Endocarditis

Infective endocarditis is defined as an infection of the endocardial surface of the heart, which may include one or more heart valves, the mural endocardium, or a septal defect. Endocarditis can be broken down into the following categories:

• Native valve (acute and subacute) endocarditis
• Prosthetic valve (early and late) endocarditis
• Endocarditis related to intravenous drug use

Native valve endocarditis (acute and subacute)

Native valve acute endocarditis usually has an aggressive course. Virulent organisms, such as Staphylococcus aureus and group B streptococci, are typically the causative agents of this type of endocarditis. Underlying structural valve disease may not be present.

Subacute endocarditis usually has a more indolent course than the acute form. Alpha-hemolytic streptococci or enterococci, usually in the setting of underlying structural valve disease, typically are the causative agents of this type of endocarditis.

Prosthetic valve endocarditis (early and late)

Early prosthetic valve endocarditis occurs within 60 days of valve implantation. Staphylococci, gram-negative bacilli, and Candida species are the common infecting organisms.

Late prosthetic valve endocarditis occurs 60 days or more after valve implantation. Alpha-hemolytic streptococci, enterococci, and staphylococci are the common causative organisms.

Endocarditis related to intravenous drug use

Endocarditis in intravenous drug abusers commonly involves the tricuspid valve. S aureus is the most common causative organism.

Pathophysiology

Infective endocarditis generally occurs as a consequence of nonbacterial thrombotic endocarditis, which results from turbulence or trauma to the endothelial surface of the heart. Transient bacteremia then leads to seeding of lesions with adherent bacteria, and infective endocarditis develops.

Pathologic effects due to infection can include local tissue destruction and embolic phenomena. In addition, secondary autoimmune effects, such as immune complex glomerulonephritis and vasculitis, can occur.

Frequency

United States

Incidence is 1.4-4.2 cases per 100,000 people per year.

International

Incidence of disease appears to be similar throughout the developed world.

Mortality/Morbidity

• Increased mortality rates are associated with increased age, infection involving the aortic valve, development of congestive heart failure, central nervous system (CNS) complications, and underlying disease. Mortality rates also vary with the infecting organism.
• Mortality rates in native valve disease range from 16-27%. Mortality rates in patients with prosthetic valve infections are higher. More than 50% of these infections occur within 2 months after surgery.

Sex

The male-to-female ratio is approximately 2:1.

Age

Although endocarditis can occur at any age, the mean age of patients has gradually risen over the past 50 years. Currently, more than 50% of patients are older than 50 years.

Clinical

History

• Present illness history is highly variable. Symptoms commonly are vague, emphasizing constitutional complaints, or complaints may focus on primary cardiac effects or secondary embolic phenomena.
• Primary cardiac disease may present with signs of congestive heart failure due to valvular insufficiency. Secondary phenomena could include focal neurologic complaints due to an embolic stroke or back pain associated with vertebral osteomyelitis.
• Fever and chills are the most common symptoms.
• Anorexia, weight loss, malaise, headache, myalgias, night sweats, shortness of breath, cough, or joint pains are common complaints.
• As many as 20% of cases present with focal neurologic complaints and stroke syndromes.
• Dyspnea, cough, and chest pain are common complaints of intravenous drug users. This is likely related to the predominance of tricuspid valve endocarditis in this group and secondary embolic showering of the pulmonary vasculature.

Physical

• Fever, possibly low-grade and intermittent, is present in 90% of patients.
• Heart murmurs are heard in approximately 85% of patients. Change in the characteristics of a previously noted murmur occurs in 10% of these patients and increases the likelihood of secondary congestive heart failure.
• One or more classic signs of infective endocarditis are found in as many as 50% of patients. They include the following:
  • Petechiae - Common but nonspecific finding
  • Splinter hemorrhages - Dark red linear lesions in the nailbeds
  • Osler nodes - Tender subcutaneous nodules usually found on the distal pads of the digits
  • Janeway lesions - Nontender maculae on the palms and soles
  • Roth spots - Retinal hemorrhages with small, clear centers; rare and observed in only 5% of patients.
• Signs of neurologic disease occur in as many as 40% of patients. Embolic stroke with focal neurologic deficits is the most common etiology. Other etiologies include intracerebral hemorrhage and multiple microabscesses.
• Signs of systemic septic emboli are due to left heart disease and are more commonly associated with mitral valve vegetations. Multiple embolic pulmonary infections or infarctions are due to right heart disease.
• Signs of congestive heart failure, such as distended neck veins, frequently are due to acute left-sided valvular insufficiency.
• Splenomegaly
• Other signs
  • Stiff neck
  • Delirium
  • Paralysis, hemiparesis, aphasia
  • Conjunctival hemorrhage
  • Pallor
  • Gallops
  • Rales
  • Cardiac arrhythmia
  • Pericardial rub
  • Pleural friction rub

Causes

• Native valve endocarditis
  • Rheumatic valvular disease (30% of native valve endocarditis [NVE]) - Primarily involves the mitral valve followed by the aortic valve
  • Congenital heart disease (15% of NVE) - Underlying etiologies include a patent ductus arteriosus, ventricular septal defect, tetralogy of Fallot, or any native or surgical high-flow lesion.
  • Mitral valve prolapse with an associated murmur (20% of NVE)
  • Degenerative heart disease - Including calcific aortic stenosis due to a bicuspid valve, Marfan syndrome, or syphilitic disease
  • Approximately 70% of cases are caused by Streptococcus species including Streptococcus viridans, Streptococcus bovis, and enterococci. Staphylococcus species cause 25% of cases and generally demonstrate a more aggressive acute course.
• Endocarditis associated with intravenous drug use
  • This condition most commonly involves the tricuspid valve, followed by the aortic valve.
  • Two thirds of patients have no previous history of heart disease and no murmur on admission. A murmur may not be heard in patients with tricuspid disease because of the relatively small pressure gradient across this valve. Pulmonary manifestations may be prominent in patients with tricuspid infection: one third have pleuritic chest pain, and three quarters demonstrate chest radiographic abnormalities.
  • Diagnosis of endocarditis in intravenous drug users can be difficult and requires a high index of suspicion.
  • S aureus is the most common (<50% of cases) etiologic organism. Other causative organisms include streptococci, fungi, and gram-negative rods (eg, pseudomonads, Serratia species). Methicillin-resistant S aureus (MRSA) accounts for an increasing portion of S aureus infections and has been associated with previous hospitalizations, long-term addiction, and nonprescribed antibiotic use.
• Prosthetic valve endocarditis
  • Early disease, which presents shortly after surgery, has a different bacteriology and prognosis than late disease, which presents in a subacute fashion similar to native valve endocarditis.
  • Infection associated with aortic valve prostheses is particularly associated with local abscess and fistula formation, and valvular dehiscence. This may lead to shock, heart failure, heart block, shunting of blood to the right atrium, pericardial tamponade, and peripheral emboli to the central nervous system and elsewhere.
  • Endocarditis can occur in association with intravascular devices.
  • Infection that occurs early after surgery may be caused by a variety of pathogens, including S aureus and S epidermidis. These nosocomially acquired organisms are often methicillin-resistant (MRSA). Late disease is most commonly caused by streptococci.
• Fungal endocarditis
  • Fungal endocarditis is found in intravenous drug users and intensive care unit patients who receive broad-spectrum antibiotics.
  • Blood cultures are often negative, and diagnosis frequently is made after microscopic examination of large emboli.
• Diagnosis: Definitive diagnosis of infective endocarditis is generally made using the Duke criteria. Major criteria include (1) multiple positive blood cultures for the infecting organism and (2) echocardiographic evidence of endocardial involvement or a new regurgitant murmur on physical examination

  Treatment of Endocarditis

  Bacterial endocarditis almost always requires hospitalization for antibiotic therapy, generally given intravenously, at least at the outset. Occasionally, therapy with oral antibiotics at home will be successful.

  Antibiotic therapy usually must continue for at least a month. Most patients respond rapidly to institution of appropriate antibiotics, with over 70 percent of patients becoming afebrile (without a fever) within one week. In unusual cases, surgery may be necessary to repair or replace a damaged heart valve.

  Prevention of Endocarditis

  It is important that you mention to your physician or dentist any risk factors you may have for endocarditis.

  Those who have any predisposing factors for bacterial endocarditis (including prosthetic heart valves, previous bacterial endocarditis, congenital heart disease, rheumatic valve dysfunction, hypertrophic cardiomyopathy, and mitral valve prolapse with valvular regurgitation) should be given antibiotics before most medical or dental surgeries and whenever any significant skin infection occurs. Your physician will recommend which antibiotic(s) to take before, and in some cases, after your procedure.

  Emergency Department Care

  • Focus ED care on making the correct diagnosis and stabilizing the patient with acute disease and cardiovascular instability.
  • In most cases, the etiologic microbial agent is not known while the patient is in the ED.
  • General recommendations include drawing 3 sets of blood cultures over a few hours, and then empiric antibiotic therapy may be administered. The choice of empiric therapy can be tailored to the patient's history and circumstances.
  • General measures
    • Treatment of congestive heart failure
    • Oxygen
    • Hemodialysis (may be required in patients with renal failure)

  Consultations

  Admit all patients with suspected infectious endocarditis to the hospital for IV antibiotics while blood cultures are pending. Appropriate consultations could include cardiology, cardiothoracic surgery, and infectious disease services.

  Medication

  Empiric antibiotic therapy is chosen based on the most likely infecting organisms. Native valve disease usually is treated with penicillin G and gentamicin for synergistic treatment of streptococci. Patients with a history of IV drug use may be treated with nafcillin and gentamicin to cover for methicillin-sensitive staphylococci. Infection of a prosthetic valve may include methicillin-resistant Staphylococcus aureus; thus, vancomycin and gentamicin may be used, despite the risk of renal insufficiency. Rifampin also may be helpful in patients with prosthetic valves or other foreign bodies; however, it should be used in addition to vancomycin or gentamicin.

  Antibiotics

  Therapy must cover all likely pathogens in the context of this clinical setting.

  Penicillin G (Pfizerpen)

  DOC for streptococcal infection. Interferes with cell-wall mucopeptide synthesis of the microorganism.

  Adult

  12-18 million U/d IV divided q4h

  Pediatric

  200,000-400,000 U/kg/d IV divided q4-6h

  Probenecid can increase penicillin effectiveness by decreasing clearance; coadministration with tetracyclines can decrease effectiveness of penicillin

  Pregnancy

  B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

  Precautions

  Caution in impaired renal function

  Nafcillin (Unipen)

  Provides coverage for penicillinase-producing staphylococci. Use to initiate therapy in any patient in whom a penicillin G–resistant staphylococcal infection is suspected. Do not use for the treatment of penicillin G-susceptible staphylococci.
  Use parenteral therapy initially in severe infections. Very severe infections may require very high doses. Change to oral therapy as condition improves.
  Because of occasional occurrence of thrombophlebitis associated with parenteral route, particularly in elderly patients, administer parenterally only for a short term (24-48 h), and change to oral route if clinically possible.

  Adult

  2 g IV q4h

  Pediatric

  100-200 mg/kg/d IV divided q4-6h

  Associated with warfarin resistance when administered concurrently; effects may decrease with bacteriostatic action of tetracycline derivatives

  Pregnancy

  B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

  Precautions

  To optimize therapy, determine causative organisms and susceptibility; >10 d treatment to eliminate infection and prevent sequelae (eg, endocarditis, rheumatic fever); obtain cultures after treatment to confirm that infection is eradicated

  Gentamicin (Gentacidin, Garamycin)

  Offers synergistic benefit with penicillins in the treatment of gram-positive cocci. Use of high-dose, once-daily aminoglycosides has not been evaluated in endocarditis.

  Adult

  1.5 mg/kg IV loading dose, followed by 1 mg/kg IV tid

  Pediatric

  7.5 mg/kg/d IV divided tid

Coadministration with other aminoglycosides, cephalosporins, penicillins, and amphotericin B may increase nephrotoxicity; aminoglycosides enhance effects of neuromuscular blocking agents thus prolonged respiratory depression may, occur
Coadministration with loop diuretics may increase auditory toxicity of aminoglycosides; possible irreversible hearing loss of varying degrees may occur (monitor regularly)

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Narrow therapeutic index (not intended for long-term therapy); caution in renal failure (not on dialysis), myasthenia gravis, hypocalcemia, and conditions that depress neuromuscular transmission; adjust dose in renal impairment

Vancomycin (Vancocin)

Used for penicillin-resistant streptococci, methicillin-resistant staphylococci (eg, S epidermidis), and enterococci.
Potent antibiotic directed against gram-positive organisms and is active against enterococci. Also useful in the treatment of septicemia and skin structure infections.
To avoid toxicity, the current recommendation is to assay vancomycin trough levels after the third dose drawn, 0.5 h prior to next dosing. Use CrCl to adjust the dose in patients with renal impairment.

Adult

30 mg/kg/d IV divided bid

Pediatric

40-60 mg/kg/d IV divided q6-8h

Erythema, histaminelike flushing, and anaphylactic reactions may occur when administered with anesthetic agents; taken concurrently with aminoglycosides, risk of nephrotoxicity may increase above that with aminoglycoside monotherapy; effects in neuromuscular blockade may be enhanced when coadministered with nondepolarizing muscle relaxants

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in renal failure, neutropenia; "red man" syndrome is caused by too-rapid IV infusion (dose given over a few minutes) but rarely happens when dose given as 2-h administration or as PO or IP administration; "red man" syndrome is not an allergic reaction

Rifampin (Rifadin, Rimactane)

Used synergistically in the treatment of staphylococcal infections associated with a foreign body, such as a prosthetic heart valve.
Inhibits DNA-dependent RNA polymerase activity in susceptible cells. Specifically, it interacts with bacterial RNA polymerase but does not inhibit the mammalian enzyme. Cross-resistance has been shown only with other rifamycins.

 

Adult

300 mg PO q8h

Pediatric

20 mg/kg/d PO qd; not to exceed 600 mg/d

Induces microsomal enzymes, which may decrease effects of acetaminophen, oral anticoagulants, barbiturates, benzodiazepines, beta-blockers, chloramphenicol, oral contraceptives, corticosteroids, mexiletine, cyclosporine, digitoxin, disopyramide, estrogens, hydantoins, methadone, clofibrate, quinidine, dapsone, tazobactam, sulfonylureas, theophyllines, tocainide, and digoxin
Blood pressure may increase with coadministration of enalapril; coadministration with isoniazid may result in higher rate of hepatotoxicity than with either agent alone (discontinue one or both agents if alterations in LFTs occur)
Rifampin and isoniazid when given after halothane anesthesia have been associated with hepatotoxicity and hepatic encephalopathy
Combination of isoniazid and rifampin may result in a higher rate of hepatotoxicity than when either agent is given alone; thus, discontinue one or both agents if alterations in LFTs occur

 

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Obtain CBCs and baseline clinical chemistries prior to and throughout therapy; in liver disease, weigh benefits against risk of further liver damage; interruption of therapy and high-dose intermittent therapy are associated with thrombocytopenia that is reversible if therapy is discontinued as soon as purpura occurs; if treatment is continued or resumed after appearance of purpura, cerebral hemorrhage or death may occur

Linezolid (Zyvox)

Prevents formation of functional 70S initiation complex, which is essential for bacterial translation process. Bacteriostatic against enterococci and staphylococci and bactericidal against most strains of streptococci. Used as alternative in patients allergic to vancomycin and for treatment of vancomycin-resistant enterococci. Effective against methicillin-resistant Staphylococcus aureus

Adult

600 mg PO/IV q12h for 14-28 d

Pediatric

Not established