Infective endocarditis

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
- HACEK group
- Coxiella
- Brucella
Fungi
- Candida
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 imaging
Refer to Modified Duke criteria

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	≥6 weeks
	+ 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	≥6 weeks
	+ 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
NVE/PVE	+ gentamicin	1 mg/kg IV q8h	4-6 weeks
NVE/PVE	ampicillin	2 g IV q4h	6 weeks	alternative regimen if CrCl <50
NVE/PVE	+ ceftriaxone	2 g IV q12h	6 weeks	alternative regimen if CrCl <50
Enterococcus susceptible to penicillin and resistant to aminoglycosides
NVE/PVE	ampicillin	2 g IV q4h	6 weeks
NVE/PVE	+ ceftriaxone	2 g IV q12h	6 weeks
Enterococcus resistant to penicillin and susceptible to vancomycin and aminoglycosides
NVE/PVE	vancomycin	15 mg/kg IV q12h	6 weeks
NVE/PVE	+ gentamicin	1 mg/kg IV/IM q8h	6 weeks
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	crystalline 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
NVE	+ gentamicin	3 mg/kg IV/IM q24h	2 weeks
NVE	vancomycin	15 mg/kg IV q12h	4 weeks	use if allergy, target 10-15 μg/mL
PVE	crystalline penicillin G	6 MU IV q4h	6 weeks
PVE	± gentamicin	3 mg/kg IV/IM q24h	2 weeks
PVE	ceftriaxone	2 g IV/IM q24h	6 weeks
PVE	± 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	crystalline penicillin G	6 MU IV q4h	4 weeks
NVE	+ 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	crystalline penicillin G	6 MU IV q4h	6 weeks
PVE	+ gentamicin	3 mg/kg IV/IM q24h	6 weeks
PVE	ceftriaxone	2 g IV/IM q24h	6 weeks
PVE	+ gentamicin	3 mg/kg IV/IM q24h	6 weeks
PVE	vancomycin	15 mg/kg IV q12h	6 weeks	use if allergy
Streptococcus pneumoniae
NVE	penicillin		4 weeks
NVE	cefazolin		4 weeks
NVE	ceftriaxone		4 weeks
PVE	penicillin		6 weeks
PVE	cefazolin		6 weeks
PVE	ceftriaxone		6 weeks
Streptococcus pyogenes
NVE	crystalline penicillin G		4 weeks
NVE	ceftriaxone		4 weeks
PVE	crystalline penicillin G		6 weeks
PVE	ceftriaxone		6 weeks
Group B, C, or G Streptococcus
NVE	crystalline penicillin G		4 weeks
NVE	± gentamicin		2 weeks
NVE	ceftriaxone		4 weeks
NVE	± gentamicin		2 weeks
PVE	crystalline penicillin G		6 weeks
PVE	± gentamicin		2 weeks
PVE	ceftriaxone		6 weeks
PVE	± gentamicin		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

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
- Procedures involving incision of respiratory mucosa, including tonsillectomy and bronchoscopic biopsy
- Procedures on infected tissue (skin, bone, joint, etc)

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.