Current Diagnosis & Treatment in Infectious Diseases

Section II - Clinical Syndromes

11. Infective Endocarditis

James M. Steckelberg MD

Walter R. Wilson MD

Essentials of Diagnosis

  • Persistent bacteremia with typical microorganisms: for native valves, viridans group streptococci, Streptococcus bovis, HACEK group microorganisms, or community-acquired Staphylococcus aureusor enterococci in the absence of a primary focus.
  • Bacteremia, typically continuous in the absence of antimicrobial therapy.
  • Evidence of endocardial involvement: a new regurgitant murmur or echocardiographic demonstration of valvular vegetations, prosthetic valve dehiscence, or perforation.
  • Supporting findings: predisposing cardiac risk factors or intravenous drug use, vascular phenomena such as emboli, immune-mediated phenomena such as glomerulonephritis.

General Considerations

The term “infective endocarditis” refers to infection involving the endocardial surfaces of the heart. Typically, valvular surfaces are affected together with adjacent areas subject to trauma or shear forces from turbulent blood flow. Endocarditis has been recognized as a distinct clinical entity for well over 100 years but continues to be an important diagnostic and therapeutic challenge for clinicians in the modern era.

In studies in geographically defined populations, endocarditis occurs at a frequency of 4–5 cases/ 100,000 person years. Endocarditis occurs ninefold more frequently among people ≥65 years old than among younger persons. The incidence rate is two- to threefold higher in men than in women at all ages. Cardiac abnormalities associated with turbulent blood flow increase the risk of endocarditis (Table 11-1). Although the association between dental infection or procedures and infective endocarditis has been recognized since the 1930s, only a minority of cases have a clearly implicated dental procedure. Intravenous drug abuse may be associated with endocarditis which most often affects the tricuspid valve but may cause infection of the aortic or mitral valve as well. Endocarditis associated with intravenous drug abuse is most often caused by S aureus, gram-negative bacilli (including Pseudomonas spp.), or Candida.

Unlike most other bacterial infections, untreated endocarditis is uniformly fatal, typically within weeks to months. Accurate diagnosis and prompt therapy are therefore paramount.

Clinical Findings

The clinical manifestations of endocarditis are highly varied (Table 11-2). Patients may experience a prolonged, insidious onset of flulike symptoms over weeks to months, especially if partially treated with oral antibiotics empirically or for an erroneous diagnosis of minor infection. Other patients present with a more abrupt, devastating onset of flagrant sepsis with rapid cardiac valvular destruction and cardiac decompensation, typically with S aureus infection.

  1. Signs and Symptoms.Most patients with endocarditis have daily fever. Other nonspecific symptoms include rigors; night sweats; malaise; anorexia; muscular, joint, or back pain; and weight loss. Physical examination may reveal evidence of preexisting (Table 11-1) or new cardiac abnormalities, including murmurs or congestive heart failure. Splenomegaly is present in a minority of patients. Osler nodes are painful nodules, typically on the pulps of the toes or fingers. Janeway lesions are painless erythematous macules characteristically on the soles of the feet or palms. Roth spots are hemorrhagic retinal or conjunctival lesions with central pallor.

Osler nodes, Janeway lesions, and Roth spots, if found, are highly suggestive of infective endocarditis but will be absent in 80–90% of cases.

  1. Laboratory Findings.Blood cultures should always be obtained promptly when endocarditis is suspected, before antimicrobial therapy is begun. For most microorganisms that cause endocarditis (Box 11-1), bacteremia is continuous, and ≥90% of the first two sets of blood cultures obtained will be positive in the absence of recent antimicrobial therapy. Occasionally, endocarditis is caused by fastidious organisms (such as the HACEK group of oral gram-negative microorganisms or nutritionally variant viridans streptococci), which require longer periods of incubation of blood cultures or special culture techniques for optimal growth. Alerting the microbiology laboratory to the suspicion of endocarditis will aid in optimizing culture techniques.

Table 11-1. Cardiac conditions associated with endocarditis.1

Endocarditis prophylaxis recommended
   High-risk category:
      Prosthetic cardiac valves, including bioprosthetic and homograft valves
      Previous bacterial endocarditis
      Complex cyanotic congenital heart disease (eg, single ventricle states, transposition of the great arteries, tetralogy of Fallot)
      Surgically constructed systemic pulmonary shunts or conduits
   Moderate-risk category:
      Most other congenital cardiac malformations (other than above and below)
      Acquired valvar dysfunction (eg, rheumatic heart disease)
      Hypertrophic cardiomyopathy
      Mitral valve prolapse with valvar regurgitation, thickened leaflets, or both
Endocarditis prophylaxis not recommended
   Negligible-risk category (no greater risk than the general population):
      Isolated secundum atrial septal defect
      Surgical repair of atrial septal defect, ventricular septal defect, or patent ductus arteriosus(without residua beyond 6 mo)
      Previous coronary artery bypass graft surgery
      Mitral valve prolapse without valvar regurgitation
      Physiologic, functional, or innocent heart murmurs
      Previous Kawasaki disease without valvar dysfunction
      Previous rheumatic fever without valvar dysfunction
      Cardiac pacemakers (intravascular and epicardial) and implanted defibrillators

1Source: JAMA 1997; 277:1794–1801.

  1. In established endocarditis, anemia and an elevated sedimentation rate are present in the majority but not all patients. The leukocyte count typically is normal or mildly elevated despite the presence of ongoing bacteremia, except in fulminant S aureusinfection, in which leukocytosis is the rule. Polyclonal hypergammaglobulinemia, hypocomplementemia, and false-positive rheumatoid factor, Lyme serology, or syphilis serology may be found and reflect ongoing immunologic activation. Microhematuria or elevated creatinine and urinary sediment findings suggesting glomerulonephritis may be seen in advanced, late infection. Glomerulonephritis is caused by the deposition of circulating immune complexes on kidney basement membranes.

Table 11-2. Common clinical findings in infective endocarditis.

History of cardiac risk factors or IVDA
Fever, malaise, night sweats
New regurgitant murmur, heart failure
Less commonly, Janeway lesions, Osler nodes, Roth spots
Persistently positive blood cultures for typical organisms are the hallmark of endocarditis
Vegetations seen by echocardiography—transesophageal more sensitive than transthoracic
Anemia, elevated ESR are common but nonspecific
WBC usually normal or mildly elevated

  1. Imaging.Echocardiography demonstrates cardiac valvular vegetations in from < 60–95% of patients. Transesophageal echocardiography, while more invasive, is more sensitive for detecting valvular vegetations or perforations (especially in patients with prosthetic valves) as well as intracardiac complications of endocarditis such as myocardial abscesses. Although echocardiographic examination is frequently helpful, the absence of vegetations as seen by echocardiography does not completely exclude a diagnosis of infective endocarditis. Among patients with right-sided cardiac involvement, chest x-ray may show multiple, migratory pulmonary infiltrates resulting from septic pulmonary emboli.

Differential Diagnosis

The differential diagnosis of infective endocarditis is broad and includes many diseases discussed in Chapter 18. In addition to many infectious etiologies, rheumatologic conditions such as systemic lupus erythematosus or vasculitides and malignancies are the main categories to be considered. Numerous noninfectious processes may cause marantic (noninfectious) cardiac valvular vegetations or false-positive echocardiographic studies (Table 11-3).

Complications

Intracardiac Complications. Cardiac valvular destruction with resulting valvular insufficiency and cardiac failure is the most common intracardiac complication of infective endocarditis. Valvular dysfunction can occur from perforation of a valve leaflet, destruction of supporting apparatus such as an infected ruptured mitral chordae, or dehiscence of a prosthetic valve. Alternatively, large, bulky vegetations may occasionally result in valve outflow obstruction mimicking valvular stenosis.

Perivalvular extension of infection with abscess formation is associated more commonly with S aureus infections, infections of the aortic valve, and infections of prosthetic valves. Perivalvular extension may be clinically silent or manifested by conduction delays, persistent bacteremia or fever on appropriate therapy, fistulous tracts between cardiac chambers or the pericardial space, or prosthetic valve dehiscence. As noted above, transesophageal echocardiography is more accurate (positive predictive value, 87%; negative predictive value, 89%) than transthoracic echocardiography for the detection of perivalvular abscesses. The development of new atrioventricular block on electrocardiography has 88% specificity for abscess but poor sensitivity (45%).

Extracardiac Complications. Arterial emboli occur in 20–40% of patients with infective endocarditis. Symptomatic emboli occur most frequently in the central nervous system; other sites include abdominal viscera (especially the spleen), kidneys, peripheral arteries, coronary arteries, and (in right-sided endocarditis) the pulmonary arteries. About half of the embolic events occur before diagnosis. Endocarditis therefore should be considered in the differential diagnosis of every patient who presents with fever and an embolic event, such as a stroke. Overall, the incidence of emboli falls from 13 events/1000 patient days during the first week of effective antimicrobial therapy to < 1.2 events/1000 patient days after 2 weeks of antimicrobial therapy.

BOX 11-1 Microbiology of Infective Endocarditis

 

Native Valves

Prosthetic Valves

More Frequent

· Viridans group streptococci

· S aureus (most common organism in IVDU)

· Enterococci

· Coagulase-negative staphylococci (especially in the first 2 months postoperatively)

· Viridans group streptococci

· S aureus

· Enterococci

Less Frequent

· HACEK group organismsa

· S bovis

· Coagulase-negative staphylococci

· Fungi (especially Candida)

· Corynebacteria, diphtheroids

· Enterobacteriaceae

aHemophilus aphrophilus and related species, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella spp.

The relationship between vegetation size, as measured by echocardiography, and embolic events is complex. Not all studies have distinguished between an association with past embolic events (due in part to a longer course of illness associated with larger vegetations) and the ability to predict future embolic events. Some studies have suggested that large vegetations (>1 cm), especially in the mitral position, are associated with higher embolic risk. In one study, vegetations were predictive of future embolic events only in patients with viridans group streptococcal infection and not in patients with other microorganisms. Staphylococcal infections had the highest incidence of embolic events, irrespective of vegetations.

Table 11-3. Causes of noninfective vegetative endocarditis.1

Associated with neoplasia:
   Atrial myxoma
   Marantic endocarditis (adenocarcinoma)
   Neoplastic disease (lymphoma, rhabdomyosarcoma)
   Carcinoid
Associated with autoimmune diseases:
   Rheumatic heart disease
   Systemic lupus erythematosus (Libmann-Sacks endocarditis)
   Antiphospholipid syndrome
   Polyarteritis nodosa
   Behçet's disease
Postvalvular surgery:
   Thrombus
   Stitch after surgery
   Other postvalvular surgery changes
Miscellaneous
   Eosinophilic heart disease
   Ruptured mitral chordae
   Myxomatous degeneration

1Source: Berbari & Steckelberg, Mayo Clin Proc 1997; 72: 532–42.

Mycotic (infectious) aneurysms occur in 1–5% of patients with endocarditis, most commonly at bifurcation points in the central nervous system, although aortic, visceral, and peripheral arterial mycotic aneurysms also occur. Mycotic aneurysms may be caused by any of the microorganisms that cause endocarditis; the term “mycotic” in this context does not imply a fungal etiology. Clinically, the presentation of mycotic aneurysms in patients with endocarditis is highly variable.

In some patients, a sudden, catastrophic intracranial hemorrhage without premonitory symptoms is the first indication of an aneurysm. In others, severe, localized headache or neurological symptoms such as evidence of a mass lesion, altered sensorium, or focal deficits such as hemianopsia or cranial neuropathy may indicate an embolus preceding an aneurysm or a premonitory aneurysmal leak. Patients suspected of an intracranial mycotic aneurysm should undergo contrast-enhanced computerized tomographic scanning or magnetic resonance angiography. In selected cases or when surgical intervention is planned, four-vessel cerebral angiography is indicated.

Treatment of mycotic aneurysms is complex; more than half of intracerebral aneurysms resolve or decrease in size with antimicrobial therapy, whereas in other patients enlargement, rupture, or the formation of new aneurysms occurs. The decision to intervene surgically should be individualized and depends on the number of aneurysms, their location and course, as well as patient risk factors for surgery.

Abscess formation distant from the heart may complicate endocarditis as a consequence of the sustained and sometimes prolonged bacteremia. Identification of this complication is especially important, since a persistent metastatic focus of infection may cause relapse of the endocarditis or require an altered treatment regimen. Persistence of fever or intermittent bacteremia despite appropriate antimicrobial therapy, localized pain or tenderness, or laboratory abnormalities referable to the involved organ (such as abnormal liver function tests) provides clues to the diagnosis. Abscesses occur most frequently in the spleen, liver, brain, or disk spaces. Bacteremic seeding of muscle or single or multiple joint spaces may also be seen, most often associated with S aureus endocarditis.

Renal failure, once commonly seen in end-stage infective endocarditis, is now rarely seen. Microhematuria or red cell casts may be present in the urine. Renal failure may occur due to glomerulonephritis associated with endocarditis, renal infarcts due to emboli, or as complications of drug therapy. Renal failure due to immune complex deposition in glomeruli associated with infective endocarditis typically improves with the institution of appropriate antimicrobial therapy.

Treatment

Effective medical treatment of infective endocarditis requires identification and susceptibility testing of the responsible microorganism; sustained bactericidal antimicrobial therapy singly or in combination, usually in high concentrations, based on the susceptibility of the microorganism (Tables 11-4,11-5,11-6,11-7,11-8 and 11-9); identification and treatment of complications, including abscesses and complications of drug therapy; identification and eradication of the original source of infection (such as a dental abscess) if possible; and patient education about future endocarditis antimicrobial prophylaxis (Tables 11-1, 11-10,11-11,11-12 and 11-13).

Surgical intervention is necessary in about a third of patients with endocarditis and is lifesaving in some situations. The most common indication for valve replacement or valve repair surgery is congestive heart failure or hemodynamic instability due to valvular dysfunction that is unresponsive to medical therapy. In this setting, immediate surgery is indicated; a delay to complete a longer course of antimicrobial therapy may increase surgical mortality. Other accepted indications for surgery include sustained, persistent

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bacteremia despite appropriate antimicrobial therapy, especially in the setting of resistant microorganisms (eg, fungi) or myocardial abscess, and relapse with highly resistant microorganisms. Some patients with multiple emboli despite effective antimicrobial therapy may benefit from surgery.

Table 11-4. Suggested regimens for therapy of native valve endocarditis due to penicillin-susceptible viridans streptococci and Streptococcus bovis (minimum inhibitory concentration ≤0.1 µg/mL).1

Antibiotic

Dosage and Route

Duration, wk

Comments

Aqueous crystalline penicillin G sodium
or
Ceftriaxone sodium

12–18 million U/24 h IV either continuously or in six equally divided doses
2 g once daily IV or IM2

4

4

Preferred in most patients older than 65 y and in those with impairment of the eighth nerveor renal function

Aqueous crystalline pencillin G sodium
With gentamicin sulfate3

12–18 million U/24 h IV either continuously or in six equally divided doses
1 mg/kgIM or IV every 8 h

2

2

When obtained 1 h after a 20–30 min IV infusion or IM injection, serum concentration of gentamicin of approximately 3 µg/mL is desirable; trough concentration should be <1 µg/mL

Vancomycin hydrochloride4

30 mg/kg per 24 h IV in two equally divided doses, not to exceed 2 g/24 h unless serum levels are monitored

4

Vancomycin therapy is recommended for patients allergic to β-lactams (see text); peak serum concentrations of vancomycin should be obtained 1 h after completion of the infusion and should be in the range of 30–45 µg/mL for twice-daily dosing

1Dosages recommended are for patients with normal renal function. For nutritionally variant streptococci, see Table 11-6. IV indicates intravenous; IM, intramuscular.

2Patients should be informed that IM injection of ceftriaxoneis painful.
3Dosing of gentamicin on a mg/kg basis will produce higher serum concentrations in obese patients than in lean patients. Therefore, in obese patients, dosing should be based on ideal body weight. (Ideal body weight for menis 50 kg + 2.3 kg per inch over 5 feet, and ideal body weight for women is 45.5 kg + 2.3 kg per inch over 5 feet.) Relative contraindications to the use of gentamicin are age >65 y, renal impairment, or impairment of the eighth nerve. Other potentially nephrotoxic agents (eg, nonsteroidal anti-inflammatory drugs) should be used cautiously in patients receiving gentamicin.
4Vancomycin dosage should be reduced in patients with impaired renal function. Vancomycin given on a mg/kg basis will produce higher serum concentrations in obese patients than in lean patients. Therefore, in obese patients, dosing should be based on ideal body weight. Each dose of vancomycin should be infused over at least 1 h to reduce the risk of the histamine-release “red man” syndrome.
Reprinted from JAMA 1995; 274:1706–1713.

Table 11-5. Therapy for native valve endocarditis due to strains of viridans streptococci and Streptococcus bovis relatively resistant to penciillin G (minimum inhibitory concentration >0.1 µg/mL and <0.5 µg/mL).1

Antibiotic

Dosage and Route

Duration, wk

Comments

Aqueous crystalline penicillin G sodium

18 million U/24 h IV either continuously or in six equally divided doses

4

Cefazolin or other first-generation cephalosporins may be substituted for penicillin in patients whose penicillin hypersensitivity is not of the immediate type

With gentamicin sulfate2

1 mg/kg IM or IV every 8 h

2

 

Vancomycin hydrochloride3

30 mg/kg per 24 h IV in two equally divided doses, not to exceed 2 g/24 h unless serum levels are monitored

4

Vancomycin therapy is recommended for patients allergic to β-lactams

1Dosages recommended are for patients with normal renal function. IV indicates intravenous; IM, intramuscular.

2For specific dosing adjustment and issues concerning gentamicin (obese patients, relative contraindications), see Table 11-4 footnotes.
3For specific dosing adjustment and issues concerning vancomycin (obese patients, length of infusion), see Table 11-4 footnotes.
Reprinted from JAMA 1995; 274:1706–1713.

Echocardiographic appearance per se of vegetations should not be used as the sole criterion for surgical intervention. Patients at risk of emboli from valvular vegetations demonstrable on echocardiography may be considered candidates for surgical intervention if emboli continue to occur after 2 weeks of effective antimicrobial therapy, or in those patients with large mobile vegetations located on the anterior leaflet of the mitral valve. However, generalizations should not be made regarding surgical intervention in these patients, and the decision for cardiac surgery to prevent systemic embolization should be individualized for each patient.

Prognosis

As noted above, untreated infective endocarditis is uniformly fatal. The prognosis with accurate diagnosis and treatment is highly variable, depending on the microorganism, the degree of valvular destruction before antimicrobial treatment, and whether prosthetic material is involved. In uncomplicated viridans group streptococcal infection of a native valve, outcome is frequently excellent, including prompt response of fever and systemic symptoms to antimicrobial therapy and cure rates exceeding 98% with approved regimens in patients who survive to complete therapy. In contrast, mortality in prosthetic valve infection with staphylococci, gram-negative bacilli, or fungi remains in the range of ≥25–50%, despite aggressive medical and surgical therapy.

Table 11-6. Standard therapy for endocarditis due to enterococci.1

Antibiotic

Dosage and Route

Duration, wk

Comments

Aqueous crystalline penicillin G sodium

18–30 million U/24 h IV either continuously or in six equally divided doses

4–6

 

With gentamicin sulfate2

1 mg/kg IM or IV every 8 h

4–6

4-wk therapy recommended for patients with symptoms <3 mo in duration; 6-wk therapy recommended for patients with >3 mo in duration

Ampicillin sodium

12 g/24 hIV either continuously or in six equally divided doses

4–6

 

With gentamicin sulfate3

1 mg/kg IM or IV every 8 h

4–6

 

Vancomycin hydrochloride2,3

30 mg/kg per 24 h IV in two equally divided doses, not to exceed 2 g/24 h unless serum levels are monitored

4–6

Vancomycin therapy is recommended for patients allergic to β-lactams; cephalosporins are not acceptable alternatives for patients allergic to pencillin

With gentamicin sulfate2

1 mg/kg IM or IV every 8 h

4–6

1All enterococci causing endocarditis must be tested for antimicrobial susceptibility in order to select optimal therapy (see text).

This table is for endocarditis due to gentamicin- or vancomycin-susceptible enterococci, viridans streptococci with a minimum inhibitory concentration of >0.5 µg/mL, nutritionally variant viridans streptococci, or prosthetic valve endocarditis caused by viridans streptococci or Streptococcus bovis. Antibiotic dosages are for patients with normal renal function.IV indicates intravenous; IM, intramuscular.
2For specific dosing adjustment and issues concerning gentamicin (obese patients, relative contraindications), see Table 11-4 footnotes.
3For specific dosing adjustment and issues concerning vancomycin (obese patients, length of infusion), see Table 11-4 footnotes.
Reprinted from JAMA 1995; 274:1706–1713.

Table 11-7. Therapy for endocarditis due to staphylococcus in the absence of prosthetic material.1

Antibiotic

Dosage and Route

Duration

Comments

Methicillin-Susceptible Staphylococci

Regimens for non-β-lactam-allergic patients

Naficillin sodium or oxacillin sodium

2 g IV every 4 h

4–6 wk

Benefit of additional aminogly cosides has not been established

With optional addition of gentamicin sulfate2

1 mg/kg IM or IV every 8 h

3–5 d

Regimens for β-lactam-allergic patients

Cefazolin (or other first-generation cephalosporins in equivalent dosages)

2 g IV every 8 h

4–6 wk

Cephalosporins should be avoided in patients with immediate-type hypersensitivity to penicillin

With optional addition of gentamicin2

1 mg/kg IM or IV every 8 h

3–6 d

Vancomycin hydrochloride3

30 mg/kg per 24 h IV in two equally divided doses, not to exceed 2 g/24 h unless serum levels are monitored

4–6 wk

Recommended for patients allergic to pencillin

Methicillin-Resistant Staphylococci

Vancomycin hydrochloride3

30 mg/kg per 24 h IV in two equally divided doses, not to exceed 2 g/24 h unless serum levels are monitored

4–6 wk

1For treatment of endocarditis due to penicillin-susceptible staphylococci (minimum inhibitory concentration ≤0.1 µg/mL), aqueous crystalline penicillin G sodium (Table 1, first regimen) can be used for 4 to 6 wk instead of nafcillin or oxacillin. Shorter antibiotic courses have been effective in some drug addicts with right-sided endocarditis due to Staphylococcus aureus (see text). See text for comments on use of rifampin. IV indicates intravenous; IM, intramuscular.

2For specific dosing adjustment and issues concerning gentamicin (obese patients, relative contraindications), see Table 11-4 footnotes.
3For specific dosing adjustment and issues concerning vancomycin (obese patients, length of infusion), see Table 11-4 footnotes.
Reprinted from JAMA 1995; 274:1706–1713.

Table 11-8. Treatment of staphylococcal endocarditis in the presence of a prostheticvalve or other prosthetic material.1

Antibiotic

Dosage and Route

Duration, wk

Comments

Regimen for Methicillin-Resistant Staphylococci

Vancomycin hydrochloride2

30 mg/kg per 24 h IV in 2 or 4 equally divided doses, not to exceed 2 g/24 h unless serum levels are monitored

≥6

With rifampin3
And with gentamicin sulfate4,5

300 mg orally every 8 h
1.0 mg/kg IM or IV every 8 h

≥6
2

Rifampin increases the amount of warfarin sodium required for antithrombotic therapy.

Regimen for Methicillin-Susceptible Staphylococci

Nafcillin sodium or oxacillin sodium

2 g IV every 4 h

≥6

First-generation cephalosporins or vancomycin should be used in patients allergic to β-lactam.

With rifampin3

300 mg orallyevery 8 h

≥6

And with gentamicin sulfate4,5

1.0 mg/kg IM or IV every 8 h

2

Cephalosporins should be avoided in patients with immediate-type hypersensitivity to penicillin or with methicillin-resistant staphylococci.

1Dosages recommended are for patients with normal renal function. IV indicates intravenous; IM, intramuscular.

2For specific dosing adjustment and issuesconcerning vancomycin (obese patients, length of infusion), see Table 11-4 footnotes.
3Rifampin plays a unique role in the eradication of staphylococcal infection involving prosthetic material (see text); combination therapy is essential to prevent emergence of rifampin resistance.
4For specific dosing adjustment and issues concerning gentamicin (obese patients, relative contraindications), see Table 11-4 footnotes.
5Use during initial 2 wk.
Reprinted from JAMA 1995; 274:1706–1713.

Table 11-9. Therapy for endocarditis due to HACEK microorganisms(Haemophilus parainfluenzae, Haemophilus aphrophilus, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella kingae).1

Antibiotic

Dosage and Route

Duration, wk

Comments

Ceftriaxone sodium2

2 g once daily IV or IM2

4

Cefotaxime sodium or other third-generation cephalosporins may be substituted

Ampicillin sodium3

12 g/24 h IV either continuously or in 6 equally divided doses

4

With gentamicin sulfate4

1 mg/kg IM or IV every 8 h

4

1Antibiotic dosages are for patients with normal renal function. IV indicates intravenous; IM, intramuscular.

2Patients should be informed that IM injection of ceftriaxone is painful. For patients unable to tolerate β-lactam therapy, consult text.
3Ampicillin should not be used if laboratory tests show β-lactamase production.
4For specific dosing adjustment and issues concerning gentamicin (obese patients, relative contraindications), see Table 11-4 footnotes.
Reprinted from JAMA 1995; 274:1706–1713.

Table 11-10. Dental procedures and endocarditis prophylaxis.1

Endocarditis prophylaxis recommended2
   Dental extractions
   Periodontal procedures including surgery, scaling and root planning, probing, and recall maintenance
   Dental implant placement and reimplantation of avulsed teeth
   Endodontic (rootcanal) instrumentation or surgery only beyond the apex
   Subgingival placement of antibiotic fibers or strips
   Initial placement of orthodontic bands but not brackets
   Intraligamentary local anesthetic injections
   Prophylactic cleaning of teeth or implants where bleeding is anticipated
Endocarditis prophylaxis not recommended
   Restorative dentistry3 (operative and prosthodontic) with or without retraction cord4
   Local anesthetic injections (nonintraligamentary)
   Intracanal endodontic treatment; post-placement and buildup
   Placement of rubber dams
   Postoperative suture removal
   Placement of removable prosthodontic or orthodontic appliances
Taking of oral impressions
Fluoride treatments
Taking of oral radiographs
Orthodontic appliance adjustment
Shedding of primary teeth

1Source: JAMA 1997; 277:1794–1801.
2Prophylaxis is recommended for patients with high- and moderate-risk cardiac conditions.
3This includes restoration of decayed teeth (filling cavities) and replacement of missing teeth.
4Clinical judgment may indicate antibiotic use in selected circumstances that may create significant bleeding.

Table 11-11. Other procedures and endocarditis prophylaxis.1

Endocarditis prophylaxis recommended
   Respiratory tract
      Tonsillectomy, adenoidectomy, or both
      Surgical operations that involve respiratory mucosa
      Bronchoscopy with a rigid bronchoscope
   Gastrointestinal tract2
      Sclerotherapy for esophageal varices
      Esophageal stricture dilation
      Endoscopic retrograde cholangiography with biliary obstruction
      Biliary tract surgery
      Surgical operations that involve intestinal mucosa
   Genitourinary tract
      Prostatic surgery
      Cytoscopy
      Urethral dilation
Endocarditis prophylaxis not recommended
   Respiratory tract
      Endotracheal intubation
      Bronchoscopy with a flexible bronchoscope, with or without biopsy3
      Tympanostomy tube insertion
   Gastrointestinal tract
      Transesophageal echocardiography3
      Endoscopy with or without gastrointestinal biopsy
   Genitourinary tract
      Vaginal hysterectomy3
      Vaginal delivery3
      Cesarean section
      In uninfected tissue:
  Urethral catheterization
  Uterine dilatation and curettage
  Therapeutic abortion
  Sterilization procedures
  Insertion or removal of intrauterine devices
      Other
  Cardiac catheterization, including balloon angioplasty
  Implanted cardiac pacemakers, implanted defibrillators, and coronary stents
  Incision or biopsy of surgically scrubbed skin
  Circumcision

1Reprinted with permission from JAMA 1997; 277:1794–1801.

2Prophylaxis is recommended for high-risk patients; it is optional for medium-risk patients.
3Prophylaxis is optional for high-risk patients.

Table 11-12. Prophylactic regimens for dental, oral, respiratory tract, or esophageal procedures.1

Situation

Agent2

Regimen

Standard general prophylaxis

Amoxicillin

Adults: 2.0 g; children: 50 mg/kg orally 1 h before procedure

Unable to take oral medications

Ampicillin

Adults: 2.0 g IMor IV; children: 50 mg/kg IM or IV within 30 min before procedure

Allergic to penicillin

Clindamycin or cephalexin3

Adults: 600 mg; children: 20 mg/kg orally 1 h before procedure

Cefadroxil

Adults: 2.0 g; children: 50 mg/kg orally 1 h before procedure

Azithromycin or clarithromycin

Adults: 500 mg; children: 15 mg/kg orally 1 h before procedure

Allergic to penicillin and unable to take oral medications

Clindamycin

Adults: 600 mg; children: 20 mg/kg IV within 30 min before procedure

Cefazolin3

Adults: 1.0 g; children: 25 mg/kg IM or IV within 30 min before procedure

1Reprinted with permission from JAMA 1997; 277:1794–1801. Abbreviations: IM, intramuscularly; IV, intravenously.

2Total children's dose should not exceed adult dose.
3Cephalosporins should not be used in individuals with immediate-type hypersensitivity reaction (urticaria, angiodema, or anaphylaxis) to penicillins.

Even after cure of infective endocarditis, subsequent need for valve replacement because of valvular insufficiency is not uncommon, especially in the setting of aortic valve infection. Persons who have had infective endocarditis are at ≥100-fold increased risk of recurrent infection, compared with the general population.

Prevention

Patients with known cardiac risk factors for infective endocarditis should have regular professional dental care and practice good oral hygiene. The American Heart Association recommends specific antimicrobial prophylaxis for patients who have cardiac abnormalities associated with increased risk of endocarditis and who are undergoing certain invasive procedures associated with a risk of transient bacteremia caused by microorganisms commonly causing endocarditis (Tables 11-1,11-10,11-11,11-12 and 11-13).

Table 11-13. Prophylactic regimens for genitourinary/gastrointestinal (excluding esophageal) procedures.1

Situation

Agent2

Regimen3

High-risk patients

Ampicillin plus gentamicin

Adults: ampicillin,2.0 g IM or IV, plus gentamcin, 1.5 mg/kg (not to exceed 120 mg) within 30 min of starting procedure; 6 h later, ampicillin, 1 g IM/IV, or amoxicillin, 1 g orally. Children: ampicillin, 50 mg/kg IM or IV (not to exceed 2.0 g) plus gentamicin 1.5mg/kg within 30 min of starting the procedure; 6 h later, ampicillin, 25 mg/kg IM/IV, or amoxicillin, 25 mg/kg orally

High-risk patients allergic to ampicillin/amoxicillin

Vancomycin plus gentamicin

Adults: vancomycin, 1.0 g IV over 1–2 h, plus gentamicin,1.5 mg/kg IV/IM (not to exceed 120 mg); complete injection/infusion within 30 min of starting procedure.
Children: vancomycin, 20 mg/kg IV over 1–2 h, plus gentamicin, 1.5 mg/kg IV/IM; complete injection/ infusion within 30 min of starting procedure

Moderate-risk patients

Amoxicillin or ampicillin

Adults: amoxicillin,2.0 g orally 1 h before procedure, or ampicillin, 2.0 g IM/IV within 30 min of starting procedure.
Children:amoxicillin, 50 mg/kg orally 1 h before procedure, or ampicillin, 50 mg/kg IM/IVwithin 30 min of starting procedure

Moderate-risk patients allergic to ampicillin/amoxicillin

Vancomycin

Adults: vancomycin, 1.0 g IV over 1–2 h, complete infusion within 30 min of starting procedure
Children: vancomycin, 20 mg/kg IV over 1–2 h; complete infusion within 30 min of starting procedure.

1Source: JAMA 1997;277:1794–1801.

2Total children's dose should not exceed adult dose.
3No second dose ofvancomycin or gentamicin is recommended. Abbreviations: IM, intramuscularly; IV, intravenously.

REFERENCES

Dajani AS et al: Prevention of bacterial endocarditis. Recommendations by the American Heart Association. J Am Med Assoc 1997;277:1794.

Patel R, Steckelberg JM: Infections of the heart. In Murphy JG (editor): Mayo Clinic Cardiology Review, Futura Publishing Co, 1997.

Wilson WR et al: Antibiotic treatment of adults with infective endocarditis due to streptococci, enterococci, staphylococci, and HACEK microorganisms. J Am Med Assoc 1995;274:1706.

Wilson WR, Steckelberg JM (editors): Infective endocarditis. Infect Dis Clin North Am 1993;7.