Class I
Patients at risk for infective endocarditis who have unexplained fever for more than 48 h should have at least 2 sets of blood cultures obtained from different sites.(Level of Evidence: B)
Class III
Patients with known valve disease or a valve prosthe- sis should not receive antibiotics before blood cul- tures are obtained for unexplained fever. (Level of Evidence: C)
Infective endocarditis may be suspected in a patient with a cardiac murmur suggestive of organic valvular or congen- ital heart disease or in a patient with a prosthetic heart valve by the presence of fever, anemia, hematuria, and physical findings such as petechiae, Osler’s nodes, Janeway lesions, Roth spots, splenomegaly, and splinter hemorrhages. A definitive diagnosis may be made with positive blood cultures and/or characteristic echocardiographic findings. The diagnosis of infective endocarditis is often imprecise, because bacteremia can occur without endocardial infection, and endocarditis can occur with negative blood cultures, especially if a patient has received antibiotics for minor undiagnosed febrile illness (30). The role of echocardiogra-
phy has emerged with visualization of vegetation by trans- thoracic echocardiography in approximately 60% to 75% of patients and by transesophageal echocardiography in more than 95% of patients (718).
Criteria for the diagnosis of infective endocarditis were proposed by Van Reyn et al. (719) based on the combina- tion of blood cultures, clinical signs, and symptoms. Durack et al proposed a new set of diagnostic criteria that placed echocardiographic findings of endocardial lesions on an equal footing as positive blood cultures (720). The Duke criteria designated a patient as “definite,” “rejected,” or “possible” with regard to the likelihood of infective endo- carditis. Because the designation of “possible” infective endocarditis seemed overly broad based on 1 minor criterion if the patient did not meet requirements for “rejected” (721), a more recent modification of the Duke criteria has been developed with the intent to improve diagnostic specificity without sacrificing sensitivity (722). These modified Duke criteria are shown in Table 22, which defines major and minor criteria, and inTable 23, which uses the diagnostic classifications of definite, possible, or rejected.
The diagnosis of infective endocarditis in a patient with a pathological murmur or a valvular prosthesis and unex- plained fever lasting more than 72 h should include an assessment for vascular and immunologic phenomena, 3 to 5 sets of blood cultures, and a transthoracic echocardiogram. When the echocardiogram is technically inadequate, is nondiagnostic, or is negative for infective endocarditis, transesophageal echocardiography should be obtained. 4.1. Antimicrobial Therapy
Antimicrobial therapy in endocarditis is guided by identifi- cation of the causative organism. The majority (80%) of cases of endocarditis are due to streptococcal and staphylo- coccal organisms. The latter species is also the most fre- quent organism in endocarditis resulting from intravenous drug abuse. Eighty percent of tricuspid valve infection is by
Staphylococcus aureus. This organism is also a frequent cause of infective endocarditis in patients with insulin-dependent diabetes mellitus. With prosthetic valve endocarditis, a wide spectrum of organisms can be responsible within the first year of operation. However, in “early” prosthetic valve endocarditis, usually defined as endocarditis during the first 2 months after surgery, Staphylococcus epidermidis is the predominant offending organism. Late-onset prosthetic valve endocarditis follows the profile of native valve endo- carditis, that is, streptococci (viridans) andstaphylococci.En- terococcus faecalisandE. faeciumaccount for 90% of entero- coccal endocarditis, which is usually associated with malignancy or manipulation of the genitourinary or gastro- intestinal tract. Gram-positive and Gram-negative bacilli are relatively uncommon causes of endocarditis. In recent years, the HACEK group of organisms (Haemophilus, Ac- tinobacillus, Cardiobacterium, Eikenella, andKingellaspecies) has become an important cause of endocarditis. These organisms cause large vegetations (greater than 1 cm),
large-vessel embolism, and congestive heart failure. They should be considered along with fungal endocarditis when large vegetations are noted. Fungi, especially Candida, are important causes of endocarditis in patients with prosthetic valves, compromised immune systems, and intravenous drug abuse. Several of the AHA recommendations for antimi- crobial regimens, updated in 2005, are given in Tables 24 through 29 (723). Complete treatment regimens for resis- tant organisms are provided in that statement from the
AHA which can be found at http://www.american-
heart.org/presenter.jhtml?identifier⫽2158(723).
4.2. Culture-Negative Endocarditis
Culture-negative endocarditis most frequently (62%) results from prior antibiotic treatment before blood cultures are drawn (724,725). Other reasons for negative blood cultures include infections due to Candida; Aspergillus; other fas- tidious, slow-growing organisms (726) such as Q-fever and Bartonella organisms; and noninfective endocarditis such as Libman-Sacks endocarditis in patients with systemic lupus erythematosus. A proposed regimen for culture-negative, presumed bacterial endocarditis (723) is shown inTable 30.
Table 22. Definition of Terms Used in the Proposed Modified Duke Criteria for the Diagnosis of Infective Endocarditis*
Major criteria
Blood culture positive for IE
Typical microorganisms consistent with IE from 2 separate blood cultures: Viridansstreptococci, Streptococcus bovis,HACEK group,Staphylococcus aureus;or Community-acquiredenterococciin the absence of a primary focus; or
Microorganisms consistent with IE from persistently positive blood cultures, defined as follows: At least 2 positive cultures of blood samples drawn more than 12 h apart; or
All of 3 or a majority of greater than 4 separate cultures of blood (with first and last sample drawn at least 1 h apart)
Single positive blood culture forCoxiella burnettior anti-phase 1 IgG antibody titer greater than 1:800
Evidence of endocardial involvement
Echocardiogram positive for IE (TEE recommended in patients with prosthetic valves, rated at least “possible IE” by clinical criteria, or complicated IE [paravalvular abscess]; TTE as first test in other patients), defined as follows:
Oscillating intracardiac mass on valve or supporting structures, in the path of regurgitant jets, or on implanted material in the absence of an alternative anatomic explanation; or
Abscess; or
New partial dehiscence of prosthetic valve
New valvular regurgitation (worsening or changing of pre-existing murmur not sufficient) Minor criteria
Predisposition, predisposing heart condition, or injection drug use Fever, temperature greater than 38°C
Vascular phenomena, major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhages, and Janeway’s lesions
Immunologic phenomena; glomerulonephritis, Osler’s nodes, Roth’s spots, and rheumatoid factor
Microbiological evidence: positive blood culture but does not meet a major criterion,† or serological evidence of active infection with organism consistent with IE
Echocardiographic minor criteria eliminated
*Modifications are shown in bold type. †Excludes single positive cultures for coagulase-negative staphylococci and organisms that do not cause endocarditis. Reprinted with permission from Li JS, Sexton DJ, Mick N, et al. Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis. Clin Infect Dis 2000;30:633– 8 (722).
IE indicates infective endocarditis; TEE, transesophageal echocardiography; and TTE, transthoracic echocardiography.
Table 23. Definition of Infective Endocarditis According to the Proposed Modified Duke Criteria*
Definite infective endocarditis Pathological criteria
(1) Microorganisms demonstrated by culture or histological examination of a vegetation, a vegetation that has embolized, or an intracardiac abscess specimen; or
(2) Pathological lesions; vegetation, or intracardiac abscess confirmed by histological examination showing active endocarditis Clinical criteria
(1) 2 major criteria, or
(2) 1 major criterion and 3 minor criteria; or (3) 5 minor criteria
Possible infective endocarditis
(1)1 major criterion and 1 minor criterion;or (2)3 minor criteria
Rejected
(1) Firm alternate diagnosis explaining evidence of infective endocarditis; or
(2) Resolution of infective endocarditis syndrome with antibiotic therapy for less than 4 days; or
(3) No pathological evidence of infective endocarditis at surgery or autopsy, with antibiotic therapy for less than 4 days; or (4) Does not meet criteria for possible infective endocarditis, as noted above
*Modifications are shown in bold type. Reprinted with permission from Li JS, Sexton DJ, Mick N, et al. Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis. Clin Infect Dis 2000;30:633– 8 (722).
Table 24. Therapy of Native Valve Endocarditis Caused by Highly Penicillin-Susceptible Viridans GroupStreptococciand
Streptococcus bovis
Regimen Dosage and Route*
Duration,
wk Comments
Aqueous crystalline penicillin G sodium
12–18 million U per 24 h IV either continuously or in 4 or 6 equally divided doses
4 Preferred in most patients greater than 65 y of age or patients with impairment of 8th cranial nerve function or renal function
or
Ceftriaxone sodium 2 g per 24 h IV/IM in 1 dose 4
Pediatric dose†: penicillin 200 000 U per kg per 24 h IV in 4–6 equally divided doses; ceftriaxone 100 mg per kg per 24 h IV/IM in 1 dose
Aqueous crystalline penicillin G sodium
12–18 million U per 24 h IV either continuously or in 6 equally divided doses
2 Two-week regimen not intended for
patients with known cardiac or extracardiac abscess or for those with creatinine clearance of less than 20 ml per min, impaired 8th cranial nerve function, orAbiotrophia,Granulicatella, or Gemella spp.infection. Gentamicin dosage should be adjusted to achieve peak serum concentration of 3–4 mcg per ml and trough serum concentration of less than 1 mcg per ml when 3 divided doses are used; nomogram used for single daily dosing.
or
Ceftriaxone sodium 2 g per 24 h IV/IM in 1 dose 2
plus
Gentamicin sulfate‡ 3 mg per kg per 24 h IV/IM in
1 dose
2
Pediatric dose: penicillin 200 000 U per kg per 24 h IV in 4–6 equally divided doses; ceftriaxone 100 mg per kg per 24 h IV/IM in 1 dose; gentamicin 3 mg per kg per 24 h IV/IM in 1 dose or 3 equally divided doses§ Vancomycin hydrochloride储 30 mg per kg per 24 h IV in 2
equally divided doses not to exceed 2 g per 24 h unless concentrations in serum are inappropriately low
4 Vancomycin therapy recommended only for
patients unable to tolerate penicillin or ceftriaxone; vancomycin dosage should be adjusted to obtain peak (1 h after infusion completed) serum concentration of 30–45 mcg per ml and a trough concentration range of 10–15 mcg per ml Pediatric dose: 40 mg per kg per
24 h IV in 2–3 equally divided doses
Minimum inhibitory concentration less than or equal to 0.12 mcg per ml. *Dosages recommended are for patients with normal renal function. †Pediatric dose should not exceed that of a normal adult. ‡Other potentially nephrotoxic drugs (e.g., nonsteroidal anti-inflammatory drugs) should be used with caution in patients receiving gentamicin therapy. §Data for once-daily dosing of aminoglycosides for children exist, but no data for treatment of infective endocarditis exist.储Vancomycin dosages should be infused during course of at least 1 h to reduce risk of histamine-release “red man” syndrome. Modified from Baddour LM, Wilson WR, Bayer AS, et al. Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association. Circulation 2005;111:e394 – 434 (723).
4.3. Endocarditis in HIV-Seropositive Patients
Endocarditis in patients who are HIV (human immunode- ficiency virus) seropositive usually occurs as a complication of injection drug use or long-term indwelling central cath- eters. S aureus is the most frequent pathogen. When endocarditis is not related to intravenous drug use, right- and left-sided valves are equally involved. Intravenous drug use is the most common cause of tricuspid valve endocar- ditis. Endocarditis-related mortality in patients with ac- quired immune deficiency syndrome (AIDS) exceeds that of HIV-positive patients without AIDS. Thus, it is recom- mended that endocarditis in patients with AIDS be treated with maximum-duration antibiotic regimens (723). 4.4. Indications for Echocardiography in Suspected or Known Endocarditis
Echocardiography is useful for the detection and charac- terization of the hemodynamic and pathological conse-
quences of infection. These consequences include valvu- lar vegetations; valvular regurgitation; ventricular dysfunction; and associated lesions such as abscesses, shunts, and ruptured chordae (727). The indications for transthoracic and transesophageal echocardiography are dis- cussed in the “ACC/AHA/ASE 2004 Guidelines for the Clinical Application of Echocardiography” (2) and the 2005 AHA endocarditis guidelines (723). Transesophageal imaging is more sensitive in detecting vegetations than transthoracic imaging (718,723,728), particularly in patients with prosthetic valves, and in determining the presence and severity of impor- tant complications such as abscesses and perforations. In patients with prosthetic valves, it is reasonable to proceed directly to transesophageal imaging as the first-line diagnostic test when endocarditis is suspected. Echocardiography can be useful in the case of culture-negative endocarditis (729) or the diagnosis of a persistent bacteremia the source of which remains unidentified after appropriate evaluation (2).
Table 25. Therapy of Native Valve Endocarditis Caused by Strains of Viridans Group Streptococci andStreptococcus bovisRelatively Resistant to Penicillin
Regimen Dosage* and Route
Duration,
wk Comments
Aqueous crystalline penicillin G sodium
24 million U per 24 h IV either continuously or in 4 to 6 equally divided doses
4 Patients with endocarditis caused by penicillin-resistant (MIC greater than 0.5 mcg per ml) strains should be treated with regimen recommended for enterococcal endocarditis or
Ceftriaxone sodium 2 g per 24 h IV/IM in 1 dose 4 Recommended for enterococcal endocarditis (see Table 26) (723)
plus
Gentamicin sulfate† 3 mg per kg per 24 h IV/IM in 1 dose
2
Pediatric dose‡: penicillin 300 000 U per 24 h IV in 4 to 6 equally divided doses; ceftriaxone 100 mg per kg per 24 h IV/IM in 1 dose; gentamicin 3 mg per kg per 24 h IV/IM in 1 dose or 3 equally divided doses Vancomycin hydrochloride‡ 30 mg per kg per 24 h IV in 2
equally divided doses not to exceed 2 g per 24 h, unless serum concentrations are inappropriately low
4 Vancomycin§ therapy is recommended only for patients unable to tolerate penicillin or ceftriaxone therapy
Pediatric dose: 40 mg per kg per 24 h in 2 or 3 equally divided doses
Minimum inhibitory concentration (MIC) greater than 0.12 mcg per ml to less than or equal to 0.5 mcg per ml. *Dosages recommended are for patients with normal renal function. †See Table 24 for appropriate dosage of gentamicin. ‡Pediatric dose should not exceed that of a normal adult. §See Table 24 for appropriate dosage of vancomycin. Modified from Baddour LM, Wilson WR, Bayer AS, et al. Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association. Circulation 2005;111:e394 – 434 (723).
4.4.1. Transthoracic Echocardiography in Endocarditis Class I
1. Transthoracic echocardiography to detect valvular