EMA Cited · Infectious disease · Cardiology

Infective endocarditis

Updated Nov 3, 2026Adults · ED management8 sources · 7 checked in PubMed2 figuresESC 2023 · Duke-ISCVID 2023

Bottom line

Think of it in any fever with a predisposition: a prosthetic valve, earlier endocarditis, a cardiac device, congenital or significant valve disease, or injection drug use.¹ About 90% of patients have fever.²
Blood cultures before antibiotics. ESC asks for at least 3 sets 30 minutes apart.³ The 2023 Duke-ISCVID criteria need only 2 and dropped the timing rule.¹
Echo as soon as you suspect it. Transthoracic first, then transesophageal if inconclusive, and usually even after a positive transthoracic study.^3,4
Empiric antibiotics must cover staphylococci, streptococci and enterococci in native valve and late prosthetic valve endocarditis.³
It is deadly and often surgical. In a 40-country registry, 17.1% died in hospital and surgery was indicated in 69.3%.⁵ New severe heart failure means emergency surgery.³

Recognize

Predispositions: earlier endocarditis, a prosthetic valve (surgical or transcatheter), earlier valve repair, congenital heart disease, more than mild regurgitation or stenosis, a cardiac device, hypertrophic obstructive cardiomyopathy, and injection drug use.¹
Presentation: fever in about 90%, often with malaise, anorexia, weight loss and myalgia. A new murmur is heard in 50–80%. Look for heart block and heart failure.²
Emboli: stroke or meningitis, septic pulmonary emboli (mostly tricuspid disease in people who inject drugs), and splenic or renal infarcts presenting as flank pain or hematuria.²
Skin and eyes: Janeway lesions, conjunctival hemorrhages and purulent purpura count as vascular phenomena; Osler nodes and Roth spots as immunologic phenomena.¹

Close-up of a palm with scattered small flat red spots over the thenar and hypothenar areas — FIG 1Janeway lesions. Flat, painless red macules on the palm of a man with staphylococcal endocarditis.Warfieldian · Wikimedia Commons · CC BY-SA 4.0

First steps

Blood cultures before antibiotics: at least 3 sets of 10 mL, aerobic and anaerobic, from a peripheral vein, 30 minutes apart.³
Labs: CBC, urinalysis for hematuria, and ESR or CRP, which are raised in over 90%.²
Echo as soon as endocarditis is suspected. Transthoracic is first line; transesophageal if it is inconclusive.³ ESC recommends transesophageal echo even after a positive transthoracic study, except in clear-cut isolated right-sided native valve disease.⁴
Image by symptoms: for neurologic signs, MRI with and without gadolinium, or CT with and without contrast if MRI is not possible.³ Chest X-ray then CT for respiratory symptoms.²
Start empiric antibiotics promptly once cultures are drawn.³
Call the Endocarditis Team early: cardiology, cardiac imaging, cardiac surgery, infectious diseases and microbiology.³

FIG 2 · Decision flowCited

Suspect it: fever with a predisposition such as a prosthetic valve, earlier endocarditis, a device or injection drug use; a new murmur; or emboli.^1,2
Blood cultures before antibiotics. ESC: 3 sets, 30 minutes apart. Duke-ISCVID: at least 2 sets, no timing rule.^3,1
Empiric antibiotics promptly, covering staphylococci, streptococci and enterococci; the regimen depends on valve type and time since valve surgery.^3,4
Echo now: transthoracic first, transesophageal if inconclusive. Repeat in 5–7 days if negative and suspicion stays high.^3,4
New focal neurologic deficit?
Yes
Brain MRI, or CT with and without contrast.³
No thrombolysis. Thrombectomy may be considered in selected patients.^3,6
Either way
Heart failure, uncontrolled infection, or a mobile vegetation over 10 mm?
Yes
Call cardiac surgery now: emergency surgery (within 24 h) for new NYHA class IV heart failure; urgent (3–5 days) for large mobile vegetations.^3,4
No
Admit and involve the Endocarditis Team.³

FIG 2Suspected endocarditis in the emergency department. Drawn for this page from the ESC 2023 guideline and the 2023 Duke-ISCVID criteria. Each box carries its own citations.^3,1

Duke-ISCVID criteria (2023)

Criterion	What counts
Major
Typical organism	In ≥ 2 separate blood culture sets: S. aureus, S. lugdunensis, E. faecalis, streptococci other than S. pneumoniae and S. pyogenes, HACEK and a few others. With intracardiac prosthetic material, also coagulase-negative staphylococci and several others
Nontypical organism	In ≥ 3 separate blood culture sets
Imaging	Echo or cardiac CT showing vegetation, perforation, aneurysm, abscess, pseudoaneurysm or fistula; significant new regurgitation; new prosthetic dehiscence; or abnormal valve uptake on FDG PET/CT
Minor
Predisposition	See Recognize, above
Fever	> 38.0 °C (100.4 °F)
Vascular	Arterial emboli, septic pulmonary infarcts, cerebral or splenic abscess, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhages, Janeway lesions, purulent purpura
Immunologic	Positive rheumatoid factor, Osler nodes, Roth spots, immune complex glomerulonephritis
Microbiologic	Positive cultures that fall short of a major criterion
Examination	New regurgitant murmur, only if echo is unavailable. A changed murmur is not enough

Definite: 2 major, or 1 major and 3 minor, or 5 minor. Possible: 1 major and 1 minor, or 3 minor. Separate venipunctures are recommended but no longer required, and the timing rules between sets were removed.¹ Counting E. faecalis as a typical organism raised the sensitivity for definite endocarditis from 70% to 96%.³

Empiric antibiotics

Situation	ESC 2023 empiric regimen	Class
Community-acquired native valve, or prosthetic valve ≥ 12 months after surgery	Ampicillin plus ceftriaxone, or (flu)cloxacillin plus gentamicin	IIa, C
Prosthetic valve < 12 months after surgery, or healthcare-associated	Vancomycin or daptomycin, plus gentamicin and rifampin	IIb, C
Beta-lactam allergy	Cefazolin or vancomycin, plus gentamicin	IIb, C

Regimens from the ESC guideline's empiric table as reproduced in a published summary.^3,4 Give doses per institutional protocol, label and infectious diseases pharmacy; the guideline's dose table could not be read. When daptomycin is used, ESC calls for a high dose of 10 mg/kg once daily, and it targets a vancomycin AUC/MIC of 400–600.³

Sources disagree

The ESC empiric regimen for community-acquired native valve disease is ampicillin with ceftriaxone, or (flu)cloxacillin with gentamicin.^3,4 REBEL EM, a US source, lists vancomycin plus cefepime instead.² Follow your local protocol and infectious diseases advice.

Beta-lactams beat vancomycin for susceptible staphylococci; ESC uses cefazolin in penicillin-allergic patients for that reason.³
Later, not in the ED: in stable left-sided endocarditis after at least 10 days of IV therapy, switching to oral antibiotics was noninferior (composite outcome 9.0% vs 12.1%, n = 400).⁷

When to call the surgeon

Three indications: heart failure, uncontrolled infection, and prevention of emboli.⁴
Timing: emergency means within 24 hours; urgent means within 3–5 days.⁴ New NYHA class IV heart failure needs emergency surgery.³
Large vegetations: urgent surgery is considered for mobile vegetations over 10 mm. The risk of neurologic complications is especially high above 30 mm.^3,4
Early surgery trial (EASE, n = 76, large vegetations and severe valve disease): surgery within 48 hours cut death or embolism at 6 weeks from 23% to 3%. Six-month mortality did not differ significantly (3% vs 5%).⁸
Surgery withheld when indicated independently predicted death in the EURO-ENDO registry, alongside heart failure, vegetation > 10 mm, cerebral complications and abscess.⁵

Stroke and anticoagulation

No thrombolysis. ESC finds antithrombotic and thrombolytic therapy not beneficial in endocarditis stroke; mechanical thrombectomy may be considered in selected cases.³
In a systematic review of 52 published cases, IV thrombolysis carried 4.14 times the risk of intracranial hemorrhage. Thrombectomy trended toward better outcomes.⁶
Anticoagulation: continue it in left-sided endocarditis when there was a pre-existing indication and no other contraindication.³
Surgery after stroke: early surgery is supported after ischemic stroke unless neurologic status is poor; after hemorrhagic stroke it is generally delayed beyond 4 weeks.⁴

Disposition

Admit, and involve the Endocarditis Team of the heart valve center.³
Consult infectious diseases and cardiothoracic surgery from the ED.²
Outpatient therapy is a later decision for stable patients after an IV phase, and injection drug use is listed as a contraindication to outpatient oral therapy.⁴

Pitfalls

Giving antibiotics before the blood cultures are drawn.³
Giving thrombolysis for a stroke in a febrile patient with a murmur.^3,6
Stopping at a normal transthoracic echo when suspicion is high. Get a transesophageal study, and repeat at 5–7 days.^3,4
Counting a changed or louder murmur as a criterion. Only a new regurgitant murmur counts, and only when echo is unavailable.¹
Delaying the surgical call in new severe heart failure. It needs emergency surgery.³
Missing it because the fever is vague. Presentations are often nonspecific.²

How strong is the evidence?

The ESC empiric regimens are class IIa or IIb at level C, which means expert opinion.⁴ The early surgery trial enrolled only 76 patients.⁸ Stroke reperfusion data come from published case series.⁶ The Duke-ISCVID criteria were built by an international expert working group.¹ The ESC guideline's recommendation tables are published as images; class and level here come from a published summary.⁴

On-shift teaching

Questions to ask a learner at the bedside. Tap a question to see the answer. Every answer uses facts cited above.

Q1What makes a case definite under the 2023 Duke-ISCVID criteria?

2 major, or 1 major and 3 minor, or 5 minor criteria (or pathologic proof).¹

Q2How many blood culture sets does a typical organism need for a major criterion, and does timing matter?

At least 2 separate sets. Nontypical organisms need 3. Duke-ISCVID removed the timing rules.¹ ESC still asks for 3 sets 30 minutes apart before antibiotics.³

Q3Which organism did the new criteria add as typical, and what did it do to sensitivity?

Enterococcus faecalis, now a typical organism.¹ Counting it raised the sensitivity for definite endocarditis from 70% to 96%.³

Q4A febrile patient with a murmur has a stroke within the thrombolysis window. Do you give a lytic?

No. ESC finds thrombolysis not beneficial; thrombectomy may be considered.³ Published cases show 4.14 times the intracranial hemorrhage risk with IV thrombolysis.⁶

Q5What did the EASE trial show about early surgery?

In 76 patients with large vegetations and severe valve disease, surgery within 48 hours cut death or embolism at 6 weeks from 23% to 3%, without a significant 6-month mortality difference.⁸

Q6Which organisms must empiric therapy cover in native valve endocarditis?

Staphylococci, streptococci and enterococci.³ ESC suggests ampicillin plus ceftriaxone, or (flu)cloxacillin plus gentamicin (class IIa, C).⁴

References

Evidence base

What this page is built on

8 sources, cited 74 times. Dots are sources, filled by how far each was read; stronger color means a larger share of the citations. Tap a tier to see its sources.

Read in full · 4Abstract read · 4Record only · 0Link checked · 0

Checked by the writer, not a physician. The dots show how each source was read, not that anyone has confirmed the claims.

Not for clinical use

AI-generated draft. Not reviewed by a physician. This page is for education only and may contain errors, including in doses. Do not use it to diagnose, treat or make decisions about any patient. Rely on your own clinical judgment, your institution's protocols and current drug labeling. Reading this page does not create a physician-patient relationship. Full terms