Endocarditis

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

Acute endocarditis is a hectically febrile illness that rapidly damages cardiac structures, hematogenously seeds extracardiac sites, and, if untreated, progresses to death within weeks.

Subacute endocarditis follows an indolent course; causes cardiac valve damage if at all, rarely metastasizes; and is gradually progressive unless complicated by a major embolic event or ruptured mycotic aneurysm.

Predisposing conditons: congenital heart disease, chronic rheumatic heart disease, IVDA, degenerative valve disease, intracardiac devices, and health care associated infection.

Risk of prosthetic valve infection is high during the first 6 months after valve replacement; gradually declines to a low, stable rate thereafter; and is similar for mechanical and bioprosthetic devices.

PVE arising within 2 mo of valve surgery is generally due to intraoperative contamination of the prosthesis or a bacteremic postoperative complication. Coagulase negative Stap (CoNS), S. aureus, facultative GNB, diphtheroids, and fungi.

Portal of entry:

• • Oral cavity, skin, upper respiratory tract: S. viridans, staphylococci, and HACEK (Hemophilus, Actinobacillus, Cardiobacterium, Eikenella, and Kingella) causing community-acquired native valve endocarditis.

  • S. bovis originates from the GIT, where it is associated with polyps and colonic tumors, and enterococci enter the blood stream from the genitourinary tract.

  • Health care-associated native valve endocarditis is the consequence of bacteremia arising from intravascular catheter infections, nosocomial wound and urinary tract infections, and chronic invasive procedures such as HD.

  • Endocarditis complicates 6-25% of episodes of catheter-associated S. aureus bacteremia, detected by TEE.

  • PVE arising >12 month after valve surgery is due to organism seen in community-acquired valve endocarditis, and portal of entry is the same.

  • PVE due to CoNS that presents 2-12 mo after surgery often represents delayed-onset nosocomial infection. At least 85% of CoNS strains that cause PVE within 12 months of surgery are MRCoN. The rate of MRCoNS decreases to 25% in causing PVE when presented >1 year after surgery.

  • TV pacemaker lead-and/or implanted defib associated endocarditis is usually nosocomial. Majority of episodes occur within weeks of implantation or generator change and are caused by S. aureus or CoNS.

  • Endocarditis occuring among IVDA, especially when the inf involves TV, is commonly caused by S. aureus strains, many of which are MRS. Also polymicorbial.

  • Left sided valve inf in addicts have a more varied etiology and involve valves, often damaged by prior episodes of endocarditis. A number of these cases are caused by Pseudomonas aeruginosa and Candida species, and sporadic cases are due to unusual organisms such as Bacillus, Lactobacillus, and Corynebacterium species.

  • 5-15% of pt with endocarditis have negative blood cultures, and 1/3 -1/2 are negative due to prior ABx exposure.

Pathogenesis: Inj endothelium seeded or development of NBTE (nonbacterial thrombotic endocarditis) > site of bacterial seeding and lodging during episodes of transient bacteremia. NBTE common in MR, AS, AR, VSD, and Congenital heart disease, rheumatic heart disease.

NBTE also arises from a hyperocoagulable state, this phenomenon gives rise to the clinical entity of marantic endocarditis (uninfected vegetation seen in patients with malignancy and chronic diseases) and to bland vegetations complicating SLE and antiphospholipid antibody syndrome.

Organisms that commonly cause endocarditis have surface adhesin molecules, collectively called microbial surface components recognizing matrix molecules (MSCRAMMs), that mediate adherence to NBTE sites or injured endothelium.

Clinical manifestations:

Acute course: Beta-hemolytic streptococci, S. aureus, pneumococci. S. lugdunensis, enterococci.

Subacute course: S. viridans, enterococci, CoNS, HACEK group. S. aureus also causes subacute disease.

Indolent: Bartonella sp. and Q fever, C. burnetii

Nonspecific clinical features.

Febrile patient, valvular abnormalities, behavioral pattern (IVDA) predisposing to endocarditis, bacteremia with organisms that frequently cause endocarditis, arterial emboli, cardiac valvular incompetence. Low grade fever in subacute presentations, rarely exceeds 39.4C (103F). In acute exceeds 39.4-40C (103-104F). Fever is blunted or absent in patients who are elderly or severely debilitated or who have marked cardiac or renal failure.

Murmurs are heard in only 30-45% of cases but ultimately are detected in 85%. CHF in 30-40% of Pts, due to valve dysfx or endocarditis-associated myocarditis or an intracardiac fistula. CHF due to aortic valve dysfx rapidly progresses than does that due to mitral valve dysfx. Perivalvular abscesses > intracardiac fisutlae (root of aorta into cardiac chambers or between cardiac chambers). Abscesses may burrow from Aortic valve annulus through the epicardium, causing pericarditis. Varying degrees of heart block occur when the conduction system is involved. Emboli to a coronary artery may result in myocardial infarction, however embolic transmural infarcts are rare.

Fever, chills, sweats, anorexia, wt. loss, malaise, myalgias, arthralgias, back pain, heart murmur, arterial emboli, splenomegaly, clubbing, neurologic manifestations, peripheral manifestations (Osler's nodes, subungual H'ges, Janeway lesions, Roth's spots), petechiae, Lab manifestations: anemia, leukocytosis, microscopic hematuria, ESR, CRP, Rheumatoid factor, circulating immune complexes, decreased serum complement.

Blood cultures:

In the absence of prior ABx therapy, 3 sets of blood cultures (2 bottles each set) must be taken with each set separated by at least 1 hour, and blood obtained from different venipuncture sites over 24h. If the Cx remain negative after 48-72 h, two or three additional blood culture sets should be obtained, and the lab should be consulted for advice regarding optimal culture techniques. Empirical Abx Tx should not be administered in Pts who are hemodynamically stable, with subacute endocarditis, especially if they have received ABx within the preceding 2 weeks.

Pts with acute endocarditis or with deteriorating hemodynamics who may require urgent surgery should be treated empirically immediately after three sets of BC are obtained over several hours.

Echocardiography:

Anatomic confirmation, sizing of vegetations, detection of intracardiac complications, and assessment of cardiac function.

TTE cannot image <2 mm diameter veg. In 20% cases is technically inadequate due to body habitus and emphysema. Detects veg in only 65% of cases. Not adequate for evaluating PVE and detecting intracardiac complication.

TEE dectects vegetations in >90% of Pts with definite endocarditis.

• • S. aureus has surpassed viridans group streptococci as the leading cause of IE in several recent case series

  • The classic peripheral stigmata: bacteremia or fungemia, evidence of active valvulitis, peripheral emboli, and immunologic vascular phenomena may be few or absent in right sided endocarditis. This may occur during acute courses of IE, particularly among patients who are injection drug users (IDUs), in whom IE is often the result of S aureus infection of right-sided heart valves. Right-sided IE can cause septic pulmonary emboli.

  • Acute IE may evolve too quickly for the development of immunologic vascular phenomena, which are more characteristic of subacute IE.

Use of Echocardiography During Diagnosis and Treatment of Endocarditis

• • Early

    • Echocardiography as soon as possible (.12 h after initial evaluation)

    • TEE preferred; obtain TTE views of any abnormal findings for later comparison

    • TTE if TEE is not immediately available

    • TTE may be sufficient in small children

• Repeat echocardiography

  • • TEE after positive TTE as soon as possible in patients at high risk for complications

    • TEE 7–10 d after initial TEE if suspicion exists without diagnosis of IE or with worrisome clinical course during early treatment of IE

• Intraoperative

  • • Prepump

    • Identification of vegetations, mechanism of regurgitation, abscesses, fistulas, and pseudoaneurysms

• Postpump

  • • Confirmation of successful repair of abnormal findings

    • Assessment of residual valve dysfunction

    • Elevated afterload if necessary to avoid underestimating valve

    • insufficiency or presence of residual abnormal flow

• Completion of therapy

  • • Establish new baseline for valve function and morphology and ventricular

    • size and function

    • TTE usually adequate; TEE or review of intraoperative TEE may be needed for complex anatomy to establish new baseline

Treatment of Endocarditis Caused by Specific Organisms

S. viridans:

• MIC <0.12 mcg/mL:

  • PCN G, 12-19 million units IV q24h or ceftriaxone, 2 g IV q24h + gentamicin, 2 g qd or 1 mg/kg q8h.

  • Vancomycin, 1 g IV q24hif PCN allergic.

  • Give for duration of 4 wks (2 wks total if in combination with gentamicin).

  • 2 wk course not indicated for PVE. PVE, major embolic need extended tx.

• MIC 0.12-0.5 mcg/mL:

  • PCN G, 4 million units IV q4h or ceftriaxone, 2 g IV q24h + gentamicin, 2 g qd or 1 mg/kg q8h.

  • Vancomycin, 1 g IV q24h if PCN allergic.

  • 4 wk total with 2 wk of gentamicin

• MIC >0.5 mcg/mL:

  • Ampicillin/sulbactam, 3 g IV q6h + gentamicin. Vancomycin, 1 g IV q24h + gentamicin, 2 g IV qd

  • 4-6 wk total.

Enterococcus species:

• PCN-susceptibile:

  • Ampicillin, 2 g IV q6h+ gentamicin, 2 g IV qd or 1 mg/kg q8h

  • Vancomycin, 1 g IV q24h

  • 4-6 wk

• PCN-resistant:

  • Beta-lactamase: ampicillin/sulbactam, 3 g IV q6h + gentamicin, 2 g IV qd or 1 mg/kg q8h

  • Intrinsically resistant: Vancomycin, 1 g IV q24h + gentamicin, 2 g IV qd or 1 mg/kg q8h

  • 6 wk duration.

• Vancomycin and ampicillin-resistant:

  • Linezolid, 600 mg IV q12h, or daptomycin, 6 mg/kg/d

  • Quinupristin/dalfopristin, +/- doxycycline

  • Give for 8 wk or more

  • Consult ID specialist

Baseline and weekly audiometry recommended for Pts receiving aminoglycosides for >7 days. Monitor aminoglycoside and vancomycin levels. Goal for vancomycin trough 20 mcg/mL.

• ABE often requires empiric therapy before culture results become available.

  • S. aureus: Vancomycin 15 mg/kg IV q12h + gentamicin or tobramycin 1 mg/kg IV q8h. MSSA: oxacillin 2 g IV q4h, is superior to vancomycin.

S. pyogenes and S. pneumonia: PCN-G, 2-4 MU IV q4h x 4-6 wks. If PCN-resistant pneumococci, tx with ceftriaxone, 2 g IV q12h x 4-6 wks. S. bovis bacteremia and endocarditis are associated with lower GIT disease, including neoplasms. Also Groups B and G streptococcal endocarditis may also be associated with lower intestinal pathology.

Treatment regimen for Streptococcus mitis oralis: Alpha hemolytic Streptococcus mitis:

Penicillin 4 million units q4h and Gentamicin as per pharmacy dose

Continue penicillin for four weeks and Gentamicin for two weeks from the start date

Can consider penicillin pump if patient goes to a LTAC facility ( Run 24 Million units in 23hours)

Aim for gentamicin peaks 3-5, trough <1

If creatinine goes up to 1.3, hold gentamicin

Monitor for side effects from Aminoglycosides

As per guidelines, stable patients need atleast once per week BUN/Cr.

Definition of Infective Endocarditis According to the Modified Duke Criteria

Definite infective endocarditis

Pathological criteria

• Microorganisms demonstrated by culture or histological examination of a vegetation, a vegetation that has embolized, or an intracardiac abscess specimen; or

• Pathological lesions; vegetation or intracardiac abscess confirmed by histological examination showing active endocarditis

• Clinical criteria

  • 2 major criteria; or

  • 1 major criterion and 3 minor criteria; or

  • 5 minor criteria

• Possible IE

  • 1 major criterion and 1 minor criterion; or

  • 3 minor criteria

• Rejected

  • Firm alternative diagnosis explaining evidence of IE; or

  • Resolution of IE syndrome with antibiotic therapy for .4 days; or

  • No pathological evidence of IE at surgery or autopsy, with antibiotic therapy for .4 days; or

  • Does not meet criteria for possible IE as above