Best Dx/Best Rx: Infective Endocarditis

From: Subject: Best Dx/Best Rx: Infective Endocarditis Date: Wed, 3 Jun 2009 21:41:30 -0700 MIME-Version: 1.0 Content-Type: multipart/related; type="text/html"; boundary="----=_NextPart_000_020B_01C9E494.0E5D5460" X-MimeOLE: Produced By Microsoft MimeOLE V6.00.2900.5579 This is a multi-part message in MIME format. ------=_NextPart_000_020B_01C9E494.0E5D5460 Content-Type: text/html; charset="Windows-1252" Content-Transfer-Encoding: quoted-printable Content-Location: http://www.acpmedicine.com/acp/newrxdx/rxdx/dxrx0718.htm Best Dx/Best Rx: Infective Endocarditis

Infective=20 Endocarditis

David T. Durack, M.B., D.Phil.
Duke = University School=20 of Medicine

Adolf W. Karchmer, M.D.
Harvard Medical=20 School

Defin= ition/Key=20 Clinical Features
Diffe= rential=20 Diagnosis
Best = Tests
Best = Therapy
Best = References

Definition/Key=20 Clinical Features=20

Localized microbial infection of cardiac = valves or mural=20 endocardium caused by bacteria, fungi, rickettsiae, or = chlamydiae=20

Subacute Bacterial Endocarditis = (SBE)=20

Insidious onset=20
Fever=20
Sweats=20
Weakness=20
Myalgias=20
Arthralgias=20
Malaise=20
Anorexia=20
Fatigue=20
Splenomegaly, clubbing, and Osler nodes in = long-standing=20 SBE

Acute Bacterial=20 Endocarditis=20

Abrupt onset=20
Rigors=20
Fevers as high as 102.9=B0 to 105.1=B0 F = (39.4=B0 to 40.6=B0 C),=20 often remittent=20
Cardiac=20
- Murmur=20
- New aortic diastolic murmur suggests = dilatation of the=20 aortic annulus or eversion, rupture, or fenestration of an aortic=20 leaflet=20
- Sudden onset of loud mitral pansystolic = murmur=20 suggests rupture of chorda tendineae or fenestration of a mitral = valve=20 leaflet=20
- Congestive heart failure=20
- Cardiac rhythm disturbances
- Occasionally, pericarditis =

Cutaneous=20
- Petechiae of the conjunctivae, oropharynx, = skin, and=20 legs=20
- Linear subungual =93splinter=94 hemorrhages = of the lower=20 or middle nail bed=20
- Osler nodes=20
- Janeway lesions

Musculoskeletal=20
- Myalgias=20
- Arthralgias=20
- Arthritis=20
- Low back pain=20
- Rheumatoid factor in up to 50% of patients = with=20 endocarditis for > 6 wk=20
- Clubbing of fingers in < 15% of = patients=20

Ocular=20
- Petechial hemorrhages, flame-shaped = hemorrhages, Roth=20 spots, and cotton-wool exudates in the retina =

Embolic=20
- Significant arterial emboli occur in = 30%=9650% of=20 patients, causing the following:=20
  - Stroke=20
  - Monocular blindness=20
  - Acute abdominal pain, ileus, and = melena=20
  - Pain and gangrene in the = extremities=20
- CNS emboli are common=20
- Coronary emboli, often asymptomatic, can = cause=20 myocardial infarction=20
- Pulmonary emboli common in right-sided = endocarditis,=20 causing pulmonary infarcts or focal pneumonitis =

Splenic=20
- Splenomegaly in 15%=9630% of patients =
- Splenic infarcts in up to 40% of = patients=20
- Splenic abscesses in ~ 5% of patients =

Renal=20
- Microscopic hematuria in ~ 50% of = patients=20
- Embolic renal infarction=20
- Diffuse membranoproliferative=20 glomerulonephritis

Mycotic aneurysms=20
- Occur in any artery in 2%=968% of patients, = causing the=20 following:=20
  - Pain or headache=20
  - Pulsatile mass=20
  - Fever=20
  - Sudden expanding hematoma=20
  - Signs of major blood loss=20

Neurologic=20
- Neurologic complications occur in 25%=9640% = of=20 cases=20
- Strokes caused by cerebral embolisms in ~ = 15% of=20 cases, causing the following:=20
  - Altered level of consciousness=20
  - Seizures=20
  - Fluctuating focal neurologic signs=20
- Cerebral aneurysms occur in 1%=965% of = cases, causing=20 the following:=20
  - Headache=20
  - Focal signs=20
  - Acute intracerebral or subarachnoid = hemorrhage=20 caused by rupture=20
  - Mild meningeal irritation resulting from = slow=20 leakage
- Brain abscesses may occur in acute = endocarditis caused=20 by Staphylococcus aureus=20
- Seizures

Endocarditis Associated with Parenteral = Drug=20 Use=20

High fevers, chills, rigors, malaise, cough, = and=20 pleuritic chest pain=20
Septic pulmonary emboli causing sputum = production,=20 hemoptysis, and signs suggesting pneumonia=20
Cardiac murmurs=20
Tricuspid insufficiency=20
Metastatic infections=20
Neurologic manifestations=20
Peripheral emboli

Prosthetic Valve Endocarditis =

Occurs in 1%=962% of cases at 1 yr and in = 4%=965% of cases=20 at 4 yr after implantation=20
Infection of perivalvular tissues=20
Valvular dysfunction=20
Myocardial abscesses=20
Fever=20
Petechiae, Roth spots, Osler nodes, Janeway=20 lesions=20
Emboli

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Differential=20 Diagnosis=20

Tuberculosis, salmonellosis, gastrointestinal = and=20 genitourinary infections, and other disorders causing fever of = undetermined=20 origin=20
Juvenile rheumatoid arthritis, polymyalgia=20 rheumatica=20
Acute rheumatic fever=20
Marantic endocarditis=20
Polyarteritis nodosa=20
Systemic lupus erythematosus with = antiphospholipid=20 antibody syndrome=20
Cardiac myxoma=20
Neoplasms

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Best=20 Tests=20

Echocardiography=20
- Transthoracic echocardiography=20
  - For detecting vegetations in native valve=20 endocarditis: sensitivity, 60%; specificity, 90%=20
  - For detecting abscess: sensitivity, = 18%=9628%;=20 specificity, 99%
Transesophageal echocardiography=20
- For detecting vegetations in native valve=20 endocarditis: sensitivity, 95%; specificity, 100%=20
- For detecting abscess: sensitivity, = 76%=9687%;=20 specificity, 96%=20
- Better than transthoracic for evaluating = patients with=20 suspected prosthetic valve endocarditis and for detecting = paravalvular=20 abscesses
Blood culture=20
- Incubate for 5 days (Bartonella = species may=20 need > 5 days for isolation)=20
- Blood cultures are negative in 5%=9620% of = patients with=20 endocarditis
Serologic tests=20
- Can diagnose endocarditis caused by = Bartonella,=20 Legionella, and Brucella species; Chlamydia = psittaci=20 and Coxiella burnetii in cases of culture-negative=20 endocarditis
Duke criteria for the diagnosis of infective=20 endocarditis=20
- Definite=20
  - Pathologic criteria=20
    - Microorganisms: demonstrated by culture = or=20 histologically in a vegetation, in a vegetation that has = embolized, or=20 in an intracardiac abscess specimen=20
    - Pathologic lesions: vegetation or = intracardiac=20 abscess confirmed by histologic examination showing active=20 endocarditis=20
    - Clinical criteria (see definition of = terms,=20 below)=20
      - Two major criteria=20
      - One major and three minor = criteria=20
      - Five minor criteria=20
- Possible=20
  - Findings consistent with infective = endocarditis that=20 fall short of =93definite=94 but are not =93rejected=94 =
- Rejected=20
  - Firm alternative diagnosis for = manifestations of=20 infective endocarditis=20
  - Resolution of endocarditis syndrome with = antibiotic=20 therapy for ≤ 4 days=20
  - No pathologic evidence of infective = endocarditis at=20 surgery or autopsy, with antibiotic therapy for ≤ 4 = days
Definitions of terms used in Duke criteria for = diagnosis=20 of infective endocarditis=20
- Major criteria=20
  - Positive blood cultures for any one of the = following:=20
    - Typical microorganism consistent with = diagnosis=20 from two separate blood cultures
    - Viridans streptococci, Streptococcus = bovis,=20 or HACEK organisms (Haemophilus, Actinobacillus=20 actinomycetemcomitans, Cardiobacterium hominis,=20 Eikenella, Kingella)
    - Community-acquired S. aureus or=20 enterococci, in the absence of a primary focus
  - Persistently positive blood cultures, = defined as=20 microorganisms consistent with diagnosis from any one of the = following:=20
    - At least two blood samples drawn > 12 = hr=20 apart=20
    - Three of three or a majority of more = than three=20 blood cultures drawn, with first and last samples drawn at least = 1 hr=20 apart
- Evidence of endocardial involvement=20
  - Echocardiogram positive for infective = endocarditis=20 (any one of the following)=20
    - Oscillating intracardiac mass on valve = or=20 supporting structures, in the path of regurgitant jets, or on = implanted=20 material, in the absence of an alternative anatomic = explanation=20
    - Abscess=20
    - New partial dehiscence of prosthetic = valve=20
    - New valvular regurgitation (changing of=20 preexisting murmur not sufficient)
- Minor criteria=20
  - Predisposition: predisposing heart = condition or I.V.=20 drug use=20
  - Fever: temperature ≥ 100.4=B0 F = (38=B0 C)=20
  - Vascular phenomena: major arterial emboli, = septic=20 pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage,=20 conjunctival hemorrhages, Janeway lesions=20
  - Immunologic phenomena: glomerulonephritis, = Osler=20 nodes, Roth spots, rheumatoid factor=20
  - Microbiologic evidence: positive blood = culture but=20 not meeting a major criterion (see above; excludes single positive = cultures for coagulase-negative staphylococci, diphtheroids, and = organisms=20 that do not commonly cause endocarditis) or serologic evidence of = active=20 infection with organism consistent with infective endocarditis =
  - Echocardiogram consistent with infective=20 endocarditis but not meeting a major criterion (see above)=20

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Best=20 Therapy

Drug Therapy

Effective treatment requires identification of = the=20 etiologic agent and determination of its antimicrobial = susceptibility=20
Antibiotic therapy for subacute or indolent = disease can=20 be delayed until results of blood cultures are known; in fulminant = infection=20 or valvular dysfunction requiring urgent surgical intervention, begin=20 empirical antibiotic therapy promptly after blood cultures have been=20 obtained=20
For prosthetic valve endocarditis, treat for = 6=968=20 wk

Penicillin-Susceptible Viridans and Other=20 Nonenterococcal Streptococci (minimum inhibitory concentration [MIC] = < 0.2=20 =B5g/ml)

Penicillin G: preferred regimen=20
- Dose: 12=9618 million units I.V. daily in = divided doses=20 q. 4 hr for 4 wk
Penicillin G + gentamicin or ceftriaxone: = preferred=20 regimen=20
- Dose: penicillin G, dose as above; = gentamicin, 3 mg/kg=20 I.M. or I.V. daily in divided doses q. 8 hr for 2 wk (peak serum=20 concentration should be ~ 3 =B5g/ml and trough concentrations < 1 = =B5g/ml);=20 ceftriaxone, 2 g I.V. daily as a single dose for 2 wk =
Vancomycin: for patients with history of = penicillin=20 hypersensitivity
- Dose: 30 mg/kg I.V. daily in divided doses = q. 12 hr=20 for 4 wk

Relatively Penicillin-Resistant=20 Streptococci

MIC 0.2=960.5 =B5g/ml=20
- Penicillin G + gentamicin: preferred = regimen=20
  - Dose: penicillin G, 20=9630 million units = I.V. daily=20 in divided doses q. 4 hr for 4 wk; gentamicin, 3 mg/kg I.M. or = I.V. daily=20 in divided doses q. 8 hr for 2 wk (peak serum concentration should = be ~ 3=20 =B5g/ml and trough concentrations < 1 =B5g/ml) =
MIC > 0.5 =B5g/ml
- Penicillin G + gentamicin: preferred = regimen=20
  - Dose: penicillin G, 20=9630 million units = I.V. daily=20 in divided doses q. 4 hr for 4 wk; gentamicin, 3 mg/kg I.M. or = I.V. daily=20 in divided doses q. 8 hr for 4 wk (peak serum concentration should = be ~ 3=20 =B5g/ml and trough concentrations < 1 =B5g/ml) =
- Vancomycin: regimen for patients with = history of=20 penicillin hypersensitivity
  - Dose: 30 mg/kg I.V. daily in divided doses = q. 12 hr=20 for 4 wk

Enterococci

Penicillin G + gentamicin: preferred = regimen=20
- Dose: penicillin G, 20=9630 million units = I.V. daily in=20 divided doses q. 4 hr for 4=966 wk; gentamicin, 3 mg/kg I.M. or I.V. = daily in=20 divided doses q. 8 hr for 4=966 wk (peak serum concentration should = be ~ 3=20 =B5g/ml and trough concentrations < 1 =B5g/ml)
Ampicillin + gentamicin=20
- Dose: ampicillin, 12 g I.V. daily in divided = doses q.=20 4 hr for 4=966 wk; gentamicin, dose as above
Vancomycin + gentamicin: regimen for patients = with=20 history of penicillin hypersensitivity=20
- Dose: vancomycin, 30 mg/kg I.V. daily in = divided doses=20 q. 12 hr for 4=966 wk; gentamicin, dose as above =

Staphylococci (Methicillin Susceptible) in the = Absence=20 of Prosthetic Material

Nafcillin or oxacillin + gentamicin = (optional):=20 preferred regimen=20
- Dose: nafcillin or oxacillin, 12 g I.V. = daily in=20 divided doses q. 4 hr for 4=966 wk; gentamicin, 3 mg/kg I.M. or I.V. = daily in=20 divided doses q. 8 hr for 3=965 days (peak serum concentration = should be ~ 3=20 =B5g/ml and trough concentrations <1 =B5g/ml)
Cefazolin + gentamicin (optional): alternative = regimen=20 for patients with history of penicillin hypersensitivity=20
- Dose: cefazolin, 12 g I.V. daily in divided = doses q. 4=20 hr for 4=966 wk; gentamicin, dose as above
Vancomycin: alternative regimen for patients = with=20 history of penicillin hypersensitivity
- Dose: 30 mg/kg I.V. daily in divided doses = q. 12 hr=20 for 4=966 wk

Staphylococci (Methicillin Resistant) in the = Absence of=20 Prosthetic Material

Vancomycin
- Dose as above

Staphylococci (Methicillin Susceptible) in the = Presence=20 of Prosthetic Material

Nafcillin or oxacillin + rifampin + gentamicin =
- Dose: nafcillin or oxacillin, 12 g I.V. = daily in=20 divided doses q. 4 hr for 6=968 wk; rifampin, 300 mg p.o., q. 8 hr = for 6=968 wk;=20 gentamicin (administer during the initial 2 wk), 3 mg/kg I.M. or = I.V. daily=20 in divided doses q. 8 hr for 2 wk

Staphylococci (Methicillin Resistant) in the = Presence of=20 Prosthetic Material

Vancomycin + rifampin + gentamicin=20
- Dose: vancomycin, 30 mg/kg I.V. daily in = divided doses=20 q. 12 hr for 6=968 wk; rifampin, 300 mg p.o., q. 8 hr for 6=968 wk; = gentamicin=20 (administer during the initial 2 wk), 3 mg/kg I.M. or I.V. daily in = divided=20 doses q. 8 hr for 2 wk

HACEK Organisms

Ceftriaxone or another third-generation = cephalosporin=20
- Dose: 2 g I.V. daily as a single dose for 4 = wk=20

Surgical = Intervention=20

Indications for surgical debridement of = vegetations and=20 infected perivalvular tissue, with valve replacement or repair as=20 needed=20
- Moderate to severe heart failure=20
- Vegetations that obstruct the valve = orifice=20
- Perivalvular invasion and abscess = formation=20
- Uncontrolled infection for > 1=963 wk = despite maximal=20 antimicrobial therapy=20
- Fungal endocarditis=20
- Prosthetic valve endocarditis with = perivalvular=20 invasion=20
- Endocarditis caused by Pseudomonas = aeruginosa=20 or other gram-negative bacilli that has not responded after 7=9610 = days of=20 maximal antimicrobial therapy

Endocarditis Associated with Parenteral Drug = Use=20

In intravenous drug users with isolated = right-sided=20 S. aureus endocarditis, surgery should be postponed and = antibiotic=20 therapy continued for a prolonged period

Antithrombotic Therapy=20

Anticoagulants can cause or worsen hemorrhage = in=20 patients with endocarditis but may be carefully administered when=20 needed=20
Prothrombin time should be carefully = maintained at INR=20 of 2.0=963.0=20
Anticoagulation should be reversed immediately = in the=20 event of CNS complications and interrupted for 1=962 wk after acute = embolic=20 stroke=20
Avoid heparin during active endocarditis if = possible=20

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Best = References

Cabell, et al: Arch Intern Med 162:90, 2002=20

Durack: JAMA 290:3250, 2003

Lisby, et al: Infect Dis Clin North Am 16:393,=20 2002

Olaison, et al: Cardiol Clin 21:235, = 2003

Towns, et al: Cardiol Clin 21:197, = 2003

March 2005

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