INFECTIVE ENDOCARDITIS

Dr. K. NANDHINI M.D.,

ASSISTANT PROFESSOR
DEPT OF GENERAL MEDICINE
INTRODUCTION
In developed countries, the incidence of endocarditis ranges from 4 to 7 cases per 100,000
population per year

predisposing conditions

In developing countries- Chronic rheumatic heart disease.

In developed countries –
• Congenital heart diseases,
• Illicit IV drug use,
• Degenerative valve disease, and
• Intracardiac devices.
 Organisms
The oral cavity, skin, and upper respiratory tract
• Viridans streptococci,
• Staphylococci, and
• HACEK organisms

(Haemophilus species, Aggregatibacter species, Cardiobacterium hominis, Eikenella

corrodens, and Kingella kingae).
Gastrointestinal tract , polyps and colonic tumors- Streptococcus gallolyticus subspecies
gallolyticus
Genitourinary tract- Enterococci
• Health care–associated NVE caused by Staphylococcus aureus, coagulase-negative
staphylococci (CoNS).

• Early PVE— PVE arising within 2 months of valve surgery is generally nosocomial and is the
result of intraoperative contamination of the prosthesis or a bacteremic postoperative
complication. This nosocomial origin is reflected in the primary microbial causes: S. aureus,
CoNS, facultative gram-negative bacilli, diphtheroids, and fungi.

• Delayed-onset PVE are nosocomial infection presents 2–12 months after surgery due to CoNS

• Late PVE -beginning >12 months after surgery—are from community- acquired NVE.

• Injection drug use–associated endocarditis, involving the tricuspid valve, is commonly caused
by S. aureus, which in many cases is resistant to methicillin.
Staphylococcus
Streptococcus
Enterococci
 PATHOGENESIS

• Endothelial injury allows either direct infection by virulent organisms or the

development of a thrombus—a condition called nonbacterial thrombotic
endocarditis (NBTE).
• NBTE also arises as a result of a hypercoagulable state; this gives rise to marantic
endocarditis- uninfected vegetations seen in malignancy and chronic
diseases ,systemic lupus erythematosus and antiphospholipid antibody syndrome.
• This thrombus serves as a site of bacterial attachment during transient bacteremia.
• Organisms enter the bloodstream adhere at sites of NBTE.
• The organisms have surface adhesin molecules, collectively called microbial
surface components recognizing adhesin matrix molecules (MSCRAMMs), that
mediate adherence to NBTE
• Adherence is facilitated by
• Fibronectin-binding proteins present on many gram-positive bacteria.
• By clumping factor (a fibrinogen and fibrin-binding surface protein) on S.
aureus.
• By glucans or Fim A on streptococci.
• By fibrinogen-binding surface proteins (Fss2), on Enterococcus faecalis.
• Fibronectin-binding proteins are required for S. aureus invasion of intact
endothelium; thus these surface proteins may facilitate infection of previously
normal valves
• Adherent organisms proliferate to form dense microcolonies.
• Microorganisms also induce platelet deposition and a localized procoagulant
state by eliciting tissue factor from the endothelium
• Fibrin deposition combines with platelet aggregation and microorganism
proliferation to generate an infected vegetation.
• Organisms deep in vegetations are metabolically inactive (nongrowing) and
relatively resistant to killing by antimicrobial agents.
• Proliferating surface organisms are shed into the bloodstream continuously.

• The clinical manifestations are due to embolization of vegetation fragments,

deposition of circulating immune complexes or immune responses to
deposited bacterial antigens.
Clinical presentation
• Acute endocarditis is typically caused by β-Hemolytic streptococci, S. aureus, and
pneumococci, Staphylococcus lugdunensis (a coagulase-negative species) .

• Subacute endocarditis is typically caused by viridans streptococci, enterococci, CoNS, and the
HACEK group

• Acute endocarditis rapidly damages cardiac structures, seeds extracardiac sites, and, if
untreated, progresses to death within weeks.
• Subacute endocarditis follows an indolent course; causes structural cardiac damage only
slowly, rarely metastasizes.
Clinical features
• New/worsened regurgitant
• Fever murmur
• Chills and sweats • Arterial emboli
• Splenomegaly
• Anorexia, weight loss, malaise • Clubbing
• Myalgias, arthralgias • Neurologic manifestations
• Back pain • Peripheral manifestations (Osler’s
• Heart murmur nodes, subungual hemorrhages,
Janeway lesions, Roth’s spots)
• Petechiae
Clinical features
• In acute endocarditis , temperatures of 39.4°–40°C (103°–104°F) are often
noted.
• In patients with subacute presentations, fever is typically low- grade.
• Valvular damage and ruptured chordae may result in new regurgitant
murmurs.
• Valve dysfunction leads to Congestive heart failure
• Extension of infection beyond valve leaflets into adjacent annular or myocardial
tissue results in perivalvular abscesses,
• Abscesses may interrupt the conduction system, leading to varying degrees of
heart block
• Mitral perivalvular abscesses, which are usually more distant from the
conduction system, only rarely cause conduction abnormalities.
Noncardiac Manifestations
• Septic embolization -Janeway lesions, subungual haemorrhage,

• Embolic arterial occlusion causes regional pain or ischemia-induced organ dysfunction

(e.g., of the kidney, spleen, bowel, extremity).

• Cerebrovascular emboli presenting as strokes or occasionally as encephalopathy .

• Purulent meningitis, intracranial hemorrhage due to haemorrhagic infarcts and

seizures.

• Mycotic aneurysms are focal dilations of arteries occurring at points in the artery wall
that have been weakened by infection in the vasa vasorum or where septic emboli have
lodged.
Hematogenous seeded focal infection occurs most often in the skin, spleen,
kidneys, skeletal system, and meninges

Immune complex deposition

On the glomerular basement membrane causes diffuse hypocomplementemic

glomerulonephritis and renal dysfunction, which typically improve with effective
antimicrobial therapy,

Osler’s nodes ,

Roth spots.
Endocarditis associated with injection drug use

• is limited to the tricuspid valve and presents with fever but with faint or no murmur and no
peripheral manifestations.

• Septic pulmonary emboli, which are common with tricuspid endocarditis, cause cough, pleuritic chest
pain, nodular pulmonary infiltrates, and occasionally empyema or pyopneumothorax.

Infection of the aortic or mitral valves presents with the typical clinical features of endocarditis,
including peripheral manifestations.

CIED endocarditis may be associated with obvious (especially within 6 months of device manipulation) or
cryptic generator pocket infection and results in fever, minimal murmur, and pulmonary symptoms due
to septic emboli.
• Early PVE, typical symptoms may be obscured by comorbidity associated with recent
surgery.

• Late-onset PVE presents with typical clinical features.

• In both early and late PVE, perivalvular infection is common and often results in
partial valve dehiscence, regurgitant murmurs, CHF, or disruption of the conduction
system
Laboratory manifestations

• Anemia
• Leukocytosis
• Microscopic hematuria
• Elevated erythrocyte sedimentation rate Elevated C-reactive protein level
• Circulating immune complexes Decreased serum complement
The MODIFIED DUKE
Criteria emphasize Bacteraemia and echocardiographic findings

The requirement for multiple positive blood cultures over time

• An organism that causes both endocarditis and non-endocarditis-related
bacteraemia (e.g., S. aureus, enterococci) must be recovered in multiple blood
cultures (i.e, persistent bacteremia) and in the absence of an extracardiac
focus of infection.
• Organisms that rarely cause endocarditis but commonly contaminate blood
cultures (e.g., diphtheroids, CoNS) must be found in repeated blood cultures
to satisfy a major criterion
 Major Criteria
1. Positive blood culture
Typical microorganism for infective endocarditis from two separate blood cultures or
Persistently positive blood culture, defined as recovery of a microorganism consistent with infective
endocarditis from:
• Blood cultures drawn >12 h apart; or
• All of 3 or a majority of ≥4 separate blood cultures, with first and last drawn at least 1 h apart or
Single positive blood culture for Coxiella burnetii or phase I IgG antibody titer of >1:800

2. Evidence of endocardial involvement -Positive echo cardio gram

Oscillating intracardiac mass on valve or supporting structures or
Abscess, or
New partial dehiscence of prosthetic valve, or
New valvular regurgitation
Minor Criteria

1. Predisposition: predisposing heart conditions or injection drug use

2. Fever ≥38.0°C (≥100.4°F)
3. Vascular phenomena:
• major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial
hemorrhage, conjunctival hemorrhages, Janeway lesions
4. Immunologic phenomena:
• glomerulonephritis, Osler’s nodes, Roth’s spots, rheumatoid factor
5. Microbiologic evidence: positive blood culture but not meeting major
criterion
Diagnosis
The diagnosis is established with certainty only when vegetations
are examined histologically and microbiologically.

DUKES CRITERIA- developed as a research tool,

Definite endocarditis
• Documentation of two major criteria,
• One major criterion and three minor criteria,
• Or five minor
The Diagnosis Of Endocarditis Is Rejected
• if an alternative diagnosis is established,
• if symptoms resolve and do not recur with ≤4 days of antibiotic therapy, or
• if surgery or autopsy after ≤4 days of antimicrobial therapy yields no histologic
evidence of endocarditis.

Possible Infective Endocarditis

• one major and one minor criterion or
• three minor criteria are fulfilled.
ANTIMICROBIAL THERAPY

• To cure endocarditis, all bacteria in the vegetation must be killed.

• It is difficult because the bacteria are largely nongrowing and metabolically
inactive and thus are less easily killed by antibiotics.
• Accordingly, therapy must be bactericidal and prolonged.
• Antibiotics are generally given parenterally to achieve serum concentrations
that, through passive diffusion, result in effective concentrations in the depths
of the vegetation.
• The regimens for the treatment of PVE (except that caused by staphylococci)
are similar to those used to treat NVE
Organism-Specific Therapies
Streptococci
• The recommended therapies for streptococcal endocarditis are based on the minimal
inhibitory concentration (MIC) of penicillin for the causative isolate
• The regimens for moderately penicillin-resistant streptococci, & PVE is same
• Aminoglycoside-containing regimens for the treatment of patients at increased risk
for aminoglycoside toxicity (renal or eighth cranial nerve)
Enterococci
• Enterococci are killed by the synergistic interaction of a cell wall–active antibiotic
combined with an aminoglycoside
Staphylococci

The regimens based on the

• presence or absence of a prosthetic valve or foreign device and

• The susceptibility of the isolate to methicillin,

Thus, empirical therapy for possible staphylococcal NVE should use a regimen
that covers methicillin-resistant organisms.

Rifampin is an essential component because it kills staphylococci that are

adherent to foreign material in a biofilm.
Empirical Therapy and Treatment for Culture-Negative
Endocarditis
Based on
• Acute vs. subacute presentation, NVE, early or late PVE,
• Patient’s predispositions & epidemiologic clues (region of residence, animal exposure) must be
considered.

Acute endocarditis / injection drug user /health care–associated NVE should cover MRSA
and potentially antibiotic-resistant gram-negative bacilli. Treatment with vancomycin plus
gentamicin
NVE /sub- acute presentation- vancomycin plus ceftriaxone is reasonable.
PVE for ≤1 year- vancomycin, gentamicin, and cefepime
PVE in place for >1 year is similar to that for culture-negative NVE.
 CIED Endocarditis
• Antimicrobial therapy for CIED is adjunctive to complete removal of the device.

• The antimicrobial selected is based on the causative organism and should be used as
recommended for NVE ,

• CIED endocarditis and for those with bacteremia that continues after device removal - 4 to 6
week course of endocarditis-targeted therapy is recommended

• In the absence of another source, S. aureus bacteremia (and persistent CoNS bacteremia)
in patients with a CIED is likely to be indicative of CIED or valvular endocarditis and
should be managed accordingly.

• Attempted salvage of an infected CIED with antibiotics alone is usually unsuccessful and
should be reserved for patients whose devices cannot be removed or who refuse removal.
Outpatient Antimicrobial Therapy
• Fully compliant, clinically stable patients who are no longer bacteremic, Afebrile

• Recommended regimens should not be compromised to accommodate outpatient

therapy.

• Tests to detect renal, hepatic, and hematologic toxicity should be

performed periodically.
• Serum concentrations of aminoglycosides and vancomycin should be
monitored periodically
• Blood cultures should be repeated daily until sterile .

• Blood cultures become sterile within 2 days after the start of appropriate therapy when
infection is caused by viridans streptococci, enterococci, or HACEK organisms.

• In S. aureus endocarditis, β-lactam therapy results in sterile cultures in 3–5 days,

• IN MRSA endocarditis, positive cultures may persist for 7–9 days with vancomycin or
daptomycin treatment.

• When fever persists for 7 days despite appropriate antibiotic therapy, patients should be
evaluated for paravalvular abscess, extracardiac abscesses
INDICATION FOR SURGERY
OUTCOME

• In developed countries, overall survival rates are 80–85%;

• Overall survival rates 1 year after successful endocarditis treatment are 80–90%.

• Whereas 85–90% of injection drug users survive their initial episode of S. aureus endocarditis.
However, if addiction is not successfully addressed in the latter group, the longer-term prognosis is
guarded.

• Survival rates for patients with NVE caused by viridans streptococci, HACEK organisms, or
enterococci (susceptible to synergistic therapy) are 85–90

• PVE beginning within 2 months after valve replacement results in mortality rates of 40–50%,
Prophylaxis
Prophylaxis is recommended only when

There is manipulation of gingival tissue or

The periapical region of the teeth or

perforation of the oral mucosa

(including surgery on the respiratory tract).

Prophylaxis is not advised for patients

Undergoing gastrointestinal or genitourinary tract

procedures.
Antibiotic Regimens for Prophylaxis
Standard oral regimen

• Amoxicillin: 2 g PO 1 h before procedure

Inability to take oral medication

• Ampicillin: 2 g IV or IM within 1 h before procedure

Penicillin allergy –

Standard regimen

• 1. Clarithromycin or azithromycin: 500 mg PO 1 h before procedure

• 2. Cephalexin : 2 g PO 1 h before procedure

• 3. Clindamycin: 600 mg PO 1 h before procedure

inability to take oral medication

• 1. Cefazolin or ceftriaxone : 1 g IV or IM 30 min before procedure

• 2. Clindamycin: 600 mg IV or IM 1 h before procedure

Do not use cephalosporins in patients with immediate hypersensitivity (urticaria,

angioedema, anaphylaxis) to penicillin.
 CASE STUDY
• A 21-year-old male presented to hospital with complaints of fever between 101°F
and 103°F for four weeks, palpitation, and dyspnea on exertion for 6 months not
responsive to conventional medical treatment.
• At the time of admission, his BP was110/62 mm Hg, HR was 100 beats per minute,
and RR was 28 breaths per minute.
• On auscultation, mid-diastolic murmur was found.
• Laboratory investigation showed Hb of 11 g/dL, TLC of 14,390/µL, blood urea of 29
mg/dl, serum creatinine of 0.9 mg/dL, and CRP of 68.3mg/dL.
• The blood culture showed a growth of Staphylococcus hemolytic.
• TTE, there was prolapse and perforation of the noncoronary cusp along with small
vegetation over the same cusp of the aortic valve. There was severe aortic
regurgitation.
• The patient was treated with IV ceftriaxone and vancomycin for six weeks and
gentamicin for two weeks.
• An AVR with a mechanical valve was performed, following which the patient had
an uneventful recovery and was discharged in stable condition.
REFERENCE
• Pg no 967, chapter 123, Infective Endocarditis, 21st edition
• Singh SP, Singh D. Infective Endocarditis: A Case Series. Journal of
Cardiac Critical Care TSS. 2020 Sep 10;4(02):156-60.
• Durack DT. Prevention of infective endocarditis. New England Journal
of Medicine. 1995 Jan 5;332(1):38-44.
THANK YOU