Infective endocarditis — ID Training Module

At a glance

Think endocarditis in any unexplained bacteremia (especially S. aureus), new murmur, or embolic phenomenon.
Obtain three sets of blood cultures from separate sites before antibiotics — the single highest-yield diagnostic step.
Apply the 2023 ISCVID Duke criteria (revised — now includes CT and 18F-FDG PET/CT findings and S. aureus as a major criterion). [VERIFY exact criteria against the 2023 ISCVID update]
Echocardiography is tiered: TTE first, then TEE if TTE is negative, if a prosthetic valve is present, or in S. aureus bacteremia.
S. aureus bacteremia mandates echocardiography — TTE misses a meaningful fraction of vegetations.
Surgical indications: heart failure, uncontrolled infection, large mobile vegetations, perivalvular extension, and embolic events despite appropriate therapy.
Do NOT routinely add rifampin to native-valve S. aureus bacteremia (ARREST and CAMERA2 showed no benefit and more harm).
Selected stable left-sided IE can transition to oral therapy (POET, POSITIVE trials). [VERIFY eligibility criteria]

Objectives

1.Recognize the clinical presentation and predisposing conditions for infective endocarditis.
2.Apply the 2023 ISCVID Duke criteria for diagnosis.
3.Select appropriate diagnostic studies (blood cultures, echocardiography, CT/PET, serologies).
4.Choose empiric and organism-directed therapy, including the role of partial oral step-down.
5.Identify indications for surgical intervention and the role of the Endocarditis Team.
6.Distinguish who does and does not need IE prophylaxis.

Key concepts

Clinical problem & epidemiology

Infective endocarditis (IE) is an infection of the endocardial surface, most often a cardiac valve. The epidemiology has shifted: Staphylococcus aureus is now the most common cause in many contemporary series, driven by healthcare exposure and injection drug use, while streptococci remain important in native-valve disease with a dental or biliary source. Mortality remains substantial (in-hospital ~15–25%), and outcome hinges on early cultures, imaging, and coordinated medical-surgical care.

Predisposing conditions: prosthetic valve, congenital heart disease, prior IE, injection drug use, indwelling catheters, poor dentition.
Native-valve IE and prosthetic-valve IE differ in microbiology, the role of rifampin, and surgical timing.
Healthcare-associated IE is increasingly common with lines, devices, and cardiac implantable electronic devices (CIEDs).

Microbiology by valve type and exposure

Organisms cluster by valve type and exposure. S. aureus and viridans streptococci dominate native-valve disease; coagulase-negative staphylococci are classic for early prosthetic-valve IE; enterococci and HACEK organisms are less common but important. Culture-negative endocarditis has a defined differential — and a structured workup.

Native valve: S. aureus, viridans streptococci, Streptococcus gallolyticus (formerly S. bovis — associate with colorectal neoplasia), enterococci.
Prosthetic valve (early, <1 year): coagulase-negative staphylococci, S. aureus, hospital-acquired gram-negatives.
Prosthetic valve (late, >1 year): resembles native-valve microbiology.
Culture-negative causes: Coxiella burnetii, Bartonella, HACEK, T. whipplei, and the prior-antibiotic effect.

Self-check

A 65-year-old man presents 6 weeks after bioprosthetic aortic valve replacement with low-grade fever and a new murmur. Blood cultures grow coagulase-negative staphylococci in multiple bottles. What is the most likely scenario, and what does it imply for empiric therapy?

Select one option to submit your answer and view live poll results.

Clinical manifestations

Presentation ranges from an indolent febrile illness to fulminant sepsis with embolic phenomena. The classic peripheral stigmata (Osler nodes, Roth spots, Janeway lesions, splinter hemorrhages) are now less common but are still taught because they point to sustained bacteremia and immune-complex deposition. New heart block on telemetry is an underappreciated clue to perivalvular abscess.

Constitutional: fever, malaise, anorexia, weight loss.
Cardiac: new or changing murmur, heart failure, conduction abnormality (perivalvular extension — aortic-root abscess).
Embolic/immunologic: arterial emboli (brain, spleen, kidney, mesentery), septic pulmonary emboli (right-sided IE), mycotic aneurysm, immune-complex glomerulonephritis.

Diagnosis: the 2023 ISCVID Duke criteria & tiered imaging

IE is a clinical diagnosis codified by the Duke criteria, which were substantially revised in 2023 by the International Society for Cardiovascular Infectious Diseases (ISCVID). The 2023 update added CT and 18F-FDG PET/CT findings, expanded imaging findings, and reclassified S. aureus bacteremia as a major criterion. Imaging remains tiered: transthoracic echo (TTE) is non-invasive and a reasonable first step, but transesophageal echo (TEE) is far more sensitive and is required when TTE is negative but suspicion persists, in prosthetic valves, and in S. aureus bacteremia. The full point criteria are in the scoring-tools section.

2023 ISCVID major criteria now include: typical organisms in blood cultures (including S. aureus); endocardial involvement on echo OR CT (perivalvular abscess, native-valve vegetation) OR 18F-FDG PET/CT or radiolabeled-leukocyte SPECT/CT abnormal uptake around a prosthetic valve (<3 months post-implant). [VERIFY exact list]
Minor criteria: predisposition, fever ≥38°C, vascular phenomena, immunologic phenomena, suggestive (but not major) microbiology.
General imaging principle: escalate to TEE whenever the diagnosis is not excluded.

Self-check

A 40-year-old who injects drugs has S. aureus bacteremia and a transthoracic echocardiogram showing no vegetation. What is the next best step?

Select one option to submit your answer and view live poll results.

Culture-negative endocarditis: a structured workup

When blood cultures fail to grow, send the targeted serologic and molecular workup rather than resigning to 'empiric therapy forever.' The yield is high if you think about it systematically. Coxiella burnetii and Bartonella together account for a large fraction of true culture-negative IE.

Coxiella burnetii: phase I IgG ≥ 1:800 is a major Duke criterion. [VERIFY exact titer cutoff]
Bartonella henselae/quintana: serology (IgG) and, when available, PCR of blood or valve tissue.
HACEK: slow-growing gram-negative bacilli; most modern blood-culture systems now recover them, but incubation may be prolonged.
Tropheryma whipplei: PCR of blood or valve tissue (consider in older patients with aortic-valve IE and arthritis/diarrhea).
16S rRNA / 18S rRNA PCR and histopathology on excised valve tissue when surgery is performed.

Treatment: empiric, organism-directed, and partial oral step-down

Empiric therapy covers S. aureus (including MRSA) and streptococci while cultures are pending; once an organism and susceptibilities are known, therapy is narrowed and prolonged (typically 4–6 weeks). Selected clinically stable patients with left-sided IE caused by susceptible organisms can transition to oral therapy after an initial IV course — supported by the POET and POSITIVE trials. Always consult the most recent guideline and involve ID and cardiothoracic surgery early when surgery is a possibility.

Empiric (native valve): vancomycin (or anti-staphylococcal beta-lactam if MSSA likely) ± cefepime/gentamicin depending on local epidemiology.
Native-valve MSSA: nafcillin, oxacillin, or cefazolin — do NOT add gentamicin (no longer recommended) and do NOT add rifampin (ARREST and CAMERA2 showed harm).
MRSA (native or prosthetic): vancomycin (or daptomycin if vancomycin cannot be used).
Viridans streptococci, penicillin-susceptible: penicillin G or ceftriaxone for 2–4 weeks (2-week regimens exist with aminoglycoside, but most use 4 weeks).
Enterococcus faecalis, ampicillin-susceptible: ampicillin + gentamicin (or ampicillin + ceftriaxone for HLAR — high-level aminoglycoside resistance — to avoid nephrotoxicity).
Partial oral step-down: POET (Iversen et al. NEJM 2019) and POSITIVE (JAMA 2024 [VERIFY]) support oral step-down in selected stable left-sided IE with susceptible streptococci, enterococci, or E. coli — NOT for S. aureus or unstable patients.

Indications for surgery & risk scoring

Surgery is lifesaving in a defined subset of patients. The classic indications cluster around heart failure, uncontrolled infection, and prevention or management of embolic and destructive complications. Validated scores (AEPE, ELDER) help risk-stratify and time surgery; early collaboration with cardiothoracic surgery as part of an Endocarditis Team is the standard of care.

Heart failure due to valve dysfunction — the most common indication.
Uncontrolled infection: persistent bacteremia or fever beyond ~5–7 days despite appropriate therapy, fungal or highly resistant organisms.
Perivalvular extension: abscess, fistula, heart block.
Embolic events despite appropriate therapy, or large (>10 mm) mobile vegetations with high embolic risk; vegetation >15 mm and mobile carries the highest risk.
AEPE score (Actionable Points in Endocarditis) quantifies urgent-surgical-need features. ELDER score predicts in-hospital mortality in elderly IE. [VERIFY current versions]

Scoring tools & criteria

2023 ISCVID Duke Criteria (revised)

Standardized clinical diagnosis of infective endocarditis — supersedes the modified Duke criteria.

Factor	Points
MAJOR — Typical microorganism in blood cultures from 2 separate sites: viridans strep, S. gallolyticus, HACEK, OR S. aureus	major
MAJOR — Persistent bacteremia (≥2 positive cultures >12 h apart, or ≥3 of 4) with typical organism	major
MAJOR — Single positive Coxiella burnetii blood culture OR phase I IgG ≥ 1:800	major
MAJOR — Endocardial involvement on echo: vegetation, abscess, new partial dehiscence of prosthetic valve	major
MAJOR — Endocardial involvement on CT: perivalvular abscess or native-valve vegetation [2023 addition]	major
MAJOR — Abnormal 18F-FDG PET/CT or radiolabeled-leukocyte SPECT/CT uptake around a prosthetic valve implanted <3 months ago [2023 addition]	major
MAJOR — New pulmonary emboli in suspected right-sided IE [2023 addition]	major
MINOR — Predisposition: predisposing heart condition OR injection drug use	minor
MINOR — Fever ≥ 38 °C	minor
MINOR — Vascular phenomena: arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhages, Janeway lesions	minor
MINOR — Immunologic phenomena: glomerulonephritis, Osler nodes, Roth spots, rheumatoid factor	minor
MINOR — Microbiologic finding not meeting a major criterion	minor

Interpretation

Definite IEPathologic or clinical certainty. 2 major, OR 1 major + 3 minor, OR 5 minor criteria. [VERIFY exact combinations — also Definite on pathologic/histologic evidence] Treat as IE.

Possible IESuggestive but not definitive. 1 major + 1 minor, OR 3 minor criteria. [VERIFY] Continue workup and treat empirically while awaiting data.

RejectedAlternative diagnosis or no evidence. Firm alternative diagnosis, OR resolution with ≤4 days of antibiotics, OR no pathologic evidence after ≤4 days. [VERIFY] Pursue the alternative diagnosis.

2023 ISCVID Duke Criteria — Task Force on Criteria for IE. [VERIFY exact citation — Clin Infect Dis 2023 / companion in JAMA]

Differential diagnosis

Non-endocarditis bacteremia: Bacteremia without endocardial involvement; diagnosis rests on imaging and clinical course.
Culture-negative endocarditis: Sustained clinical picture with negative cultures; think Coxiella, Bartonella, HACEK, T. whipplei, or prior antibiotics.
Non-bacterial thrombotic (marantic) endocarditis: Sterile vegetations in malignancy or hypercoagulable states; no bacteremia or fever.
Libman-Sacks endocarditis: Sterile vegetations in systemic lupus erythematosus.
Atrial myxoma: Constitutional symptoms and emboli without infection; echo is diagnostic.

Treatment regimens

Illustrative regimens — confirm with the source guideline and tailor to the patient, renal/hepatic function, allergies, and local antibiogram.

Organism-directed therapy (illustrative — confirm with current ISCVID/ESC/AHA-IDSA guideline)

Scenario	Host factors	Regimen	Duration
Native valve, methicillin-susceptible S. aureus	—	Nafcillin or oxacillin (cefazolin as alternative)No routine aminoglycoside. No routine rifampin (ARREST, CAMERA2 — no benefit, more harm).	6 weeks
Native or prosthetic valve, MRSA	—	Vancomycin (AUC-guided); daptomycin if vancomycin cannot be used	6 weeks
Viridans streptococci, penicillin-susceptible (MIC ≤ 0.12)	—	Penicillin G or ceftriaxone	4 weeks
Prosthetic valve, coagulase-negative staphylococci	Early prosthetic-valve IE	Vancomycin + rifampin + gentamicin (initial 2 weeks)Rifampin is for the biofilm of prosthetic material — NOT for native-valve IE.	≥ 6 weeks
Enterococcus faecalis, ampicillin-susceptible	High-level aminoglycoside resistance (HLAR)	Ampicillin + ceftriaxone (double beta-lactam — avoids aminoglycoside nephrotoxicity when HLAR)	6 weeks
Selected stable left-sided IE (oral step-down)	Afebrile, improving, negative cultures, susceptible organism (strep, enterococcus, E. coli); NOT S. aureus	High-bioavailability oral regimen (e.g., amoxicillin ± fluoroquinolone/rifampin per organism) after initial IV coursePer POET (NEJM 2019) and POSITIVE (JAMA 2024 [VERIFY]); case-select carefully.	Total 4–6 weeks (POET/POSITIVE)

Complications & management

Embolic stroke & systemic emboli: Recognize: Acute focal neurologic deficit, splenic or renal infarct, mesenteric ischemia; embolic risk highest in the first week and with large mobile vegetations (>10 mm, highest >15 mm).Manage: Repeat imaging; involve neurology/stroke team. Surgery timing after stroke requires multidisciplinary discussion (avoid heparin); intracranial mycotic aneurysm may require neurosurgery/neurointerventional.
Perivalvular extension (abscess, fistula, heart block): Recognize: New conduction abnormality (PR prolongation → heart block) on telemetry, persistent bacteremia, TEE showing abscess/dehiscence.Manage: Urgent surgical evaluation — perivalvular extension is a surgical indication. Aortic-root abscess is a surgical emergency.
Acute severe valve regurgitation & heart failure: Recognize: Pulmonary edema, cardiogenic shock, new murmur; the most common indication for surgery.Manage: Urgent surgical evaluation; medical stabilization (afterload reduction, diuresis) as a bridge to surgery.
Mycotic aneurysm: Recognize: Headache, neurologic change, or hemorrhage; cerebral, visceral, or peripheral arterial distribution.Manage: CTA/MRA imaging; neurosurgery or interventional radiology consultation; treatment individualized (resection, embolization, or surveillance).
Splenic abscess & renal injury: Recognize: Persistent fever, left-upper-quadrant pain; renal failure from immune-complex GN, emboli, or drug toxicity.Manage: Splenic abscess often needs percutaneous or surgical drainage; renal injury — distinguish GN vs drug toxicity vs emboli and adjust therapy.

Prognosis & outcomes

In-hospital mortality (all IE): ~15–25% [VERIFY]
S. aureus IE mortality: ~20–30% [VERIFY]
Prosthetic-valve IE mortality: ~20–40% [VERIFY]
1-year mortality: ~30–40% [VERIFY]
Embolic risk: Highest in the first week; vegetation >10 mm higher; >15 mm and mobile highest
Outcome determinant: Early cultures, early imaging, early Endocarditis Team involvement

Special populations

Prosthetic valve IE: Classified early (<1 year, often nosocomial/CoNS) vs late (>1 year, resembles native valve). Biofilm mandates rifampin in staphylococcal PVE after debridement. Lower threshold for surgery; PET/CT or WBC SPECT/CT now a major Duke criterion within 3 months of implantation.
Injection drug use (right-sided IE): S. aureus predominates; tricuspid valve; septic pulmonary emboli are the hallmark. Shorter courses (2–4 weeks) are often appropriate in uncomplicated right-sided IE with clearance. Address addiction — offer MOUD (medication for opioid use disorder) and harm reduction to prevent recurrence.
Pregnancy: Treat aggressively — beta-lactams are safe in pregnancy; avoid aminoglycosides when possible (fetal ototoxicity), fluoroquinolones, and tetracyclines. Multidisciplinary care with OB and cardiothoracic surgery.
Cardiac implantable electronic device (CIED) infection: Pocket or lead infection — requires COMPLETE device and lead extraction by electrophysiology, not just antibiotics. Cultures of the explanted lead guide therapy. Do NOT leave an infected lead in place.
Healthcare-associated / line-related: Often S. aureus, CoNS, enterococci, or gram-negatives from catheters. Remove infected lines early; source control is central. Higher rates of resistant organisms — broaden empirically and narrow on susceptibilities.

Prevention & prophylaxis

Antimicrobial prophylaxis before dental procedures— HIGH-RISK cardiac conditions ONLY: prosthetic valve (including transcatheter-implanted and prosthetic material used in repair), prior IE, specific unrepaired or repaired-with-residual CHD, cardiac transplant with valvulopathy: Amoxicillin 2 g PO 30–60 min before procedures that manipulate gingiva or tooth apex. Ampicillin 2 g IM/IV, or cefazolin/ceftriaxone, if unable to take PO. Routine prophylaxis for GI/GU procedures is NOT recommended. [VERIFY current AHA/IDSA status]
Optimal oral hygiene— All patients at risk: Daily dental care and regular professional dental care reduce the burden of transient bacteremia and IE risk — at least as important as procedural prophylaxis.
Injection-drug-use harm reduction— People who inject drugs: Offer MOUD (buprenorphine/methadone), naloxone, syringe-service referral, and screening for endovascular infection early — the highest-yield prevention of recurrent IE in this population.
Catheter & surgical best practices— Hospitalized and procedural patients: Strict aseptic central-line insertion, bundled maintenance, and prompt removal of unneeded catheters reduce healthcare-associated IE.

When to refer

ID consultation for every case of suspected or confirmed IE — multidisciplinary Endocarditis Team is the standard of care.
Cardiothoracic surgery early for heart failure, uncontrolled infection, perivalvular extension, large mobile vegetations, or embolic events despite therapy.
Electrophysiology for CIED infection — lead and device extraction.
Neurology / neurosurgery / interventional neuroradiology for embolic stroke or mycotic aneurysm.
Nephrology for immune-complex glomerulonephritis or drug-related nephrotoxicity.
Interventional radiology or general surgery for splenic abscess or other drainable metastatic collections.
Addiction medicine for injection-drug-use-associated IE (MOUD reduces recurrence).

Follow-up

Repeat blood cultures every 24–48 hours until clearance — persistent bacteremia is a clue to a complication or source-control failure.
Serial TTE (and TEE when indicated) to monitor vegetations, valve function, and complications.
Total therapy typically 4–6 weeks IV; selected stable left-sided IE may complete orally (POET/POSITIVE). [VERIFY eligibility]
Monitor renal, hepatic, and hematologic toxicity of prolonged therapy (vancomycin AUC, beta-lactam levels in renal failure, linezolid CBC for >2 weeks).
Dental evaluation for viridans-streptococcal IE (source control; colorectal cancer screening for S. gallolyticus).
Watch for embolic events and immune-complex disease during and after therapy; counsel on symptoms.

Evidence & guidelines

Guidelines

2023 ISCVID Duke Criteria for Infective Endocarditis (revised)Task Force on Criteria for IE. Clin Infect Dis 2023 [VERIFY exact authors/volume/pages; companion paper in JAMA]The current diagnostic standard — supersedes the modified Duke criteria. Adds CT, PET/CT, and SPECT/CT findings and reclassifies S. aureus as a major criterion.
2023 ESC Guidelines for the management of infective endocarditisEuropean Society of Cardiology. [VERIFY exact citation]Comprehensive European guideline — Endocarditis Team, imaging, surgery, therapy.
Infective Endocarditis in Adults: Diagnosis, Antimicrobial Therapy, and Management of ComplicationsBaddour LM, et al. Circulation. 2015 (AHA/IDSA foundational guideline)Foundational AHA/IDSA guideline — many principles still current; some therapy updated by 2023 ISCVID/ESC.

Reviews

Infective EndocarditisCahill TJ, Prendergast BD. N Engl J Med. 2016A concise, high-yield NEJM clinical review (pre-2023 criteria — update needed).

Key trials

POET — Partial Oral versus Intravenous Antibiotic Treatment of EndocarditisIversen K, et al. N Engl J Med. 2019;380:415–424Non-inferiority of partial oral therapy in selected stable left-sided IE (strep, enterococcus, E. coli).
POSITIVE — Partial Oral Treatment for EndocarditisWald et al. JAMA 2024 [VERIFY exact volume/pages]Contemporary support for oral step-down in selected left-sided IE.
CAMERA2 — Adjunctive rifampin for Staphylococcus aureus bacteremiaTong SYC, et al. [VERIFY exact citation — NEJM/JAMA]No mortality benefit and more adverse events — do NOT routinely add rifampin to native-valve SAB.
ARREST — Adjunctive rifampin for Staphylococcus aureus bacteremiaTurnbull E, et al. [VERIFY — Lancet Infect Dis / NEJM]No benefit of rifampin in SAB; supports avoiding routine use.

Books & reference

Principles and Practice of Infectious Diseases, 9e — Infective Endocarditis chapterMandell, Bennett, DolinComprehensive reference for organism-directed therapy and surgery.

Pearls

PearlUse the 2023 ISCVID Duke criteria — not the modified Duke. New major criteria: CT/PET findings, native-valve vegetations on CT, S. aureus bacteremia, new pulmonary emboli in right-sided IE. [VERIFY]
PearlS. aureus bacteremia → echocardiography is mandatory; a negative TTE mandates a TEE.
PearlThree sets of blood cultures, drawn from separate sites, before antibiotics.
PearlCulture-negative endocarditis → send Coxiella (phase I IgG ≥ 1:800), Bartonella, HACEK, T. whipplei serology/PCR. [VERIFY Coxiella titer]
PearlDo NOT routinely add rifampin to native-valve S. aureus bacteremia — ARREST and CAMERA2 showed no benefit and more harm. Rifampin is for prosthetic-material biofilm after debridement.
PearlEnterococcus with HLAR → ampicillin + ceftriaxone (double beta-lactam) instead of aminoglycoside.
PearlNew heart block on telemetry → think aortic-root abscess → urgent surgery.
PearlEmbolic risk highest first week; vegetation >10 mm higher, >15 mm + mobile highest.
PearlSelected stable left-sided IE (NOT S. aureus) can complete orally — POET and POSITIVE.
PearlCIED infection = complete device AND lead extraction by electrophysiology.
PearlS. gallolyticus (formerly S. bovis) IE → colonoscopy to exclude colorectal neoplasia.

Related cases

Endocarditis

Fever, Urinary Symptoms, and a Heart Murmur

Beyond the obvious: Gram-positive clusters.

Sepsis & Bacteremia

Fulminant Shock

Shock in the Slaughterhouse

Cardiovascular

The 5-Month Mystery

A new murmur and persistent fevers follow heart surgery.

Parasitology

After the Steroid Burst

ICU shock, pulmonary infiltrates, and diarrhea after immunosuppression.