunological phenomena, and microbiological evidence not meeting major criteria). Definite IE requires two major, one major plus three minor, or five minor criteria. The Duke criteria have lower sensitivity for prosthetic valve, cardiac device, right-sided, and culture-negative endocarditis.

4. Investigations and AU-specific cutoffs

1. Blood cultures: take at least three sets from separate venipuncture sites before commencing antibiotics. Two sets should be taken immediately, and the third at least one hour later. Three sets identify the causative pathogen in approximately 90% of cases. Sample volume optimisation is more important than timing relative to fever onset. In children, three sets are ideal but two are acceptable with volume optimisation.

2. Echocardiography: transoesophageal echocardiogram (TOE) is significantly more sensitive than transthoracic echocardiogram (TTE) due to superior valve visualisation, especially for prosthetic valve and cardiac device-associated IE. If TTE is negative in suspected prosthetic valve or device-associated IE, proceed to TOE where available.

3. Additional investigations include full blood count (leucocytosis, anaemia of chronic disease), C-reactive protein and erythrocyte sedimentation rate (elevated), renal function (acute kidney injury is common), urinalysis (haematuria from immune complex glomerulonephritis), and chest X-ray or CT chest (for right-sided IE with pulmonary emboli). Brain CT or MRI is indicated when neurological complications are suspected. The role of 18F-FDG PET/CT in diagnosis has not yet been accurately defined in the AU setting.

5. Management

Management of IE requires a dedicated multidisciplinary endocarditis team comprising an infectious diseases physician or clinical microbiologist, a cardiologist, and a cardiac surgeon. This team approach significantly reduces IE mortality. Where a dedicated team is unavailable, early consultation with all three specialties is essential.

Patients with the following features require urgent discussion with or transfer to a centre with an endocarditis team: prosthetic valve or cardiac device infection, severe valvular regurgitation, heart failure, vegetations larger than 10 mm, recurrent embolism, extravalvular complications (abscess, fistula, heart block), acute kidney injury, septic shock, neurological complications, staphylococcal or other virulent organism infection, and persistent bacteraemia or fever beyond seven days.

Antimicrobials must be given intravenously to ensure adequate drug concentrations. Total treatment duration is typically four to six weeks of intravenous therapy. Beta-lactams form the backbone of treatment for most IE; substituting vancomycin for beta-lactams when a beta-lactam is indicated is less effective and risks resistance selection and increased toxicity. Avoid clindamycin, lincomycin, and teicoplanin, as treatment failure rates are unacceptably high.

After at least one to two weeks of inpatient treatment, selected stable patients may transition to ambulatory antimicrobial therapy (also known as hospital in the home or OPAT in other systems), provided they meet all criteria: medically stable with no cardiac surgery requirement, afebrile for at least 72 hours with negative blood cultures, no active heart failure, vegetations less than 10 mm on TOE, no intracardiac abscess, no new conduction abnormalities, no neurological findings, and no uncontrolled extracardiac infection.

If valve culture taken at the time of surgery is negative, continue antibiotics to complete the recommended course or for at least a further two weeks, whichever is longer. A positive valve culture mandates four to six weeks of postoperative antibiotic therapy.

6. Pharmacology and AU PBS notes

Empirical therapy for native valve IE pending culture results typically combines a beta-lactam active against streptococci and staphylococci with gentamicin (for gram-negative cover). Gentamicin once daily is the preferred aminoglycoside for empirical therapy due to proven efficacy.

For confirmed streptococcal IE, multiple-daily dosing of gentamicin is recommended for synergistic therapy in Australia; the Antibiotic Expert Group does not endorse routine once-daily gentamicin dosing for streptococcal or enterococcal IE due to insufficient evidence, though once-daily dosing (3 mg/kg) may be considered in ambulatory therapy for streptococcal IE.

For patients with penicillin hypersensitivity: nonsevere allergy permits a cephalosporin-based regimen; severe immediate allergy (anaphylaxis, angioedema, hypotension) requires expert advice, with options including cephalosporin under supervision, desensitisation, or a non-beta-lactam agent; severe delayed allergy (DRESS, Stevens-Johnson syndrome, toxic epidermal necrolysis) mandates a non-beta-lactam regimen. Patients should be allergy delabelled where possible before commencing a vancomycin-based course, as vancomycin is inferior to beta-lactams for susceptible organisms and increases nephrotoxicity risk, particularly in combination with gentamicin. Therapeutic drug monitoring is mandatory for both gentamicin and vancomycin during IE treatment.

PBS note: prolonged intravenous antibiotic courses for IE are typically supplied under hospital authority or ambulatory care programs. Partial oral step-down therapy is not endorsed by the eTG Antibiotic Expert Group as standard practice in the AU setting given the availability and established outcomes of ambulatory parenteral programs.

7. Complications and monitoring

Major complications include: heart failure (from valvular destruction, the most common indication for surgery), perivalvular abscess and cardiac fistula, complete heart block (from septal extension), stroke and other systemic emboli, mycotic aneurysm (especially intracranial), metastatic abscess (brain, spleen, kidneys), acute kidney injury (from immune complex glomerulonephritis or aminoglycoside nephrotoxicity), and relapse or reinfection.

Monitoring schedule during treatment: daily clinical review for signs of heart failure, embolic events, and new neurological symptoms; blood cultures at 48 to 72 hours after commencing antibiotics and until negative; regular renal function and gentamicin and vancomycin levels (at least twice weekly or more frequently if renal function changes); repeat TOE if clinically deteriorating or if assessing suitability for ambulatory therapy; audiological and vestibular assessment if gentamicin is continued beyond 48 hours; cardiology review at least weekly in ambulatory program with immediate return-to-hospital instruction for any fever, breathlessness, or new neurological symptoms. Survivors require long-term surveillance given high risk of further IE episodes.

Written for Australian practice and grounded in the guidance named above. Study material only — not medical advice. Always check against current guidelines.