Infective endocarditis

Question 1

TTE vs TOE for diagnosis of endocarditis

Other investigations used in infective endocarditis

Answer 1

• TTE and TOE have similar specificity but TTE sensitivity much lower for endocarditis
  
  • TTE sen 70% (50% in PVE) - better day 5-7, consider repeat if initial negative and high clinical suspicion
  • TOE sen 96% (92% PVE)
  • Generally start with TTE. Recommend TOE after (particularly if prosthetic valve/cardiac device) regardless if negative or positive (exception if right sided valve involvement with good images)
• ECHO criteria for infective endocarditis:
  
  • Vegetations
  • Aortic root abscess
  • Valve regurgitations

Other investigations:

• Multi-slice CT can be used to detect abscesses with a diagnostic accuracy similar TOE
• MRI → cerebral MRI greater sensitivity than CT in identifying cerebral complications of IE → significant as in a non-definite IE case, confirming cerebral complications gives you a minor Duke Criterion

Question 2

Valves involved in endocarditis

Answer 2

• Incidence of endocarditis higher in bioprosthetic valves rather than mechanical valves

Question 3

Predisposing conditions associated with infective endocarditis

Answer 3

• Current IV drug use
• Previous IE
• Invasive procedure in last 60 days
• Chronic iV access
• Endocavitary device → pacemaker, ICD
• Congential heart disease
• Native valve predisposition
• Generally native valve > prosthetic valve > paemaker/ICD

Question 4

Microbiologic aetiology of infective endocarditis

Answer 4

In order of most common

• Staph. aureus
• Viridans group streptococci e.g. strep mutans group, strep sanguinis group, strep mitis group
• Coagulase negative staphylocci → mostly prosthetic valve, or pacemaker/ICD associated
• Enterococci
• Strep bovis and other strep
• HACEK organisms → Haemophilus species, Aggregatibacter species, Actinomycetemcomitans, cardiobacterium hominis, eikenella corrodens, kingella kingae
• Fungi/years
• Polymicrobial (1%)
• 10% culture negative

Considerations in elderly:

• Higher prevalence of CONS, enterococci, strep gallolyticus (predisposing bowel lesions) - consider colonscopy
• Drug regimens more likely to cause toxicity

Question 5

Management of enterococcus faecalis endocarditis

Answer 5

• Penicillin/amoxicillin 4-6 weeks PLUS gentamicin OD for 2-4 weeks
• If CrcL <50 → Ampicillin + ceftriaxone (6 weeks)

Ampicillin + ceftriaxone as effective as amoxicillin + gent and safer

Gent can be given as single daily dose and safely shortened from 4-6 week course to 2 weeks only

All enterococci

Reduced susceptibility to beta lactam antibiotics, decreases susceptibility to amoxicillin, penicillin. High level resistance to cephalosporins → requires addition of synnergy antibiotic to increase cure rates

• Addition of gentamicin → 4 log reduction in colony count

Question 6

RCTs looking at PO antibiotics for treatment of infective endocarditis

Answer 6

Iversen et al NEJM 2019 (POET Study)

• Left sided endocarditis, staphlycocci, streptococci, enterococci and coagulase negative staphylococci
• IV treatment vs switch to 2 x PO antibiotics (each with a different mechanism of action)
• Primary end point
  
  • All cause mortality
  • Unplanned cardiac surgery
  • Embolic event
  • Relapse of bacteraemia within 6 months
• PO arm non inferior
  
  • First study of its type - needs to be repeated
  • Very select group
  • Not all organisms responsible for endocarditis included
  • Argument that a lot of patients could have been cured by the time they were randomised (all got 10 days IV antibiotics before randomisation)

Question 7

Empiric therapy native valve endocarditis

Answer 7

• Benzylpenicillin 1.8g Q4H

PLUS

• Flucloxacillin 2g Q4H

PLUS

• Gentamicin

Flucloxacillin more effective than vancomycin for MSSA staph - if risk for MRSA replace benpen with vancomycin

If pen allergic → cefazolin + vanc + gent

Question 8

Empiric treatment of prosthetic valve endocarditis

Answer 8

• Fluclox + vanc + gent
• Pen allergic → replace fluclox with cefazolin
• Needs cardiothoracic surgery involvement

Question 9

Treatment of viridans group streptococci endocarditis

Answer 9

• 4 weeks ben pen or ceftriaxone

OR

• 2 weeks ben pen/ceftriaxone PLUS gentamicin
  
  • Synergistic killing effect on VGS and S. gallolyticus
  • Cure rates similar to those with 4 weeks monotherapy

Question 10

Treatment of MSSA infective endocarditis

Answer 10

• Flucloxacillin 2g Q4H 4-6 weeks
• Pen allergic → cafazolin
• Vancomycin is delayed severe hypersensitivity (desensitise if immediate)

Prosthetic valve endocarditis

• Flucloxacillin 12g/day for 6 weeks
• Some guidelines suggest rifampicin + gentamicin but significant toxicities

Question 11

Treatment of MRSA infective endocarditis

Answer 11

Native valve endocarditis

• IV vancomycin 6/52
  
  • Ceftaroline, daptomycin, linezolid (or adding cefazolin for synergistic effect) are other options

Prosthetic valve endocarditis

• Evidence poor, high mortality
• Some Guidelines add rifampicin and gentamicin for PVE as with MSSA but risk of toxicities
• Consult with cardiothoracics

Question 12

Notes on culture negative endocarditis

Answer 12

• IE with x3 negative blood cultures after 7 days
• Usually due to previous antibiotics
• Fastidious organisms
  
  • Q fever, bartonella, streps, legionella, whipples, mycoplasma hominis, chlamydophila, fungi, brucella
  • Can’t be cultured lol → coxiella burnetii, bordatella, chlamydia, legionella
• Ceftriaxone 2g OD 4-6 weeks for HACEK organisms

Question 13

Notes on prosthetic valve endocarditis

Answer 13

• Longer courses of therapy (+6 weeks therapy). Consider adding rifampicin for S. aureus
• TOE mandatory for diagnosis
• PET may have a role
• Poorer prognosis (often older, comorbid)
• Early → perioperative contamination
  
  • Usually involves junction between sewing ring and annulus - more likely to get perivalvular abscess and dehiscence
• Late
  
  • Often on the leaflets
  • Similar micro to NVE

Question 14

Notes on right sided infective endocarditis

Answer 14

• 5-10% IE, often IVDU
  
  • Also cardiac devices, congenital heart disease
• Right sided vegetations - lower bacterial densities
• Staph. aureus 60-90%
• Often two weeks of treatment is sufficient
  
  • If bacteraemia cleared quickly, no large vegetations or septic pulmonary emboli or complications

Question 15

Indications for surgery in infective endocarditis

Answer 15

• Severe AR or MR
• Heart failure (from valve dysfunction) - most freqent complication and most common indication for surgery
• Fungal or MDR organism
• Perivalvular abscess
• Prosthetic valve endocarditis
• Uncontrolled infection, ongoing emboli on therapy/persistent bacteraemia
• Size of vegetation (>1cm)

Question 16

Notes on cardiac device infections

Answer 16

• Either local device infection OR cardiac device related infective endocarditis (extending to electrode leads, cardiac valve leaflets, or endocardial surface)
  
  • Hard to defferentiate in practice
• Staphylococci, and especially CONS, account for 60-80%
• Need to remove hardware, often do 4-6 weeks (minimum 2 weeks post removal)

Question 17

Cardiac conditions for which endocarditis prophylaxis is recommended

Answer 17

• Prosthetic heart valve
• Rheumatic valvular heart disease
• Previous endocarditis
• Unrepaired cyanotic congenital heart disease
• Surgical or catheter repair of congenital heart disease within 6 months of repair procedure

Prophylaxis required for:

• All dental procedures involving manipulation of gingival tissue or the periapical region of teeth or perforation of the oral mucosa
• Tonsillectomy/adenoidectomy
• Procedures involving infected tissues (for which you would be giving antibiotics anyway)
• ?Lithotripsy

Antibiotics - amoxicillin, clindamycin if pen allergic (for dental procedures)

Question 18

General measures for prevention of endocarditis in medium- to high-risk individuals

Answer 18

Question 19

Notes on microbiological diagnosis of infective endocarditis

Answer 19

• 3 sets of blood cultures 30 minutes apart
• When organism identified → should repeat cultures after 48 - 72 hours to determine if cleared
• Pathological examination of resected valvular tissue/embolic fragments → gold standard for diagnosis IE
• When high clinical suspicion and cultures remain negative after 48 hours → look for fastidious organisms and add on ANA, RF, antiphospholipid antibodies +/- anti-pork antibodies if bio-prosthetic valve

Question 20

Diagnostic criteria for infective endocarditis

Answer 20

Definite IE

• Pathological criteria
  
  • Microorganisms demonstrated by culture or on histological exam of a vege, vege that hsa embolised or intracardiac abscess or
  • Patholigcal lesions; vegetation/intracardiac abscess confirmed by histological exam showing active endocarditis
• Clinical critera
  
  • 2 major criteria or
  • 1 major criterion and 3 minor criteria or
  • 5 minor criteria

Possible IE

• 2 major and 1 minor
• 3 minor

Rejected IE

• Resolution of symptoms suggesting IE with antibiotics therapy ≤4 days
• No pathological evidence IE at surgery or autopsy

Question 21

Predictors of poor outcome in patients with infective endocarditis

Answer 21

Question 22

Complications of infective endocarditis

Answer 22

• Heart failure
  
  • Usually due to new/worsening MR/AR
  • In NVE often aortic > mitral
• Perivalvular extension of infection
  
  • Abscess, psuedoaneursyms, fistulae
  • Poor prognosis, high liklihood of need for surgery
• Systemic embolism (20-50%) → risk highest first 2 weeks therapy
  
  • CNS → stroke, TIA, haemorrhage, brain abscess, meningitis. Seen in S.aureus more commonly than other organisms
  • Spleen → emboli common and often asymptomatic. Abscess uncommon.
  • Myocarditis and pericarditis
  • Conduction disturbances → uncommon - mainly heart blocks and generally associated with perivalvular complications
  • MSK → frequent athralgia, myalgia, back pain. Can see vertebral osteomyelitis.
  • Acute renal failure → immune complex and vasculitic GN, renal infarction (septic emboli), haemodynamic (severe sepsis, cardiac surgery), AIN related to antibiotics

Question 23

Factors associated with increased risk of relapses

Answer 23