Endocarditis

Native + prosthetic valve IE · complete reference · Modified Duke Criteria · all regimens + doses + durations · Full Card

Symptoms / Associated Sx

• Fever (90% — low-grade in subacute; high-grade in S. aureus); new or changed regurgitant murmur (85% — best single physical exam finding; absence does NOT exclude IE in early infection or right-sided disease); constitutional symptoms (malaise, fatigue, night sweats, anorexia, weight loss — subacute viridans strep presents over weeks to months)

• Embolic phenomena (30–40%): ischemic stroke or TIA (most clinically significant); splenic infarct (left flank pain + left shoulder pain); renal infarct (hematuria + flank pain); septic pulmonary emboli (right-sided IE — IVDU: cough, pleuritic CP, multiple cavitary lung nodules on CXR/CT)

• Peripheral stigmata (pathognomonic when present but low sensitivity): Osler nodes (painful, tender, erythematous nodules on fingertips and toes — immune complex vasculitis); Janeway lesions (painless, flat, hemorrhagic macular lesions on palms and soles — septic emboli); Roth spots (retinal hemorrhages with pale center — fundoscopy; immune complex vasculitis); splinter hemorrhages (linear dark streaks under nails — non-specific; also trauma)

• Signs of valvular destruction: acute severe AR (Austin Flint murmur; wide pulse pressure; water-hammer pulse; APE); acute severe MR (holosystolic murmur; APE; flash pulmonary edema); new HF signs = surgical emergency — emergent surgery ↓mortality

• Right-sided IE (IVDU, intracardiac device): tricuspid valve most common; septic pulmonary emboli (cough, hemoptysis, cavitary nodules); fever; bacteremia; murmur often absent or soft; less common: acute pulmonary HTN; paradoxical emboli via PFO

• CIED (cardiac implantable electronic device) infection: pocket infection (erythema, warmth, swelling, erosion over generator); lead vegetation (fever + bacteremia without obvious source → TEE for lead vegetation); lead endocarditis = device extraction required

Neg

• Pt denies fever + bacteremia + echo vegetation meeting Duke criteria — argues against definitive IE (bacteremia alone without echo findings = uncomplicated bacteremia requiring standard treatment course, NOT prolonged IE therapy; TEE mandatory to exclude occult vegetation before labeling as "simple bacteremia" in S. aureus bacteremia)

• Pt denies sterile blood cultures with fever + murmur + systemic lupus features (rash, arthritis, serositis, positive ANA/anti-dsDNA) — argues against infectious IE; Libman-Sacks endocarditis (sterile valve thickening in SLE) — no antibiotics; treat underlying SLE; always draw cultures before attributing fever + murmur to non-infectious cause

• Pt denies fever + positive blood cultures without echo vegetation in hypercoagulable state/malignancy — argues against infectious IE; marantic (non-bacterial thrombotic) endocarditis — sterile thrombus on valve leaflets; no fever; culture-negative; treat hypercoagulable state/malignancy; anticoagulation not antibiotics

• Pt denies recent streptococcal pharyngitis + migratory polyarthritis + carditis + Sydenham chorea + elevated ASO titer in a child — argues against acute rheumatic fever (Jones criteria: 2 major or 1 major + 2 minor; mitral regurgitation from valvulitis; benzathine penicillin + anti-inflammatory; secondary prophylaxis)

Social History (SHx)

• IVDU (type, frequency, injection sites, shared equipment — S. aureus dominant; right-sided IE; ↑mortality; harm reduction counseling; addiction medicine consult); prior IE (10× recurrence risk — same valve at high risk); prior cardiac surgery or prosthetic valve (type: mechanical vs bioprosthetic; date; IE changes antibiotic regimen + surgical threshold); intracardiac device (CIED: type, implant date, prior pocket infections)

• Recent dental procedures (oral streptococci portal), GI procedures (colonoscopy — Enterococcus, S. bovis), GU procedures (E. coli, Enterococcus), line infections (CoNS, S. aureus from CVC); immunosuppression (solid organ transplant, HIV [CD4 count], chemotherapy — fungal IE risk); structural CHD (bicuspid AoV, MVP, VSD — endothelialized jets create vegetations at low-pressure site)

• Travel history (Q fever/Coxiella in endemic areas — France, UK, Australia; serology required as blood cultures never positive)

Main Etiology

• S. aureus (MSSA/MRSA) ~30–40%: most aggressive and most common; highest mortality (20–30%); ↑perivalvular abscess + valve destruction; IVDU + healthcare-associated (CVC, hemodialysis); bacteremia must be assumed IE until proven otherwise — TEE for ALL S. aureus bacteremia

• Viridans group streptococci ~20–30%: subacute course; oral flora; dental procedures; mitral valve most common; highly susceptible to PCN; excellent prognosis with appropriate therapy; strep gallolyticus/bovis → colonoscopy mandatory (↑colorectal cancer association)

• Enterococcus spp. ~10%: GI/GU portal; E. faecalis most common; intrinsically resistant to many antibiotics; high-level aminoglycoside resistance (HLAR) common → ampicillin + ceftriaxone (Rocephin) preferred regimen avoiding nephrotoxic aminoglycoside; VRE = linezolid (Zyvox) or daptomycin (Cubicin)

• CoNS (S. epidermidis): primarily PVE (biofilm on prosthetic material); rare in native valve IE; methicillin resistance common

• HACEK group: culture-negative at 5 days (slow-growing); request prolonged incubation; ceftriaxone (Rocephin) 2 g IV daily ×4 weeks (native) or 6 weeks (prosthetic)

• Fungi (Candida/Aspergillus): IVDU, TPN, immunocompromised, prolonged broad-spectrum antibiotics; large friable vegetations; ↑emboli; near-universal surgical indication; Candida: micafungin (Mycamine) 150 mg IV daily or liposomal amphotericin B (AmBisome) 3–5 mg/kg IV daily followed by fluconazole (Diflucan) suppression

• Culture-negative IE (~10–15%): prior antibiotics (most common reason); HACEK (prolonged incubation); Coxiella burnetii/Q fever (serology — IgG Phase I >1:800); Bartonella quintana/henselae (homeless/louse-exposed/cat-exposed; serology + PCR); Tropheryma whipplei (Whipple disease — PCR); Brucella (exposure to livestock/unpasteurized dairy; serology)

RF

• High risk: IVDU (strongest RF for S. aureus IE), prior IE (10× recurrence), prosthetic valve or valvular repair, intracardiac device (pacemaker/ICD leads), complex CHD (especially cyanotic), prior IE, dialysis with CVC (S. aureus bacteremia)

• Moderate risk: bicuspid aortic valve, MVP with MR, rheumatic heart disease, poor dentition, recent invasive procedures (dental, GI, GU), immunosuppression, chronic indwelling IV catheter

Data

• Blood cultures ×3 sets from 3 separate venipuncture sites 30 min apart BEFORE antibiotics (most important diagnostic and therapeutic step; 2+ positive cultures from separate sites OR continuously positive cultures = major Duke criterion; draw from arm veins not CVCs when possible; 10 mL per bottle; aerobic + anaerobic; request prolonged incubation if HACEK suspected; sensitivity: 3 sets = 96–99% yield; yield drops to 50–75% if antibiotics given first)

• Modified Duke Criteria (Major criteria: [1] positive blood cultures: typical IE organism in ≥2 separate cultures OR continuously positive cultures >12h apart OR single positive Coxiella burnetii culture; [2] positive echo: vegetation OR abscess OR new partial valve dehiscence OR new regurgitation; Minor criteria: [1] predisposing condition; [2] fever >38°C; [3] vascular phenomena — septic arterial emboli, pulmonary infarcts, Janeway lesions, conjunctival hemorrhage; [4] immunologic phenomena — GN, Osler nodes, Roth spots, positive rheumatoid factor; [5] microbiologic — positive culture not meeting major criterion; Definite IE = 2 major OR 1 major + 3 minor OR 5 minor; Possible IE = 1 major + 1 minor OR 3 minor; Rejected = firm alternative diagnosis OR fever <4 days on antibiotics OR no pathologic evidence)

• TTE (transthoracic echo) (sensitivity 65–75% for native valve; 30–40% for prosthetic valve — acoustic shadowing; perform first for image quality assessment; identifies: vegetation [mobile echogenic mass on valve], regurgitant lesion severity, valve perforation, abscess [discrete wall thickening adjacent to aortic root], periannular fistula)

• TEE (transesophageal echo) — mandatory if: TTE negative but clinical suspicion high; prosthetic valve; intracardiac device; prior TEE negative but bacteremia persists; surgical planning (sensitivity 90–95% for native valve IE; 80–90% for PVE; superior visualization of: posterior mitral valve, perivalvular abscesses, annular fistulae, leaflet perforation; always perform TEE before cardiac surgery for IE)

• ECG serial — daily (PR interval measurement daily — new PR prolongation or first-degree AV block = aortic root abscess extending to AV node = surgical emergency; new left or right bundle branch block = similar significance; Mobitz II or complete AV block = immediate surgical consultation)

• CBC (leukocytosis [WBC >12K] in acute/S. aureus IE; normal or mild elevation in subacute; anemia of chronic inflammation — normocytic; thrombocytopenia in severe sepsis or DIC from prolonged infection)

• BMP (Cr — immune complex GN; antibiotics dose adjustment; AKI from septic emboli; vancomycin nephrotoxicity monitoring; Na+ — prognosis; K+ — arrhythmia risk)

• ESR + CRP (elevated in active IE; CRP preferred — faster response; serial CRP monitoring: failing to ↓50% by Week 2 = persistent infection/abscess/inadequate therapy → repeat TEE + expand workup)

• UA with microscopy (hematuria + RBC casts = immune complex glomerulonephritis from circulating immune complexes; proteinuria; pyuria if renal abscess or UTI as portal; always do urinalysis in suspected IE)

• CT chest/abdomen/pelvis with contrast (septic pulmonary emboli in right-sided IE: multiple peripheral wedge-shaped consolidations or cavitary nodules; splenic infarct: wedge-shaped hypodensity; renal infarct; vertebral osteomyelitis/psoas abscess; mycotic aneurysm — CT angiography if neurologic symptoms; required before surgery if abdominal/pelvic emboli suspected)

• MRI brain with DWI (embolic stroke: multiple small scattered infarcts in different vascular territories = embolic pattern highly specific; microhemorrhages; hemorrhagic transformation; baseline before surgery; may affect surgical timing if large hemorrhagic infarct)

• PET-CT with FDG (for PVE when TTE/TEE equivocal) (abnormal peri-prosthetic FDG uptake = major Duke criterion per 2023 ESC guidelines; distinguishes infection from sterile post-surgical inflammation by intensity and pattern; identifies metastatic infection foci)

• Vancomycin AUC/MIC monitoring (2020 ASHP/IDSA/SIDP consensus: AUC-guided dosing replaces trough-only monitoring; target AUC/MIC 400–600 mg·h/L for MRSA; initial dose based on weight; pharmacist-guided dosing recommended; check AUC at steady state [after 3–4 doses]; avoid AUC >650 — nephrotoxicity; avoid AUC <400 — treatment failure)

DDx

Bacteremia without IE (positive cultures without echo vegetation or structural criteria — TEE mandatory in S. aureus bacteremia to exclude; 2–4 week course usually sufficient without IE) · Libman-Sacks/SLE endocarditis (sterile vegetation; ANA + anti-dsDNA positive; culture-negative; treat SLE — no antibiotics) · Marantic/NBTE endocarditis (hypercoagulable/malignancy; sterile thrombus; no fever; culture-negative; treat hypercoagulable state) · Acute rheumatic fever (strep pharyngitis + Jones criteria + ↑ASO titer — children; benzathine penicillin + ASA/naproxen) · CIED infection without lead vegetation (pocket erythema/erosion — device extraction; TEE to exclude lead endocarditis) · Post-pericardiotomy syndrome (fever + pericardial effusion after cardiac surgery — ESR↑; sterile; aspirin [Bayer]/colchicine [Colcrys]; no antibiotics)

Home Meds

• Hold: immunosuppressants (↑infection risk; ↓ability to clear bacteremia; discuss with rheumatology/transplant team); NSAIDs (ibuprofen [Advil]/naproxen [Aleve] — mask fever + ↑renal toxicity with aminoglycoside); anticoagulation (warfarin [Coumadin]/DOACs) — ↑hemorrhagic transformation of embolic stroke; hold ×2 weeks after embolic neurologic event; restart decision with neurology + ID

• Anticoagulation in native valve IE: generally avoid (no proven embolic prevention benefit; ↑hemorrhagic transformation risk of cerebral septic emboli); mechanical valve patients requiring anticoag → discuss with ID, neurology, and cards — risk-benefit individualized; UFH preferred over warfarin (Coumadin) if anticoag mandatory (more rapid reversal)

• Continue: heart failure medications (BB + ACEi if hemodynamically tolerated — not in acute decompensation); antiarrhythmics as appropriate

Plan — Complete

• Immediate Steps (Day 1):

  • Blood cultures ×3 sets from 3 separate venipuncture sites 30 min apart BEFORE antibiotics — this is the most important first action

  • ID consult + cardiac surgery consult — both on Day 1 of suspected IE (not Day 3 or "when cultures finalize")

  • TTE first → TEE if TTE negative + high clinical suspicion or prosthetic valve or CIED

  • Apply Modified Duke Criteria; calculate score from available data

  • ECG — PR interval baseline; repeat daily

• Empiric antibiotic therapy (after cultures drawn):

  • Community-acquired native valve, no IVDU: vancomycin (Vancocin) 25–30 mg/kg IV q8–12h (target AUC/MIC 400–600); transition at 48–72h based on culture results

  • Healthcare-associated or IVDU or gram-negative concern: vancomycin (Vancocin) + cefepime (Maxipime) 2 g IV q8h or piperacillin/tazobactam (Zosyn) 4.5 g IV q6h

  • Do NOT start empiric antibiotics before ×3 blood cultures unless hemodynamically unstable (septic shock → cultures stat then empiric immediately)

• Targeted therapy — native valve (by organism):

  • MSSA: nafcillin (Nallpen) 2 g IV q4h ×4–6 weeks OR oxacillin (Bactocill) 2 g IV q4h ×4–6 weeks (preferred over vancomycin for MSSA — IDSA 2015: nafcillin/oxacillin superior to vancomycin for MSSA IE — lower relapse, ↓mortality); penicillin allergy (non-anaphylactic): cefazolin (Ancef) 2 g IV q8h; anaphylactic PCN allergy: vancomycin (Vancocin) AUC 400–600

  • MRSA: vancomycin (Vancocin) 25–30 mg/kg IV q8–12h (AUC/MIC 400–600) ×6 weeks; daptomycin (Cubicin) 10 mg/kg IV daily as alternative (AVOID in pulmonary IE — inactivated by surfactant; ensure pre-daptomycin CK level)

  • Viridans streptococci (MIC ≤0.12 mcg/mL — highly susceptible): penicillin G 12–18 million units IV daily as continuous infusion ×4 weeks OR ceftriaxone (Rocephin) 2 g IV daily ×4 weeks; add gentamicin (Garamycin) 3 mg/kg/day IV ×2 weeks for synergy (avoid if CrCl <50 or age >65); viridans strep MIC 0.12–0.5: ceftriaxone (Rocephin) ×4 weeks + gentamicin (Garamycin) ×2 weeks; MIC >0.5 (resistant): treat as enterococcal

  • Enterococcus (susceptible — preferred regimen): ampicillin (Ampicin) 2 g IV q4h + ceftriaxone (Rocephin) 2 g IV q12h ×6 weeks (IDSA 2015 preferred — avoids nephrotoxic aminoglycoside; effective even with HLAR; superior in HLAR strains); alternative: ampicillin + gentamicin (Garamycin) 1 mg/kg IV q8h ×4–6 weeks (only if HLAR excluded; trough <1 mcg/mL; CrCl weekly); VRE: linezolid (Zyvox) 600 mg IV/PO q12h or daptomycin (Cubicin) 10 mg/kg IV daily

  • HACEK: ceftriaxone (Rocephin) 2 g IV daily ×4 weeks (native) or 6 weeks (prosthetic); ampicillin-sulbactam (Unasyn) 3 g IV q6h if susceptible

  • Fungal (Candida): micafungin (Mycamine) 150 mg IV daily OR liposomal amphotericin B (AmBisome) 3–5 mg/kg IV daily; suppress with fluconazole (Diflucan) 400 mg PO daily indefinitely if no surgery; cardiac surgery usually required for fungal IE

  • Coxiella burnetii/Q fever IE: doxycycline (Vibramycin) 100 mg PO BID + hydroxychloroquine (Plaquenil) 200 mg PO TID ×18 months (minimum) — IgG Phase I titer monitoring q6 months

  • Bartonella IE: ceftriaxone (Rocephin) 2 g IV daily ×6 weeks + gentamicin (Garamycin) ×2 weeks; suppress with doxycycline (Vibramycin) 100 mg PO BID ×3 months

• Targeted therapy — prosthetic valve (by organism):

  • MSSA PVE: nafcillin (Nallpen) 2 g IV q4h + rifampin (Rifadin) 300 mg PO q8h ×≥6 weeks + gentamicin (Garamycin) 1 mg/kg IV q8h ×2 weeks (add rifampin only after bacteremia clears ×3–5 days)

  • MRSA/CoNS PVE: vancomycin (Vancocin) + rifampin (Rifadin) 300 mg PO/IV q8h ×≥6 weeks + gentamicin (Garamycin) 1 mg/kg IV q8h ×2 weeks; rifampin adds biofilm penetration on prosthetic material — key difference from native valve regimen

  • Viridans strep/Enterococcus PVE: same agents as native valve but extend to ≥6 weeks

• Surgical indications (2023 ACC/AHA guidelines):

  • Emergency surgery (within 24h): hemodynamic instability (CS from valve dysfunction); tamponade; vascular catastrophe from very large mobile vegetation

  • Urgent surgery (within days): heart failure not responding to medical therapy; perivalvular abscess or fistula (abscess = echogenic zone of thickened tissue adjacent to aortic root with heterogeneous density; fistula = color Doppler flow between cardiac chambers); new high-degree AV block (PR prolongation → Mobitz II → complete block = abscess extension to conduction system); vegetation >10 mm highly mobile on mitral valve + prior embolic event

  • Elective surgery (during hospitalization after antibiotics): prosthetic valve early IE with perivalvular extension; uncontrolled infection despite ≥5–7 days adequate antibiotics; high-risk organisms (fungal, MRSA, gram-negative non-HACEK) with PVE

  • Relative indication: vegetation >10 mm on mitral anterior leaflet; recurrent emboli despite antibiotics

• CIED (pacemaker/ICD) infection management: complete device extraction (generator + all leads) is standard of care for CIED infection with lead endocarditis or pocket infection extending to leads (HRS 2019 guidelines); antibiotics alone = 50% failure rate; transvenous lead extraction by experienced operator; replace device at new site once bacteremia cleared; temporary pacing as bridge if device-dependent

• Neurologic complications: embolic stroke in IE — withhold anticoagulation (↑hemorrhagic transformation); MRI DWI at presentation (baseline); neurology consult; delay surgery if large hemorrhagic infarct (>3 cm) — surgical timing with neurology + neurosurgery (generally >4 weeks post-hemorrhagic stroke if possible; may need to operate earlier if IE indications are urgent); mycotic aneurysm → CT angiography; rupture → neurosurgery

• PT/OT eval and treat — bed rest during bacteremic phase (embolic risk with activity); mobilize once afebrile ×48h + cultures clearing; stroke rehabilitation if neurologic deficit; addiction medicine consult in IVDU IE; fall risk assessment (emboli risk)

• Trend daily: temperature curve (goal defervescence by Day 5–7 on appropriate therapy; persistent fever >7 days = abscess, metastatic infection, drug fever, inadequate therapy — repeat TEE + CT); blood cultures q48h until 2 consecutive negative sets (document clearance date — this is Day 0 for counting antibiotic duration); BMP (Cr daily — vancomycin + aminoglycoside nephrotoxicity; AKI from IE itself); vancomycin AUC/MIC (target 400–600); aminoglycoside trough (target <1 mcg/mL for gentamicin [Garamycin]); ESR + CRP weekly (monitor response — failing to ↓50% by Week 2 = concern); ECG daily PR interval; CBC weekly (anemia + leukocytosis trend); LFTs weekly (hepatotoxicity from rifampin [Rifadin])

• Escalation triggers: new PR prolongation or AV block → cardiac surgery immediately (perivalvular abscess with conduction involvement — surgical emergency; do not wait for cultures or imaging confirmation) · new acute HF from valvular destruction (new severe MR or AR) → cardiac surgery urgently (APE + cardiogenic shock from acute severe regurgitation = most common fatal complication of IE) · bacteremia not clearing by Day 7 → TEE + CT abdomen/pelvis for occult abscess/metastatic infection + ID re-consultation · septic cerebral emboli + hemorrhagic conversion → neurology + neurosurgery + hold anticoag ×2–4 weeks · S. aureus bacteremia not clearing → TTE → TEE → consider valve surgery even without established vegetation (persistent S. aureus bacteremia >72h = very high suspicion for IE) · Candida/Aspergillus IE → cardiac surgery consultation urgently + antifungal escalation · renal failure from aminoglycoside → hold gentamicin (Garamycin) + ID consult (switch regimen if HLAR not present) · vancomycin nephrotoxicity (AUC >650 + Cr ↑) → ↓vancomycin dose; consider daptomycin (Cubicin) switch with ID

• Discharge — OPAT (outpatient parenteral antibiotic therapy): PICC line placed; ID to arrange home infusion with weekly nurse visits; total antibiotic duration counted from FIRST NEGATIVE blood culture date (not from diagnosis or admission date); dental evaluation + treatment before OPAT complete (correct portal of entry); echocardiography at 1 month post-treatment completion (check for resolution of vegetation and regurgitation); colonoscopy referral if S. bovis/S. gallolyticus IE (↑colorectal cancer — colonoscopy in all cases); cardiology + ID f/u within 1–2 weeks; patient education: warning signs of relapse (fever, new murmur, embolic events, malaise) → ED immediately; dental prophylaxis for high-risk procedures: amoxicillin (Amoxil) 2 g PO 30–60 min before dental/surgical procedures if prior IE, prosthetic valve, or complex CHD (AHA 2021 guidelines); addiction medicine + harm reduction counseling in IVDU IE

⚠ Red Flags

• S. aureus bacteremia without TEE — S. aureus bacteremia has IE in 20–30% of cases even with no obvious cardiac history; TEE is mandatory for ALL S. aureus bacteremia (not optional); 2–4 week course for "uncomplicated" bacteremia is only appropriate after TEE excludes IE and metastatic seeding

• New PR prolongation or AV block on serial ECG → perivalvular abscess extending to conduction system → cardiac surgery emergency; do not wait for TEE confirmation if Mobitz II or complete AV block develops; call cardiac surgery now

• Acute new severe AR or MR from valve destruction → APE + cardiogenic shock → emergency surgery; most common fatal complication of IE; medical management of acute severe regurgitation from IE has very high mortality; surgical valve replacement is the definitive treatment

• Starting antibiotics before blood cultures → diagnostic yield ↓from 96% to 50–75%; even 30 minutes of culture drawing before first dose dramatically improves yield; always draw 3 sets FIRST unless hemodynamic collapse demands immediate empiric therapy

• Adding rifampin (Rifadin) to vancomycin in MRSA PVE before bacteremia clears → rifampin-resistant mutants emerge rapidly in the presence of active bacteremia; wait until ×3–5 days of blood culture negativity before adding rifampin (Rifadin) in PVE

• Treating MSSA IE with vancomycin when nafcillin or oxacillin is available → IDSA 2015 guidelines: nafcillin/oxacillin consistently superior to vancomycin for MSSA IE (↓relapse, ↓treatment failure, ↓mortality); always de-escalate to antistaphylococcal penicillin when MSSA confirmed

• Incomplete CIED extraction in CIED infection with lead vegetation → antibiotics alone have 50% failure rate; complete device extraction including all leads is standard of care per HRS 2019; partial extraction (generator only) = treatment failure

Senior IM Resident Pearls

• Modified Duke Criteria — know all inputs: 2 major criteria = definite IE; 1 major + 3 minor = definite; 5 minor = definite; Major: (1) positive blood cultures — typical organism ×2+ separate cultures; (2) positive echo — vegetation OR abscess OR new partial dehiscence; Minor: predisposing condition + fever + vascular phenomena + immunologic + microbiologic not meeting major; Possible = 1 major + 1 minor OR 3 minor; calculate and document at admission; drives diagnostic and treatment decisions

• S. aureus bacteremia = IE until proven otherwise: IE in 20–30% of all S. aureus bacteremia; TEE mandatory in ALL S. aureus bacteremia (not optional; TTE insufficient sensitivity); "uncomplicated" S. aureus bacteremia criteria: TTE/TEE negative, no CIED, no prosthetic valve, defervescence ×72h on antibiotics, no metastatic foci, IDU negative → 14-day course; any criterion violated → 6-week course; always call ID for all S. aureus bacteremia

• Nafcillin/oxacillin vs vancomycin in MSSA — always de-escalate: IDSA 2015: beta-lactam (nafcillin [Nallpen]/oxacillin [Bactocill]) is superior to vancomycin for MSSA IE — ↓relapse, ↓mortality, ↓treatment failure; vancomycin is inferior due to poor S. aureus bactericidal activity; always de-escalate from empiric vancomycin to nafcillin/oxacillin when MSSA confirmed; cefazolin (Ancef) acceptable for non-anaphylactic PCN allergy

• Ampicillin + ceftriaxone (Rocephin) for Enterococcal IE — preferred over aminoglycoside: IDSA 2015: ampicillin + ceftriaxone → comparable efficacy to ampicillin + gentamicin with significantly less nephrotoxicity; effective regardless of high-level aminoglycoside resistance (HLAR); preferred in patients with CrCl <50, age >65, or HLAR confirmed; avoids aminoglycoside-mediated renal failure in a typically ill population

• Serial ECG and PR monitoring — the conduction system alarm for abscess: new PR prolongation (even 20 ms increase) = perivalvular abscess extending toward AV node; complete AV block = surgical emergency; always compare ECG to prior strip; this finding mandates immediate cardiac surgery consultation; missing it = preventable death from abscess rupture or heart block

• Antibiotic duration counted from FIRST NEGATIVE blood culture: duration starts from first negative blood culture, not from diagnosis or admission; document this date precisely in the chart; late counting error = inadequate treatment duration; for MSSA native valve IE = 4–6 weeks from first negative culture; MRSA = 6 weeks; enterococcal = 6 weeks; streptococcal = 4 weeks

• Streptococcus bovis/gallolyticus IE — colonoscopy mandatory: S. gallolyticus IE has 25–80% association with colorectal neoplasm (adenoma or carcinoma); colonoscopy is mandatory in all S. gallolyticus/bovis IE regardless of GI symptoms; document in discharge plan; repeat at 3 years if initial colonoscopy negative

• Common mistake — culture-negative IE management: IE with negative cultures → do NOT stop antibiotic search; common causes: prior antibiotics (most common), HACEK (request prolonged incubation ×2 weeks), Coxiella/Q fever (serology: IgG Phase I >1:800), Bartonella (serology + PCR), Brucella (livestock/dairy exposure + serology); serologies take time — order them at admission if culture-negative IE suspected; doxycycline (Vibramycin) empirically for culture-negative IE with epidemiologic risk factors while awaiting serology