Empiric antimicrobial therapy
›Principles
›Cultures before antibiotics when feasible
›Three sets preferred
›Empiric coverage targets
›Staphylococcus aureus including MRSA when risk
›Viridans streptococci and Streptococcus gallolyticus
›Enterococcus species
›Gram-negative coverage in acute severe or healthcare-associated settings
›Time-to-antibiotics
›If shock, initiate immediately after cultures (ACEP Level B)
›Native valve empiric regimens
›Subacute presentation without healthcare-associated risk
›Regimen bundle
›Vancomycin IV
›Loading 25-30 mg/kg actual body weight once if severe infection
›Maintenance 15-20 mg/kg IV every 8-12 hours
›AUC target 400-600 mg·h/L when feasible
›If creatinine clearance reduced, extend dosing interval
›Ceftriaxone IV
›2 g IV every 24 hours
›Acute presentation or healthcare-associated risk
›Regimen bundle
›Vancomycin IV
›Loading 25-30 mg/kg once if unstable
›Maintenance 15-20 mg/kg IV every 8-12 hours with renal adjustment
›Cefepime IV
›2 g IV every 8 hours
›If creatinine clearance reduced, dose adjust per renal function
›Prosthetic valve empiric regimens
›Early prosthetic infection or healthcare-associated
›Regimen bundle
›Vancomycin IV
›Loading 25-30 mg/kg once if unstable
›Maintenance 15-20 mg/kg IV every 8-12 hours with renal adjustment
›Cefepime IV
›2 g IV every 8 hours with renal adjustment
›Gentamicin IV for synergy
›1 mg/kg IV every 8 hours
›If renal dysfunction, extend interval
›Trough target <1 mg/L
›Rifampin PO or IV
›300 mg every 8 hours
›Start after bacteremia controlled in staphylococcal PVE when feasible (Class IIa)
›Late prosthetic infection without healthcare-associated features
›Regimen bundle
›Vancomycin IV
›Dosing per weight and renal function
›Ceftriaxone IV
›2 g IV every 24 hours
Targeted antimicrobial therapy after organism identification
›Staphylococcus aureus
›MSSA native valve
›Nafcillin or oxacillin IV
›2 g IV every 4 hours
›Cefazolin IV alternative
›2 g IV every 8 hours
›Duration
›Minimum 6 weeks from first negative culture (Class I)
›MRSA native valve
›Vancomycin IV
›AUC target 400-600 mg·h/L
›Daptomycin IV alternative
›8-10 mg/kg IV every 24 hours
›Duration
›Minimum 6 weeks (Class I)
›Prosthetic valve staphylococcal infection
›Vancomycin IV or antistaphylococcal beta-lactam for MSSA
›Vancomycin AUC 400-600 mg·h/L for MRSA
›Nafcillin or oxacillin 2 g IV every 4 hours for MSSA
›Rifampin PO or IV
›300 mg every 8 hours
›Gentamicin IV synergy
›1 mg/kg IV every 8 hours
›Typical course 2 weeks for synergy component (Class IIa)
›Duration
›Minimum 6 weeks total therapy (Class I)
›Viridans streptococci and Streptococcus gallolyticus
›Penicillin susceptible
›Penicillin G IV
›12-18 million units per 24 hours continuous infusion or divided every 4-6 hours
›Ceftriaxone IV
›2 g IV every 24 hours
›Gentamicin IV synergy optional in selected short-course protocols
›3 mg/kg IV every 24 hours
›Avoid in renal dysfunction (Class IIb)
›Duration
›Typically 4 weeks native valve (Class I)
›Typically 6 weeks prosthetic valve (Class I)
›Enterococcus faecalis
›Preferred beta-lactam double therapy
›Ampicillin IV
›2 g IV every 4 hours
›Ceftriaxone IV
›2 g IV every 12 hours
›Duration
›6 weeks (Class I)
›Aminoglycoside-based synergy alternative
›Ampicillin IV
›2 g IV every 4 hours
›Gentamicin IV
›1 mg/kg IV every 8 hours with trough target <1 mg/L
›Nephrotoxicity risk
›Prefer double beta-lactam in CKD (Class IIa)
›HACEK organisms
›Ceftriaxone IV
›2 g IV every 24 hours
›Duration
›4 weeks native valve
›6 weeks prosthetic valve
›Fungal endocarditis
›Candida species therapy set
›Liposomal amphotericin B IV
›3-5 mg/kg IV every 24 hours
›Flucytosine PO adjunct
›25 mg/kg PO every 6 hours with level monitoring
›Early surgical evaluation
›High relapse risk without surgery (Class I)
›Aspergillus therapy set
›Voriconazole IV or PO
›6 mg/kg every 12 hours for 2 doses
›Then 4 mg/kg every 12 hours
›Early surgical evaluation
›Class I in invasive disease pattern
Supportive and complication-directed care
›Heart failure and pulmonary edema
›Oxygen and ventilation support
›If severe, noninvasive ventilation or intubation
›Diuretics when volume overloaded
›Furosemide IV dosing per prior exposure and renal function
›Afterload reduction when appropriate
›If hypertensive pulmonary edema without shock
›Surgical consult urgency
›Acute severe regurgitation with pulmonary edema (Class I)
›Neurologic complications
›Ischemic stroke pathway
›Avoid thrombolysis when IE suspected (Class III harm)
›Mechanical thrombectomy consideration per stroke criteria with multidisciplinary discussion (Class IIb)
›Intracranial hemorrhage pathway
›Neurosurgery consult
›Anticoagulation reversal when indicated
›Mycotic aneurysm concern
›Vascular or neurosurgery consultation
›If intracranial aneurysm on imaging
›Antiplatelet and anticoagulation considerations
›New initiation not routine solely for embolic prevention (Class III no benefit)
›Prosthetic valve anticoagulation individualized
›If CNS hemorrhage, urgent multidisciplinary reassessment
Surgical indications and timing
›Indications for early surgery
›Heart failure from valve dysfunction
›Severe acute regurgitation (Class I)
›Uncontrolled infection
›Perivalvular abscess or fistula (Class I)
›Persistent bacteremia beyond 48-72 hours on therapy (Class I)
›Difficult-to-treat organisms
›Fungal IE (Class I)
›Highly resistant bacteria (Class I)
›Embolic risk reduction
›Vegetation >10 mm with embolic event (Class IIa)
›Vegetation >15 mm even without embolism (Class IIb)
›Timing modifiers
›Recent intracranial hemorrhage
›Delay surgery when feasible with neurosurgical input (Class IIa)
›Ischemic stroke without hemorrhage
›Surgery not necessarily delayed if cardiac indication urgent (Class IIa)