01OverviewDefinition, clinical context and the essential points that orientate the chapter.
IE is an infection of endocardial surfaces, most often valves or cardiac devices. Presentation may be fulminant or subacute and non-specific; early Endocarditis Team involvement improves diagnostic and surgical coordination.
Diagnosis combines microbiology and imaging in the ESC criteria. Neither one negative culture nor one negative echo excludes disease after prior antibiotics, with prosthetic material, or when clinical probability is high.
Treatment is prolonged, bactericidal and organism-specific. Doses below are ESC adult guideline examples for hospital specialist use; product licensing varies and UK microbiology/local antimicrobial policy takes precedence.
Key points
- Think IE in unexplained fever or bacteraemia plus a prosthetic valve, previous IE, congenital lesion, intracardiac device, valve disease, haemodialysis, injection drug use or recent invasive infection.
- When clinically safe, take three sets of peripheral blood cultures at 30-minute intervals before antibiotics; never wait for fever spikes.
- Perform TTE promptly and TOE when TTE is negative/inconclusive but suspicion remains high, for prosthetic valves/devices, or to define complications.
- If initial echo is negative but suspicion remains high, repeat TTE/TOE in 5–7 days; cardiac CT, FDG-PET/CT or WBC SPECT/CT is especially useful for prosthetic/perivalvular/device disease.
- Empirical IV therapy depends on native versus prosthetic valve, time since surgery, healthcare acquisition, prior antibiotics, allergy, renal function and local resistance—there is no universal UK regimen.
- Change empirical treatment to susceptibility-directed therapy as soon as the organism is identified, usually within 24–48 hours; NVE courses range 2–6 weeks and PVE usually requires at least 6 weeks.
- Emergency surgery within 24 hours is indicated for aortic/mitral NVE or PVE causing refractory pulmonary oedema or cardiogenic shock; urgent surgery is generally within 3–5 days for other uncontrolled HF/infection/embolism indications.
- NICE says antibiotic prophylaxis is not routinely offered for dental, GI/GU or respiratory procedures; prioritise oral health and shared specialist/dental consideration in exceptional high-risk circumstances.
02AetiologyUnderlying causes, associations and risk factors, with why each one matters.
Abnormal native endocardium
Turbulent flow across damaged valves or selected congenital lesions injures endocardium and creates a surface for microbial adhesion. Oral, skin or other transient bacteraemia can then seed it.
Prosthetic valve or cardiac device infection
Prosthetic material, repair rings and intracardiac leads provide surfaces for bacterial adhesion and biofilm. Recent surgery, repeated healthcare contact and pocket or bloodstream infection increase risk.
Sustained bloodstream exposure
Injection drug use, haemodialysis, vascular catheters and invasive infection can repeatedly introduce organisms into blood. Injection drug use often involves right-sided valves, whereas healthcare-associated bacteraemia may involve native or prosthetic valves and intracardiac devices.
Previous endocarditis
Earlier infection leaves scarred, irregular endocardial surfaces and may have required prosthetic repair. This makes recurrent microbial seeding more likely and places the patient in a high-risk group.
03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.
- 1Endocardial injury
Turbulent jets or device trauma may disrupt endothelium, allowing platelet and fibrin deposition; prosthetic material also provides an adhesive surface without requiring native endothelial injury. These sites can become a nidus for infection.
- 2Microbial seeding
Transient or sustained bacteraemia brings organisms able to adhere to the nidus or foreign material. Risk depends on microbial properties, bloodstream burden and the cardiac substrate.
- 3Vegetation growth
Organisms proliferate within layers of fibrin and platelets, forming vegetations that limit immune clearance. Infection can sustain bacteraemia and progressively damage valve or adjacent tissue.
- 4Local extension
Infection may perforate a leaflet or spread into the annulus, myocardium or conduction system. Acute regurgitation, abscess, fistula, prosthetic dehiscence or atrioventricular block can result.
- 5Distant injury
Friable vegetation fragments embolise to systemic or pulmonary arteries, depending on valve side. Persistent antigen exposure also drives immune-complex deposition, particularly within renal glomeruli.
04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.
Fever, sweats, weight loss, malaise, anorexia or unexplained raised inflammatory markers, sometimes without a clear source.
New/changing murmur, new regurgitation, HF, prosthetic dysfunction or new conduction delay; new AV block suggests peri-annular abscess until proved otherwise.
Stroke, splenic/renal infarct, limb ischaemia, vertebral pain, pulmonary septic emboli in right-sided IE, glomerulonephritis, splinter haemorrhages, Janeway lesions or Osler nodes.
Previous IE, prosthetic valve/repair material, cyanotic or selected congenital disease, CIED, haemodialysis, injection drug use and recent S. aureus/Enterococcus bacteraemia raise pre-test probability.
Refractory pulmonary oedema/cardiogenic shock from valve dysfunction, abscess/fistula, enlarging vegetation, prosthetic dehiscence, persistent sepsis or recurrent emboli requires immediate surgical discussion.
05InvestigationsWhat to request, why it matters and how to interpret it.
Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.
- 01
Three sets of peripheral blood cultures before antibioticsFirst step - Why
- Establish continuous bacteraemia and permit susceptibility-directed therapy.
- Interpretation and limitations
- Take at 30-minute intervals when stable; draw from separate peripheral sites with adequate volume. In shock, obtain cultures rapidly but do not delay antibiotics. Repeat cultures until sterile.
- 02
Baseline bloods and urinalysis - Why
- FBC, CRP/ESR, U&E/eGFR, LFT, coagulation, lactate if unwell and urine for microscopic haematuria/protein.
- Interpretation and limitations
- Anaemia, inflammatory response, AKI or glomerulonephritis support severity and determine antimicrobial safety; normal markers do not exclude subacute IE.
- 03
Urgent TTE - Why
- Detect vegetation, new regurgitation, obstruction, ventricular effect or effusion.
- Interpretation and limitations
- Positive imaging supports a major criterion; sensitivity is lower with prostheses, devices, small vegetations and obesity.
- 04
TOE - Why
- Investigate high suspicion after negative/inconclusive TTE, prosthetic/device IE, or abscess/dehiscence/surgical anatomy.
- Interpretation and limitations
- Repeat TTE/TOE in 5–7 days if initial imaging is negative but suspicion remains high.
- 05
Cardiac CT and nuclear imaging - Why
- Define peri-annular complications and prosthetic/device infection when echo is limited; FDG-PET/CT or WBC SPECT/CT can provide a major imaging criterion.
- Interpretation and limitations
- Interpret postoperative uptake with expert nuclear/cardiac imaging input; CT is also valuable for coronary/surgical planning.
- 06
Embolic and source imaging - Why
- CT/MRI brain, chest, abdomen or spine when neurological, pulmonary, abdominal or back symptoms occur; assess dental, skin, line and other portals.
- Interpretation and limitations
- Emboli/abscesses influence surgical timing and duration; intracranial haemorrhage changes antithrombotic and surgical decisions.
- 07
Culture-negative pathway - Why
- Confirm prior antibiotics and obtain targeted serology/PCR for Coxiella, Bartonella and other epidemiology-driven pathogens; analyse excised tissue by culture/histology/molecular tests.
- Interpretation and limitations
- Use infection-specialist/microbiology direction rather than broad indiscriminate serology.
06Differential diagnosisRealistic alternatives and the features that help distinguish them.
Uncomplicated bacteraemia or another infection source
Pneumonia, urinary infection or line sepsis can cause fever and positive cultures without endocardial infection. A convincing alternative source, prompt culture clearance and unrevealing cardiac imaging lower IE probability, but one negative echocardiogram does not exclude high-probability disease.
Non-bacterial thrombotic endocarditis
Malignancy or systemic autoimmune disease can produce sterile valve vegetations and emboli. Persistently negative cultures after adequate microbiological investigation, limited evidence of infection and an active underlying disorder support this alternative, while prior antibiotics can still make IE culture-negative.
Atrial myxoma
An intracardiac tumour can cause fever, raised inflammatory markers, obstruction and systemic emboli. Echocardiography may show a chamber mass, often attached to the atrial septum by a stalk, rather than a valve-based vegetation.
Systemic vasculitis
Vasculitis may cause fever, skin lesions, renal injury and cerebral events, but IE itself can produce immune phenomena and some positive antibodies. Microbiology, serial cardiac imaging, the wider disease pattern and sometimes tissue diagnosis are more discriminating than serology alone.
07ManagementImmediate care, first-line treatment, alternatives and escalation.
01First hourSuspected IEFirst stepCompatible infection plus cardiac risk or embolic/valvular features.+
- 1Admit, involve microbiology/infection and the Endocarditis Team early; assess haemodynamic, neurological and embolic complications.
- 2If stable, take three peripheral blood-culture sets at 30-minute intervals before antimicrobials. If unstable, draw cultures immediately and start treatment without avoidable delay.
- 3Obtain ECG, baseline renal/liver/haematology tests and urgent TTE; proceed to TOE for prosthesis/device, inadequate TTE, high suspicion or complication mapping.
- 4Repeat cultures until clearance and repeat echo in 5–7 days if initial imaging is negative but probability remains high.
02EmpiricalInitial IV antibiotics before identificationCultures obtained and IE treatment cannot await identification.+
- 1Use the local UK antimicrobial guideline and microbiologist: regimen must cover the likely organisms for valve type, timing and acquisition.
- 2ESC example for community NVE or late PVE at least 12 months after surgery: ampicillin 12 g/day IV in 4–6 doses plus ceftriaxone 4 g/day IV/IM in 2 doses; OR flucloxacillin 12 g/day IV in 4–6 doses plus gentamicin 3 mg/kg IV/IM once daily.
- 3ESC example for early PVE under 12 months or healthcare-associated IE: vancomycin 30 mg/kg/day IV in 2 doses OR daptomycin 10 mg/kg IV once daily, combined with gentamicin 3 mg/kg once daily and rifampicin 900–1200 mg/day IV/PO in 2–3 doses; adapt for local Gram-negative epidemiology.
- 4EscalationDe-escalate to pathogen/susceptibility-directed treatment within 24–48 hours. In foreign-material infection, start rifampicin only after 3–5 days of effective therapy once bacteraemia has cleared, unless the specialist team directs otherwise.
03TargetedExamples after organism identificationOrganism and susceptibility known.+
- 1Penicillin-susceptible oral streptococcus/S. gallolyticus: penicillin G 12–18 million units/day IV in 4–6 doses or continuous, amoxicillin 100–200 mg/kg/day IV in 4–6 doses, or ceftriaxone 2 g IV once daily—4 weeks for NVE, 6 weeks for PVE.
- 2Enterococcus faecalis: ampicillin 12 g/day IV in 4–6 doses plus ceftriaxone 4 g/day IV in 2 doses for 6 weeks is an important renal-sparing synergistic regimen; organism/species and resistance must be confirmed.
- 3HACEK: ceftriaxone 2 g IV once daily for 4 weeks in NVE or 6 weeks in PVE.
- 4MSSA NVE: flucloxacillin 12 g/day IV in 4–6 doses for 4–6 weeks is a common ESC regimen; do not add an aminoglycoside for staphylococcal NVE because renal toxicity increases without benefit.
04SurgeryDo not wait for antibiotic completionHeart failure, uncontrolled infection or high embolic risk.+
- 1Emergency surgery within 24 hours: aortic/mitral NVE or PVE with severe regurgitation, obstruction or fistula causing refractory pulmonary oedema or cardiogenic shock.
- 2Urgent surgery, usually within 3–5 days: HF without refractory shock, abscess/pseudoaneurysm/fistula, enlarging vegetation, prosthetic dehiscence/new AV block, persistent sepsis/bacteraemia, fungal or multiresistant infection when operable.
- 3Embolic prevention: urgent surgery for persistent vegetation at least 10 mm after one or more embolic events despite antibiotics, or vegetation at least 10 mm with another surgical indication; individualise isolated large vegetation with surgical risk.
- 4Remove the complete CIED system without delay for definite device infection. Right-sided IE surgery is considered for severe TR with RV dysfunction, bacteraemia persisting at least 1 week, recurrent pulmonary emboli/respiratory failure, or residual tricuspid vegetation over 20 mm after recurrent emboli.
Key medicines and prescribing safety6 treatments · regimens, roles and cautions+
Empirical community NVE/late PVE — ESC regimen example, not a universal UK prescription
Ampicillin 12 g/day IV in 4–6 doses PLUS ceftriaxone 4 g/day IV/IM in 2 doses; OR flucloxacillin 12 g/day IV in 4–6 doses PLUS gentamicin 3 mg/kg IV/IM once daily.Use only after cultures and specialist review; beta-lactam allergy, renal function, weight, prior therapy and local resistance change the regimen. Gentamicin requires levels and renal monitoring.
Empirical early PVE/healthcare-associated IE — ESC regimen example
Vancomycin 30 mg/kg/day IV in 2 doses OR daptomycin 10 mg/kg IV once daily, PLUS gentamicin 3 mg/kg once daily PLUS rifampicin 900–1200 mg/day IV/PO in 2–3 doses.Low-level evidence and not universally appropriate; follow local microbiology, renal adjustment and therapeutic drug monitoring. Daptomycin needs CK monitoring. Rifampicin has major interactions/hepatotoxicity and, for foreign material, is generally delayed until bacteraemia clears.
Ceftriaxone — ESC targeted example
2 g IV once daily for susceptible oral streptococcal IE (4 weeks NVE, 6 weeks PVE) or HACEK IE (4 weeks NVE, 6 weeks PVE).Severe immediate beta-lactam allergy, biliary adverse effects and interactions/compatibility require review. Do not extrapolate this dose/duration to unidentified or resistant organisms.
Ampicillin plus ceftriaxone — ESC targeted E. faecalis example
Ampicillin 12 g/day IV in 4–6 doses plus ceftriaxone 4 g/day IV in 2 doses for 6 weeks.Confirm species and susceptibility; this double-beta-lactam strategy is not established for E. faecium. Monitor renal function, FBC, LFT and beta-lactam allergy.
Flucloxacillin — ESC targeted MSSA NVE example
12 g/day IV in 4–6 doses for 4–6 weeks.Renal/hepatic adjustment and sodium load may matter; monitor FBC, U&E and LFT. Do not add gentamicin in staphylococcal NVE. PVE requires a different foreign-material regimen.
Dental prophylaxis — UK NICE position
No routine antibiotic dose: NICE does not routinely recommend prophylaxis for dental, GI/GU or respiratory procedures.Do not prescribe a universal pre-dental dose simply because a murmur or valve lesion exists. Procedures through active infection require therapeutic antibiotics covering likely IE organisms, which is a different indication.
08ComplicationsImportant consequences, why they occur and why they matter clinically.
Acute valve failure and pulmonary oedema
Leaflet destruction, perforation or prosthetic dehiscence can produce severe acute regurgitation. The ventricle cannot adapt rapidly, causing pulmonary oedema, low output or cardiogenic shock.
Peri-annular abscess and heart block
Extension beyond the valve can create abscess, pseudoaneurysm or fistula. Involvement near the conduction system causes new atrioventricular block and signals a need for urgent anatomical and surgical review.
Systemic or pulmonary embolism
Left-sided vegetations can cause stroke, splenic or renal infarction and limb ischaemia; right-sided infection produces pulmonary septic emboli. Embolic findings materially influence surgical timing.
Intracranial infection or haemorrhage
Septic emboli may cause brain abscess, infarction or infected arterial aneurysm, which can rupture. Neurological involvement changes decisions about antithrombotic treatment and cardiac surgery timing.
Immune and septic organ injury
Immune-complex glomerulonephritis, persistent sepsis and antimicrobial toxicity can all impair kidney function. Multiorgan injury complicates drug selection, worsens prognosis and may persist despite microbiological control.
09Monitoring and follow-upTreatment response, safety checks and longer-term review.
- Repeat blood cultures after treatment starts until sterile; persistent positivity prompts source, device, abscess and surgery review.
- Daily early review of U&E/eGFR, fluid status and clinical response; FBC/LFT at least serially during prolonged beta-lactam or rifampicin treatment.
- Use local therapeutic-drug-monitoring targets for vancomycin and gentamicin; check levels at the prescribed times and after renal/dose changes.
- With daptomycin check baseline and at least weekly CK, more often with renal impairment or myalgia; review statins.
- With rifampicin check LFT and extensive drug interactions, including anticoagulants, antiepileptics, contraceptives and immunosuppressants.
- Repeat echo with clinical deterioration, new murmur/HF/AV block, persistent infection or embolism; do not wait for a scheduled scan.
- Before discharge document antibiotic completion plan, valve/device status, surgery follow-up, oral-health prevention and recurrence red flags.
10Special situationsVariants, exceptions and circumstances that change the usual approach.
Cultures come before convenience
Three properly filled peripheral sets before antibiotics have far greater diagnostic value than cultures drawn later through an indwelling line.
New AV block is anatomical information
In aortic-valve IE it strongly suggests peri-annular extension/abscess and accelerates TOE/CT and surgical review.
The antibiotic clock
Duration is generally counted from the first day of effective therapy—often the day cultures become negative—not automatically reset on surgery unless valve cultures remain positive.
Prosthetic imaging is multimodal
A negative TTE is weak reassurance; TOE, cardiac CT and FDG-PET/CT or WBC SPECT/CT can reveal peri-prosthetic disease.
Stroke is not an invitation to thrombolyse
Systemic thrombolysis is not recommended for IE-related embolic stroke because intracranial haemorrhage risk is high; coordinate neurology and the Endocarditis Team.
NICE prophylaxis wording matters
‘Not routinely’ is not a blanket statement that risk never matters; unusual high-risk cases need documented shared specialist/dental decision-making, not automatic prescribing.
11Common pitfallsFrequent interpretation and management errors.
- 01
Giving antibiotics before adequate cultures in a stable patient and creating culture-negative IE.
- 02
Accepting one negative TTE in prosthetic-valve or high-probability disease.
- 03
Using an empirical regimen without considering valve timing, healthcare exposure, allergy, renal function and local resistance.
- 04
Continuing aminoglycoside with MSSA native-valve IE despite nephrotoxicity and no benefit.
- 05
Waiting for a full antibiotic course before referring severe HF, abscess, persistent sepsis or embolic-risk disease for surgery.
- 06
Giving routine dental prophylaxis to every person with valve disease contrary to NICE.