Infective endocarditis

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Background

  • Infection of endocardium, generally involving the heart valves, either prosthetic or native

Microbiology

Risk Factors

  • Cardiac
  • Non-cardiac
    • Intravenous drug use
    • Indwelling intravenous lines
    • Immunosuppression
    • Recent dental work or surgical procedure associated with bacteremia

Clinical Manifestations

Subacute Bacterial Endocarditis

  • Insidious onset with more pronounced constitutional symptoms progressing over weeks to months

Differential Diagnosis

Diagnosis

  • Based on a combination of clinical exam, laboratory investigations, and ultrasound
  • FDG-PET cardiac imaging is a new imaging modality
    • Can be useful when TEE and CTA are inconclusive, and may be able to diagnose IE earlier than those other modalities
      • May be most helpful in cases of prosthetic valves or other cardiac hardware
    • However, it is non-specific, and cannot differentiate between infection and inflammation
      • In these cases, a tagged WBC scan with SPECT can be helpful
    • False positives with inadequate preparation, or other inflammatory disorders
      • Most commonly is patients getting glucose (including in IV therapies) during the fasting period
    • False negatives can be from very small lesion, or several weeks of antibiotics (needs to be off fo r2 to 4 weeks)
    • To request, should have TEE done beforehand, then fax special access request to Ottawa
      • Response within 24-48 hours, with imaging to be done at local PET (St. Joseph's)

Management

Antimicrobial Selection

Valve Antibiotic Dose Duration Notes
MSSA and other oxacillin-susceptible Staphylococcus
NVE oxacillin 2 g IV q4h 6 weeks can treat for 2 weeks in uncomplicated right-sided NVE
NVE cefazolin 2 g IV q8h 6 weeks in patients with non-anaphylactoid penicillin allergy
PVE oxacillin 2 g IV q4h ≥6 weeks use cefazolin or vancomycin if allergy
+ rifampin 300 mg IV/PO q8h
+ gentamicin 1 mg/kg IV/IM q8h 2 weeks
MRSA and other oxacillin-resistant Staphylococcus
NVE vancomycin 15 mg/kg IV q12h 6 weeks target trough 10-20 μg/mL
NVE daptomycin ≥8 mg/kg/dose 6 weeks
PVE vancomycin 15 mg/kg IV q12h ≥6 weeks target vancomycin trough of 10-20 μg/mL
+ rifampin 300 mg IV/PO q8h
+ gentamicin 1 mg/kg IV/IM q8h 2 weeks
Enterococcus susceptible to penicillin and gentamicin
NVE/PVE ampicillin 2 g IV q4h 4-6 weeks 4 weeks if symptoms <3 months;
6 weeks if symptoms >3 months or if PVE
+ gentamicin 1 mg/kg IV q8h
NVE/PVE ampicillin 2 g IV q4h 6 weeks alternative regimen if CrCl <50
+ ceftriaxone 2 g IV q12h
Enterococcus susceptible to penicillin and resistant to aminoglycosides
NVE/PVE ampicillin 2 g IV q4h 6 weeks
+ ceftriaxone 2 g IV q12h
Enterococcus resistant to penicillin and susceptible to vancomycin and aminoglycosides
NVE/PVE vancomycin 15 mg/kg IV q12h 6 weeks
+ gentamicin 1 mg/kg IV/IM q8h
Enterococcus resistant to penicillin, aminoglycosides, and vancomycin
NVE/PVE linezolid 600 mg IV/PO q12h >6 weeks
NVE/PVE daptomycin 10-12 mg/kg IV q24h >6 weeks
Viridans Streptococcus or Streptococcus gallolyticus highly susceptible to penicillin (MIC ≤0.12 μg/mL)
NVE penicillin G 3-4 MU IV q4h 4 weeks
NVE ceftriaxone 2 g IV/IM q24h 4 weeks
NVE penicillin or ceftriaxone as above 2 weeks
+ gentamicin 3 mg/kg IV/IM q24h
NVE vancomycin 15 mg/kg IV q12h 4 weeks use if allergy, target 10-15 μg/mL
PVE penicillin G 6 MU IV q4h 6 weeks
± gentamicin 3 mg/kg IV/IM q24h 2 weeks
PVE ceftriaxone 2 g IV/IM q24h 6 weeks
± gentamicin 3 mg/kg IV/IM q24h 2 weeks
PVE vancomycin 15 mg/kg IV q12h 6 weeks use if allergy
Viridans Streptococcus or Streptococcus gallolyticus relatively resistant to penicillin (MIC >0.12 μg/mL)
NVE penicillin G 6 MU IV q4h 4 weeks
+ gentamicin 3 mg/kg IV/IM q24h 2 weeks
NVE vancomycin 15 mg/kg IV q12h 4 weeks use if allergy, target 10-15 μ/mL
PVE penicillin G 6 MU IV q4h 6 weeks
+ gentamicin 3 mg/kg IV/IM q24h
PVE ceftriaxone 2 g IV/IM q24h 6 weeks
+ gentamicin 3 mg/kg IV/IM q24h
PVE vancomycin 15 mg/kg IV q12h 6 weeks use if allergy
Streptococcus pneumoniae
NVE penicillin 3-4 MU IV q4h 4 weeks can use high dose if penicillin-resistant but without meningitis
NVE cefazolin 2 g IV q8h 4 weeks
NVE ceftriaxone 2 g IV/IM q24h 4 weeks
PVE penicillin 3-4 MU IV q4h 6 weeks can use high dose if penicillin-resistant but without meningitis
PVE cefazolin 2 g IV q8h 6 weeks
PVE ceftriaxone 2 g IV/IM q24h 6 weeks
Streptococcus pyogenes
NVE penicillin G 3-4 MU IV q4h 4 weeks can use high dose if penicillin-resistant but without meningitis
NVE ceftriaxone 2 g IV/IM q24h 4 weeks
PVE penicillin G 3-4 MU IV q4h 6 weeks can use high dose if penicillin-resistant but without meningitis
PVE ceftriaxone 2 g IV/IM q24h 6 weeks
Group B, C, or G Streptococcus
NVE penicillin G 3-4 MU IV q4h 4 weeks can use high dose if penicillin-resistant but without meningitis
± gentamicin 3 mg/kg IV/IM q24h 2 weeks
NVE ceftriaxone 2 g IV/IM q24h 4 weeks
± gentamicin 3 mg/kg IV/IM q24h 2 weeks
PVE penicillin G 3-4 MU IV q4h 6 weeks can use high dose if penicillin-resistant but without meningitis
± gentamicin 3 mg/kg IV/IM q24h 2 weeks
PVE ceftriaxone 2 g IV/IM q24h 6 weeks
± gentamicin 3 mg/kg IV/IM q24h 2 weeks
HACEK bacterium
NVE ceftriaxone 2 g IV/IM q24h 4 weeks
PVE ceftriaxone 2 g IV/IM q24h 6 weeks
NVE/PVE ciprofloxacin 500 mg PO q12h 6 weeks
Non-HACEK Gram-negative bacillus
NVE/PVE β-lactam 6 weeks poor data guiding management
± aminoglycoside or fluoroquinolone

Indications for Early Surgery

  • Early valve surgery (that is, before discharge and completion of antibiotics) is recommended in some scenarios
  • Left-sided endocarditis
    • Acute heart failure
    • Fungal endocarditis
    • Highly-resistant organisms
    • Heart block, annular or aortic abscess, or perforating valve lesion
    • Bacteremia or fever lasting more than 5-7 days despite appropriate antimicrobials
    • Severe valvular regurgitation and mobile vegetations >1 cm
    • Prosthetic valve endocarditis with recurrent emboli despite appropriate antimicrobials
    • Relapsed prosthetic valve endocarditis
  • Right-sided endocarditis
    • Severe tricuspid valve regurgitation with right heart failure despite medical therapy
    • Persistent infection with difficult-to-treat organisms
    • Tricuspid valve vegetation >2 cm
    • Recurrent pulmonary emboli despite appropriate antimicrobials

Early Oral Therapy

Organism Oral Regimens
Penicillin-susceptible streptococci (MIC <= 0.12) amoxicillin alone (native valve only)
amoxicillin + rifampin
linezolid +/- rifampin
moxifloxacin + (rifampin or linezolid)
Penicillin-intermediate streptococci (MIC 0.25-1) or enterococci amoxicillin + (rifampin or linezolid)
linezolid +/- rifampin
moxifloxacin + rifampin
MSSA levofloxacin + (rifampin or linezolid)
linezolid +/- rifampin
co-trimoxazole
dicloxacillin + rifampin
MRSA and CoNS levofloxacin + (rifampin or linezolid)
linezolid +/- rifampin
co-trimoxazole

Prevention

  • Prophylaxis is recommended for high-risk patients who are undergoing higher-risk procedures
    • High-risk patients include:
      • Prosthetic heart valve
      • Previous infective endocarditis
      • Unrepaired cyanotic congenital heart disease, or repaired within the past six months with prosthetic material in situ, or repaired with residual defect and with material in situ
      • Cardiac transplantation with valvulopathy
    • High-risk procedures include:
      • Dental procedures with manipulation of the gingiva or periapical region of teeth, perforation of mucosa
        • This includes professional cleaning procedures
      • Procedures involving incision of respiratory mucosa, including tonsillectomy and bronchoscopic biopsy
      • Procedures on infected tissue (skin, bone, joint, etc)
  • Antibiotic options are:
    • Amoxicillin 2 g PO once, 30-60 minutes prior to procedure
    • If allergy: clindamycin 600 mg PO once, 30-60 minutes prior to procedure

Further Reading

  1. ↑ Iversen K, Ihlemann N, Gill SU, Madsen T, Elming H, Jensen KT, Bruun NE, Høfsten DE, Fursted K, Christensen JJ, Schultz M, Klein CF, Fosbøll EL, Rosenvinge F, Schønheyder HC, Køber L, Torp-Pedersen C, Helweg-Larsen J, Tønder N, Moser C, Bundgaard H. Partial Oral versus Intravenous Antibiotic Treatment of Endocarditis. N Engl J Med. 2019 Jan 31;380(5):415-424. doi: 10.1056/NEJMoa1808312. Epub 2018 Aug 28. PMID: 30152252.
  2. ↑ John A Wildenthal, B.S, Andrew Atkinson, PhD, Sophia Lewis, MD PhD, Sena Sayood, MD, Nathanial S Nolan, MD MPH, Nicolo L Cabrera, MD, Jonas Marschall, MD, Michael J Durkin, MD MPH, Laura R Marks, MD PhD, Outcomes of Partial Oral Antibiotic Treatment for Complicated S. aureus Bacteremia in People Who Inject Drugs, Clinical Infectious Diseases, 2022;, ciac714, https://doi.org/10.1093/cid/ciac714
  3. ↑ Freling S, Wald-Dickler N, Banerjee J, Canamar CP, Tangpraphaphorn S, Bruce D, Davar K, Dominguez F, Norwitz D, Krishnamurthi G, Fung L, Guanzon A, Minejima E, Spellberg M, Spellberg C, Baden R, Holtom P, Spellberg B. Real-world Application of Oral Therapy for Infective Endocarditis: A Multicenter Retrospective, Cohort Study. Clin Infect Dis. 2023 Mar 7:ciad119. doi: 10.1093/cid/ciad119. Epub ahead of print. PMID: 36881940.
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