Infective Endocarditis — Management and Prevention

Infective endocarditis (IE) is a life-threatening infection of the endocardial surface of the heart — most often a native or prosthetic heart valve, but sometimes a septal defect or an indwelling intracardiac device — that develops when endothelial injury from turbulent flow, a structural or congenital abnormality, or an indwelling catheter/device allows fibrin and platelets to deposit and bacteria (or, less commonly, fungi) from a bacteremic episode to adhere and form a vegetation.^[1] Left untreated or inadequately treated, the infected vegetation can destroy the valve itself, extend into adjacent cardiac tissue as an abscess, and shower septic emboli to the brain, lungs, spleen, kidneys, or extremities — making IE a genuinely multisystem emergency that needs a coordinated antimicrobial, surgical, and multidisciplinary "endocarditis team" response, not antibiotics alone.^[2]

Presentation ranges from fulminant to indolent

IE does not present as one syndrome — the same infection can appear as a fulminant, rapidly destructive illness (typical of Staphylococcus aureus) or as a subacute, low-grade illness evolving over weeks (typical of viridans streptococci) — so a well-appearing patient does not rule out IE, particularly with a known predisposing risk factor.

Constitutional and cardiac findings

• Fever — the most consistent finding, though it may be low-grade or intermittent in subacute disease.
• Fatigue, malaise, anorexia, weight loss, night sweats, and arthralgia/myalgia.
• A new or changing heart murmur — a new regurgitant murmur is typical; a long-standing, unchanged murmur is far less suggestive.
• Signs of heart failure — dyspnea, orthopnea, pulmonary edema — from acute valvular destruction.
• Rigors, pleuritic chest pain, cough, and hemoptysis, particularly in right-sided IE from septic pulmonary emboli.

Extracardiac (immunologic and embolic) stigmata

• Splinter hemorrhages (nail bed).
• Janeway lesions — painless, erythematous macules, typically on the palms or soles (embolic).
• Osler nodes — painful, tender nodules on the finger or toe pads (immunologic).
• Roth spots — retinal hemorrhages with a pale centre.
• Conjunctival or buccal/oral mucosal petechiae.
• Splenomegaly.
• Clubbing — usually reflects more chronic, longstanding infection.
• Focal neurologic deficits, flank pain/hematuria, or limb ischemia from embolization to the brain, kidney, or extremities.

• Structural or congenital heart disease, including valvulopathy (rheumatic, degenerative, or bicuspid aortic valve) and unrepaired or incompletely repaired congenital heart defects.
• A prosthetic heart valve or other implanted prosthetic cardiac material (annuloplasty ring, transcatheter valve, ventricular assist device).
• A previous episode of infective endocarditis.
• An indwelling intravascular catheter, a cardiac implantable electronic device (pacemaker/ICD), or hemodialysis vascular access.
• Injection drug use.
• Poor dental hygiene or active periodontal/dental infection.
• A recent invasive dental, surgical, or genitourinary/gastrointestinal procedure in a patient with a predisposing cardiac condition.
• Immunosuppression, including HIV infection and long-term immunosuppressive therapy.
• Diabetes mellitus and chronic hemodialysis-dependent kidney disease.

Conditions commonly confused with IE on presentation

History and physical examination

• Time course of illness and predisposing risk factors — recent dental or surgical procedures, dental health, known cardiac disease/malformation, prior cardiac surgery or valve replacement, prior IE, injection drug use, and any recent placement or manipulation of an intravascular device.
• A thorough medication history, including drug allergies. In a patient receiving oral anticoagulation, assess the ongoing need for anticoagulation (including temporarily holding it) if IE is suspected or documented, and note any antibiotic already taken that could suppress blood culture results.
• Physical findings beyond the extracardiac stigmata above: spinal tenderness or focal neurologic deficits (metastatic infection); a new murmur, pulmonary edema, or hypotension (cardiac decompensation).

Laboratory investigations

• Blood cultures before starting antibiotics are essential to identify the pathogen and its susceptibilities. Take at least 3 blood culture sets from separate venipuncture sites, with the first and last samples at least 1 hour apart (or, alternatively, at least 3 sets within a 1-2 hour interval), using an adequate blood volume per bottle to maximize yield. Repeat blood cultures 24-72 hours into therapy to confirm clearance of bacteremia — this also marks the actual start date for counting treatment duration.^[1]
• CBC and differential, electrolytes, glucose, urea, creatinine, liver function tests, ESR and/or CRP, and complement C3/C4.
• Urinalysis — hematuria, proteinuria, pyuria, or red cell casts.
• If blood cultures remain negative, pursue serologic and/or molecular diagnostics for difficult-to-grow pathogens such as Coxiella burnetii and Bartonella spp., and involve infectious diseases and clinical microbiology.

Imaging

• Baseline ECG and chest x-ray.
• Echocardiography in every patient with suspected or documented IE. Transthoracic echocardiography (TTE) is typically performed first, especially with low clinical suspicion. Transesophageal echocardiography (TEE) is more sensitive for an abscess, a small vegetation, extension into tissue surrounding the valve, or assessment of a prosthetic valve, and should be used for high-risk patients (e.g., S. aureus bacteremia) or moderate-to-high clinical suspicion.
• Repeat or follow-up echocardiography to assess response to therapy, disease progression, or a new complication (unexplained worsening heart failure, a new murmur, a new conduction abnormality), or to help decide on surgery.

The Modified Duke Criteria

The Modified Duke Criteria remain the widely accepted clinical standard for classifying suspected IE as definite, possible, or rejected, based on pathologic, clinical, laboratory, and radiologic findings — clinical judgment should still be applied alongside the criteria given how heterogeneous IE presentations can be.^[3]

HACEK refers to Haemophilus spp., Aggregatibacter spp., Cardiobacterium hominis, Eikenella corrodens, and Kingella spp. A proposed 2023 Duke-International Society for Cardiovascular Infectious Diseases (Duke-ISCVID) revision updates the organism list, blood-sampling and imaging criteria, and the treatment of prior IE and cardiac devices; external validation studies since publication have found increased sensitivity but decreased specificity compared with the modified Duke criteria above, so it has not replaced the modified Duke criteria as the adopted clinical standard.^[4] Unlike a simple additive point-sum score, both versions combine pathologic findings with a categorical count of major/minor clinical criteria rather than a single numeric total — a teaching table is provided above, but no live calculator, since a checkbox point-sum cannot safely represent this categorical logic or the pathologic/imaging criteria it also depends on.

• Eradicate the infecting organism and sterilize the vegetation.
• Prevent and manage complications — heart failure, periannular abscess, systemic or septic embolization, and conduction abnormalities.
• Preserve or restore valve function, including appropriately timed surgery when antibiotics alone cannot achieve this.
• Avoid or minimize drug toxicity, particularly nephrotoxicity and ototoxicity from prolonged aminoglycoside, vancomycin, or daptomycin therapy.
• Prevent relapse and reinfection.
• Prevent IE in patients with a cardiac condition genuinely at highest risk of a severe outcome, through targeted antibiotic prophylaxis before qualifying dental procedures.

• Surgical intervention is a core part of therapy, not a last resort — indicated for life-threatening heart failure from valvular damage, persistent or recurrent emboli, a large (over 10 mm) vegetation (especially with prior embolization or on the anterior mitral leaflet), failure of appropriate antimicrobial therapy to control infection, severe valvular failure (abscess, dehiscence, perforation, or rupture), extension into surrounding cardiac tissue, or relapsing infection. Timing is decided jointly with cardiothoracic surgery and infectious diseases as part of a multidisciplinary "endocarditis team"; arrange early transfer to a cardiovascular surgery centre if this capability is not available locally.^[1]
• Remove or exchange any infected intravascular catheter or cardiac implantable electronic device (pacemaker/ICD lead) — source control is essential, since antibiotics alone will not sterilize an infected foreign body.
• For people who inject drugs, involve addiction medicine and harm-reduction services from the outset — ongoing injection drug use increases both relapse and reinfection risk, and a multidisciplinary approach, including consideration of valve-sparing rather than valve-replacing surgery where feasible, improves long-term outcomes.^[7]
• Optimize dental health and arrange dental evaluation, especially before elective valve surgery/prosthetic material placement or in a patient with poor dentition — good oral hygiene and regular dental care meaningfully reduce IE risk in a high-risk patient, independent of antibiotic prophylaxis.
• Educate the patient and family to seek prompt medical attention for recurrent fever, new or worsening shortness of breath, or a new neurologic or embolic symptom during and after treatment.

Pregnancy

IE in pregnancy is uncommon but carries substantial maternal and fetal risk; manage with combined obstetric, cardiology, and infectious diseases input. Beta-lactams (penicillin G, ampicillin, cloxacillin, cefazolin, ceftriaxone) are considered safe throughout pregnancy and remain first-line whenever the organism is susceptible. Vancomycin can be used when indicated, with the same trough/AUC-based monitoring as in a non-pregnant patient. Gentamicin crosses the placenta and carries a recognized risk of fetal ototoxicity — use only when no equally effective alternative exists, for the shortest effective duration, with close monitoring. Rifampin is generally continued when genuinely needed for confirmed prosthetic valve staphylococcal IE, since the maternal benefit of adequate source control outweighs its modest signal of risk; discuss with obstetrics. Doxycycline is avoided in pregnancy (fetal bone/teeth effects) — use a cephalosporin or macrolide alternative for prophylaxis instead. Surgery, when indicated, should not be withheld because of pregnancy — the maternal risk of unrepaired severe valvular disease or uncontrolled infection generally exceeds the surgical risk, though timing and technique are planned jointly with obstetrics.

Breastfeeding

Penicillins, cephalosporins, and vancomycin are compatible with breastfeeding. Gentamicin has minimal oral bioavailability in the infant and is generally considered compatible for a short, defined course. For dental prophylaxis, amoxicillin, cephalexin, azithromycin, and clarithromycin are all compatible with breastfeeding; avoid doxycycline where a compatible alternative exists.

Pediatrics

Pediatric IE is uncommon and is managed with pediatric cardiology and infectious diseases involvement — dosing for organism-directed IV therapy is weight-based and follows dedicated pediatric IE guidance rather than a simple adult-dose conversion; do not extrapolate adult mg doses without pediatric-specific confirmation.^[8] Pediatric dosing for dental antibiotic prophylaxis is well established and included directly in Drug Tables (weight-based, not to exceed the adult dose).

Renal impairment

Adjust vancomycin, aminoglycoside (gentamicin, streptomycin), and daptomycin dosing and intervals for renal function, and monitor levels/AUC closely — these are the agents most likely to cause, or be affected by, acute kidney injury during a prolonged IE course.^[9] Ampicillin plus ceftriaxone (rather than an aminoglycoside-containing regimen) is specifically preferred for enterococcal IE when creatinine clearance is reduced.

Older adults

Older patients are at higher risk of both ototoxicity and nephrotoxicity from aminoglycoside therapy — this is part of why gentamicin has been removed from routine staphylococcal native valve regimens, and why any aminoglycoside-containing regimen in an older adult warrants closer monitoring and, where an equally effective alternative exists, avoidance.

People who inject drugs

Right-sided (typically tricuspid) IE due to S. aureus is the dominant pattern. Address ongoing substance use with addiction medicine and harm-reduction involvement from admission — this materially affects both relapse risk and eligibility for outpatient parenteral therapy. Outpatient parenteral antimicrobial therapy (OPAT) can be used in this population but requires stringent entry criteria and close follow-up given lower acceptance and higher barriers to structured support; a valve-sparing surgical approach is preferred over valve replacement where feasible, given the elevated reinfection risk with continued injection drug use.^[7]

• Repeat blood cultures 24-72 hours into therapy to confirm clearance of bacteremia — this also sets the actual start date for counting treatment duration (from the first negative culture, not from day 1 of antibiotics).
• Vancomycin and aminoglycoside trough/AUC monitoring per current consensus guidance, plus periodic renal function; weekly creatine kinase for daptomycin; audiometric/vestibular assessment for any prolonged (beyond about 2 weeks) or high-dose aminoglycoside course.^[9]
• Periodic CBC and liver function tests — beta-lactam-induced cytopenias/interstitial nephritis, linezolid myelosuppression, and rifampin hepatotoxicity are all monitored this way.
• Follow-up (and, where clinically indicated, repeat) echocardiography to assess response to therapy, detect a new complication (worsening regurgitation, new abscess, new conduction abnormality), and support surgical planning — repeat urgently for a new murmur, new heart failure, a new embolic event, or persistent fever/bacteremia despite appropriate therapy.
• Colonoscopy referral for any patient with Streptococcus gallolyticus (bovis) IE or bacteremia, to investigate for an underlying colorectal malignancy.
• Dental evaluation and ongoing routine dental care — both as part of the initial workup (looking for a dental source) and as long-term secondary prevention.
• Distinguish relapse (same organism, typically within weeks to a few months of completing therapy) from reinfection (a new organism or a new exposure) at any recurrence, since this changes both the antibiotic plan and the surgical/source-control assessment.

1. Persistent fever or bacteremia beyond 5-7 days of appropriate, organism-directed therapy: obtain (or repeat) echocardiography — preferably TEE — to look for an undrained abscess, extension into adjacent tissue, or another undrained metastatic focus of infection, and reassess for an infected device/catheter requiring removal.
2. Confirm the antibiotic choice, dose, and (for vancomycin/aminoglycosides) actual achieved levels are appropriate for the identified organism and its susceptibilities — involve infectious diseases if this has not already happened.
3. New heart block, worsening regurgitation, or new/worsening heart failure at any point: urgent surgical evaluation — do not wait for the antibiotic course to finish.
4. A new embolic event: reassess vegetation size and mobility and the case for earlier surgery, but weigh timing carefully against recent neurologic injury — surgery after a major stroke is typically deferred in consultation with neurology and the endocarditis team unless an urgent indication (heart failure, uncontrolled infection, a very high ongoing embolic risk) outweighs the risk of surgery-associated hemorrhagic transformation.
5. Suspected relapse or reinfection after completing therapy: confirm which one it is (the same organism on a similar timeline suggests relapse; a new organism or a new exposure suggests reinfection), obtain new cultures before any retreatment, and reassess the case for surgery rather than simply repeating the same antibiotic course.
6. A true, well-documented beta-lactam allergy that is limiting first-line options: refer for allergy evaluation and possible desensitization rather than defaulting to a broader-spectrum or less effective alternative for the entire course.

• Starting empiric antibiotics before an adequate set of blood cultures has been drawn — one of the most consequential and avoidable errors in suspected IE, since it can permanently obscure the diagnosis.
• Continuing gentamicin routinely for staphylococcal native valve IE — no longer recommended given its toxicity without a proven added benefit in this specific setting.
• Using rifampin as monotherapy, or adding it before source control/adequate bactericidal partner-drug levels are established — rifampin should always be combined with another active agent to prevent rapid resistance.
• Giving dental antibiotic prophylaxis to a patient who does not have one of the current, narrower high-risk cardiac conditions — a common holdover from older, broader guidance.
• Using clindamycin for dental antibiotic prophylaxis — no longer recommended given its association with Clostridioides difficile infection; use doxycycline (or a macrolide/cephalosporin, as appropriate) instead.
• Missing the prophylaxis dosing window — the dose must be given 30-60 minutes before the procedure; if it was missed beforehand, it may still be given up to 2 hours afterward, but later than that is not effective.
• Forgetting the colonoscopy referral for S. gallolyticus (bovis) IE.
• Treating a static, long-standing, unchanged heart murmur as a new finding suggestive of IE.
• Deciding on IV-to-oral stepdown without infectious diseases involvement — this is a selected-patient, specialist-directed decision, not a routine step.
• Counting treatment duration from the first dose of antibiotics rather than from the first negative blood culture.

How to use these tables: Doses are adult doses and require patient-specific confirmation (renal function, weight, allergy history). Begin counting duration from the date of the first negative blood culture. Pediatric IE treatment dosing is weight-based and specialist-directed (pediatric cardiology/infectious diseases) unless a specific pediatric dose is shown. Select any drug name to open its complete Pharmasist Drug Database page.

Organism-directed therapy — Staphylococci

Staphylococci (MSSA, MRSA, and coagulase-negative staphylococci) account for a large share of both native and prosthetic valve IE.

Organism-directed therapy — Viridans group streptococci and Streptococcus gallolyticus (bovis)

Selection depends on penicillin MIC susceptibility tier.

Organism-directed therapy — Enterococci

Enterococcal IE generally requires 4-6 weeks of combined beta-lactam and aminoglycoside (or alternative synergy) therapy; choice depends on penicillin, aminoglycoside, and vancomycin susceptibility.

Organism-directed therapy — Gram-negative bacteria (HACEK and non-HACEK)

HACEK organisms (Haemophilus spp., Aggregatibacter spp., Cardiobacterium hominis, Eikenella corrodens, Kingella spp.) are fastidious, slow-growing Gram-negative bacilli.

Culture-negative IE

No single default empiric regimen — base the choice on a thorough review of host factors, comorbidities, injection drug use, animal/insect exposure, indwelling devices, and prior procedures, in consultation with infectious diseases and clinical microbiology.

Consider serologic and molecular diagnostics for Coxiella burnetii, Bartonella spp., Tropheryma whipplei, or Chlamydia spp. when culture-negative IE is unexplained.^[1] Coxiella burnetii (Q fever) endocarditis specifically is treated with a prolonged combination of doxycycline plus hydroxychloroquine under infectious diseases direction, given for a duration measured in months to years rather than weeks — this is a distinctly different course than the standard bacterial IE regimens above and must be individualized by a specialist.

IV Antibiotic Reference — Aminoglycosides

IV Antibiotic Reference — Cephalosporins

IV Antibiotic Reference — Glycopeptides

IV Antibiotic Reference — Lipopeptides

IV Antibiotic Reference — Oxazolidinones

IV Antibiotic Reference — Penicillins

IV Antibiotic Reference — Rifamycins

IV Antibiotic Reference — Carbapenems

For resistant HACEK or other resistant Gram-negative organisms only, under infectious diseases direction.

IV/Oral Antibiotic Reference — Fluoroquinolones

Beta-lactam-allergic HACEK alternative; also used in specialist-selected oral stepdown combinations.

IV/Oral Antibiotic Reference — Tetracyclines

Dental/Procedural Antibiotic Prophylaxis

For the specific high-risk cardiac conditions and qualifying dental procedures defined in Choose Initial Treatment only. Administer 30-60 minutes before the procedure (up to 2 hours after if inadvertently missed beforehand). Clindamycin is no longer recommended for this indication.

Unable to take oral medication

Avoid IM injection in an anticoagulated patient.

Allergic to penicillin or ampicillin, able to take oral medication

Allergic to penicillin or ampicillin, unable to take oral medication