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

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

Native valve endocarditis (NVE)

• Treat with either an oxacillin relative or cefazolin
  • No role for gentamicin or rifampin
  • If brain abscesses, use nafcillin/cloxacillin instead of cefazolin
  • Unknown if combo cloxacillin + vancomycin is helpful
• Duration
  • 6 weeks for uncomplicated left MSSA NVE
  • 6+ weeks for complicated left MSSA NVE
  • 2 to 4 weeks for uncomplicated right-sided Staph. aureus endocarditis
• Daptomycin or vancomycin for left MRSA IE
• If penicillin allergy, can use cefazolin, vancomycin, daptomycin; not clindamycin (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

Gram-negative bacilli

• Surgery is generally indicated
• Treat with a combination of a beta-lactam and an aminoglycoside or fluoroquinolone
• Duration is 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