Native-valve infective endocarditis

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Native-valve infective endocarditis is microbial infection of endocardial valve tissue, usually after bloodstream organisms adhere to damaged or inflamed endothelium and become embedded in platelet–fibrin vegetation.

Staphylococcus aureus can infect previously normal valves and causes acute destructive disease. Viridans streptococci, Streptococcus gallolyticus and enterococci more often produce subacute presentations; epidemiology and portals direct the wider organism search.

Diagnosis rests on repeated blood cultures, echocardiographic or other cardiac imaging and clinical manifestations. Prior antibiotics are a common cause of culture-negative disease and should be avoided before samples when stability permits.

Management requires an endocarditis team because antimicrobial exposure, embolic imaging, dentistry, device and line removal, source control and cardiac-surgery timing interact. Neurological embolism does not automatically preclude surgery but demands multidisciplinary timing.

Key points

Suspect infective endocarditis with persistent fever plus a murmur, embolic event, vascular or immune phenomenon, risk valve or unexplained bacteraemia.
In a stable adult, obtain three correctly filled peripheral blood-culture sets from separate venepunctures before any antibiotic.
Do not wait for the full sampling sequence in septic shock; collect cultures rapidly and start intravenous treatment.
TTE is the first echocardiographic test, while TOE follows when TTE is negative or inadequate but suspicion remains high or complications need definition.
A normal early echocardiogram does not exclude endocarditis; repeat imaging is required when clinical probability remains high.
Apply Duke or contemporary diagnostic criteria as a framework, not a replacement for endocarditis-team judgment.
Antibiotic choice and duration are organism-, valve-, renal- and complication-specific and should be prescribed with infection specialists from susceptibility.
Surgery is time critical for heart failure, uncontrolled infection, abscess, difficult organisms and selected embolic-risk vegetations.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Staphylococcal bloodstream seeding

Staphylococcus aureus from skin, lines, wounds or injection exposure can adhere to intact valves and cause rapidly destructive acute infection.

Streptococcal oral entry

Viridans streptococci enter transiently from oral disease and procedures and preferentially adhere to previously damaged endocardial surfaces.

Enterococcal and gastrointestinal sources

Enterococci and Streptococcus gallolyticus can follow urinary or gastrointestinal portals and should prompt source-directed evaluation. in susceptible exposed adults.

Fastidious and fungal organisms

Prior antibiotics, Coxiella, Bartonella, HACEK organisms and fungi cause culture-negative or difficult disease linked to specific exposures and host factors.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Endothelial injury and thrombus
Turbulent flow or inflammation exposes matrix and creates a sterile platelet–fibrin nidus on valve endothelium. during active invasive disease.
2
Microbial adhesion and vegetation
Circulating organisms bind the nidus and proliferate within layered fibrin and platelets that impede immune and antimicrobial penetration.
3
Valve and annular destruction
Continued infection perforates leaflets, ruptures chordae and extends into annulus, producing acute regurgitation, abscess and conduction injury.
4
Embolic fragmentation
Friable vegetation breaks away into systemic or pulmonary arteries, causing infarction, abscess and infected aneurysm according to valve side.
5
Immune-complex injury
Persistent antigen exposure generates circulating immune complexes that deposit in kidney, skin and vessels and cause inflammatory manifestations.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Persistent febrile illness

Fever, sweats, malaise, weight loss and raised inflammatory markers persisting without a clear source should prompt valve and bloodstream assessment.

New valve dysfunctionRed flag

A new regurgitant murmur, heart-failure signs or pulmonary oedema supports valve destruction, although absence of a murmur does not exclude disease.

Embolic presentationRed flag

Stroke, splenic or renal infarction, acute limb ischaemia, pulmonary embolic nodules in right-sided disease or focal pain may reveal endocarditis.

Peripheral vascular signs

Conjunctival or splinter haemorrhage, Janeway lesions and infected arterial aneurysm reflect vascular injury but are neither sensitive nor always present.

Immune phenomena

Glomerulonephritis, low complement, Roth spots and tender Osler nodes reflect immune-complex disease during more prolonged infection.

High-risk bloodstream contextRed flag

Staphylococcus aureus, enterococcal or persistent bacteraemia, injection exposure, haemodialysis and recent invasive infection greatly increase pre-test probability.

Red flags requiring action

New severe regurgitation with pulmonary oedema or cardiogenic shock requires emergency valve-surgery assessment.
Persistent fever or positive cultures despite active therapy suggests abscess, resistant organism or uncontrolled focus.
New PR prolongation or atrioventricular block can indicate peri-annular extension and abscess.
Acute focal neurological deficit may be embolic infarction, haemorrhage or infected aneurysm and changes surgical timing.
Severe back pain, hot joint or focal limb pain may represent metastatic vertebral, joint or arterial infection.
Staphylococcus aureus bacteraemia is never dismissed as contamination and requires endocarditis assessment.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

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 peripheral blood-culture setsFirst step
Why
Recover the organism and susceptibility before antimicrobial exposure in a stable patient.
Interpretation and limitations
Obtain correctly filled aerobic and anaerobic bottles from separate venepunctures; continuous bacteraemia means sets need not wait for fever spikes.
02
Transthoracic echocardiography
Why
Provide the initial assessment of vegetation, regurgitation, ventricular function and haemodynamic consequence.
Interpretation and limitations
TTE is first line but sensitivity is limited by small vegetations and image quality; a negative study does not end a high-probability evaluation.
03
Transoesophageal echocardiography
Why
Define small vegetations, valve perforation, abscess and peri-annular extension when suspicion or complication risk is high.
Interpretation and limitations
Perform after negative or inconclusive TTE with ongoing suspicion and for detailed surgical planning; repeat when disease evolves despite an initially negative study.
04
ECG and continuous rhythm review
Why
Detect conduction delay and arrhythmia from peri-annular extension or haemodynamic stress.
Interpretation and limitations
New PR prolongation or atrioventricular block is a red flag for abscess and requires urgent repeat imaging and surgical discussion.
05
Full blood count, renal, liver, urinalysis and CRP
Why
Assess systemic inflammation, immune-complex injury, organ function and safe antimicrobial dosing.
Interpretation and limitations
Microscopic haematuria and renal decline may be immune or embolic; CRP trends response but cannot prove sterilisation or exclude abscess.
06
CT, MRI or vascular imaging
Why
Investigate neurological, abdominal, spinal, joint or arterial embolic and metastatic complications from symptoms and operative planning.
Interpretation and limitations
Choose imaging for the clinical target. Intracranial haemorrhage or infected aneurysm materially changes anticoagulation and cardiac-surgery timing.
07
Culture-negative organism testing
Why
Identify Coxiella, Bartonella, fungi and other fastidious causes when routine cultures remain negative.
Interpretation and limitations
Review prior antibiotics and exposure first; order serology, molecular tests and valve-tissue studies with microbiology rather than using an indiscriminate panel.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Non-infective endocarditis

Malignancy and autoimmune disease can produce sterile vegetations and emboli without sustained positive cultures or a microbial portal.

Atrial myxoma

Intracardiac tumour causes constitutional and embolic symptoms and a changing murmur but follows a distinct imaging attachment pattern.

Occult malignancy or inflammation

Weight loss, fever and raised markers may reflect cancer, vasculitis or connective-tissue disease without valve infection.

Alternative bacteraemic source

Pneumonia, urinary infection, line sepsis and osteomyelitis can cause fever and positive cultures, while still potentially seeding a valve.

Acute rheumatic carditis

Post-streptococcal immune valve inflammation causes murmur and systemic features without continuous bacterial growth in blood. on focused clinical assessment.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01CULTURESample before treatment when safeFirst stepEndocarditis is suspected and the patient is haemodynamically stable without immediate organ-threatening sepsis.

1Take three peripheral blood-culture sets from separate venepunctures before any antibiotic and document every recent antimicrobial dose.
2Perform TTE promptly, ECG, renal and liver assessment, urinalysis and focused examination for heart failure, emboli, portals and metastatic infection.
3Contact cardiology and infection specialists at diagnosis suspicion rather than waiting for all criteria to accumulate.
4If cultures remain negative, review antibiotic exposure and use exposure-directed serology, molecular testing and planned deep or valve tissue studies.

02UNSTABLETreat sepsis without diagnostic delayShock, pulmonary oedema, severe valve failure or rapidly progressive organ dysfunction is present.

1Use ABCDE, obtain multiple blood-culture sets rapidly, measure lactate and start oxygen and physiology-guided fluid and vasopressor support.
2Begin the locally approved empirical native-valve regimen immediately with infection-specialist advice, adjusted for allergy, renal function, valve history and likely source.
3Arrange urgent TTE and TOE and activate cardiac surgery for severe regurgitation, abscess, conduction change or uncontrolled sepsis.
4Image acute neurological or vascular complications without allowing avoidable delays in lifesaving infection and cardiac care.

03DIRECTUse organism-specific prolonged therapyBlood or valve microbiology identifies the pathogen and susceptibility.

1Narrow to the most bactericidal, least toxic regimen appropriate to organism and native-valve anatomy and document the treatment start point.
2For methicillin-susceptible Staphylococcus aureus, use high-dose intravenous flucloxacillin under the endocarditis protocol and obtain clearance cultures.
3For streptococci, enterococci, HACEK, fungi or culture-negative disease, use the exact specialist combination and monitoring schedule rather than a generic sepsis course.
4Review line need, dental and skin portals, metastatic foci, renal toxicity and candidacy for outpatient therapy only after clinical stability.

04OPERATERefer early for valve surgeryHeart failure, peri-annular extension, uncontrolled infection, difficult organism or high embolic risk meets a surgical indication.

1Discuss the patient at a dedicated endocarditis meeting with cardiac surgery, cardiology, infection, imaging and relevant neurological specialists.
2Define valve destruction, abscess, ventricular function, coronary needs and embolic burden and balance operative urgency against intracranial haemorrhage or major infarction.
3At operation send multiple valve and abscess specimens for culture, histology and molecular testing and communicate previous antimicrobial exposure.
4Continue directed postoperative therapy for the specialist-defined duration and monitor prosthetic material and surgical complications.

Key medicines and prescribing safety4 treatments · regimens, roles and cautions

Provides likely-organism coverage before cultures while avoiding an under-dosed generic sepsis regimen.

Empirical native-valve endocarditis regimen

Give the exact local intravenous endocarditis combination after three culture sets when stable, adjusted for acuity, allergy, renal function, valve history and healthcare exposure.

Obtain infection-specialist input urgently; empirical choices vary, aminoglycosides and glycopeptides require levels and renal monitoring, and therapy must be narrowed when cultures return.

Provides high-dose bactericidal beta-lactam treatment after susceptibility confirms methicillin-sensitive staphylococcal disease.

Flucloxacillin for MSSA native-valve disease

Give 2 g intravenously every four hours for methicillin-susceptible Staphylococcus aureus native-valve endocarditis, with specialist-defined duration usually measured in weeks.

Clarify immediate penicillin allergy, monitor hepatic and renal function and sodium load, obtain clearance cultures and investigate persistent positivity for abscess or metastatic infection.

Treats MRSA or selected beta-lactam-resistant or allergy-constrained Gram-positive endocarditis under specialist direction.

Vancomycin for resistant Gram-positive disease

Use the local intravenous loading and maintenance protocol based on actual body weight, renal function and measured serum exposure when glycopeptide therapy is indicated.

Document target exposure, monitor kidney function and concentrations, review nephrotoxins and switch to a superior beta-lactam promptly when susceptibility and allergy permit.

Provides synergistic activity in selected enterococcal or other defined regimens rather than routine native-valve empirical treatment.

Gentamicin specialist combination component

Use only the exact organism-specific weight-, renal- and serum-level-guided intravenous endocarditis schedule when the specialist protocol demonstrates a combination benefit.

Avoid reflex use; record dosing weight and levels, monitor creatinine and auditory or vestibular toxicity and stop promptly when toxicity or protocol duration is reached.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Acute heart failure

Leaflet perforation, chordal rupture or prosthetic dehiscence causes severe regurgitation, pulmonary oedema and cardiogenic shock. without timely definitive management.

Peri-annular abscess

Infection extends beyond valve into annulus, conduction tissue and myocardium, causing heart block, fistula and uncontrolled sepsis.

Systemic embolisation

Vegetation fragments cause stroke, splenic and renal infarction, limb ischaemia, mesenteric injury and infected arterial aneurysm.

Metastatic infection

Bacteraemia seeds vertebrae, joints, spleen and soft tissue, producing focal pain and persistent microbiological failure. without timely definitive management.

Immune renal injury

Immune-complex glomerulonephritis causes haematuria, proteinuria and renal decline that complicates antimicrobial dosing and surgery. without timely definitive management.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Take repeat blood cultures until documented clearance and re-culture any recurrent fever or clinical deterioration.
Review temperature, heart-failure signs, murmur, embolic symptoms, neurological examination and new focal pain every day.
Use serial ECG and repeat echocardiography for conduction change, persistent bacteraemia, new heart failure or suspected extension.
Monitor renal, hepatic and haematological toxicity and serum levels required by the exact antimicrobial regimen.
Track CRP as a contextual response marker while prioritising culture clearance, physiology and source-control evidence.
Assess all intravascular lines daily and remove unnecessary or infected devices after safe access planning.
Before discharge document surgery plan, antimicrobial end date, outpatient monitoring, dental and portal care and emergency symptoms.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Fever timing does not guide cultures

Endocardial infection produces near-continuous bacteraemia, so cultures are taken before antibiotics rather than waiting for a temperature spike.

A negative TTE may be incomplete

Small vegetations and peri-annular extension can escape transthoracic imaging, making TOE and repeat studies necessary in high-probability disease.

Conduction change is anatomy

New atrioventricular delay near the aortic root can signal infection extending into conduction tissue and requires urgent surgical imaging.

Culture negativity often has a cause

Prior antibiotics are common, while Coxiella, Bartonella and fungi require exposure-led testing and sometimes valve molecular analysis.

Neurology changes timing not purpose

Embolic stroke may strengthen the need for surgery, while intracranial haemorrhage changes cardiopulmonary-bypass timing and demands joint specialist review.

S aureus is never a casual isolate

Even one credible positive blood-culture episode requires clearance, source, endocarditis and metastatic-focus assessment.

11Common pitfallsFrequent interpretation and management errors.

01
Do not give antibiotics before adequate blood cultures in a stable patient with suspected endocarditis.
02
Do not exclude disease after one negative TTE when pre-test probability remains high.
03
Do not treat Staphylococcus aureus in blood as contamination.
04
Do not use a short generic bacteraemia course when valve infection is possible or confirmed.
05
Do not ignore new back pain, hot joint, abdominal pain or neurological deficit as unrelated symptoms.
06
Do not wait until heart failure or abscess becomes irreversible before discussing the patient with cardiac surgeons.