4.1. General Recommendations

Therapy of infective endocarditis has been evolving over all the years of its recognition and should be guided by the organism involved. The streptococci are the easiest organisms to eradicate in bacterial endocarditis, but there still is a 100% mortality in patients who are not treated for this organism. In the case of streptococci, there are

Table 2

Proposed New Criteria for Diagnosis of Infective Endocarditis

Definite infective endocarditis Pathologic criteria:

Microorganisms: demonstrated by culture or histology in a vegetation,or in a vegetation that has embolized, or in an intracardiac abscess, or Pathologic lesions: vegetation or intracardiac abscess present, confirmed by histology showing active endocarditis

Clinical criteria, using specific definitions listed in Table 3:

2 major criteria, or 1 major and 3 minor criteria, or 5 minor criteria

Possible infective endocarditis Findings consistent with infective endocarditis that fall short of "Definite," but not "rejected"

Rejected Firm alternate diagnosis for manifestations of endocarditis, or

Resolution of manifestations of endocarditis, with antibiotic therapy for 4 days or less, or No pathologic evidence of infective endocarditis at surgery or autopsy, after antibiotic therapy for 4 d or less unique therapeutic regimens because they are more easily killed than other organisms and on most occasions can be treated simply with penicillin intravenously for 2 wk. Another situation where there may be a special regimen in many cases is the HACEK organisms (14). These pathogens are more difficult to eradicate and thus a 4-6 wk antibiotic regimen of intravenous therapy is usually recommended.

Staphylococcal endocarditis (S. aureus and S. epidermidis) can present the clinician with some special problems, especially the risk of embolization and resistance to p lactam drugs. Many intravenous antibiotics may be chosen to treat staphylococcal endocarditis, including nafcillin, oxacillin, cefazolin, and vancomycin (P-lactam-resis-tant strains). Often, two or more antibiotics are used for a synergistic effect; generally an aminoglycoside and/or rifampin are added to a P-lactam or vancomycin. In many cases, the 6-wk duration of treatment is considered to be much safer than a 4-week duration especially if the aortic valve is involved, a prosthetic valve is infected, the organism is relatively resistant to antibiotics (e.g., Gram-negative bacilli, fungi), or the patient suffered complications of infective endocarditis (e.g., emboli, heart failure) (15).

Each bacterial species in infective endocarditis therapy can be expected to respond best according to its specific antibiotic sensitivities. Ample references and reviews are available to guide the clinician in selecting appropriate drugs (3-7,14). It should be noted that the antibiotic sensitivity data for Enterococcus spp. may not correlate with clinical outcome; thus, high-dose ampicillin plus an aminoglycoside has been recom-

Table 3

Definitions of terminology used in the proposed new criteria

Major Criteria oo

Positive blood culture for infective endocarditis

Typical microorganism for infective endocarditis from two separate blood cultures

Viridans streptococci,* Streptococcus bovis, HACEK group, or Community-acquired Staphylococcus aureus or enterococci, in the absence of a primary focus. OR

Persistently positive blood culture, defined as recovery of a microorganism consistent with infective endocarditis from:

1. Blood cultures drawn more than 12 hours apart, or

2. All of three or a majority of four or more separate blood cultures, with first and last drawn at least 1 hour apart

Evidence of endocardial involvement Positive echocardiogram for infective endocarditis

1. Oscillating intracardiac mass, on valve or supporting structures, or in the path of regurgitant jets, or on implanted material, in the absence of an alternative anatomic explanation, or

2. Abscess, or

3. New partial dehiscence of prosthetic valve.

New valvular regurgitation (increase or change in pre-existing murmur not sufficient)

Minor Criteria Predisposition: predisposing heart condition or intravenous drug use

Vascular phenomena: major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhages, Janeway lesions

Immunologic phenomena: glomenulonephritis, Osler's nodes, Roth spots, rheumatoid factor

Microbiologic evidence: positive blood culture but not meeting major crite rion as noted previously! or serologic evidence of active infection with organism consistent with infective endocarditis

Echocardiogram: consistent with infective endocarditis but not meeting major criterion as noted previously

HACEK = Haemophilus spp., Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella spp., and Kingella kingae

*Including nutritional variant strains fExcluding single positive cultures for coagulase-negative staphylococci and organisms that do not cause endocarditis mended. In some instances vancomycin is preferred over ampicillin (plus an aminoglycoside) (15). Care should be taken to use bactericidal antibiotic therapy when available. Antibiotic levels in the patient's serum should exceed the minimum bactericidal concentration for the particular causative agent.

4.2. Empiric Therapy

In older patients with suspected infective endocarditis and who are clinically stable with no complications, antimicrobial therapy can be withheld until a specific pathogen is identified (48 h). Antibiotics should be initiated empirically in suspected cases of infective endocarditis with the following conditions: (1) hypotension or sepsis, (2) new regurgitant murmur, (3) congestive heart failure, (4) embolic events, or (5) aortic valve involvement (15). However, if the index of suspicion for infective endocarditis is high, empiric treatment may be started and then therapy adjusted after culture and sensitivity data return. Appropriate empiric regimens include ampicillin (or penicillin G), nafcillin (or oxacillin) and an aminoglycoside. Vancomycin may be substituted for patients with penicillin allergy. For prosthetic valve endocarditis, treatment can be empirically begun with vancomycin and an aminoglycoside with or without rifampin. The latter regimen may also be useful for "culture-negative" endocarditis (negative blood cultures off antibiotics). Careful monitoring for drug toxicity, especially with aminoglycosides and vancomycin, is essential in the elderly.

4.3. Indications for Surgery

It is important during the therapy of infective endocarditis to always be alert for the possible indications for surgery. Cardiac surgery to remove and replace a diseased valve is often absolutely necessary. A higher mortality will result if surgery is delayed, and especially if cardiac complications (e.g., heart failure) are present. The findings that would usually indicate that surgery is necessary include, the development of new-onset or worsening heart failure; the development of an audible new murmur on therapy, especially a regurgitant lesion, and onset of large numbers of emboli, and, in particular, emboli to crucial organs (12). Another possible indication for surgery would be a mobile large vegetation seen on TEE or TTE. This is an area of continued debate, but with the availability of TEE, it seems that this may become a more common indication for surgery, in particularly in the elderly because of the severe sequelae that result from embolization in elderly patients (4,12).

4.4. Embolic Complications

When assessing an ongoing infective endocarditis case, one of the most important things to consider is the risk of embolization (16). In native valves, some of the risks associated with embolization include double valve endocarditis, mitral valve endocarditis, and certain organisms (e.g., fungi, staphylococci). It is also worth noting that about 50% of all embolic events still occur before the admission of the patient or before the patient's diagnosis is reached. One of the features that appears to decrease the risk of embolization is aspirin therapy (17). Whether other forms of anticoagulation also decrease the risk of embolization is not yet established. Emboli may create a need for further surgery, for instance, splenectomy or drainage of a paraspinous abscess, or resection of a mycotic aneurysm (4). Because of the risk of embolization in the elderly,

Table 4

Infective Endocarditis Chemoprophylaxis for Oral and Respiratory Tract Procedures

Standard regimen0 Amoxicillin, 3 g orally, given 1 h before procedure. For penicillin-allergic patients, give erythromycin ethylsuccinate 800 mg or erythromycin stearate 1 g orally 2 h before procedure.

Alternative regimens Ampicillin 2 g intravenously or intramuscularly 30 min before procedure. Clindamycin 300 mg intravenously 30 min before procedure. Vancomycin 1 g intravenously infused over 60 min, beginning 1 h before procedure. No repeat dose necessary.

"Includes prosthetic heart valves and high-risk patients. Notice that postprocedure doses are eliminated. Table 5

Infective Endocarditis Chemoprophylaxis for Gastrointestinal and Genitourinary Procedures

Ampicillin 2 g intravenously or intramuscularly and gentamicin0 1.5 mg/kg (not to exceed 80 mg) intravenously or intramuscularly 30 min before the procedure (adjust dose and interval for gentamicin in patients with renal dysfunction). (Amoxicillin 1.5 g orally 6 h after initial dose may replace parenteral ampicillin.)6

In penicillin-allergic patients, ampicillin is replaced by vancomycin 1 g intravenously (infused over 60 min) before procedure (or adjusted for renal dysfunction). Gentamicin0 is administered as previously described.6

"Equivalent aminoglycoside may be substituted.

6Notice that post-procedure doses are eliminated. Data from ref. (24).

which produces many adverse later effects, all measures that could decrease the risk of embolization should be considered.

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