Infective Endocarditis (Cardiovascular Infections)

• Etiologic Agents of Infective Endocarditis

  • Staphylococcus

  • Streptococcus

  • Enterococcus

• What are the principles of antimicrobial therapy? (7)

  • 1) The Inoculum Effect

    • Infective endocarditis is a HIGH inoculum infection

    • Some abx are less active against highly dense bacterial populations

    • The MIC at the site of infection may be HIGHER than anticipated by IN VITRO susceptibility testing

  • 2) Vegetation sterilization requires bactericidal drugs

    • Combination therapy for synergy may be required

  • 3) Prolonged therapy is usually required

    • Required due to high bacterial densities within vegetation and slow bactericidal activity of some abx

    • Right-sided infections tend to have lower bacterial densities

  • 4) Drug penetration is a major concern

    • Vegetation (composed of fibrin and platelets) become a mechanical barrier

  • 5) Need to optimize for PK/PD parameters

  • 6) Total duration for therapy

    • Start counting the days of therapy when blood cultures become negative

  • 7) For regimens with >1 antibiotics → administer abx at the same time or close together as possible to maximize synergistic killing

    • WE WANT -CIDAL!!!

STREPTOCOCCI

• Treatment of Viridians group Streptococci: NATIVE VALVE

  • Penicillin-SUSCEPTIBLE (4)

    • 1) Penicillin G (4 wks) → avoids nephrotoxicity & ototoxicity of AGs

    • 2) Ceftriaxone (4 wks) → avoids nephrotoxicity & ototoxicity of AGs

    • 3) Pen G or Ceftaroline + Gentamicin (2 wks)

      • → NOT recommended with extracardiac infection or CrCl < 20

    • 4) Vancomycin (4 wks) → For penicillin or ceftriaxone intolerance

  • Relatively penicillin-RESISTANT (3)

    • 1) Penicillin G (4 wks) + Gentamicin (2 wks)

    • 2) Ceftriaxone (4 wks)

    • 3) Vancomycin (if beta-lactam intolerant)

  • Highly penicillin RESISTANT (2)

    • 1) Ampicillin OR Pen G OR Ceftriaxone + Gentamicin (4-6 wks)

    • 2) Vancomycin (4-6 wks)

• PROSTHETIC VALVE

  • Penicillin SUSCEPTIBLE (2)

    • 1) Penicillin G OR Ceftriaxone (6 wks) ± Gentamicin (2 wks)

    • 2) Vancomycin (4-6 wks)

  • Penicillin RESISTANT (2)

    • 1) Pen G OR Ceftriaxone (6 wks) + Gentamicin (6 wks)

    • 2) Vancomycin (4-6 wks)

STAPHYLOCOCCUS

• Staphylococcus Aureus

  • In non-IV drug use → Primarily involves the LEFT heart

  • In IV drug use → Primarily involves the tricuspid valve (RIGHT side)

• Coagulase-negative Staph (CoNS)

  • Staphylococcus epidermis → Often Oxacillin RESISTANT

  • Staphylococcus lugdunensis → Often Oxacillin SUSCEPTIBLE

• NATIVE VALVE

  • Right sided Infective Endocarditis (IV-drug use) - (3)

    • 1) IV Beta-lactam or IV Daptomycin (2 wks)

    • 2) IV Vancomycin (>2 wks)

    • 3) PO Ciprofloxacin + Rifampin in MSSA (4 wks)

      • MSSA must be fluoroquinolone-susceptible

  • Left-sided Infective Endocarditis (non-IV drug use) - (2)

    • Oxacillin-SUSCEPTIBLE (Staph. epidermis)

      • Nafcillin or Oxacillin (preferred) (6 wks)

      • Cefazolin (if pencillin-allergic)

      • *Gentamicin not necessary

    • Oxacillin-RESISTANT (Staph. lugdunensis)

      • Vancomycin (6 wks)

      • Daptomycin (6 wks)

      • *Gentamicin not necessary

  • Why is NAFCILLIN first line over Oxacillin?

    • Cefazolin is MORE vulnerable to beta-lactamases than Nafcillin

• PROSTHETIC VALVE → Triple therapy!!!

  • Oxacillin-SUSCEPTIBLE

    • Nafcillin OR Oxacillin (≥6 wks) + Rifampin (≥6 wks) + Gentamicin*

      • *Gentamicin for two weeks only

  • Oxacillin-RESISTANT

    • Vancomycin (≥6 wks) + Rifampin (≥6 wks) + Gentamicin*

      • *Gentamicin for two weeks only

ENTEROCOCCI

• Enterococci are inhibited BUT NOT KILLED by Beta-lactams and vancomycin

  • Entero → relatively IMPERMEABLE to aminoglycosides

• NATIVE VALVE OR PROSTHETIC VALVE

  • 1) Ampicillin OR Penicillin G + Gentamicin if CrCl > 50mL/min

  • 2) Double beta-lactam: Ampicillin + Ceftriaxone if CrCl < 50mL/mi

• NATIVE VALVE OR PROSTHETIC VALVE

  • If unable to tolerate Beta-lactams, intrinsic resistance, or Beta-lactamase producers → → → Tx = Vancomycin + Gentamicin

• NATIVE VALVE OR PROSTHETIC VALVE

  • If Vancomycin-resistant enterococci (VRE)

    • 1) Linezolid

    • 2) Daptomycin ± Ampicillin OR Ceftaroline