Infective Endocarditis in Adults (IDSA 2015)

Baddour LM, Wilson WR, Bayer AS, Fowler VG, Tleyjeh IM, Rybak MJ, Barsic B, Lockhart PB, Gewitz MH, Levison ME, Bolger AF. Infective endocarditis in adults: diagnosis, antimicrobial therapy, and management of complications. Circulation. 2015 Oct 13;132(15):1435-86. doi: 10.1161/CIR.0000000000000296

Echo

TTE in all cases
TEE if TTE negative and ongoing suspicion
Repeat TEE in 3-5 days if first TEE negative and ongoing suspicion
Repeat TTE/TEE as needed if clinical situation changes
Repeat TTE after the course of antibiotics for a new baseline

Treatment by Valve

Depends on bacteria, native vs prosthetic valve involvement, and associated complications
In general, 4 weeks for NVE, 6 weeks for PVE; possibly 2 weeks for NVE without complications if treated with two agents

Indications for Early Surgery

Early surgery means during initial hospitalization and before completion of a full course of antibiotics

Left-sided NVE

Class I
- Valve dysfunction resulting in heart failure
- Fungal or resistant organisms (e.g. vanco-resistant Enterococcus, multidrug-resistant GNBs)
- Heart block, annular or aortic abscess, or destructive penetrating lesions
- Persistent infection (persistent bacteremia or fever for more than 5-7 days) following appropriate antimicrobials
Class IIa
- Recurrent emboli and persistent or enlarging vegetations despite appropriate antimicrobials
- Severe valve regurgitation and mobile vegetations >10mm
Class IIb
- Mobile vegetations >10mm, particularly when involving the anterior mitral valve leaflet and other relative indications for surgery

Prosthetic valve endocarditis (PVE)

Class I
- Heart failure from valve dehiscence, intracardiac fistula, or severe valve dysfunction
- Persistent bacteremia despite appropriate antibiotics for 5-7 days
- Heart block, annular or aortic abscess, or destructive penetrating lesions
- Fungal or highly resistant organisms
Class IIa
- Recurrent emboli despite appropriate antibiotic therapy
- Mobile vegetations >10mm

Right-sided NVE

Class I
- Repair rather than replacement is preferred
Class IIa
- Certain complications
- Right heart failure with poor response to medical therapy
- Sustained infection with fungi or MDR bacteria
- Lack of response to appropriate antimicrobials
- Tricuspid vegetations ≥20mm with recurrent PEs despite antimicrobials
Reasonable to avoid in injection drug users

Treatment by Organism

Viridans group streptococci

Viridans group Strep that cause IE include Strep. sanguis, Strep. oralis (Strep. mitis), Strep. salivarius, Strep. mutans, and Gemella morbillorum
Strep. anginosus (milleri) group includes Strep. intermedius, Strep. anginosus, and Strep. constellatus
Strep. galloluticus (Strep. bovis)
Abiotrophia defectiva and Granulicatella (previously known as nutritionally-variant streptococci)

Native valve

MIC ≤0.12 mcg/mL
- PCN or CTX for 4 weeks
- PCN or CTX, plus gentamicin for 2 weeks
- Vanco for 4 weeks if intolerant, targeting levels of 10-15
MIC >0.12 & <0.5 mcg/mL
- PCN for 4 weeks, with concurrent gentamicin for first 2 weks
- CTX alone for 4 weeks
- Vancomycin for 4 weeks if intolerant
MIC ≥0.5 mcg/mL or A.defectiva or Granulicatella
- Amp or PCN, plus gentamicin
- Vancomycin if intolerant
- CTX plus gentamicin, if susceptible to CTX

Prosthetic valve

PCN or CTX for 6 weeks, with or without gentamicin for first 2 weeks
Extend gentamicin to 6 weeks if MIC >0.12 mcg/mL
Vancomycin if intolerant

Groups A, B, C, D, G Strep and Strep. pneumoniae

Penicillin-resistant S. pneumoniae

ceftriaxone + vanco + rifampin

Strep. pneumoniae

PCN/CFZ/CTX for 4 weeks
- 6 weeks for PVE
High-dose PCN or CTX if penicillin-resistant without meningitis
High-dose CTX if penicillin-resistant with meningitis
CTX plus vanco plus ridampin if cefotaxime MIC >2 mcg/mL

Strep. pyogenes (Group A Strep)

PCN or CTX for 4-6 weeks
Vancomycin if intolerant

Group B, C, G Strep

PCN or CTX for 4-6 weeks
PCN or CTX for 4-6 weeks, with gentamicin for first 2 weeks

Staphylococci

Native valve endocarditis (NVE)

No role for gentamicin or rifampin
Brain abscesses, use nafcillin/cloxacillin unstead of cefazolin
Unknown if combo clox+vanco is helpful
Duration
- 6 weeks for uncomplicated left MSSA NVE
- 6+ weeks for complicated left MSSA NVE
- 2 to 4 weeks for uncomplicated right Staph. aureus endocarditis
Dapto or vanco for left MRSA IE
PCN allergies: can use cefazolin, vanco, dapto; not clinda (higher relapse)
No role for additional rifampin

Prosthetic valve endocarditis (PVE)

CoNS
- vanco+rif for 6+ weeks, with gent in first 2 weeks
- CoNS resistant to gent, other AG
- CoNS resistant to AGs, FQ
Staph aureus
- Combo therapy, based on poor evidence
- Beta-lactam or vanco, plus gent for first 2 weeks
- With rifampin, based on poor evidence

Enterococci

Gent 3mg/kg/d split q8h
Options
- amp/pcn + gent
- amp + ctx
- avoid steptomycin if CrCl < 50
- vanco + gent x 6 weeks if allergic
- if resistant: vanco + AG, or dapto + amp, or dapto + ceftaroline
Duration
- 4-6 weeks for NVE depending on preceding duration of symptoms
- 6 weeks for amp/ctx
- 6 weeks for PVE

HACEK

Consider them ampicillin-resistant unless susceptibilities are available
Treat with ceftriaxone; no role for gentamicin
Second-line agent is a fluoroquinolone
Duration is 4 weeks for native-valve and 6 weeks for prosthetic valve

GNBs

Surgery
Combo of beta-lactam + AG/FQ x 6 weeks

Culture-negative IE

Native valve endocarditis
- Acute (days): S. aureus, beta-hemolytic streptococci, aerobic GNBs
- Subacute (weeks): S. aureus, VGS, HACEK, enterococci
Prosthetic valve endocarditis
- <1 yr: staphylococci, enterococci, aerobic GNBs
- >1 yr: staphylococci, VGS, enterococci

Scenario	Common organisms
IDU	Staph. aureus (including MRSA), Coagulase-negative staphylococci, β-hemolytic streptococci, fungi, aerobic GNBs (incl. Pseudomonas aeruginosa), and polymicrobial
Cardiac devices	Staph. aureus, Coagulase-negative staphylococci, fungi, aerobic GNBs, Corynebacterium
GU, including OB	Enterococcus, GBS (Strep. agalactiae), Listeria, aerobic GNBs, Neisseria gonorrhoeae
Chronic skin disorders	Staph. aureus, β-hemolytic streptococci
Dental conditions	Viridans group streptococci, nutritionally-variant streptococci, Abiotrophia defectiva, Granulicatella, Gemella, HACEK
Alcohol + cirrhosis	Bartonella, Aeromonas, Listeria, Strep. pneumoniae, β-hemolytic streptococci
Burn	Staph. aureus, aerobic GNBs (incl. Pseudomonas aeruginosa), fungi
Diabetes	Staph. aureus, β-hemolytic streptococci, Strep. pneumoniae
Early PVE (≤1 year)	Coagulase-negative staphylococci, Staph. aureus, aerobic GNBs, fungi, Corynebacterium, Legionella
Late PVE (> year)	Coagulase-negative staphylococci, Staph. aureus, Viridans group streptococci, Enterococcus, fungi, Corynebacterium
Dog or cat exposure	Bartonella, Pasteurella, Capnocytophaga
Milk, etc.	Brucella, Coxiella, Erysipelothrix

Fungi

Needs surgery in most cases
- Early surgery for left NVE
- Valve dysfunction causing heart failure
- ...
Anticoagulation
- If CNS embolism, stop a/c for 2+ weeks
- Adjunctive ASA/plavix not suggested
Lifelong oral azole suppression therapy followed intravenous therapy

Anticoagulation

Stop all anticoagulation after stroke for at least 2 weeks, even with mechanical valve

Follow-up

At or before completion of antimicrobials

TTE for new baseline before or at end of antibiotics
Refer to addictions service if appropriate
Education on signs of IE
Education on antibiotic prophylaxis for IE
Thorough dental evaluation
Remove PICC line

Short-term follow-up

3 sets of blood cultures for any febrile illness
Examine for heart failure
Assess for toxicity from antimicrobial therapy
- Delayed ototoxicity from aminoglycosides
- C. difficile-associated diarrhea

Long-term follow-up (months to years)

3 sets of blood cultures for any febrile illness
TTE in select patients
Good oral hygiene and frequent dentist visits