Infective endocarditis — Duke criteria, microbiology, antimicrobials and surgical indications

Definition / Overview

• Infective endocarditis (IE) is a microbial infection of the endocardial surface of the heart, most commonly involving cardiac valves but also potentially affecting mural endocardium, septal defects, or intracardiac devices.
• Classified broadly as native valve endocarditis (NVE) or prosthetic valve endocarditis (PVE), and further as acute (aggressive, typically S. aureus) or subacute (indolent, typically viridans streptococci).
• Early PVE is arbitrarily defined as onset within 12 months of valve surgery; predominantly caused by coagulase-negative staphylococci, S. aureus, gram-negative bacilli, and Candida spp. reflecting intraoperative or perioperative inoculation.
• Late PVE shares the microbial spectrum of community-acquired NVE.
• Incidence is rising globally, driven by ageing populations, more intravascular devices, and increased IV drug use.

Pathophysiology

• Endothelial disruption, from turbulent flow, instrumentation, or congenital/degenerative structural disease, allows deposition of platelets and fibrin, creating a sterile thrombotic nidus.
• Transient bacteraemia seeds this nidus; organisms adhere via surface adhesins (notably S. aureus fibronectin-binding proteins).
• The infected vegetation is poorly penetrated by host defences and many antimicrobials, necessitating prolonged, bactericidal therapy at high serum concentrations.
• Consequences arise through three mechanisms: 1. Local destruction, valve regurgitation, perivalvular extension (ring abscess, fistula), conduction system involvement 2. Embolic events, vegetations fragment and seed distant organs (brain, kidney, spleen, coronary arteries, lungs in right-sided disease) 3. Immune-complex deposition, glomerulonephritis, vasculitis, Osler nodes, Roth spots

Clinical Features & Diagnosis

Symptoms and Examination

• Fever is near-universal; constitutional symptoms (malaise, night sweats, weight loss) dominate subacute presentations.
• Peripheral stigmata, their presence strongly raises the pre-test probability for IE and should be sought systematically:

• New or changing cardiac murmur is a key sign; aortic regurgitation developing acutely is haemodynamically catastrophic.
• PR interval prolongation on ECG suggests aortic root/perivalvular abscess extending toward the AV node, a finding demanding urgent imaging and surgical review.
• Splenomegaly, microscopic haematuria, and new neurological deficits are common accompaniments.

Modified Duke Criteria

The modified Duke criteria integrate microbiological, echocardiographic, and clinical data to stratify diagnostic probability. Clinical judgment must always inform interpretation, the criteria are a guide, not a substitute for reasoning.

Major Criteria

Microbiological:

• Two separate blood cultures growing a typical IE organism (viridans streptococci, Streptococcus gallolyticus, S. aureus, HACEK group organisms, or community-acquired enterococci) in the absence of a primary focus elsewhere.
• Persistently positive blood cultures: $\geq 2$ cultures drawn $> 12$ hours apart, OR all of 3 or a majority of $\geq 4$ cultures with first and last drawn $\geq 1$ hour apart.
• Single positive blood culture or phase I IgG titre $\geq 1:800$ for Coxiella burnetii (Q fever endocarditis).

Echocardiographic:

• Oscillating intracardiac mass on a valve, supporting structure, or in the path of a regurgitant jet, without an alternative anatomic explanation.
• Perivalvular abscess.
• New partial dehiscence of a prosthetic valve.
• New valvular regurgitation (an increase or change in pre-existing murmur alone does not suffice).

Minor Criteria

• Predisposing cardiac condition or IV drug use.
• Fever $\geq 38°C$.
• Vascular phenomena: arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial haemorrhage, conjunctival petechiae, Janeway lesions.
• Immunological phenomena: glomerulonephritis, Osler nodes, Roth spots, positive rheumatoid factor.
• Microbiological evidence not meeting major criteria (positive culture but atypical organism or pattern), or serological evidence of an IE-consistent organism.

Diagnostic Classification

Exam point: Pathological criteria (culture or histology of a vegetation or intracardiac abscess demonstrating a microorganism, or histology showing active endocarditis) independently define definite IE regardless of clinical criteria.

Investigation & Monitoring

Blood Cultures

• Three sets from separate venepuncture sites, ideally at the peak of fever and before antibiotics, 85-90% of cases are identified from the first two sets.
• Allow each set to incubate for at least 5 days; notify the laboratory if fastidious organisms (HACEK, Brucella, Coxiella, Bartonella) are suspected.
• Culture-negative IE (approximately 10%) requires serological and PCR investigation for atypical pathogens.

Echocardiography

• Transthoracic echocardiography (TTE) is the initial study; sensitivity for NVE vegetations is approximately 60-75%.
• Transoesophageal echocardiography (TOE) is mandatory when:
• TTE is non-diagnostic but clinical suspicion remains high.
• Prosthetic valve IE or intracardiac device IE is suspected (TOE sensitivity $>90\%$).
• Perivalvular complications (abscess, fistula, dehiscence) need evaluation.
• S. aureus bacteraemia: TOE should be performed routinely given the high rate of cryptic IE.

Other Investigations

Microbiology

Common Organisms

Management

Principles

• Multidisciplinary "endocarditis team", infectious diseases, cardiology, cardiothoracic surgery, and microbiology, should be engaged early; evidence supports improved outcomes with this model.
• Targeted IV bactericidal antimicrobials for 4-6 weeks from the date blood cultures clear and source control is achieved.
• Empiric therapy is required when haemodynamic instability, aggressive organism, or rapidly destructive course precludes awaiting cultures.

Antimicrobial Therapy

Empiric Regimens (Pre-culture or Culture-Negative)

Targeted Regimens

Streptococcal NVE (fully penicillin-sensitive, MIC $\leq 0.125$ mg/L):

• Benzylpenicillin 1.2-2.4 g IV q4h for 4-6 weeks.
• Addition of gentamicin for the first 2 weeks permits a shortened 2-week course in low-risk patients.
• Ceftriaxone 2 g IV once daily is an alternative allowing outpatient completion.

Streptococcal NVE (reduced penicillin sensitivity):

• Benzylpenicillin + gentamicin for 4-6 weeks; or vancomycin + gentamicin if penicillin-resistant or allergic.

Staphylococcal NVE (methicillin-sensitive, MSSA):

• Flucloxacillin 2 g IV q4h for $\geq 4$ weeks. Flucloxacillin is superior to vancomycin for MSSA and should be used whenever allergy permits.
• Routine addition of gentamicin is not recommended for NVE (increased nephrotoxicity without mortality benefit).

Staphylococcal NVE (MRSA or penicillin allergy):

• Vancomycin, target AUC/MIC 400-600; or daptomycin 8-10 mg/kg IV once daily.

Staphylococcal PVE (MSSA):

• Flucloxacillin + rifampicin 300-450 mg q12h for $\geq 6$ weeks, with gentamicin for the first 2 weeks.
• Rifampicin's role is biofilm penetration; it should never be started as monotherapy given rapid resistance emergence.

Enterococcal IE:

• Amoxicillin 2 g IV q4h + gentamicin 3 mg/kg/day for 4-6 weeks (6 weeks for PVE).
• High-level aminoglycoside resistance: substitute gentamicin with ampicillin + ceftriaxone (dual beta-lactam synergy, particularly for Enterococcus faecalis).
• Vancomycin-resistant enterococcus (VRE): daptomycin ± ampicillin; seek specialist ID input.

HACEK organisms:

• Ceftriaxone 2 g IV once daily for 4 weeks (NVE) or 6 weeks (PVE).

Fungal IE:

• Liposomal amphotericin B or an echinocandin (depending on susceptibility); step-down to long-term azole suppression. Surgical valve replacement is almost universally required.

Monitoring During Therapy

• Vancomycin: AUC-guided dosing preferred; monitor renal function twice weekly; watch for nephrotoxicity, especially with concurrent gentamicin.
• Gentamicin: Serum levels and renal function every 48-72 hours; minimise duration to reduce nephrotoxicity and ototoxicity; generally avoid beyond 2 weeks.
• Rifampicin: Anticipate drug-drug interactions (CYP3A4 inducer), LFTs at baseline and during therapy.
• Repeat blood cultures 48-72 hours after starting therapy to confirm clearance; persistent bacteraemia demands reassessment (undrained focus, metastatic seeding, wrong antibiotic).

Surgical Indications

Approximately 50% of IE cases require cardiac surgery during the index admission. Early surgical consultation is critical; delay increases mortality when surgery is indicated.

Indications and Timing

• Neurological injury complicates the timing decision: haemorrhagic stroke is generally a contraindication to surgery for at least 4 weeks; ischaemic stroke without haemorrhagic transformation may permit earlier surgery if the indication is compelling and the infarct volume is small.

Complications & Special Considerations

Right-Sided IE (Tricuspid Valve)

• Predominantly in people who inject drugs; S. aureus is overwhelmingly the commonest pathogen.
• Presents with septic pulmonary emboli (pleuritic chest pain, haemoptysis, cavitating lung infiltrates).
• Surgery is less frequently needed; 4-6 weeks of IV therapy is standard but some data support 2-week regimens in uncomplicated MSSA tricuspid IE in people who inject drugs.

Device-Related IE (Pacemaker/ICD)

• Requires complete device removal in addition to antimicrobial therapy; extraction should be performed at a centre with surgical backup.
• Pocket infection without lead involvement may be managed more conservatively in selected cases.

IE in Pregnancy

• Rare but high maternal and foetal mortality; S. aureus and streptococci predominate.
• Penicillins and cephalosporins are safe; avoid aminoglycosides (foetal ototoxicity) when possible; avoid daptomycin (limited safety data).
• Surgery carries significant foetal loss risk but should not be withheld when the maternal indication is compelling.

Colorectal Malignancy Screening

• S. gallolyticus bacteraemia/IE has a strong association with occult colorectal neoplasia; colonoscopy is mandatory after the acute episode has been treated.

Antibiotic Prophylaxis, Current Position

• Routine antibiotic prophylaxis prior to dental or other invasive procedures is no longer recommended for patients at risk of IE in current Australian and New Zealand guidelines.
• Patients at elevated risk (prosthetic valves, prior IE, complex congenital heart disease, hypertrophic cardiomyopathy) should receive clear education about:
• Maintaining meticulous oral hygiene.
• Symptoms that may indicate IE and when to seek urgent review.
• Risks associated with invasive and non-medical procedures (body piercing, tattooing).

Long-Case Integration: Consultant Reasoning Approach

• Pre-test probability: Elevated by structural heart disease, prosthetic valves, intravascular devices, IV drug use, recent dental or invasive procedures, or prior IE. Frame your history to uncover these.
• Blood culture stewardship: Never withhold cultures to expedite empiric therapy in a stable patient, the microbiological diagnosis drives everything that follows.
• Echocardiography decision: TOE rather than TTE when clinical probability is high and TTE is negative, or whenever PVE or device IE is in question. A negative TOE in a patient with true high probability does not exclude IE, consider repeat imaging at 5-7 days.
• Surgical timing viva: Be prepared to articulate why and when surgery is needed, the competing risks of operating during active infection versus waiting, and how neurological events modify the calculus.
• Prognosis: In-hospital mortality is approximately 20% overall; S. aureus carries approximately 30% mortality, bowel organisms approximately 14%, and streptococci approximately 6%. Recurrence occurs in approximately 15% by 2 years, disproportionately in people who continue to inject drugs.
• Equity lens: People who inject drugs are a high-risk and often marginalised group. Non-judgmental care, harm reduction counselling, and addiction medicine involvement improve outcomes and represent best practice, address this explicitly if the long case presents a patient in this context.

Sources

• Therapeutic Guidelines (eTG)
• National Heart Foundation of Australia clinical guidelines
• Australian Medicines Handbook (AMH)