Infective endocarditis: 2023 ESC diagnosis, antibiotics, surgery and prevention

What changed in the 2023 ESC guideline

The 2023 document updates the 2015 ESC guideline because new data were published after 2015.^[1] Antibiotic recommendations now follow EUCAST clinical breakpoints. Outpatient parenteral or oral treatment is included on the strength of the POET randomised trial and other trials.^[1]

• Diagnosis: the major and minor criteria changed, and new algorithms set the sequence of imaging for native valve, prosthetic valve and device-related IE.^[1]
• Device infection: Cardiac implantable electronic device (CIED)-related IE is treated as right-sided endocarditis for diagnostic purposes.^[1]
• E. faecalis: it is now a typical endocarditis organism, regardless of the place of acquisition or the source of infection. In a prospective study of 344 patients with E. faecalis bacteraemia, this raised sensitivity for definite IE from 70% to 96%.^[1]
• Classification: definite, possible and rejected IE are now part of the ESC criteria, and possible IE includes 1 major criterion with 1 or 2 minor criteria.^[1] The task force notes that these new criteria should be prospectively validated.^[1]
• Invasive non-dental procedures: systemic prophylaxis may now be considered for high-risk patients (not intermediate-risk patients or the general population) undergoing an invasive diagnostic or therapeutic procedure of the respiratory, gastrointestinal or genitourinary tract, skin or musculoskeletal system; this moved from a Class III position to Class IIb, Level C.^[1]

Definition and burden

IE is defined by infection of a native or prosthetic heart valve, the endocardial surface, or an indwelling cardiac device.^[6] In 2019 its estimated incidence was 13.8 cases per 100 000 people per year, with 66 300 deaths worldwide.^[1]

The outlook is poor. ESC 2023 puts in-hospital mortality at 15% to 30%, largely unchanged over two decades.^[1] The 2020 ACC/AHA guideline gives in-hospital mortality of 15% to 20% and 1-year mortality approaching 40%, and states that IE is fatal unless treated appropriately.^[2]

In the 2009 ICE-PCS cohort, the commonest organisms were S. aureus (31%), oral streptococci (17%) and CoNS (11%).^[1] Other registries report rising E. faecalis and CoNS IE, particularly in the elderly.^[1] Women make up about one-third of cases, and surgery is performed less often in women.^[1]

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Classification

The ACC/AHA guideline classifies endocarditis by whether a native or prosthetic valve is affected and by the timing of infection after valve intervention.^[2] ESC 2023 uses several overlapping labels, and each one changes a decision.

^[1]

The two PVE cut-offs are a common exam trap: 12 months in the empirical antibiotic table, 6 months in the early-PVE surgical recommendation.^[1]

PVE starting in the peri-operative period mainly involves S. aureus, Staphylococcus epidermidis or nosocomial organisms such as Gram-negative pathogens or fungi. Late PVE more often mimics NVE, with mostly streptococcal and staphylococcal infection.^[1] S. aureus is more common with mechanical valves, whereas alpha-haemolytic streptococci, enterococci and CoNS are commoner with bioprosthetic valves.^[1] Mycobacterium chimaera PVE is an uncommon nosocomial infection that can result from contaminated cardiopulmonary bypass heater-cooler systems; it presents many months after surgery and carries high mortality.^[1]

^[1]

How endocarditis develops

IE usually requires several conditions, including a surface or structure that bacteria could colonise, pathogens entering the bloodstream, and the competence of the host's immune response.^[1] The portals of entry vary and include skin, oral, gastrointestinal or genitourinary infection; direct inoculation in people who inject drugs (PWID) or any unsafe or unprotected vascular puncture; and healthcare exposure, including invasive procedures.^[1]

The oral cavity is an important entry port: it is colonised by commensal flora, including oral streptococci.^[1] Oral surgery procedures (including extractions, periodontal surgery, implant surgery and oral biopsies) and dental procedures that manipulate the gingival or periapical region are considered at high risk of causing bacteraemia.^[1] Daily activities such as tooth brushing, flossing and chewing may also cause bacteraemia. It is low-level but repetitive, so it may outweigh the bacteraemia from dental procedures.^[1]

Neutrophils matter in vegetation growth. Their extracellular traps entrap bacteria-platelet aggregates, which leads to expansion of the aggregates, vegetation growth and tissue destruction.^[1] Slow-growing and dormant organisms inside vegetations and biofilms tolerate most antimicrobials, which is why prolonged therapy is needed to sterilise infected valves.^[1]

Other routes to the endocardium:

• Congenital heart disease: mechanisms include turbulent flow causing shear stress and endothelial damage, intracardiac foreign material, cyanosis and repeated cardiac procedures.^[1]
• CIEDs: skin flora introduced into the pocket at incision is the usual route; seeding from a distant bacteraemia is less frequent.^[1]
• Injecting drug use: repeated injections send contaminated particles to the tricuspid valve and right heart, and can also infect left-heart structures, which carries a worse prognosis.^[1]

How the damage shows itself

Valve destruction causes heart failure. Leaflet perforation, leaflet rupture and mitral chordal rupture produce new severe regurgitation or worsen existing regurgitation.^[1] Less common causes include intracardiac fistulae, a vegetation obstructing leaflet movement, or myocardial infarction from coronary embolism.^[1]

Perivalvular extension and abscess are more frequent in aortic than mitral IE, and may be higher with bicuspid than tricuspid aortic valves. In aortic IE, extension occurs most often into the mitral-aortic intervalvular fibrosa; in mitral IE, abscesses are usually posterior or lateral.^[1]

The atrioventricular node and His bundle lie close to the septal tricuspid leaflet insertion, the aortic root below the non-coronary and right coronary cusps, and the mitral annulus.^[1] A paravalvular abscess, especially aortic, may therefore lead to atrioventricular block (AVB), and new atrioventricular (AV) conduction abnormalities on electrocardiogram (ECG) are indicative of paravalvular extension.^[1]

The brain and spleen are the most frequent sites of embolism in left-sided IE; pulmonary embolism is frequent in right-sided and pacemaker lead IE.^[1] Septic emboli are also typically found in the kidneys, and metastatic infection in the intervertebral discs and vertebrae (spondylodiscitis), muscles and joints (septic arthritis) and liver.^[1]

^[1]

Who is at risk

^[1]

ESC 2023 also defines high-risk and intermediate-risk groups for prophylaxis; they are listed under Prevention.^[1]

Clinical presentation

Think of IE in any patient with sepsis or fever of unknown origin who has risk factors.^[1] IE can be acute and rapidly progressive, or subacute or chronic with low-grade or no fever and non-specific symptoms.^[1] Fever with positive blood cultures and no other focus generally drives suspicion, especially with one or more risk factors.^[1]

^[1]

Peripheral stigmata are less frequent now. They may still be seen in severe S. aureus infection and in subacute IE (mainly streptococcal), and vascular and immunological phenomena such as splinter haemorrhages, Roth spots and glomerulonephritis remain common.^[1] The absence of clinical signs alone should not exclude IE, because their sensitivity and specificity are low.^[1]

The 2020 ACC/AHA guideline notes that about three-quarters of patients are diagnosed within 30 days of onset, so classic features such as embolic or vasculitic skin lesions, immune-complex renal disease and immunological abnormalities are often absent.^[2] S. aureus IE frequently involves normal valves and seldom shows the stigmata.^[2]

Presentations that mislead

• Neurological: consider IE in stroke, meningitis or brain abscess. Unexplained fever with a stroke in a patient with valvular disease should prompt blood cultures before empirical antibiotics.^[1]
• Heart failure: symptoms may range from mild dyspnoea to pulmonary oedema and cardiogenic shock.^[1] Cardiogenic shock can be the first presentation in up to 5%, and half of these develop it within 72 h of admission.^[1]
• Elderly and immunocompromised patients: atypical presentation is common.^[1]
• PVE: presentation is frequently atypical, particularly early after surgery, when fever and inflammation are common without prosthetic changes on imaging; persistent fever should trigger suspicion.^[1]
• After transcatheter aortic valve implantation (TAVI): fever is absent in 13–20%, and enterococci and S. aureus are the commonest organisms.^[1]
• Right-sided IE: fever, bacteraemia and pulmonary complaints (cough, chest pain or haemoptysis).^[1]
• Musculoskeletal: myalgia and back pain occur in 12–15%, and arthralgia in about 10%.^[1]
• Mimicry: a complication can mimic a wide range of conditions, such as rheumatological, neurological or autoimmune disorders, or even malignancy.^[1]

Differential diagnosis

^[1]

Investigations

Blood cultures

Blood cultures come before antibiotics. Take at least three sets at 30-minute intervals, each with 10 mL of blood, for aerobic and anaerobic incubation.^[1] Sample a peripheral vein rather than a central venous catheter, because of the risk of contamination.^[1]

Bacteraemia in IE is almost constant. There is no reason to wait for fever spikes, and a single positive culture should be regarded cautiously.^[1] Gram stain gives a presumptive identification that is passed straight to clinicians to adapt empirical therapy.^[1] Minimal inhibitory concentration (MIC) determination remains the gold standard for susceptibility testing.^[1]

The ACC/AHA guideline states that cultures are positive in 90% of patients when at least 2 samples are taken at different times, ideally more than 6 hours apart if clinical status allows, from peripheral sites before antimicrobial therapy.^[2]

Other blood tests

Anaemia, white cell count, C-reactive protein (CRP), procalcitonin, erythrocyte sedimentation rate (ESR) and markers of end-organ dysfunction can be used to estimate sepsis severity, but none is diagnostic of IE.^[1] Their main role is initial risk stratification and monitoring the response to antibiotics.^[1]

Blood culture-negative IE (BCNIE)

BCNIE is IE in which no organism grows with the usual blood culture methods. It most often follows previous antibiotics.^[1] In stable patients with subacute symptoms, no complications and a very short antibiotic course, stopping antibiotics and repeating cultures may be required.^[1] If cultures are still negative at 48 h, consult the microbiologist.^[1]

Depending on local epidemiology, systematic serology for Coxiella burnetii, Bartonella spp., Aspergillus spp., Mycoplasma pneumoniae, Brucella spp. and Legionella pneumophila should be proposed.^[1] This should be followed by specific polymerase chain reaction (PCR) assays for Tropheryma whipplei, Bartonella spp. and fungi (Candida spp., Aspergillus spp.) on blood and tissue.^[1]

^[1]

Pathological examination of resected tissue or embolic fragments remains the gold standard for diagnosis.^[1] 16S/18S rRNA PCR sequencing of cardiac tissue or embolic material has sensitivity of 41% to 96% and specificity of 90% to 100%.^[1]

Echocardiography

Echocardiography is the first-line imaging test and assesses structural and functional damage.^[1] Do it as soon as IE is suspected: valve damage, embolic events and the need for surgery increase with time to the first study.^[1] Vegetation size, defined as maximal length, is a key metric for surgical decisions.^[1] Compared with TOE, TTE has low sensitivity but good specificity.^[1]

^[1]

The ACC/AHA guideline quotes a TTE sensitivity of 50% to 90% (specificity above 90%) for detecting vegetations in native valve IE, but only 36% to 69% in prosthetic valve IE.^[2] For transoesophageal echocardiography (TEE, the ACC/AHA term for TOE), it quotes a sensitivity of 90% to 100% in native valve IE.^[2] A single negative TEE cannot rule out IE.^[2]

CT, MRI and nuclear imaging

Cardiac CT is more accurate than TOE for perivalvular and periprosthetic abscesses, pseudoaneurysms and fistulae.^[1] Echocardiography remains better for small vegetations (under 10 mm), leaflet perforations and fistulae.^[1] For neurological complications, MRI is superior to CT, but CT may be more feasible in an emergency and is an acceptable alternative, with a sensitivity of 90% and specificity of 86% for ischaemic and haemorrhagic lesions.^[1]

Central nervous system (CNS) lesions may be present in up to 60–80% of patients with IE. Most are ischaemic lesions that are often small and asymptomatic and do not change decision-making.^[1] Brain MRI can reclassify 25% of patients with an inconclusive diagnosis.^[1] Cerebral microbleeds, found in 50–60% of patients with IE, should not be considered a minor criterion because they do not match ischaemic lesions.^[1]

[18F]FDG-PET/CT has 86% sensitivity and 84% specificity in PVE in the most recent meta-analysis.^[1] In NVE the sensitivity of PET/CT and SPECT/CT is about 31%, with specificity around 98%, so a normal scan does not exclude NVE.^[1] PET/CT is less suited to detecting cerebral septic emboli and mycotic aneurysms of intracerebral arteries, because of high physiological brain uptake.^[1] Abnormal prosthetic or periprosthetic uptake (intense focal or heterogeneous) on [18F]FDG-PET/CT or white blood cell (WBC) SPECT/CT should be considered a major criterion for PVE, irrespective of the interval from surgery.^[1]

^[1]

The 2023 ESC diagnostic criteria

The modified Duke criteria have had an overall sensitivity of 80%, but echocardiography can be normal or inconclusive in up to 30% of IE involving prosthetic material.^[1] The 2015 ESC criteria therefore added multimodality imaging. In 2023 the major imaging criterion covers echocardiography, cardiac CT, [18F]FDG-PET/CT(A) and WBC SPECT/CT, while brain and whole-body imaging in symptomatic patients (symptoms suggesting septic embolic complications) can add minor criteria.^[1]

^[1]

Distant lesions include anything from embolism or haematogenous seeding, whether symptomatic or found incidentally on imaging.^[1] Finding one adds a minor criterion and can move a patient to definite or rejected IE.^[1] In the ESC algorithms, TOE is used for diagnosis and to detect perivalvular complications in all cases, unless right-sided NVE has a good-quality, conclusive TTE.^[1]

The 2020 ACC/AHA criteria

For the 2020 ACC/AHA guideline, the Modified Duke Criteria are the current standard for diagnosis. Its rules differ from ESC 2023 in several places.^[2][1]

^{[1] [2]}

S. aureus bacteraemia

ESC 2023: echocardiography should be considered in S. aureus, E. faecalis and some Streptococcus spp. bacteraemia (Class IIa, Level B).^[1] The ACC/AHA supportive text reports IE in about 30% of S. aureus bacteraemia, so TEE may be considered to rule it out.^[2] It adds that without bacteraemia lasting more than 4 days, a permanent intracardiac device, haemodialysis dependency, or spinal infection or nonvertebral osteomyelitis, the risk is relatively low and routine TEE may not be necessary.^[2]

Prognosis at admission

Rapid identification of the highest-risk patients may offer the chance to change the course of the disease, for example with urgent or emergency surgery, and improve prognosis.^[1] In EURO-ENDO, independent predictors of death were Charlson index, creatinine above 2 mg/dL, congestive heart failure, vegetation length above 10 mm, cerebral complications, abscess and failure to undertake surgery when indicated.^[5]

The Endocarditis Team

Observational studies support an Endocarditis Team for diagnosis, management and outcomes.^[1] In a Heart Valve Centre, core members include cardiologists, cardiac imaging experts, cardiovascular surgeons, an infectious disease specialist (or internist with infectious disease expertise), a microbiologist and an outpatient parenteral antibiotic therapy (OPAT) specialist.^[1] Adjunct specialties include radiology and nuclear medicine, pharmacology, neurology and neurosurgery, nephrology, anaesthesia, critical care, addiction medicine, geriatrics, social work, nursing and pathology.^[1] The team must meet frequently, and a weekly meeting is to be considered.^[1]

^[1]

A Referring Centre has no cardiovascular surgical team. Its physician should consult an infectious disease specialist and the microbiologist, and should contact the Heart Valve Centre if antibiotics fail or valve tissue destruction appears.^[1] The ACC/AHA guideline describes a Heart Valve multidisciplinary team supplemented by infectious disease and neurology specialists.^[2]

Antimicrobial therapy

Principles

Antibiotics eradicate the organism; surgery removes infected material.^[1] Bactericidal regimens beat bacteriostatic ones.^[1] Evidence comparing regimens is limited and of low to very low quality.^[1]

• Duration: at least 6 weeks for PVE, 2–6 weeks for NVE.^[1]
• Counting: the duration runs from the first day of effective therapy (a negative blood culture if cultures were initially positive), not from the day of surgery. A new full course starts only if valve cultures are positive.^[1]
• NVE replaced with a prosthesis during treatment: use the NVE regimen, not the PVE regimen.^[1]
• Aminoglycosides: not recommended in staphylococcal NVE, because no clinical benefit has been shown and they can increase renal toxicity.^[1] When indicated in other conditions (for example resistant oral streptococci), give them for no longer than 2 weeks to reduce nephrotoxicity.^[1] The key messages advise a single daily dose to reduce nephrotoxicity, but the staphylococcal PVE rows allow 1 (preferred) or 2 doses (footnoted maximum 240 mg/day), and the HACEK text gives gentamicin in 2 or 3 doses as an option.^[1]
• Rifampin: only for foreign-body infection such as PVE, started after 3–5 days of effective therapy once bacteraemia has cleared.^[1]
• Daptomycin: when indicated, it must be given at high dose (10 mg/kg once daily; 10 mg/kg/day i.v. in 1 dose in the staphylococcal and empirical regimen tables, where the empirical row combines it with gentamicin and rifampin) and combined with a second antibiotic (a beta-lactam, or fosfomycin in beta-lactam allergy) to increase activity and avoid resistance. Fosfomycin is associated with an increased risk of acute HF and renal failure because of its high sodium load, and daptomycin has been associated with eosinophilic syndromes in up to 15%.^[1]
• Two phases: up to 2 weeks of in-hospital i.v. bactericidal treatment, when indicated surgery, foreign-body removal and abscess drainage happen; then, in clinically stable patients, completion at home by OPAT or oral regimens for up to 6 weeks.^[1]

ESC 2023 adopts the 2022 EUCAST breakpoints, which sort results into three susceptibility categories. "Susceptible, standard dosing" predicts success with standard doses; "susceptible, increased exposure" predicts success when exposure is increased; "resistant" predicts failure even with increased exposure.^[1]

Empirical treatment

Start treatment promptly, after three sets of blood cultures drawn at 30-minute intervals.^[1] The choice depends on previous antibiotics, native or prosthetic valve (and early or late PVE), place of acquisition and local epidemiology.^[1] NVE and late PVE regimens should cover staphylococci, streptococci and enterococci; CoNS should be covered empirically in PVE but not in NVE, and a patient already on antibiotics should receive different ones empirically. Early PVE or healthcare-associated regimens should cover methicillin-resistant staphylococci, enterococci and, ideally, non-HACEK Gram-negatives. Switch to targeted therapy once the organism is identified within 24–48 h.^[1]

^[1]

In this table, the gentamicin cells carry a footnote capping the dose at 240 mg/day with weekly renal function and gentamicin levels, and the vancomycin cells a footnote targeting a pre-dose trough of 10–15 mg/L (details under Gentamicin and vancomycin levels).^[1] If initial cultures are negative and there is no clinical response, consider BCNIE and widen the spectrum to culture-negative pathogens.^[1] Cloxacillin or cefazolin is associated with lower mortality than other beta-lactams and vancomycin as empirical treatment for methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia or endocarditis.^[1] However, amoxicillin–clavulanate or ampicillin–sulbactam might be an effective empirical treatment for MSSA bacteraemia when de-escalated to cloxacillin or cefazolin within 96 h of the index blood culture.^[1]

Streptococci

Oral streptococci include the mitis, sanguinis, anginosus, salivarius, downei and mutans groups.^[1] With susceptible strains the cure rate is expected to be above 95%.^[1]

^[1]

The gentamicin cells in this table carry the same 240 mg/day cap and weekly monitoring footnote, and the vancomycin cells the pre-dose trough target of 10–15 mg/L.^[1] For penicillin G the starting recommended doses are the lower doses, which can be scaled up to the highest.^[1] In documented penicillin allergy, desensitisation is recommended. If it cannot be done, use a cephalosporin (non-anaphylactic reactions) or vancomycin, bearing in mind that a beta-lactam is superior to a glycopeptide.^[1] In penicillin-resistant cases, aminoglycoside treatment must be given for at least 2 weeks, and short-course regimens are not recommended.^[1]

Special streptococci:

• S. pneumoniae with meningitis: penicillin must be avoided because it penetrates cerebrospinal fluid (CSF) poorly; use ceftriaxone or cefotaxime alone or with vancomycin, according to susceptibility.^[1]
• Groups B, C and G and S. anginosus: they induce abscesses that need adjunctive surgery. Group B PVE has very high mortality and surgery is recommended. Antibiotic treatment is similar to that for oral streptococci (Recommendation Table 7), except that short (2-week) therapy is not recommended and gentamicin should be given for 2 weeks.^[1]
• Granulicatella and Abiotrophia: a prolonged course with large vegetations (above 10 mm) and high rates of complications and valve replacement (around 50%); recommended options include penicillin G, ceftriaxone or vancomycin for 6 weeks, plus an aminoglycoside for at least the first 2 weeks in PVE.^[1]

Staphylococci

S. aureus usually causes acute, destructive IE; CoNS can cause more protracted infection.^[1] Adding an aminoglycoside in staphylococcal NVE is no longer recommended because it increases renal toxicity.^[1] S. aureus PVE carries mortality above 45% and often needs early valve replacement.^[1]

^[1]

Table footnotes matter here, and each applies only to the cells that carry it. Cloxacillin is not recommended with penicillin allergy (footnote on the cloxacillin cells of the methicillin-susceptible NVE and PVE rows and the methicillin-resistant daptomycin row).^[1] The gentamicin cells carry the 240 mg/day cap and weekly monitoring footnote, and the vancomycin cells of the methicillin-resistant rows a footnote targeting a pre-dose trough of 10–15 mg/L.^[1] In the methicillin-susceptible NVE row and the two cefazolin penicillin-allergy rows, a footnote says cefazolin can replace cloxacillin only with non-immediate-type hypersensitivity to penicillin; the cefazolin cell of the non-allergic methicillin-susceptible PVE row carries no such footnote.^[1] In heart failure, the high sodium load of fosfomycin can lead to acute heart failure.^[1] High doses of ceftaroline may be associated with leucopaenia after 2 weeks, and ceftaroline can replace cloxacillin only with non-immediate-type hypersensitivity to penicillin.^[1] For penicillin-allergic MSSA IE, desensitisation can be attempted in stable patients, or cefazolin used, because vancomycin is inferior to beta-lactams.^[1]

For vancomycin in methicillin-resistant Staphylococcus aureus (MRSA) IE, target an area under the curve (AUC)/MIC of 400–600 mg·h/L (assuming an MIC of 1 mg/L), achieved within 48 h of therapy. If the MIC is above 1 mg/L, an AUC/MIC of at least 400 is unlikely to be reached, and changing therapy should be considered because of the high risk of nephrotoxicity with higher doses.^[1] Short (2-week) and oral regimens proposed for uncomplicated right-sided native valve MSSA IE cannot be applied to left-sided IE.^[1]

Enterococci

E. faecalis causes 90% of enterococcal IE and E. faecium 5%.^[1] Enterococci resist antibiotic killing, so eradication needs up to 6 weeks of synergistic bactericidal combinations: two cell wall inhibitors (ampicillin plus ceftriaxone) or one cell wall inhibitor with an aminoglycoside.^[1] An aminoglycoside MIC above 128 mg/L (high-level aminoglycoside resistance, HLAR) is associated with loss of bactericidal synergy with cell wall inhibitors, so aminoglycosides should not be used.^[1]

In several cohort studies, ampicillin plus ceftriaxone was as effective as ampicillin plus gentamicin for non-HLAR E. faecalis IE, and was associated with a beneficial safety profile, owing to the lack of nephrotoxicity.^[1] It is not effective against E. faecium.^[1] Gentamicin can be given once daily instead of the 2 or 3 divided doses previously recommended, and for non-HLAR E. faecalis IE its duration may be safely shortened from 4–6 weeks to 2 weeks.^[1]

^[1]

The gentamicin cells of the two non-HLAR rows carry a footnote capping the dose at 240 mg/day with weekly renal function and gentamicin levels; the gentamicin cell of the E. faecium row carries no footnote.^[1] For beta-lactam resistance, the table footnote says: if due to beta-lactamase production, replace ampicillin with ampicillin–sulbactam or amoxicillin with amoxicillin–clavulanate; if due to penicillin-binding protein 5 (PBP5) alteration, use vancomycin-based regimens.^[1] For multiresistance to aminoglycosides, beta-lactams and vancomycin, a further footnote lists daptomycin-based combinations, linezolid or quinupristin–dalfopristin (not active against E. faecalis) and advises consulting infectious disease specialists for other combinations.^[1] High doses of ertapenem are associated with seizures.^[1] With high-level gentamicin resistance, streptomycin 15 mg/kg/day in two equally divided doses (the footnote gives no route) can replace gentamicin if the strain is susceptible.^[1]

Gentamicin and vancomycin levels

^[1]

HACEK, other Gram-negatives, culture-negative and fungal IE

Some HACEK bacilli produce beta-lactamases, so ampicillin is no longer first line. Standard treatment is ceftriaxone 2 g/day (the text gives no route or number of doses) for 4 weeks in NVE and 6 weeks in PVE.^[1] If the organism does not produce beta-lactamase, ampicillin 12 g/day i.v. in 4 or 6 doses for 4–6 weeks plus gentamicin 3 mg/kg/day in 2 or 3 doses (route not stated) for 2 weeks is an option. Ciprofloxacin (400 mg every 8–12 h i.v. or 750 mg every 12 h orally) is a less well-validated alternative.^[1]

Non-HACEK Gram-negative bacteria caused 1.8% of IE in the ICE cohort. Recommended treatment is early surgery plus 6 weeks of bactericidal beta-lactam and aminoglycoside combinations, sometimes with an added quinolone or cotrimoxazole.^[1]

^[1]

Owing to the lack of large series, the optimal duration of treatment for these pathogens is unknown; the durations shown are based on selected case reports, and infectious disease consultation is recommended.^[1] For Brucella, adding streptomycin (15 mg/kg/24 h in 2 doses; the footnote gives no route) for the first few weeks is optional.^[1] For Bartonella, several other regimens have been reported, including ampicillin or amoxicillin (12 g/24 h i.v.) or a cephalosporin such as ceftriaxone (2 g/24 h i.v.) combined with aminoglycosides, with doses as for streptococcal and enterococcal IE.^[1] For C. burnetii, doxycycline plus hydroxychloroquine (with hydroxychloroquine level monitoring) is significantly superior to doxycycline alone.^[1]

Fungal IE is seen most in PVE, PWID and immunocompromised patients. Mortality exceeds 50%, treatment combines antifungals with a low threshold for surgery, and long-term oral azole suppression is recommended, sometimes lifelong.^[1]

Outpatient and oral step-down treatment

OPAT or oral step-down consolidates therapy once critical complications are controlled and the patient is clinically stable.^[1] ESC 2023 splits the course into a critical phase, needing at least 10 days of i.v. treatment, and a continuation phase beyond 10 days of therapy and 7 days after surgery, when OPAT or oral step-down may be feasible.^[1]

^[1]

"Highly difficult-to-treat" means organisms needing i.v. combinations that OPAT cannot deliver or strict drug-level monitoring. Examples are MRSA or vancomycin-resistant enterococci also resistant to alternative drugs such as daptomycin and linezolid, multidrug- or extensively drug-resistant Gram-negative rods, highly penicillin-resistant oral streptococci, and fungi other than Candida.^[1]

Stability criteria include blood samples, clinical parameters and TOE.^[1] Considerations for OPAT also include the home environment and self-care ability.^[1] OPAT uses the same antibiotics as the acute phase where possible.^[1] Certain combinations of two oral antibiotics should be used for oral step-down; they are listed in the guideline's supplementary Table S9, which is not reproduced here.^[1] Dalbavancin is a glycopeptide with a very long half-life that can be given weekly. Experience is in susceptible Gram-positive IE and the most effective schedule is not clear; the recommended prescription is 1.5 g loading, then 0.5–1 g weekly to complete 6 weeks (the text does not state the route).^[1]

The ACC/AHA guideline notes that POET patients had TEE within 1 to 3 days of completing treatment to confirm response.^[2]

Surgery

Why and when

Surgery may give a survival advantage of up to 20% in the first year.^[1] The three main reasons are heart failure, uncontrolled infection and prevention of septic embolism, particularly to the CNS.^[1] ESC timing terms are emergency (within 24 h), urgent (within 3–5 days) and non-urgent (within the same admission).^[1] Some cases require emergency surgery (within 24 h), irrespective of the pre-operative duration of antibiotic treatment, and unnecessary delays should be avoided once an indication for urgent surgery is established.^[1]

^[1]

Indications (left-sided NVE and PVE)

^[1]

For right-sided IE, ESC 2023 gives separate indications (see Specific situations).^[1]

Heart failure

Heart failure is the most frequent complication of IE and the main indication for urgent and emergency surgery.^[1] Its prevalence in left-sided IE ranges from 19% to 73% across series.^[1] Surgery is the only treatment associated with better survival in HF complicating IE.^[1]

The guideline text adds detail to the formal rows. Emergency surgery should be performed for new-onset New York Heart Association (NYHA) class IV heart failure symptoms, pulmonary oedema and/or cardiogenic shock, irrespective of infection status or antibiotic duration, when surgery is considered non-futile.^[1] Urgent surgery is indicated for milder HF (NYHA II–III) with severe regurgitation, echocardiographic haemodynamic compromise, or large vegetations.^[1] Without haemodynamic compromise, i.v. antibiotics and close clinical and echocardiographic observation come first, and surgery can be temporarily delayed; however, early surgery is a good option for patients with surgical indications and low surgical risk.^[1] Endocarditis Team discussion should not delay emergency operations.^[1]

The ACC/AHA guideline cites 21% in-hospital mortality with surgery against 45% with medical treatment in IE with HF.^[2]

Uncontrolled infection

Uncontrolled infection is the second most frequent indication for surgery. It means persistent infection or sepsis despite antibiotics, local infection not responding to antibiotics, or infection with resistant or very virulent organisms.^[1]

• Septic shock: vasopressors needed to keep mean arterial pressure at 65 mmHg or greater, with lactate above 2 mmol/L without hypovolaemia; it occurs in about 5–10%.^[1] The guideline text recommends urgent surgery in persistent sepsis or septic shock despite adequate antibiotics, when surgery is non-futile; the formal row (blood cultures positive for more than 1 week or persistent sepsis despite appropriate antibiotics and adequate control of metastatic foci) is Class IIa, Level B.^[1]
• Persistent infection: the definition is somewhat arbitrary; ESC 2023 uses fever and persistent positive cultures after 7 days of appropriate antibiotic treatment. Blood cultures still positive 48–72 h after starting antibiotics are an independent risk factor for hospital mortality.^[1] Surgery is indicated for persistent infection once extracardiac abscesses (splenic, vertebral, cerebral or renal) and other causes of positive cultures and fever, such as infected lines and embolic complications, have been excluded; persistent fever may also be an adverse reaction to antibiotics.^[1]
• Locally uncontrolled infection: signs include increasing vegetation size, abscess, pseudoaneurysm or fistula, and new AVB.^[1] Perivalvular extension occurs in 10–30% of NVE and more often in PVE.^[1] Confirm it with TOE, which is more sensitive and specific than TTE.^[1] Rarely, when there is no other reason for surgery and fever is easily controlled with antibiotics, small abscesses or pseudoaneurysms can be treated conservatively under close clinical and echocardiographic follow-up.^[1]
• Resistant or virulent organisms: these include fungi, multiresistant bacteria and, rarely, non-HACEK Gram-negatives; S. aureus should also be included, given its fast progression and ability to cause local tissue destruction and abscess formation, specifically if a favourable early response to antibiotics is not achieved.^[1]

Surgery for uncontrolled infection may improve 1-year survival by 15–20%.^[1]

Preventing embolism

Embolism affects 20–50% of patients. Risk is highest the day after antibiotics start, and is 10–20 times higher on the day before and after the start of antibiotic treatment than 2 weeks before and after.^[1] Embolic events may be clinically silent in up to 50% of patients.^[1]

Vegetation size and mobility are the strongest independent predictors of new embolism. Other risk factors include mitral location, a growing or shrinking vegetation on antibiotics, particular organisms (especially S. aureus, S. gallolyticus and Candida spp.), previous embolism, multivalvular involvement and biological markers.^[1] Neurological risk is particularly high with vegetations longer than 30 mm.^[1] One recent study found vegetation size predicted worse outcome only when present with other indications for surgery (HF or uncontrolled infection).^[1]

ESC 2023 cites a randomised trial of early surgery in young, low-risk patients with large vegetations and streptococcal IE: 6-month all-cause mortality did not differ, but embolism was significantly reduced.^[1] It also notes that prosthetic dehiscence has been associated with early surgery in S. aureus IE.^[1]

Deciding to operate

The Endocarditis Team decides, weighing urgency, peri-operative risk, the chance of recovering from infection and long-term prognosis.^[1] IE-specific scores include the Association for the Study and Prevention of Infective Endocarditis Study (AEPEI) score and the Society of Thoracic Surgeons (STS) IE score.^[1] Others include PALSUSE (prosthetic valve, age ≥70, large intracardiac destruction, Staphylococcus spp., urgent surgery, sex [female], EuroSCORE ≥10), de Feo and ANCLA (anaemia, NYHA class IV, critical state, large intracardiac destruction, surgery of thoracic aorta). They are retrospective and perform variably.^[1] Patients with clear indications who do not get surgery have the worst prognosis, so a decision not to operate belongs to an Endocarditis Team with experienced surgical input.^[1]

^[1]

Operative principles

• Valve preservation should only be attempted if a durable repair is expected and all infected tissue can be removed.^[1]
• Extensive aortic root abscess or periannular destruction usually needs aortic root replacement.^[1] Patches over abscess cavities are discouraged in aortic root IE, as they may be associated with recurrences, periprosthetic leaks and pseudoaneurysm formation.^[1]
• Features favouring a non-mechanical valve: early surgery after recent ischaemic stroke, intracranial bleeding, a woman of childbearing age, likely prolonged mechanical circulatory support, advanced age or frailty, poor or unknown compliance, an expected complicated and prolonged post-operative course, and patient preference.^[1]
• Infective foci need to be eradicated before antibiotics finish, to avoid reinfecting the valve.^[1]
• In-hospital mortality after IE surgery remains 10–20%, particularly over 75 years.^[1]

Neurological complications

Symptomatic cerebrovascular complications occur in up to 35% and silent ones (including ischaemia and microhaemorrhage) in up to 80%; presentation varies, but ischaemic stroke and transient ischaemic attack (TIA) are the most common.^[1] S. aureus IE is more often associated with neurological complications than IE caused by other organisms.^[1] Prompt diagnosis and early antibiotics are central to preventing them, early surgery in high-risk patients is key to preventing embolisation, and antithrombotic or thrombolytic therapies are not beneficial.^[1] Cerebral imaging is mandatory when a neurological complication is suspected: MRI with and without gadolinium, or CT with and without contrast if MRI is not possible.^[1]

^[1]

The guideline text suggests that microbleeds should not postpone surgery when it is indicated.^[1] Post-operative haemorrhagic conversion after a pre-operative stroke is reported in 2–7%.^[1] If surgery is delayed after intracranial haemorrhage, repeat CT or MRI at 1–2 weeks, or earlier with deterioration.^[1] The ACC/AHA text states that haemorrhagic stroke carries prohibitively high surgical risk for at least 4 weeks.^[2]

Other complications

• Infective (mycotic) aneurysm: rare but potentially devastating; infective cerebral aneurysms are associated with subarachnoid, intracerebral and intracranial haemorrhage, particularly in anticoagulated patients.^[1] Digital subtraction angiography is the gold standard.^[1] Neurosurgery or endovascular therapy is recommended for large aneurysms, aneurysms growing despite optimal antibiotics, and ruptured intracranial infective aneurysms (Class I, Level C).^[1]
• Spleen: infarcts are common (about 20% of patients in the EURO-ENDO registry) and very often asymptomatic; up to 5% can progress to abscess, and persistent or recurrent fever, abdominal pain and persistent bacteraemia suggest abscess or other splenic complications.^[1] After splenectomy, vaccinate against encapsulated organisms.^[1]
• Pericardium: in a large NVE series, effusion occurred in 7.8% and was associated with in-hospital HF.^[1]
• Conduction: EURO-ENDO found conduction abnormalities in 11.5% at diagnosis, including complete AVB in 2.8%.^[1] New AVB from local extension is an indication for urgent surgery.^[1] Immediate epicardial pacemaker implantation should be considered at surgery for valvular IE with complete AVB if a predictor of persistent AVB is present: pre-operative conduction abnormality, S. aureus, aortic root abscess, tricuspid involvement or previous valve surgery (Class IIa, Level C).^[1]
• Bones and joints: osteoarticular infection affects 6–8%, and spondylodiscitis 2–10% (symptomatic and asymptomatic cases).^[1] MRI or PET/CT is recommended for suspected spondylodiscitis or vertebral osteomyelitis (Class I, Level C), and TTE/TOE to rule out IE in spondylodiscitis or septic arthritis with positive blood cultures for typical IE organisms (Class I, Level C).^[1] More than 6 weeks of antibiotics should be considered for lesions caused by difficult-to-treat organisms such as S. aureus or Candida, or with severe vertebral destruction or abscess (Class IIa, Level C).^[1]
• Kidneys: acute renal failure is the second commonest complication in EURO-ENDO (almost 18%), but it should not delay cardiac surgery.^[1] Several factors may be responsible: immune complex and vasculitic glomerulonephritis, renal infarction from septic emboli, haemodynamic impairment in HF, antibiotic and other drug toxicity, and contrast nephrotoxicity.^[1] Avoid nephrotoxic antibiotics where possible, or monitor aminoglycoside and vancomycin levels and creatinine closely.^[1]

Antithrombotic therapy

IE itself is not an indication for antithrombotics or anticoagulants.^[1] In left-sided IE, anticoagulation does not seem to change the risk of stroke, cerebral haemorrhage or death at 10 weeks. Continue it when there is a pre-existing indication and no other contraindication; switching to heparin is generally preferred if there is cerebral bleeding or early surgery is indicated.^[1] No data support starting either antithrombotics or anticoagulants to treat or prevent stroke in IE.^[1]

^[1]

The ACC/AHA text advises against routine vitamin K antagonist (VKA) use in native valve IE and supports considering VKA discontinuation at presentation in patients already taking it.^[2]

Specific situations

Prosthetic valve endocarditis

PVE occurs in 1–6% of patients with prostheses, at 0.3–1.2% per patient-year.^[1] Echocardiography and blood cultures each have a sensitivity of only 60% for definite PVE.^[1] TOE is mandatory but less useful than in NVE, and a new periprosthetic leak is a major criterion that needs confirmation with another imaging modality.^[1]

In-hospital mortality is 20–40%.^[1] Withholding surgery despite a clear indication is the most important risk factor for recurrence and death.^[1] Surgery is recommended for PVE with HF, severe prosthetic dysfunction, abscess or persistent fever; uncomplicated non-staphylococcal late PVE can be managed conservatively, with close follow-up.^[1] Meticulous, radical debridement of infected material, including the original prosthesis, sutures and pledgets, is recommended.^[1] Surgery is recommended for early PVE (within 6 months of valve surgery), with new valve replacement and complete debridement (Class I, Level C).^[1]

Endocarditis after TAVI

IE after TAVI occurs at 0.3 to 1.9 per 100 patient-years, similar to surgical aortic valve replacement.^[1] Risk is higher within the first year, particularly within the first 3 months.^[1] TOE shows no vegetation in 38–60%.^[1] In-hospital and 30-day mortality is 16% to 36%, rising to 41–59% at 1 year, and surgery is performed in about 20%, a much lower rate than in NVE and surgical PVE.^[1] Valve-in-valve treatment of a dysfunctional prosthesis after healed IE can be done in selected patients, at least 1–3 months later and after a negative follow-up TOE.^[1]

Cardiac device-related IE

S. aureus and CoNS are the commonest organisms with bacteraemia in CIED infection.^[1] Suspicion should be particularly high with S. aureus bacteraemia.^[1] The absence of vegetations does not rule out IE, because vegetations may be present on extracardiac lead segments that cannot be visualised.^[1] Interpret PET/CT with caution if the device is under 6 weeks old.^[1]

^[1]

Lead extraction should be performed without delay, within the first days of admission. Percutaneous extraction is preferred, in centres with expertise in the technique and onsite surgical backup.^[1] Surgical extraction should be considered for large vegetations (for example above 20 mm) when aspiration is unavailable or fails, and is preferred if valve surgery is indicated.^[1] No removed component should be reimplanted.^[1] In pacemaker-dependent patients, an active-fixation lead may be introduced via the internal jugular vein and connected to an external pacemaker for up to 4–6 weeks, preserving the other side for reimplantation.^[1] Antibiotic prophylaxis to prevent CIED-related IE before dental and other non-cardiac interventions (such as respiratory, gastrointestinal or genitourinary procedures) is not warranted, as the risk is very low.^[1]

Right-sided IE and people who inject drugs

S. aureus causes most right-sided IE, and the tricuspid valve is affected far more often than the pulmonary valve.^[1] TTE may evaluate the tricuspid valve adequately; TOE is frequently required, particularly for the pulmonary valve or with indwelling catheters or devices.^[1] Right-sided IE is generally more benign than left-sided IE, and about 90% can be managed medically.^[1]

In PWID, empirical cover must include S. aureus: a penicillinase-resistant penicillin, vancomycin or daptomycin, by local MRSA prevalence, with gentamicin.^[1]

Two weeks of oxacillin or cloxacillin without gentamicin is effective when all of the following apply:^[1]

• MSSA is the causative organism.^[1]
• There is a good clinical and microbiological response to treatment (>96 h).^[1]
• The vegetation is 20 mm or less.^[1]
• There are no metastatic sites of infection or empyema, no cardiac or extracardiac complications, no prosthetic or left-sided valve infection, and no severe immunosuppression.^[1]

Glycopeptides (such as vancomycin) should not be used for a 2-week course.^[1]

^[1]

An isolated vegetation is not an indication for surgery.^[1] PWID have a markedly higher recurrence rate, especially in the first 6 months after surgery.^[1] Addiction treatment after PWID-related IE is recommended (Class I, Level C).^[1] The ACC/AHA text reports that pharmacotherapy such as opioid substitution with behavioural treatment halved relapse to drug use in opioid use disorder compared with behavioural therapy alone in some data.^[2]

Other groups

^[1]

Prevention

Who gets antibiotic prophylaxis

^[1]

Intermediate-risk conditions include rheumatic heart disease, non-rheumatic degenerative valve disease, congenital valve abnormalities including bicuspid aortic valve, CIEDs and hypertrophic cardiomyopathy.^[1] For them prophylaxis is not routinely recommended and may be considered individually, while prevention measures are strongly encouraged.^[1] In one study cited by ESC (Thornhill et al.), predisposing conditions conveying high and moderate risk had IE incidences of 497 and 280 cases per 100 000 per year.^[1]

Which procedures

^[1]

At-risk dental procedures include scaling and root canal procedures.^[1] Implant placement and invasive procedures on established implants should be covered in high-risk patients.^[1] No randomised trial has shown that prophylaxis before procedures prevents IE.^[1] More recent data link prophylaxis in high-risk people to less IE after invasive dental procedures, particularly extractions and oral surgery.^[1]

Regimen

^[1]

Do not use cephalosporins after anaphylaxis, angioedema or urticaria with penicillin or ampicillin.^[1] Oral streptococci are the main target.^[1] The task force does not recommend clindamycin, because its risk of adverse events appears high, mainly from Clostridioides difficile.^[1]

Hygiene and procedures

General prevention measures for people at high and intermediate risk of IE (ESC 2023 Table 5):^[1]

• Twice-daily tooth cleaning, with professional dental cleaning and follow-up at least twice yearly for high-risk patients and yearly for others.^[1]
• Strict skin hygiene, including optimised treatment of chronic skin conditions, and disinfection of wounds.^[1]
• Curative antibiotics for any focus of bacterial infection, and no self-medication with antibiotics.^[1]
• Strict infection control for any at-risk procedure, and discouraging piercing and tattooing.^[1]
• Limiting infusion catheters and invasive procedures when possible, with strict adherence to care bundles for central and peripheral cannulae.^[1]

Ensure an aseptic environment for invasive non-dental procedures.^[1]

^[1]

Carriers are treated with local mupirocin and chlorhexidine.^[1] People at risk should report that they are at risk when they have unexplained fever, so that clinicians consider screening for IE before starting antibiotics.^[1]

Follow-up and prognosis

After discharge, the main complications to watch for include recurrent infection, HF, need for valve surgery, stroke, renal replacement, psychological problems and death.^[1] Among survivors, the risk of recurrence (relapse or reinfection) varies significantly between studies, from 2% to 9% in more contemporary analyses, and reinfections have been shown to have worse outcomes than relapses.^[1]

^[1]

Factors associated with relapse (ESC 2023 Table 13):^[1]

• Inadequate antibiotic treatment (agent, dose or duration), or resistance to conventional regimens.^[1]
• Resistant organisms: Brucella, Legionella, Chlamydia, Mycoplasma, Mycobacterium and Bartonella spp., C. burnetii and fungi.^[1]
• S. aureus or Enterococcus spp. IE, and polymicrobial infection in PWID.^[1]
• Periannular extension, PVE, persistent metastatic foci (abscesses) and a positive valve culture.^[1]
• Fever persisting on the 7th post-operative day.^[1]
• Chronic kidney disease, especially on dialysis; high-risk behaviour or inability to adhere to treatment; poor oral hygiene.^[1]

Partial oral treatment and OPAT in selected stable patients are not associated with a higher risk of recurrence.^[1]

To monitor the risk of secondary heart failure, an initial clinical evaluation and baseline TTE should be performed when antibiotics finish and repeated if the clinical condition changes.^[1] Clinical re-assessment should be performed one or more times in the first year and yearly thereafter, depending on the individual risk profile.^[1] Inflammatory markers (WBC, CRP, procalcitonin) should be checked early after antibiotics end and repeated when clinically indicated.^[1] Because relapse risk is higher with virulent organisms, blood cultures are encouraged within the first week after treatment ends.^[1] New fever, chills or other signs of infection need immediate evaluation, including blood cultures before any empirical antibiotic.^[1]

^[1]

Long-term survival after treatment is about 85–90% at 1 year and 70–80% at 5 years.^[1] Age, comorbidity, PWID, double valve infection, recurrence and HF, especially when surgery cannot be done, predict long-term death.^[1]

ESC 2023 and ACC/AHA 2020 compared

The ACC/AHA IE section sits inside the 2020 valvular heart disease guideline. Its recommendation tables are images, so this page quotes only its supportive text and its diagnostic tables.^[2]

^{[1] [2]}

In Australia and New Zealand

• Burden: in Australia, age-adjusted IE prevalence rose from 2.63 to 10.18 per 100 000 between 1990 and 2021, while prevalence-adjusted mortality fell from 18.6 to 11.25 deaths per hundred cases. IE-associated heart failure rose.^[7]
• Victoria: IE incidence rose from 11.09 to 13.56 per 100 000 per year between 2009 and 2014, and injecting drug use-associated IE from 0.92 to 1.76.^[8] Injecting drug use-associated IE affected a much younger group (30–34 years) than IE overall (75–79 years).^[8]
• New South Wales: among 18 044 patients (2001–2020), women had a higher risk of death and fewer escalations of care. Octogenarians made up one-fifth of admissions and had the worst mortality (15.1%), yet accounted for only one in 10 intensive care unit (ICU) admissions.^[9]
• Endocarditis teams: only 28% (13 of 47) of responding Australian cardiac surgery centres had a multidisciplinary endocarditis team; identified barriers included a lack of funding, resources, expertise, time and collaboration.^[10]
• OPAT in Christchurch: OPAT was used in 67% of 172 episodes, for a median of 27 days after a median of 12 inpatient days. In the OPAT group, antibiotic-related adverse events occurred in 5%, and relapse within 1 year in 3%.^[11]
• Rheumatic heart disease in Far North Queensland: among people on the RHD register (1998–2021), native valve IE occurred at 0.7 episodes per 1000 patient-years, and 11 of 18 episodes were on prosthetic valves. Among people with an indication for benzathine penicillin G, only 1 of 6 IE episodes due to a penicillin-susceptible organism had received it in the month before presentation.^[12]
• PWID at a Melbourne tertiary referral centre (1997–2015): in 127 episodes, 53% needed intensive care, 34% involved left-sided valves and 16% ended in death.^[13]

Exam pearls

• Possible IE in 2023 ESC is 1 major plus 1 or 2 minor, or 3–4 minor. In the Modified Duke Criteria it is 1 major plus 1 minor, or 3 minor.^[1][2]
• E. faecalis is typical in ESC 2023 regardless of the place of acquisition or the source of infection; ACC/AHA requires community-acquired enterococci in the absence of a primary focus.^[1][2]
• Cerebral microbleeds are not a minor criterion, and the guideline text suggests they should not postpone indicated surgery.^[1]
• No aminoglycoside in staphylococcal NVE; rifampin only for foreign-body infection such as PVE, after 3–5 days of effective antibiotic therapy once bacteraemia has cleared.^[1]
• In HLAR enterococcal IE, ampicillin or amoxicillin (12 g/day i.v. in 4–6 doses) with ceftriaxone (4 g/day i.v. or i.m. in 2 doses) for 6 weeks is recommended (Class I, Level B); this double beta-lactam therapy is not effective against E. faecium. If an HLAR strain is susceptible to streptomycin, a footnote allows streptomycin 15 mg/kg/day in two equally divided doses (no route given) in place of gentamicin.^[1]
• Count antibiotic days from the first day of effective therapy (a negative blood culture if cultures were initially positive), not from the day of surgery.^[1]
• Persistent aortic or mitral vegetation of at least 10 mm after one or more embolic episodes despite appropriate antibiotics: urgent surgery, within 3–5 days (ESC 2023, Class I, Level B). Aortic or mitral vegetation of at least 10 mm without severe valve dysfunction, or without clinical embolism, and low surgical risk: urgent surgery may be considered (Class IIb, Level B).^[1]
• Right-sided IE: an isolated vegetation is not an indication for surgery; in patients receiving appropriate antibiotics, large residual tricuspid vegetations (above 20 mm) after recurrent septic pulmonary emboli are an indication for surgery (Class I, Level C).^[1]
• Thrombolysis: Class III in IE. Mechanical thrombectomy in embolic stroke: may be considered if expertise is available in a timely manner (Class IIb, Level C).^[1]
• ESC 2023 does not recommend clindamycin for antibiotic prophylaxis.^[1]

References14ShowHide

1. [1]Delgado V, Ajmone Marsan N, de Waha S, et al. 2023 ESC Guidelines for the management of endocarditis. Eur Heart J, 2023.PMID 37622656
2. [2]Otto CM, Nishimura RA, Bonow RO, et al. 2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation, 2021.PMID 33332150
3. [3]Iversen K, Ihlemann N, Gill SU, et al. Partial Oral versus Intravenous Antibiotic Treatment of Endocarditis. N Engl J Med, 2019.PMID 30152252
4. [4]Kang DH, Kim YJ, Kim SH, et al. Early surgery versus conventional treatment for infective endocarditis. N Engl J Med, 2012.PMID 22738096
5. [5]Habib G, Erba PA, Iung B, et al. Clinical presentation, aetiology and outcome of infective endocarditis. Results of the ESC-EORP EURO-ENDO (European infective endocarditis) registry: a prospective cohort study. Eur Heart J, 2019.PMID 31504413
6. [6]Cahill TJ, Prendergast BD. Infective endocarditis. Lancet, 2016.PMID 26341945
7. [7]Chye DM, Drummond KL, Rodrigues TS, et al. Epidemiology and health burden of infective endocarditis: a comparative analysis of Australian vs global trends from 1990 to 2021. Intern Med J, 2026.PMID 42823613
8. [8]Wright A, Otome O, Harvey C, et al. The Current Epidemiology of Injecting Drug Use-Associated Infective Endocarditis in Victoria, Australia in the Midst of Increasing Crystal Methamphetamine Use. Heart Lung Circ, 2018.PMID 28533098
9. [9]Bell A, Adegboye OA. The Epidemiology of Infective Endocarditis in New South Wales, Australia: A Retrospective Cross-Sectional Study From 2001 to 2020. Heart Lung Circ, 2023.PMID 36775764
10. [10]Robson C, Horvath R, Stuart RL, et al. A national study of infective endocarditis models of care in Australia. Intern Med J, 2025.PMID 39387620
11. [11]Campbell PO, Gallagher K, Dalton SC, et al. Safety and clinical outcomes of outpatient parenteral antibiotic therapy for infective endocarditis in Christchurch, New Zealand: A retrospective cohort study. Int J Infect Dis, 2023.PMID 37331565
12. [12]Basaglia A, Kang K, Wilcox R, et al. The aetiology and incidence of infective endocarditis in people living with rheumatic heart disease in tropical Australia. Eur J Clin Microbiol Infect Dis, 2023.PMID 37474765
13. [13]Low ZM, Krishnaswamy S, Woolley IJ, et al. Burden of infective endocarditis in an Australian cohort of people who inject drugs. Intern Med J, 2020.PMID 31841254
14. [14]ESC Scientific Document Group. Correction to: 2023 ESC Guidelines for the management of endocarditis: Developed by the task force on the management of endocarditis of the European Society of Cardiology (ESC) Endorsed by the European Association for Cardio-Thoracic Surgery (EACTS) and the European Association of Nuclear Medicine (EANM). Eur Heart J, 2025.PMID 39824219