Background
- Infection of endocardium, generally involving the heart valves, either prosthetic or native
Microbiology
- Bacteria
- Staphylococcus aureus (most common)
- Viridans group streptococci
- Coagulase-negative staphylococci
- Other streptococci
- Enterococci
- Gram-negative bacteria (5%)
- HACEK group
- Non-HACEK: particularly Pseudomonas aeruginosa and Escherichia coli
- Fungi
- Culture-negative endocarditis
Risk Factors
- Cardiac
- Prior endocarditis
- Prosthetic heart valve or implanted device
- Congenital heart disease, especially unrepaired cyanotic congenital heart disease
- Valve abnormalities
- Non-cardiac
- Intravenous drug use
- Indwelling intravenous lines
- Immunosuppression
- Recent dental work or surgical procedure associated with bacteremia
Clinical Manifestations
- In general, symptoms are fever, chills, and malaise in a patient at risk for endocarditis
- Tends to progress rapidly
- May have a new murmur, stroke syndrome, pulmonary embolism, arthralgias
- Specific organisms may be associated with specific risk factors
- Injection drug use: Viridans group streptococci and Pseudomonas aeruginosa
- Colon cancer: Streptococcus gallolyticus subspecies gallolyticus and Clostridium septicum
Subacute Bacterial Endocarditis
- Insidious onset with more pronounced constitutional symptoms progressing over weeks to months
Differential Diagnosis
- Non-infectious causes of endocarditis
- Any cause of fever or consitutional symptoms
Diagnosis
- Based on a combination of clinical exam, laboratory investigations, and ultrasound
- Refer to Modified Duke criteria
- C-reactive protein is fairly sensitive, while rheumatoid factor is fairly specific and decreases with treatment
- 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)
- Can be useful when TEE and CTA are inconclusive, and may be able to diagnose IE earlier than those other modalities
Management
- Varies by causative organism and prosthetic vs. native valve
- In patients who are in acute heart failure, may need to consider the sodium content of the antibiotics used
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 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
Prevention
- Prophylaxis is recommended for high-risk patients who are undergoing higher-risk procedures
- Patient characteristics
- 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
- Procedures
- 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)
- Dental procedures with manipulation of the gingiva or periapical region of teeth, perforation of mucosa
- Options
- 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
- Infective endocarditis in adults: diagnosis, antimicrobial therapy, and management of complications. Circulation. 2015 Oct 13;132(15):1435-86. doi: 10.1161/CIR.0000000000000296
- 2015 ESC Guidelines for the management of infective endocarditis: The Task Force for the Management of Infective Endocarditis of the European Society of Cardiology (ESC). European Heart J. 2015;36(44):3075-3128. doi: 10.1093/eurheartj/ehv319
References
- ^ Kasper Iversen, Nikolaj Ihlemann, Sabine U. Gill, Trine Madsen, Hanne Elming, Kaare T. Jensen, Niels E. Bruun, Dan E. Høfsten, Kurt Fursted, Jens J. Christensen, Martin Schultz, Christine F. Klein, Emil L. Fosbøll, Flemming Rosenvinge, Henrik C. Schønheyder, Lars Køber, Christian Torp-Pedersen, Jannik Helweg-Larsen, Niels Tønder, Claus Moser, Henning Bundgaard. Partial Oral versus Intravenous Antibiotic Treatment of Endocarditis. New England Journal of Medicine. 2019;380(5):415-424. doi:10.1056/nejmoa1808312.
- ^ John A Wildenthal, Andrew Atkinson, Sophia Lewis, Sena Sayood, Nathanial S Nolan, Nicolo L Cabrera, Jonas Marschall, Michael J Durkin, Laura R Marks. Outcomes of Partial Oral Antibiotic Treatment for Complicated Staphylococcus aureus Bacteremia in People Who Inject Drugs. Clinical Infectious Diseases. 2022;76(3):487-496. doi:10.1093/cid/ciac714.
- ^ Sarah Freling, Noah Wald-Dickler, Josh Banerjee, Catherine P Canamar, Soodtida Tangpraphaphorn, Dara Bruce, Kusha Davar, Fernando Dominguez, Daniel Norwitz, Ganesh Krishnamurthi, Lilian Fung, Ashley Guanzon, Emi Minejima, Michael Spellberg, Catherine Spellberg, Rachel Baden, Paul Holtom, Brad Spellberg. Real-World Application of Oral Therapy for Infective Endocarditis: A Multicenter, Retrospective, Cohort Study. Clinical Infectious Diseases. 2023;77(5):672-679. doi:10.1093/cid/ciad119.