Infective endocarditis: Difference between revisions

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== Background ==
==Background==
* Infection of heart valves, either prosthetic or native


*Infection of endocardium, generally involving the heart valves, either prosthetic or native
=== Organisms ===
* '''Bacteria'''
** [[Staphylococcus aureus]] (most common)
** [[Viridans group streptococci]]
** [[Coagulase-negative staphylococci]]
** Other streptococci
** [[Enterococci]]
** [[HACEK group]]
** [[Coxiella]]
** [[Brucella]]
* [[Fungi]]
** ''[[Candidal endocarditis|Candida]]''


===Microbiology===
== Clinical Manifestations ==
* Refer to [[Modified Duke criteria]]
* Specific organisms may be associated with specific risk factors
** Injection drug use: [[Viridans group streptococci]] and ''[[Pseudomonas aeruginosa]]''
** Colon cancer: ''[[Streptococcus bovis]]'' and ''[[Clostridium septicum]]''


*'''Bacteria'''
== Management ==
**[[Staphylococcus aureus]] (most common)
* Varies by causative organism and prosthetic vs. native valve
**[[Viridans group streptococci]]
**[[Coagulase-negative staphylococci]]
**Other [[streptococci]]
**[[Enterococci]]
**Gram-negative bacteria (5%)
***[[HACEK group]]
***[[Infective endocarditis caused by non-HACEK Gram-negative bacilli|Non-HACEK]]: particularly [[Pseudomonas aeruginosa]] and [[Escherichia coli]]
*'''[[Fungi]]'''
**''[[Candidal endocarditis|Candida]]''
*[[Culture-negative endocarditis]]
**[[Coxiella burnetii]]
**[[Bartonella]]
**[[Brucella]]
**[[Legionella]]
**[[Mycoplasma]]
**[[Tropheryma whipplei]]
**[[Abiotrophia]]
**[[Cutibacterium acnes]]


===Risk Factors===

*Cardiac
**Prior endocarditis
**Prosthetic heart valve or implanted device
**Congenital heart disease, especially unrepaired cyanotic congenital heart disease
**Valve abnormalities, including acquired valvular dysfunction (e.g. from [[rheumatic heart disease]]), [[hypertrophic cardiomyopathy]], [[bicuspid aortic valve]], and [[mitral valve prolapse]] (especially with valvular regurgitation or thickened leaflets)
*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|''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
**[[Acute rheumatic fever]]
**[[Libman-Sacks endocarditis]]
**[[Rheumatoid arthritis]]
**[[Marantic endocarditis]]
**[[Löeffler 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]] or [[ESC 2015 modified criteria for the diagnosis of infective endocarditis]]
**[[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)

==Management==

*Varies by causative organism and prosthetic vs. native valve
*In patients who are in [[acute heart failure]], may need to consider [[antibiotics in sodium restriction|the sodium content of the antibiotics used]]

===Antimicrobial Selection===
{| class="wikitable"
{| class="wikitable"
! Valve
!Valve
! Antibiotic
!Antibiotic
! Dose
!Dose
! Duration
!Duration
! Notes
!Notes
|-
|-
! colspan=5 | MSSA and other oxacillin-susceptible ''[[Staphylococcus]]''
! colspan="5" |MSSA and other oxacillin-susceptible ''[[Staphylococcus]]''
|-
|-
| NVE
|NVE
| [[oxacillin]] || 2 g IV q4h || 6 weeks
|[[oxacillin]]||2 g IV q4h||6 weeks
| can treat for 2 weeks in uncomplicated right-sided NVE
|can treat for 2 weeks in uncomplicated right-sided NVE
|-
|-
| NVE
|NVE
| [[cefazolin]] || 2 g IV q8h || 6 weeks
|[[cefazolin]]||2 g IV q8h||6 weeks
| in patients with non-anaphylactoid penicillin allergy
|in patients with non-anaphylactoid penicillin allergy
|-
|-
| rowspan=3 | PVE
| rowspan="3" |PVE
| [[oxacillin]]
|[[oxacillin]]
| 2 g IV q4h
|2 g IV q4h
| rowspan=2 | ≥6 weeks
| rowspan="2" |≥6 weeks
| rowspan=3 | use cefazolin or vancomycin if allergy
| rowspan="3" |use cefazolin or vancomycin if allergy
|-
|-
| + [[rifampin]]
| + [[rifampin]]
| 300 mg IV/PO q8h
|300 mg IV/PO q8h
|-
|-
| + [[gentamicin]]
| + [[gentamicin]]
| 1 mg/kg IV/IM q8h
|1 mg/kg IV/IM q8h
| 2 weeks
|2 weeks
|-
|-
! colspan=5 | MRSA and other oxacillin-resistant ''[[Staphylococcus]]''
! colspan="5" |MRSA and other oxacillin-resistant ''[[Staphylococcus]]''
|-
|-
| NVE
|NVE
| [[vancomycin]] || 15 mg/kg IV q12h || 6 weeks
|[[vancomycin]]||15 mg/kg IV q12h||6 weeks
| target trough 10-20 μg/mL
|target trough 10-20 μg/mL
|-
|-
| NVE
|NVE
| [[daptomycin]] || ≥8 mg/kg/dose || 6 weeks
|[[daptomycin]]||≥8 mg/kg/dose||6 weeks
|
|
|-
|-
| rowspan=3 | PVE
| rowspan="3" |PVE
| [[vancomycin]]
|[[vancomycin]]
| 15 mg/kg IV q12h
|15 mg/kg IV q12h
| rowspan=2 | ≥6 weeks
| rowspan="2" |≥6 weeks
| rowspan=3 | target vancomycin trough of 10-20 μg/mL
| rowspan="3" |target vancomycin trough of 10-20 μg/mL
|-
|-
| + [[rifampin]]
| + [[rifampin]]
| 300 mg IV/PO q8h
|300 mg IV/PO q8h
|-
|-
| + [[gentamicin]]
| + [[gentamicin]]
| 1 mg/kg IV/IM q8h
|1 mg/kg IV/IM q8h
| 2 weeks
|2 weeks
|-
|-
! colspan=5 | ''[[Enterococcus]]'' susceptible to [[penicillin]] and [[gentamicin]]
! colspan="5" |''[[Enterococcus]]'' susceptible to [[penicillin]] and [[gentamicin]]
|-
|-
| rowspan=2 | NVE/PVE
| rowspan="2" |NVE/PVE
| [[ampicillin]]
|[[ampicillin]]
| 2 g IV q4h
|2 g IV q4h
| rowspan=2 | 4-6 weeks
| rowspan="2" |4-6 weeks
| rowspan=2 | 4 weeks if symptoms <3 months;<br/>6 weeks if symptoms >3 months or if PVE
| rowspan="2" |4 weeks if symptoms <3 months;<br />6 weeks if symptoms >3 months or if PVE
|-
|-
| + [[gentamicin]]
| + [[gentamicin]]
| 1 mg/kg IV q8h
|1 mg/kg IV q8h
|-
|-
| rowspan=2 | NVE/PVE
| rowspan="2" |NVE/PVE
| [[ampicillin]]
|[[ampicillin]]
| 2 g IV q4h
|2 g IV q4h
| rowspan=2 | 6 weeks
| rowspan="2" |6 weeks
| rowspan=2 | alternative regimen if CrCl <50
| rowspan="2" |alternative regimen if CrCl <50
|-
|-
| + [[ceftriaxone]]
| + [[ceftriaxone]]
| 2 g IV q12h
|2 g IV q12h
|-
|-
! colspan=5 | ''[[Enterococcus]]'' susceptible to [[penicillin]] and resistant to [[aminoglycosides]]
! colspan="5" |''[[Enterococcus]]'' susceptible to [[penicillin]] and resistant to [[aminoglycosides]]
|-
|-
| rowspan=2 | NVE/PVE
| rowspan="2" |NVE/PVE
| [[ampicillin]]
|[[ampicillin]]
| 2 g IV q4h
|2 g IV q4h
| rowspan=2 | 6 weeks
| rowspan="2" |6 weeks
| rowspan=2 |
| rowspan="2" |
|-
|-
| + [[ceftriaxone]]
| + [[ceftriaxone]]
| 2 g IV q12h
|2 g IV q12h
|-
|-
! colspan=5 | ''[[Enterococcus]]'' resistant to [[penicillin]] and susceptible to [[vancomycin]] and [[aminoglycosides]]
! colspan="5" |''[[Enterococcus]]'' resistant to [[penicillin]] and susceptible to [[vancomycin]] and [[aminoglycosides]]
|-
|-
| rowspan=2 | NVE/PVE
| rowspan="2" |NVE/PVE
| [[vancomycin]]
|[[vancomycin]]
| 15 mg/kg IV q12h
|15 mg/kg IV q12h
| rowspan=2 | 6 weeks
| rowspan="2" |6 weeks
| rowspan=2 |
| rowspan="2" |
|-
|-
| + [[gentamicin]]
| + [[gentamicin]]
| 1 mg/kg IV/IM q8h
|1 mg/kg IV/IM q8h
|-
|-
! colspan=5 | ''[[Enterococcus]]'' resistant to [[penicillin]], [[aminoglycosides]], and [[vancomycin]]
! colspan="5" |''[[Enterococcus]]'' resistant to [[penicillin]], [[aminoglycosides]], and [[vancomycin]]
|-
|-
| NVE/PVE
|NVE/PVE
| [[linezolid]]
|[[linezolid]]
| 600 mg IV/PO q12h
|600 mg IV/PO q12h
| &gt;6 weeks
|&gt;6 weeks
|
|
|-
|-
| NVE/PVE
|NVE/PVE
| [[daptomycin]]
|[[daptomycin]]
| 10-12 mg/kg IV q24h
|10-12 mg/kg IV q24h
| &gt;6 weeks
|&gt;6 weeks
|
|
|-
|-
! colspan=5 | Viridans ''Streptococcus'' or ''Streptococcus gallolyticus'' highly susceptible to [[penicillin]] (MIC ≤0.12 μg/mL)
! colspan="5" |Viridans ''Streptococcus'' or ''Streptococcus gallolyticus'' highly susceptible to [[penicillin]] (MIC ≤0.12 μg/mL)
|-
|-
| NVE
|NVE
| crystalline [[penicillin]] G
|[[penicillin]] G
| 3-4 MU IV q4h
|3-4 MU IV q4h
| 4 weeks
|4 weeks
|
|
|-
|-
| NVE
|NVE
| [[ceftriaxone]]
|[[ceftriaxone]]
| 2 g IV/IM q24h
|2 g IV/IM q24h
| 4 weeks
|4 weeks
|
|
|-
|-
| rowspan=2 | NVE
| rowspan="2" |NVE
| [[penicillin]] or [[ceftriaxone]]
|[[penicillin]] or [[ceftriaxone]]
| as above
|as above
| rowspan=2 | 2 weeks
| rowspan="2" |2 weeks
| rowspan=2 |
| rowspan="2" |
|-
|-
| + [[gentamicin]]
| + [[gentamicin]]
| 3 mg/kg IV/IM q24h
|3 mg/kg IV/IM q24h
|-
|-
| NVE
|NVE
| [[vancomycin]]
|[[vancomycin]]
| 15 mg/kg IV q12h
|15 mg/kg IV q12h
| 4 weeks
|4 weeks
| use if allergy, target 10-15 μg/mL
|use if allergy, target 10-15 μg/mL
|-
|-
| rowspan=2 | PVE
| rowspan="2" |PVE
| crystalline [[penicillin]] G
|[[penicillin]] G
| 6 MU IV q4h
|6 MU IV q4h
| 6 weeks
|6 weeks
| rowspan=2 |
| rowspan="2" |
|-
|-
| ± [[gentamicin]]
|± [[gentamicin]]
| 3 mg/kg IV/IM q24h
|3 mg/kg IV/IM q24h
| 2 weeks
|2 weeks
|-
|-
| rowspan=2 | PVE
| rowspan="2" |PVE
| [[ceftriaxone]]
|[[ceftriaxone]]
| 2 g IV/IM q24h
|2 g IV/IM q24h
| 6 weeks
|6 weeks
| rowspan=2 |
| rowspan="2" |
|-
|-
| ± [[gentamicin]]
|± [[gentamicin]]
| 3 mg/kg IV/IM q24h
|3 mg/kg IV/IM q24h
| 2 weeks
|2 weeks
|-
|-
| PVE
|PVE
| [[vancomycin]]
|[[vancomycin]]
| 15 mg/kg IV q12h
|15 mg/kg IV q12h
| 6 weeks
|6 weeks
| use if allergy
|use if allergy
|-
|-
! colspan=5 | Viridans ''Streptococcus'' or ''Streptococcus gallolyticus'' relatively resistant to [[penicillin]] (MIC &gt;0.12 μg/mL)
! colspan="5" |Viridans ''Streptococcus'' or ''Streptococcus gallolyticus'' relatively resistant to [[penicillin]] (MIC &gt;0.12 μg/mL)
|-
|-
| rowspan=2 | NVE
| rowspan="2" |NVE
| crystalline [[penicillin]] G
|[[penicillin]] G
| 6 MU IV q4h
|6 MU IV q4h
| 4 weeks
|4 weeks
| rowspan=2 |
| rowspan="2" |
|-
|-
| + [[gentamicin]]
| + [[gentamicin]]
| 3 mg/kg IV/IM q24h
|3 mg/kg IV/IM q24h
| 2 weeks
|2 weeks
|-
|-
| NVE
|NVE
| [[vancomycin]]
|[[vancomycin]]
| 15 mg/kg IV q12h
|15 mg/kg IV q12h
| 4 weeks
|4 weeks
| use if allergy, target 10-15 μ/mL
|use if allergy, target 10-15 μ/mL
|-
|-
| rowspan=2 | PVE
| rowspan="2" |PVE
| crystalline [[penicillin]] G
|[[penicillin]] G
| 6 MU IV q4h
|6 MU IV q4h
| rowspan=2 | 6 weeks
| rowspan="2" |6 weeks
| rowspan=2 |
| rowspan="2" |
|-
|-
| + [[gentamicin]]
| + [[gentamicin]]
| 3 mg/kg IV/IM q24h
|3 mg/kg IV/IM q24h
|-
|-
| rowspan=2 | PVE
| rowspan="2" |PVE
| [[ceftriaxone]]
|[[ceftriaxone]]
| 2 g IV/IM q24h
|2 g IV/IM q24h
| rowspan=2 | 6 weeks
| rowspan="2" |6 weeks
| rowspan=2 |
| rowspan="2" |
|-
|-
| + [[gentamicin]]
| + [[gentamicin]]
| 3 mg/kg IV/IM q24h
|3 mg/kg IV/IM q24h
|-
|-
| PVE
|PVE
| [[vancomycin]]
|[[vancomycin]]
| 15 mg/kg IV q12h
|15 mg/kg IV q12h
| 6 weeks
|6 weeks
| use if allergy
|use if allergy
|-
|-
! colspan=5 | ''Streptococcus pneumoniae''
! colspan="5" |''Streptococcus pneumoniae''
|-
|-
| NVE || [[penicillin]] || || 4 weeks ||
|NVE||[[penicillin]]|| 3-4 MU IV q4h||4 weeks||can use high dose if penicillin-resistant but without meningitis
|-
|-
| NVE || [[cefazolin]] || || 4 weeks ||
|NVE||[[cefazolin]]|| 2 g IV q8h||4 weeks||
|-
|-
| NVE || [[ceftriaxone]] || || 4 weeks ||
|NVE||[[ceftriaxone]]|| 2 g IV/IM q24h||4 weeks||
|-
|-
| PVE || [[penicillin]] || || 6 weeks ||
|PVE||[[penicillin]]|| 3-4 MU IV q4h||6 weeks||can use high dose if penicillin-resistant but without meningitis
|-
|-
| PVE || [[cefazolin]] || || 6 weeks ||
|PVE||[[cefazolin]]|| 2 g IV q8h||6 weeks||
|-
|-
| PVE || [[ceftriaxone]] || || 6 weeks ||
|PVE||[[ceftriaxone]]|| 2 g IV/IM q24h||6 weeks||
|-
|-
! colspan=5 | ''Streptococcus pyogenes''
! colspan="5" |''Streptococcus pyogenes''
|-
|-
| NVE || crystalline [[penicillin]] G || || 4 weeks ||
|NVE||[[penicillin]] G|| 3-4 MU IV q4h||4 weeks|| rowspan="2" |can use high dose if penicillin-resistant but without meningitis
|-
|-
| NVE || [[ceftriaxone]] || || 4 weeks ||
|NVE||[[ceftriaxone]]|| 2 g IV/IM q24h||4 weeks
|-
|-
| PVE || crystalline [[penicillin]] G || || 6 weeks ||
|PVE||[[penicillin]] G|| 3-4 MU IV q4h||6 weeks|| rowspan="2" |can use high dose if penicillin-resistant but without meningitis
|-
|-
| PVE || [[ceftriaxone]] || || 6 weeks ||
|PVE||[[ceftriaxone]]|| 2 g IV/IM q24h||6 weeks
|-
|-
! colspan=5 | Group B, C, or G ''Streptococcus''
! colspan="5" |Group B, C, or G ''Streptococcus''
|-
|-
| rowspan=2 | NVE
| rowspan="2" |NVE
| crystalline [[penicillin]] G
|[[penicillin]] G
|3-4 MU IV q4h
|
| 4 weeks
|4 weeks
| rowspan="2" |can use high dose if penicillin-resistant but without meningitis
| rowspan=2 |
|-
|-
| ± [[gentamicin]]
|± [[gentamicin]]
|3 mg/kg IV/IM q24h
|
| 2 weeks
|2 weeks
|-
|-
| rowspan=2 | NVE
| rowspan="2" |NVE
| [[ceftriaxone]]
|[[ceftriaxone]]
|2 g IV/IM q24h
|
| 4 weeks
|4 weeks
| rowspan=2 |
| rowspan="2" |
|-
|-
| ± [[gentamicin]]
|± [[gentamicin]]
|3 mg/kg IV/IM q24h
|
| 2 weeks
|2 weeks
|-
|-
| rowspan=2 | PVE
| rowspan="2" |PVE
| crystalline [[penicillin]] G
|[[penicillin]] G
|3-4 MU IV q4h
|
| 6 weeks
|6 weeks
| rowspan="2" |can use high dose if penicillin-resistant but without meningitis
| rowspan=2 |
|-
|-
| ± [[gentamicin]]
|± [[gentamicin]]
|3 mg/kg IV/IM q24h
|
| 2 weeks
|2 weeks
|-
|-
| rowspan=2 | PVE
| rowspan="2" |PVE
| [[ceftriaxone]]
|[[ceftriaxone]]
|2 g IV/IM q24h
|
| 6 weeks
|6 weeks
| rowspan=2 |
| rowspan="2" |
|-
|-
| ± [[gentamicin]]
|± [[gentamicin]]
|3 mg/kg IV/IM q24h
|
| 2 weeks
|2 weeks
|-
|-
! colspan=5 | HACEK bacterium
! colspan="5" |HACEK bacterium
|-
|-
| NVE
|NVE
| [[ceftriaxone]]
|[[ceftriaxone]]
| 2 g IV/IM q24h
|2 g IV/IM q24h
| 4 weeks
|4 weeks
|
|
|-
|-
| PVE
|PVE
| [[ceftriaxone]]
|[[ceftriaxone]]
| 2 g IV/IM q24h
|2 g IV/IM q24h
| 6 weeks
|6 weeks
|
|
|-
|-
| NVE/PVE
|NVE/PVE
| [[ciprofloxacin]]
|[[ciprofloxacin]]
| 500 mg PO q12h
|500 mg PO q12h
| 6 weeks
|6 weeks
|
|
|-
! colspan="5" |Non-HACEK Gram-negative bacillus
|-
| rowspan="2" |NVE/PVE
|[[β-lactam]]
| rowspan="2" |
| rowspan="2" |6 weeks
| rowspan="2" |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 ===

* The [https://www.wikijournalclub.org/wiki/POET POET study] showed non-inferiority of early oral antibiotics (after 7 to 10 days of IV antibiotics) compared to traditional IV antibiotics for the treatment of left-sided endocarditis[[CiteRef::iversen2019pa]]
** No patient had [[MRSA]]
** All oral therapies included two antibiotics to which the isolate was susceptible
* The regimens in the study were:
** Penicillin-susceptible [[staphylococci]]: ([[amoxicillin]] or [[linezolid]]) plus ([[rifampin]] or [[fusidic acid]])
** Methicillin-susceptible [[staphylococci]]: ([[dicloxacillin]] or [[linezolid]]) plus ([[rifampin]] or [[fusidic acid]])
** Methicillin-resistant [[coagulase-negative staphylococci]]: [[linezolid]] plus ([[rifampin]] or [[fusidic acid]])
** [[Enterococcus faecalis]]: [[amoxicillin]] plus [[rifampin]], or [[linezolid]] plus ([[rifampin]] or [[moxifloxacin]])
** Penicillin-susceptible [[streptococci]] (MIC <1): [[amoxicillin]] plus [[rifampin]], or [[linezolid]] plus ([[rifampin]] or [[moxifloxacin]])
** Penicillin-resistant [[streptococci]] (MIC ≥1): [[linezolid]] plus [[rifampin]], or [[moxifloxacin]] plus ([[rifampin]] or [[clindamycin]])
* Doses were:
** [[Amoxicillin]] 1 g p.o. four times daily
** [[Clindamycin]] 600 mg p.o. three times daily
** [[Dicloxacillin]] 1 g p.o. q6h
** [[Fusidic acid]] 750 mg p.o. twice daily
** [[Linezolid]] 600 mg p.o. twice daily
** [[Moxifloxacin]] 400 mg p.o. daily
** [[Rifampin]] 600 mg p.o. twice daily
* A retrospective cohort study of people who inject drugs confirmed that these findings are likely generalizable to PWID[[CiteRef::wildenthal2022ou]]
** Details of the regimens are not available, but included primarily [[doxycycline]], [[TMP-SMX]], and [[linezolid]], as well as some beta-lactams, either as monotherapy or as combination therapy
* Another cohort study has shown that it can be effectively operationalized[[CiteRef::freling2023re]]
** Indications for step-down to oral therapy, which could take from a few days to a few weeks:
*** Clinically stable with no indication for cardiac surgery
*** Bacteremia is cleared
*** No concern regarding GI absorption
*** No psychosocial concerns where IV would be preferable
*** An appropriate oral antibiotic was available, based on in vitro susceptibility testing and published clinical data
** Recommended oral antibiotics:
*** [[Amoxicillin]] 1 g p.o. every 6 hours
*** [[Co-trimoxazole]] 960 mg/4800 mg p.o. total daily dose, divided
*** [[Dicloxacillin]] 1 g p.o. q6h
*** [[Levofloxacin]] 750 mg p.o. daily
*** [[Linezolid]] 600 mg p.o. twice daily
*** [[Moxifloxacin]] 400 mg p.o. daily
*** [[Rifampin]] 600 mg p.o. daily; preferred as second agent in prosthetic valve endocarditis
{| class="wikitable"
!Organism
!Oral Regimens
|-
| rowspan="4" |Penicillin-susceptible streptococci (MIC <= 0.12)
|[[amoxicillin]] alone (native valve only)
|-
|[[amoxicillin]] + [[rifampin]]
|-
|[[linezolid]] +/- [[rifampin]]
|-
|[[moxifloxacin]] + ([[rifampin]] or [[linezolid]])
|-
| rowspan="3" |Penicillin-intermediate streptococci (MIC 0.25-1) or enterococci
|[[amoxicillin]] + ([[rifampin]] or [[linezolid]])
|-
|[[linezolid]] +/- [[rifampin]]
|-
|[[moxifloxacin]] + [[rifampin]]
|-
| rowspan="4" |MSSA
|[[levofloxacin]] + ([[rifampin]] or [[linezolid]])
|-
|[[linezolid]] +/- [[rifampin]]
|-
|[[co-trimoxazole]]
|-
|[[dicloxacillin]] + [[rifampin]]
|-
| rowspan="3" |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 ==

* [[Infective Endocarditis in Adults (IDSA 2015)|Infective endocarditis in adults: diagnosis, antimicrobial therapy, and management of complications]]. ''Circulation''. 2015 Oct 13;132(15):1435-86. doi: [https://doi.org/10.1161/CIR.0000000000000296 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: [https://doi.org/10.1093/eurheartj/ehv319 10.1093/eurheartj/ehv319]


[[Category:Cardiac infections]]
[[Category:Cardiac infections]]

Latest revision as of 18:16, 19 September 2024

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

References

  1. ^  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.
  2. ^  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.
  3. ^  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.