155 - Endocarditis

Front 1

Vegetation - definition

Back 1

a mass of platelets, fibrin, microcolonies of microorganisms and scant inflammatory cells.

Front 2

Common infection sites (in the heart)

Back 2

endocarditis most commonly involves heart valves, but may also occur on the low-pressure side of VSD, on mural endocardial damage, or on intracardiac devices.

Front 3

Infective endarteritis

Back 3

the analogous process to endocarditis, involving arteriovenous shunts, arterio-arterial shunts (PDA) or coarctation of the aorta.

Front 4

Difference between acute and subacute endocarditis, and common pathogens causing each condition

Back 4

acute endocarditis - hectically febrile illness, rapid damage to cardiac structures, seeds extracardiac sites, without treatment progresses to death within weeks.

Pathogens -

# Beta-hemolytic streptococcus

# Staphylococcus Aureus (may also cause subacute disease)

# Staphylococcus Lugdunensis

# Pneumococci

# Enterococci (may also cause subacute)

Subacute endocarditis - indolent course, slow cardiac damage if any, rarely metastasizes, gradually progressing unless complicated by a major embolic event or a ruptured mycotic aneurysm (aneurysm arising from bacterial infection of the arterial wall).

Pathogens -

# Viridans Streptococcus

# Enterococcus

# HACEK group

# Bartonella spp, Tropheryma Whipplei, Coxiella Burnetii - exceptionally indolent.

Front 5

Epidemiology - incidence, predisposing condition in developed countries

Back 5

4-7 cases per 100,000 population per year. Remains relatively stable over decades.

Incidence notably increased among elderly.

Predisposing factors -

# congenital heart disease

# illicit drug use

# degenerative valve disease

# intracardiac devices

Chronic rheumatic heart disease is still a common factor in developing countries.

Front 6

Epidemiology - percentage of NVE associated with health-care, most common pathogens

Back 6

25-35% of native valve endocarditis (NVE) are associated with health-care.

Most commonly caused by -

# Staphylococcus Aureus.

# Coagulase-negative staphylococcus (CONS).

# Enterococci.

Front 7

Epidemiology - percentage of prosthetic valve endocarditis, period of greatest risk

Back 7

16-30% of all endocarditis involves prosthetic valves.

the risk is greatest during first 6-12 months after valve replacement.

Risk is similar for mechanical and bioprosthetic valves.

Front 8

Endocarditis - common pathogens and their site of origin

Back 8

1. Viridans Streptococci - originates from oral cavity.

2. Staphylococcus - originates from skin.

3. HACEK - originate from upper respiratory tract.

# Haemophilus spp.

# Aggregatibacter aphrophilus, Aggregatibacter Actinomycetemcomitans

# Cardiobacterium spp.

# Eikenella spp.

# Kingella spp.

Front 9

Endocarditis after catheter placement - percentage and pathogen involved

Back 9

Endocarditis complicated 6-25% of episodes of catheter-associated Staphylococcus Aureus bacteremia.

Front 10

PVE - common pathogens in different time periods

Back 10

PVE (prosthetic valve endocarditis) within 2 months of surgery is generally nosocomial (due to inoperative contamination or bacteremic postoperative complication).

Common pathogens -

# Staphylococcus Aureus.

# CONS.

# facultative gram-negative bacilli.

# Diphtheroids.

# Fungi.

PVE due to CONS 2-12 months after surgery => delayed nosocomial infection.

PVE > 12 months after surgery => similar to community-acquired NVE.

regardless time of onset - 68-85% of PVE due to CONS are resistant to methicillin.

Front 11

CIED endocarditis - incidence, time frame and common pathogens

Back 11

CIED (cardiovascular implantable electronic devices) endocarditis incidence rate - 0.5-1.14 cases per 1,000 devices.

Higher among patients with implantable defibrillator than permanent pacemaker.

Third of the patients presents within 3 months, third within 4-12 months, and third after >1 year.

Common pathogens -

# Staphylococcus Aureus.

# CONS.

Both commonly resistant to methicillin.

Front 12

Injection drug use-associated endocarditis - common site, common pathogens, association with HIV

Back 12

Right-sided endocarditis - 50% of Injection drug use-associated endocarditis are limited to the tricuspid valve. Commonly caused by Staphylococcus Aureus, often resistant to methicillin.

Left-sided endocarditis - more varied etiology -

# Staphylococcus Aureus.

# Pseudomonas Aeruginosa.

# Candida spp.

# Bacillus, Lactobacillus, Corynebacterium spp. - in sporadic cases.

Polymicrobial endocarditis occurs in drug users.

HIV infection does not significantly influence the causes of endocarditis.

Front 13

Blood cultures in endocarditis - percentage of negative cultures and common reasons for negative cultures

Back 13

5-15% of blood cultures are negative.

30-50% of them due to prior antibiotic treatment. The remainder - due to fastidious organisms.

Front 14

NBTE - definition and causes

Back 14

Nonbacterial thrombotic endocarditis - platelets-fibrin thrombus, can serve as a site of bacterial attachment during transient bacteremia.

Except for virulent bacteria (e.g. S. Aureus) that can adhere directly to intact endothelium, microorganisms adhere to NBTE.

Conditions resulting in NTBE -

# MR.

# AR.

# AS.

# VSD.

# Complex congenital heart disease.

#Hypercoagulable state - causes marantic endocarditis and bland vegetations complicating SLE and APS.

Front 15

Marantic endocarditis - definition

Back 15

Uninfected heart vegetations seen in patients with malignancy and chronic diseases.

Front 16

Clinical manifestations of endocarditis - from most frequent to least

Back 16

# Fever - 80-90%. In subacute endocarditis, fever is low-grade (<39.4). In acute endocarditis, fever often high (39.4-40). Fever may be blunted in elderly, severely debilitated and renal failure.

# Heart murmur - 80-85%.

# Chills and sweats - 40-75%.

# Anorexia, weight loss, malaise - 25-50%.

# New\worsened regurgitant murmur - 20-50%.

# Arterial emboli - 20-50%.

# Splenomegaly - 15-50%.

# Neurological manifestations - 20-40%.

# Petechia - 10-40%.

# Myalgia, arthralgia - 15-30%.

# Clubbing - 10-20%.

# Back pain - 7-15%.

# Peripheral manifestations - 2-15%.

Front 17

Laboratory findings - from most frequent to least

Back 17

# Circulating immune complexes - 65-100%.

# Anemia - 70-90%.

# Elevated ESR - 60-90%.

# Elevated CRP - >90%.

# Rheumatic factor - 50%.

# Microscopic hematuria - 30-50%.

# Decreased serum complement - 5-40%.

# Leukocytosis - 20-30%.

Front 18

Cardiac manifestations in endocarditis

Back 18

Valvular rupture or ruptured chordae may result in new regurgitant murmurs.

In acute endocarditis involving normal valve, murmur may be absent initially but ultimately detected in 85% of cases.

30-40% develop CHF due to valvular dysfunction.

CHF due to aortic valve dysfunction progresses more rapidly than mitral valve dysfunction.

Extension of infection can progress to perivalvular abscesses, which may cause intracardiac fistula and new murmurs.

Abscesses may progress to pericarditis or interrupt the conduction system, leading to various degrees of heart block.

Mitral perivalvular abscesses only rarely cause conduction abnormalities, but when they do, they most likely disrupt the AV node or proximal bundle of His.

Emboli to a coronary artery occurs in 2%, and may result in MI.

Front 19

Noncardiac manifestations - skin

Back 19

Nonsuppurative peripheral manifestations of subacute endocarditis (e.g. Janeway lesions) are associated with a prolonged infection and therefore are less common.

Septic embolization (e.g. subungual hemorrhage, Osler's nodes) are common in patients with acute S. Aureus endocarditis.

Front 20

Noncardiac manifestations - Emboli and hematogenously seeded focal infections

Back 20

Hematogenously seeded focal infections most often occur in skin, spleen, kidneys, skeletal system and meninges.

In 50% of cases there are arterial emboli, and 50% of arterial emboli precede the diagnosis.

Factors independently associated with increased risk of embolization -

# Endocarditis by Staphylococcus Aureus.

# Vegetations > 10 mm.

# Involvement of the mitral valve, especially anterior leaflet.

Focal metastatic infection (e.g. spondylodiscitis) causing musculoskeletal pain complicate 10-15% of cases.

Front 21

Noncardiac manifestation - Neurological manifestations

Back 21

Cerebrovascular emboli, presenting as stroke or sometimes encephalopathy, complicate 15-35% of endocarditis cases. 50% of them precede diagnosis.

The frequency of stroke declines during 1-2 weeks of therapy. only 3% of strokes occur after 1 week of effective therapy.

Other neurological complications -

# Aseptic or purulent meningitis.

# Intracranial hemorrhage - due to hemorrhagic infarcts or ruptured mycotic aneurysms.

# Seizures.

# Microabscesses in brain and meninges - occur commonly in Staphylococcus Aureus endocarditis.

Surgically drainable abscesses are rare.

Front 22

Noncardiac manifestations - Kidneys

Back 22

Immune complex deposition on GBM cause diffuse hypocomplementemic glomerulonephritis and renal dysfunction, which typically improves with therapy.

Embolic renal infarcts cause flank pain and hematuria, but rarely cause renal dysfunction.

Front 23

Manifestations of drug use-associated endocarditis

Back 23

50% are limited to the tricuspid valve.

Presents with fever but faint or no murmur, and no peripheral manifestations.

Septic pulmonary emboli are common in right-sided endocarditis, causing cough, pleuritic chest pain, nodular pulmonary infiltrates, and occasionally pyopneumothorax.

Front 24

Manifestations of health care-associated endocarditis

Back 24

typical manifestations

Front 25

Manifestations of CIED endocarditis

Back 25

May present with obvious\cryptic generator pocket infection, fever, minimal murmur, septic pulmonary emboli and related pulmonary symptoms.

Front 26

Manifestations of PVE

Back 26

In early onset (60 days from surgery), typical symptoms may be obscured by comorbidity associated with recent surgery.

Late onset PVE has typical manifestations.

In both early and late onset, paravalvular infection is common, causing partial valvular dehiscence, regurgitant murmurs, CHF, and conduction system abnormalities.

Front 27

Modified Duke criteria - how many criteria allow clinical diagnosis of definite endocarditis?

Back 27

one of the following combinations -

# 2 major.

# 1 major and 3 minor.

# 5 minor.

Front 28

Modified Duke criteria - how many criteria allow clinical diagnosis of possible endocarditis?

Back 28

# 1 major and 1 minor.

# 3 minor.

Front 29

Modified Duke criteria - in which cases the diagnosis of endocarditis is rejected?

Back 29

# an alternative diagnosis is established.

# symptoms resolve and do not recur after <4 days of antibiotics.

# surgery or autopsy after <4 days of antibiotics yield no histologic evidence of endocarditis.

Front 30

What allow establishing of a certain diagnosis of endocarditis?

Back 30

Diagnosis is certain only when vegetations are examined histologically and microbiologically.

Front 31

Modified Duke criteria - Major criteria

Back 31

1) Positive blood cultures - one of the following cases -

# Typical microorganism for infective endocarditis from two separate blood cultures:

Viridans Streptococci, Streptococcus gallolyticus (bovis), HACEK group, Staphylococcus Aureus;

or community-acquired Enterococci in the absence of a primary focus.

# Persistent positive blood culture consistent with infective endocarditis from:

blood cultures drawn >12 hr apart;

or all 3 or the majority of >4 separate blood culture with first and last drawn at least 1 hr apart.

# Single positive blood culture for Coxiella Burnetii or phase 1 IgG antibody titer >1:1800.

2) Evidence of endocardial involvement - one of the following -

# Positive echocardiogram:

Oscillating cardiac mass in the absence of alternative anatomical explanation;

or abscess;

or new partial dehiscence of prosthetic valve.

# New valvular regurgitation (increase or change in existing murmur not sufficient).

Front 32

Modified Duke criteria - Minor criteria

Back 32

1) Predisposition - heart conditions or injection drug use.

2) Fever > 38.

3) Vascular phenomena - major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhage, Janeway lesions.

4) Immunological phenomena - GN, Osler nodes, Roth spots, RF.

5) Microbiologic evidence - positive blood culture but not meeting major criteria, or serologic evidence of active infection by pathogen consistent with endocarditis.

Front 33

Blood cultures - general guidelines for taking blood cultures

Back 33

In patients with suspected endocarditis who have not received antibiotics in the prior 2 weeks - three 2-bottle culture sets, separated by 2 hr at least, from different venipuncture sites, over 24 hr.

If cultures remain negative after 48-72 hr - additional 2-3 culture sets + consult laboratory on techniques.

Front 34

Blood cultures - situations in which empirical antibiotics should be withheld\given

Back 34

Empirical antibiotic should be withheld in hemodynamically stable patients with subacute disease, especially those who received antibiotics in prior 2 weeks.

Patients with acute disease or deteriorating hemodynamics who may require urgent surgery should receive empirical treatment immediately after three sets of blood cultures are obtained.

Front 35

Non-blood-culture tests

Back 35

# Serologic tests - for organisms that are difficult to recover from cultures (Brucella, Bartonella, Legionella, Chlamydia psittaci, Coxiella Burnetii).

# Microscopic examination with special stains.

# PCR.

Front 36

Echocardiography - TTE limitations

Back 36

TTE detects vegetations in 65-80% of patients with definite endocarditis.

TTE limitations -

# Cannot identify vegetation <2 mm.

# 20% of patients are technically inadequate because of emphysema or body habitus.

# not optimal for evaluating prosthetic valves.

# not optimal for imaging intracardiac complications.

Therefore, TTE is used for screening patients with low initial risk and low clinical suspicion of endocarditis.

Front 37

Echocardiography - TEE benefits and downsides

Back 37

TEE detects vegetations in >90% of endocarditis patients.

TEE is optimal method for the diagnosis of PVE, myocardial abscess, valve perforation, intracardiac fistula, and vegetations in CIED patients.

Therefore, TEE is used to screen patients with high initial risk, moderate to high clinical suspicion or difficult imaging candidates.

Note that TEE yields false negative results in 6-18% of cases. Therefore, when endocarditis is likely, negative TTE does not exclude the diagnosis, but rather warrants 1-2 more tests in 7-10 days.

Front 38

Guidelines for endocarditis workup in patients with Staphylococcus Aureus bacteremia

Back 38

Because S. Aureus bacteremia is associated with a high prevalence of endocarditis, echocardiography is recommended.

In patients with increased risk of endocarditis, TEE is preferable -

# positive blood cultures for 2-4 days.

# hemodialysis dependency.

# permanent intracardiac device.

# spine infection.

# nonvertebral osteomyelitis.

# endocarditis-predisposing valve abnormality.

In patients with no high risk factors, TTE may suffice.

Front 39

Additional tests in endocarditis patients

Back 39

non-diagnostic tests that are important for the management of endocarditis patients -

# complete blood count.

# creatinine determination.

# CXR.

# ECG.

Front 40

Antibiotic treatment - what type of antibiotics must be used, duration and method of administration

Back 40

Therapy must be bactericidal and prolonged - to cure endocarditis, all bacteria in the vegetation must be killed. It is difficult to eradicate because local host defences are deficient and the bacteria are largely non-growing and metabolically inactive.

Antibiotics are generally given parenterally.

The regimens for PVE (except S. Aureus) and NVE are similar, except PVE treatment is given for several weeks longer.

Front 41

Antibiotic treatment for infective endocarditis caused by Streptococci

Back 41

1) Penicillin-susceptible streptococci, S. gallolyticus -

# Penicillin G (2-3 mU q4h for 4 weeks)

# Ceftriaxone (2 g per day IV for 4 weeks) - use in patients with non-immediate penicillin allergy.

# Vancomycin (15 mg\kg IV q12h for 4 weeks) - use in patients with severe or immediate beta-lactam allergy.

# Penicillin G (2-3 mU IV q4h for 2 weeks) or Ceftriaxone (2 g IV per day for 2 weeks) plus Gentamicin (3 mg\kg per day, IV or IM, as single dose or divided into equal doses q8h, for 2 weeks) - avoid 2-week regimen when risk of aminoglycoside toxicity is increased, and in prosthetic valve or complicated endocarditis.

2) Relatively penicillin-resistant Streptococci (0.1

# Penicillin G (4 mU q4h IV for 4 weeks) or Ceftriaxone (2 g per day IV for 4 weeks) plus Gentamicin (3 mg\kg per day, as single dose or divided into equal doses q8h, for 2 weeks).

Penicillin alone for 6 weeks, or with gentamicin during first 2 weeks, is the preferred treatment for PVE by streptococci with penicillin resistance MIC<0.1.

# Vancomycin (15 mg\kg IV q12h for 4 weeks).

3) moderately penicillin-resistant streptococci (0.5nutritionally variant organisms, Gemella spp -

# Penicillin G (4-5 mU IV q4h for 6 weeks) or Ceftriaxone (2 g IV qd for 6 weeks) plus Gentamicin (3 mg\kg qd, as single dose or divided into equal doses q8h, for 6 weeks).

# Vancomycin (15 mg\kg IV q12h for 4 weeks).

To treat PVE on complicated NVE, a course longer that 2 weeks is warranted.

Treat pneumococci B, C and G groups as Penicillin-resistant Strep.

Front 42

Antibiotic treatment for infective endocarditis caused by Enterococci

Back 42

Killing Enterococci requires a synergistic interaction of cell wall antibiotics and an aminoglycoside to which the isolate is susceptible.

If the isolate is resistant to Gentamicin and Streptomycin, cell wall antibiotic alone should be given for 8-12 weeks.

If the patient develops aminoglycoside toxicity after 2-3 weeks, stop the drug.

# Penicillin G (4-5 mU q12h IV) plus Gentamicin (1 mg\kg IV q8h) both for 4-6 weeks.

can substitute Streptomycin (7.5 mg\kg q12h) for gentamicin if there is no streptomycin-resistance.

# Ampicillin (2 g q4h IV) plus Gentamicin (1 mg\kg q8h IV) both for 4-6 weeks.

# Vancomycin (15 mg\kg q12h IV) plus Gentamicin (1 mg\kg q8h IV) both for 4-6 weeks - use for patients with penicillin allergy, and isolates resistant to penicillin and ampicillin.

# Ampicillin (2 g q4h IV) plus Ceftriaxone (2 g g12h IV) both for 4-6 weeks - use for E. Faecalis isolated with high-resistance to gentamicin and streptomycin, or for patients with high risk of aminoglycoside toxicity.

Front 43

Antibiotic treatment for infective endocarditis caused by Staphylococci

Back 43

1) MSSA NVE (no foreign devices) -

# Penicillin (4 mU q4h IV for 4-6 weeks) - if isolate is penicillin-susceptible (does not produce beta-lactamase).

# Nafcillin, oxacillin or flucloxacillin (2 g q4h IV 4-6 for weeks) - narrow spectrum beta-lactam antibiotics resistant to beta-lactamase.

# Cefazolin (2 g IV q8h for 4-6 weeks) - for patients with non-immediate penicillin allergy.

# Vancomycin (15 mg\kg q12h IV for 4-6 weeks) - for patients with immediate or severe penicillin allergy.

Additional of gentamicin, rifampicin (rifampin) or fusidic acid is not recommended.

2) MRSA NVE (no foreign devices) -

# Vancomycin (15 mg\kg q8-12h IV for 4-6 weeks).

VISA (vancomycin intermediate S. Aureus) - isolates with vancomycin MIC of 4-16 have intermediate susceptibility.

hVISA (heteroresistant VISA) - isolates with vancomycin MIC of 2 may containt subpopulation with higher MICs.

# Daptomycin (6 or 8-10 mg\kg qd IV) - alternative to vancomycin, particularly for left-sided endocarditis, VISA, hVISA or isolated with vancomycin MIC>1. Daptomycin activity is enhanced by adding nafcillin or ceftaroline (advanced-generation cephalosporins).

3) MSSA PVE -

# Nafcillin\oxacillin\flucloxacillin (2 g q4h IV for 6-8 weeks) plus Gentamicin (1 mg\kg IM or IV q8h for 2 weeks) plus Rifampicin (300 mg PO q8h for 6-8 weeks) -

Rifampicin is essential because it kills staphylococci that are adherent to foreign material in a biofilm.

Two other agents should be added to Rifampicin - if isolate is resistant to gentamicin, add other aminoglycoside, fluoroquinolone or other susceptible agent.

If the patient is severely allergic to beta-lactams, use MRSA regimen.

If the patient has minor non-immediate allergy, use cefazolin instead of nafcillin\oxacillin.

4) MRSA PVE -

# Vancomycin (15 mg\kg q12h IV for 6-8 weeks) plus Gentamicin (1 mg\kg q8h IM or IV for 2 weeks) plus Rifampicin (300 mg PO q8h for 6-8 weeks).

Front 44

Antibiotic treatment for infective endocarditis caused by HACEK group

Back 44

# Ceftriaxone (2 g qd for 4 weeks) - can be substituted by another third-generation cephalosporin.

# Ampicillin-sulbactam (3 g q6h IV for 4 weeks).

Front 45

Antibiotic treatment for infective endocarditis caused by Coxiella Burnetii

Back 45

# Doxycycline (100 mg PO q12h) plus hydroxychloroquine (200 mg PO q8h) - both 18 months for native valve and 24 months for prosthetic valve.

Follow serology to monitor response during treatment (IgG and IgA decrease 4-fold and IgM negative) and after for relapse.

Front 46

Antibiotic treatment for infective endocarditis caused by Bartonella spp.

Back 46

Gentamicin (1 mg\kg IV q8h for 3 weeks) plus one of the following -

# Ceftriaxone (2 g qd IV for 6 weeks)

# Ampicillin (2 g q4h IVfor 6 weeks)

# Doxycycline (100mg PO q12hfor 6 weeks) - if patient is allergic to beta-lactams, use doxycycline.

Front 47

Antibiotic treatment for infective endocarditis caused by Strep. Pneumonia

Back 47

1) In the absence of meningitis -

# penicillin MIC < 1 - treat with Penicillin (4 mU q4h for 4 weeks) or Ceftriaxone\cefotaxime (2 g qd for 4 weeks).

# penicillin MIC > 2 - Vancomycin (15 mg\kg q12h IV for 4 weeks).

2) If meningitis is suspected or present - start empirical treatment with vancomycin plus Ceftriaxone until susceptibility results are known.

Front 48

Antibiotic treatment for infective endocarditis caused by Pseudomonas Aeruginosa

Back 48

# anti-pseudomonal beta-lactam (ticarcillin or piperacillin) + high-dose Tobramycin (8 mg\kg per day in 3 doses).

Front 49

Antibiotic treatment for infective endocarditis caused by Enterobacteriaceae

Back 49

potent beta-lactam + aminoglycoside

Front 50

Antibiotic treatment for infective endocarditis caused by Corynebacteria

Back 50

Penicillin plus either aminoglycoside or vancomycin (if isolate is resistant to aminoglycoside)

Front 51

Antibiotic treatment for infective endocarditis caused by Candida

Back 51

Amphotericin B + flucytosine + early surgery.

Long-term (if not indefinite) suppression with oral azole is advised.

Front 52

Empirical antibiotic treatment of endocarditis and treatment of culture-negative endocarditis

Back 52

In treatment of culture-negative endocarditis, marantic endocarditis should be excluded and fastidious organisms sought out using serologic tests.

Culture-negative PVE <1 year after surgery => empirical treatment includes Vancomycin, Gentamicin, Cefepime and Rifampicin.

culture-negative PVE >1 year after surgery => similar to culture-negative NVE (Gentamicin + Ceftriaxone).

In the absence of prior antibiotic treatment, it is unlikely that S. Aureus, CONS or Enterococci will present with negative cultures => empirical treatment should rather target HACEK group, nutritionally variant organisms and Bartonella => Gentamicin + Ampicillin-Sulbactam or Ceftriaxone + Doxycycline.

Empirical treatment for acute endocarditis in an injection drug user should cover MRSA and gram-negative bacilli => Vancomycin + Gentamicin.

Health care associated endocarditis must also cover MRSA.

Front 53

CIED endocarditis treatment

Back 53

Antimicrobial treatment is adjunctive to complete device removal.

A 4-6 week course of therapy is recommended for patients with CIED endocarditis, and for bacteremia that continues during antimicrobial treatment after device removal.

Not all blood stream infection in CIED patients are endocarditis - if evidence suggesting endocarditis is lacking, BSI due to gram-negative bacillus, streptococci, enterococci and candida may not indicate endocarditis.

Front 54

Outpatient antimicrobial therapy in endocarditis

Back 54

Outpatient therapy is possible when patients are fully compliant, clinically stable, no longer bacteremic, not febrile, and have no clinical or echographic finding that suggest an impending complication.

Front 55

Monitoring antimicrobial treatment - monitoring drug toxicity

Back 55

Antibiotic toxicities (including allergies) occur in 25-40% of patients, commonly after several weeks.

Blood tests to detect renal, hepatic and hematologic toxicity should be performed periodically.

Serum concentration of aminoglycoside and vancomycin should be monitored to avoid and address toxicity.

Front 56

Monitoring antimicrobial treatment - monitoring blood cultures

Back 56

Blood cultures should be repeated daily until sterile in S. Aureus and other difficult-to-treat organisms, rechecked if fever is recurring, and redone 4-6 weeks after therapy to document cure.

Blood cultures became sterile with appropriate therapy within -

# 2 days in infection of strep. viridans, enterococcus and HACEK.

# 3-5 days in S. aureus infection.

# 7-9 days or more in MRSA infection.

Front 57

Monitoring antimicrobial treatment - persistent fever

Back 57

If fever persists more than 7 days with therapy, the patients should be reevaluated for paravalvular abscess, extracardiac abscesses or complications (embolic events).

Front 58

Monitoring antimicrobial treatment - monitoring vegetation size

Back 58

Vegetations may become smaller with therapy, but 3 months after cure 50% are unchanged and 25% are slightly larger.

Front 59

Indications for cardiac surgical intervention in patients with endocarditis

Back 59

Surgery required for optimal outcome -

# Moderate-severe CHF due to valvular dysfunction.

# Partially dehisced or unstable prosthetic valve.

# Persistent bacteremia despite optimal antibiotic treatment.

# S. Aureus PVE with intracardiac complication.

# Relapse of PVE after optimal antibiotic treatment.

Surgery to be strongly considered for optimal outcome -

# Perivalvular extension of infection.

# Poorly responsive S. aureus endocarditis involving aortic or mitral valve.

# Large (>10 mm) hypermobile vegetations with increased risk of embolism, particularly with prior embolic event or significant valvular dysfunction.

# Persistent (>10 days) unexplained fever in culture-negative NVE.

# Poorly responsive or relapsed endocarditis due to highly-resistant enterococci or gram-negative bacilli.

Front 60

Timing of cardiac surgical intervention in patients with endocarditis (strong supporting evidence)

Back 60

Emergent (same day) -

# Acute aortic regurgitation plus preclosure of mitral valve.

# Sinus of Valsalva abscess ruptured into right heart.

# Rupture of pericardial sac.

Urgent (1-2 days) -

# Valve obstruction by vegetation.

# Unstable (dehisced) prosthesis.

# Acute aortic\mitral regurgitation with heart failure.

# Septal perforation.

# Perivalvular extension of infection with\without new ECG conduction changes.

# Lack of effective antibiotic therapy.

Elective -

# Vegetation > 10 mm plus severe aortic\mitral valve dysfunction.

# Progressive paravalvular prosthetic regurgitation.

# Valve dysfunction plus persistent infection after >7-10 days of therapy.

# Fungal (mold) endocarditis.

Front 61

Surgical treatment of endocarditis - percentage, improvement in survival

Back 61

25-40% of patients with left-sided endocarditis undergo surgery during active infection, with slightly higher rates for PVE than NVE.

Surgery for current advised indication conveys a significant survival benefit (27-55%) only with >6 months follow-up.

During initial weeks after surgery, mortality risk may increase.

Front 62

Surgery indications - CHF (mortality rate with medical vs surgical treatment)

Back 62

Moderate-severe refractory CHF due to new\worsening valvular dysfunction is the major indication for surgery.

The mortality rate after 6 months with medical treatment was 50%, with surgical treatment - only 15%.

The survival benefit is seen both in NVE and PVE.

Front 63

Surgery indications - perivalvular infection (commonly involved valve, test of choice, major paravalvular complication requiring monitoring)

Back 63

Perivalvular infection is most common with aortic valve involvement, occurs in 10-15% of NVE and 45-60% of PVE.

TEE with color Doppler is the test of choice for detection.

Surgery is required for optimal outcome, especially with persistent fever, fistula, unstable or dehisced prosthesis, or relapse of infection after appropriate therapy.

Heart rate should be monitored because high-grade heart block may develop and require a pacemaker.

Front 64

Surgery indications - Uncontrolled infection (the presentation of uncontrolled infection)

Back 64

may present as -

# continued positive blood cultures.

# otherwise-unexplained persistent fever.

# pathogens without effective antimicrobial therapy - yeasts, fungi, Pseudomonas Aeruginosa, highly resistant gram-negative bacilli, Brucella spp.

Front 65

Surgery indications - S. Aureus PVE (mortality rate with medical vs surgical treatment), S. Aureus NVE (approach to different valves)

Back 65

PVE - mortality rate of S. Aureus PVE exceeds 50% with medical treatment, but reduced to 25% with surgical treatment.

NVE -

# aortic or mitral NVE - surgical treatment should be considered in patients who demonstrate vegetations on echocardiography, and who remain septic after the initial week of therapy.

# tricuspid NVE - rarely requires surgery, even with persistent fever.

Front 66

Surgery indications - Prevention of systemic emboli (how often is it the indication for surgery, in what condition is the surgery most beneficial)

Back 66

Only 3.5% of patients undergo surgery solely to prevent systemic emboli.

Net benefit from surgery to prevent emboli most likely when other surgical benefits can be achieved simultaneously (e.g. repair of moderately dysfunctional valve, debridement of paravalvular abscess).

Front 67

Surgery indications - CIED endocarditis (the recommended approach regarding device removal, re-implantation)

Back 67

Removal of all hardware is recommended for patients with established CIED infection.

Percutaneous lead extraction is preferred. Surgical removal should be considered if lead vegetation > 3mm, or there is retained hardware after percutaneous extraction.

CIED can be re-implanted percutaneously or surgically at a new site after >10-14 days of effective antimicrobial therapy.

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Surgical treatment - justifications for delaying surgery

Back 68

Delay is justified if infection is controlled, and CHF is resolved with medical treatment.

Neurological complications - can be exacerbated by cardiac surgery. Whenever feasible, cardiac surgery should be delayed for 2-3 weeks after non-hemorrhagic embolic infarction, and 4 weeks after a cerebral hemorrhage.

A ruptured mycotic aneurysm should be treated before cardiac surgery.

Relapsed endocarditis on implanted valve - follows surgery for active NVE in 2%, and PVE in 6-15%. this does not justify a delay in surgery, particularly in patients with severe heart failure, valve dysfunction and uncontrolled staphylococci infection.

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Duration of postoperative antibiotic therapy

Back 69

In uncomplicated NVE caused by susceptible organism with negative valve cultures (from excised valves) - the duration of pre plus post operative therapy should equal the total duration of the recommended regimen, with ~2 weeks of therapy administered after surgery.

In endocarditis with paravalvular abscess, partially treated PVE or culture positive valves - a full course should be given after surgery.

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Surgical treatment of extracardiac complication

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Splenic abscess - occurs in 3-5% of patients. Effective therapy requires either image-guided drainage or splenectomy.

Mycotic aneurysm - occurs in 2-15%.

# Cerebral aneurysms - present as headaches, focal neurological symptoms or hemorrhage. Some will resolve with therapy, but those that persist, enlarge or leak should be treated surgically.

# Extracerebral aneurysms - present as local pain, mass, local ischemia or bleeding. Treated surgically.

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Outcome - Factors adversely affecting outcome

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# Older age.

# Severe comorbid conditions and diabetes.

# Delayed diagnosis.

# Involvement of prosthetic valves or aortic valve.

# Invasive pathogen (S. Aureus).

# Antibiotic-resistant pathogen (Pseudomonas Aeruginosa).

# Intracardiac complications.

# Neurological complications.

# Association with health-care.

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Outcome - survival\mortality in NVE and PVE

Back 72

Patients with NVE caused by Strep. Viridans, HACEK or penicillin-susceptible enterococci - survival rate 85-90%.

S. Aureus NVE in patients who do not inject drugs - survival rate 55-70%.

S. Aureus NVE in injection drug users - survival rate 85-90%.

PVE within 2 months of valve replacement - mortality rate of 40-50%.

PVE in late-onset cases - mortality rate 10-20%.

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High risk cardiac lesions for which endocarditis prophylaxis is advised before dental procedures

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# Prosthetic heart valves.

# Prior endocarditis.

# Unrepaired cyanotic congenital heart disease, including palliative shunts or conduits.

# Completely repaired congenital heart defects in the 6 months after repair.

# Incompletely repaired congenital heart disease with residual defects adjacent to prosthetic material.

# Valvulopathy developing after cardiac transplant.

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Endocarditis prevention - is it beneficial?

Back 74

The benefit of antibiotic prophylaxis is minimal.

Most endocarditis cases do not develop after a procedure.

Infections occur no more frequently in patients undergoing procedure that matched controls who do not.

The frequency and magnitude of bacteremia after procedure and a routine day's activities is similar.

The relation between GI and GU procedures is even more tenuous.

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Endocarditis prevention - to whom and in what cases is it recommended?

Back 75

Only for patients with the highest risk for severe morbidity or death from endocarditis.

Maintaining good oral hygiene is essential.

Prophylaxis is recommended only when there is manipulation of gingival tissue or the periapical region of the tooth, or perforation of oral mucosa (including surgery of respiratory tract).

Prophylaxis is not advised for GI or GU procedures.

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Antibiotic regimens for prophylaxis of endocarditis in adults with high risk cardiac lesions

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1) standard oral regimen -

Amoxicillin (2 g PO 1 h before procedure).

2) Inability to take oral medication -

Ampicillin (2 g IV or IM within 1 h before).

3) Penicillin allergy -

# Clarithromycin \ Azithromycin (500 mg PO 1 h before).

# Cephalexin (2 g PO 1 h before) - do not use for patient with severe\immediate penicillin allergy.

# Clindamycin (600 mg PO 1 h before).

4) Penicillin allergy + inability to take oral medication -

# Cefazolin \ Ceftriaxone (1 g IV or IM 30 min before) - do not use for patients with severe\immediate penicillin allergy.

# Clindamycin (600 mg IV or IM 1 h before).