The American Heart Association (AHA) last published guidelines on the prevention of infective endocarditis in 1997. Since then, many studies have questioned the effectiveness of antibiotic prophylaxis for prevention of infective endocarditis in patients undergoing dental or gastrointestinal (GI) or genitourinary (GU) tract procedures. The AHA has revised its guidelines to reflect these new data.

Pathogenesis

Infective endocarditis is caused by interactions between the bloodstream pathogen with matrix molecules and platelets at sites of endocardial cell damage. It results from the following sequence of events: (1) formation of nonbacterial thrombotic endocarditis; (2) transient bacteremia; (3) adherence of the bacteria to nonbacterial thrombotic endocarditis; and (4) resulting bacterial proliferation.

Antibiotic Prophylaxis for Dental Procedures

It has been thought that dental procedures could cause infective endocarditis in patients with underlying cardiac risk factors, and that antibiotic prophylaxis is effective in preventing it; however, evidence for this theory is lacking. Published evidence indicates that a small number of cases of infective endocarditis are caused by dental procedures and, therefore, few patients would benefit from antibiotic prophylaxis, even if the antibiotics were 100 percent effective.

Most cases of infective endocarditis are caused by oral microflora that are probably the result of random bacteremia from routine daily activities (e.g., teeth brushing, f lossing, chewing). Therefore, more emphasis should be placed on improving oral health and access to dental care in patients with underlying cardiac conditions that are associated with the highest risk of adverse outcomes and in those who have conditions that predispose them to infective endocarditis.

Cardiac Conditions and Infective Endocarditis

Previous AHA guidelines grouped underlying cardiac conditions associated with the risk of infective endocarditis by high, moderate, and negligible risk; antibiotic prophylaxis was recommended for patients in the high-and moderate-risk groups. When updating these guidelines, the AHA considered three criteria: (1) which underlying conditions have the highest predisposition for infective endocarditis; (2) which underlying conditions have the highest risk of adverse effects from infective endocarditis; and (3) whether recommendations for prophylaxis should be based on one or both of those groups of conditions.

CONDITIONS WITH HIGH PREDISPOSITION FOR INFECTIVE ENDOCARDITIS

Persons with rheumatic heart disease, mitral valve prolapse, and congenital heart disease have an increased lifetime risk of infective endocarditis compared with persons who have no known underlying cardiac conditions.

CONDITIONS WITH HIGHEST RISK OF ADVERSE EFFECTS FROM INFECTIVE ENDOCARDITIS

Infective endocarditis is serious and life threatening, regardless of the underlying cardiac condition. Several comorbid factors (e.g., older age, diabetes, immunosuppressive conditions) can cause complications. There also are long-term consequences of infective endocarditis. For example, a cardiac valve damaged by infective endocarditis can undergo progressive functional deterioration that could result in the need for cardiac valve replacement.

In native valve viridans group streptoccocal or enterococcal infective endocarditis, disease can range from a relatively benign infection to severe valvular dysfunction, dehiscence, congestive heart failure, multiple embolic events, and death. However, the conditions listed in Table 1 almost always have an increased risk of adverse outcomes. Patients with relapsing or recurrent infective endocarditis have a greater risk of congestive heart failure, as well as an increased need for cardiac valve replacement. They also have a higher mortality rate compared with patients who have not had infective endocarditis. Patients with multiple episodes of native or prosthetic-valve infective endocarditis have a greater risk of recurrent disease, with each subsequent episode being associated with a higher risk of serious complications.

Most retrospective studies suggest that patients with complex cyanotic heart disease, as well as those with postoperative palliative shunts, conduits, or other prostheses, have a high lifetime risk of infective endocarditis. They also seem to be at highest risk of morbidity and mortality. The AHA recommends antibiotic prophylaxis for dental procedures in these patients during the first six months after the procedure. The AHA does not recommend prophylaxis after six months following a dental procedure if there is no residual defect.

ANTIBIOTIC PROPHYLAXIS

The AHA no longer recommends antibiotic prophylaxis based on an increased lifetime risk of infective endocarditis. No data prove that antibiotic prophylaxis prevents bacteremia-associated infective endocarditis that occurs after an invasive procedure. If antibiotic prophylaxis is effective, it should be given only to patients with the highest risk of adverse outcomes from infective endocarditis. Prophylaxis for dental procedures could be beneficial in patients with underlying high-risk cardiac conditions; however, the AHA recognizes that effectiveness of this therapy is unknown.

Recommended Antibiotic Regimens

GENERAL

Antibiotic prophylaxis should be given in one dose before the procedure. If the dose is not given before the procedure, it can be given up to two hours afterward; however, postoperative administration of antibiotics should be considered only if the dose before the procedure is inadvertently missed.

If the patient has a fever or other signs of systemic infection that could be the result of infective endocarditis, the physician should obtain blood cultures or other laboratory tests before administering antibiotics. Failure to do so could result in a delayed diagnosis or treatment of concomitant infective endocarditis.

DENTAL PROCEDURES

Data show that transient viridans group streptococcal bacteremia can result from dental procedures that include manipulation of the gingival or periapical region of teeth or perforation of the oral mucosa. The likelihood of bacteremia is not automatically reduced if a procedure is minimally invasive or if the patient's mouth appears healthy. For these reasons, the AHA recommends that antibiotic prophylaxis be used in patients with the conditions listed in Table 1 and in those undergoing any dental procedure that manipulates the gingival or periapical region of teeth or that perforates the oral mucosa. However, the AHA recognizes that effectiveness of antibiotic prophylaxis in this situation is unknown.

Amoxicillin is the first-line agent for oral antibiotic therapy (Table 2) because it is absorbed well in the GI tract and provides high serum concentrations. For patients who are allergic to penicillin or amoxicillin, cephalexin (Keflex) or another first-generation cephalosporin, clindamycin (Cleocin), azithromycin (Zithromax), or clarithromycin (Biaxin) can be used. No data show that one oral cephalosporin is superior to another in the prevention of infective endocarditis. Generic cephalexin is widely available and relatively inexpensive.

RESPIRATORY TRACT PROCEDURES

Respiratory tract procedures have been reported to cause transient bacteremia with a wide range of microorganisms, but no data confirm a link between these procedures and risk of infective endocarditis. Antibiotic prophylaxis, as listed in Table 2, can be considered for patients with conditions listed in Table 1 who are undergoing an invasive respiratory tract procedure that includes a biopsy or incision of the respiratory mucosa (e.g., tonsillectomy, adenoidectomy). The AHA recommends antibiotic prophylaxis against viridans group streptococci for patients with conditions listed in Table 1 who are undergoing respiratory tract procedures to manage an established infection. If the infection is caused by Staphylococcus aureus, the patient should be given an antibiotic that is active against S. aureus (e.g., cephalosporins). Vancomycin (Vancocin) can be used in patients who cannot tolerate a beta lactam antibiotic or who have an infection caused by methicillin-resistant S. aureus.

GI OR GU TRACT PROCEDURES

Antibiotic prophylaxis is not recommended to prevent infective endocarditis in patients undergoing GI or GU tract procedures (e.g., diagnostic esophagogastroduodenoscopy, colonoscopy). Patients with GI or GU tract infections can have intermittent or sustained enterococcal bacteremia. For patients who have conditions listed in Table 1 and who also have established GI or GU tract infections, and for those who are taking antibiotics for a wound infection or sepsis associated with a GI or GU tract procedure, it may be beneficial to use antibiotic prophylaxis that is active against enterococci (e.g., penicillin, ampicillin, piperacillin, vancomycin). However, there is no evidence that this type of prophylaxis will prevent enterococcal infective endocarditis.

Antibiotic prophylaxis may be beneficial for eliminating enterococci in urine in patients with a condition listed in Table 1 who are undergoing an elective cystoscopy or other urinary tract procedure and who have an enterococcal urinary tract infection or colonization. If the procedure is not elective, the antibiotics should be active against enterococci.

Amoxicillin or ampicillin is the preferred agent for enterococcal coverage. If the patient cannot tolerate ampicillin, vancomycin can be used. Consultation with an infectious disease expert is recommended if the infection is caused by resistant enterococci.

PROCEDURES ON INFECTED SKIN, SKIN STRUCTURE, OR MUSCULOSKELETAL TISSUE

Infections of the skin, skin structure, or musculoskeletal tissue are typically polymicrobial, but only those caused by staphylococci and β-hemolytic streptococci are likely to cause infective endocarditis. Patients with conditions listed in Table 1 who undergo surgical procedures involving skin, skin structure, or musculoskeletal tissue can be given a therapeutic regimen that contains agents active against staphylococci and β-hemolytic streptococci (e.g., penicillin, cephalosporins). Vancomycin or clindamycin can be used in patients unable to tolerate beta lactam antibiotics and in those with infections caused by methicillin-resistant staphylococcus.

Specific Situations and Circumstances

PATIENTS ALREADY TAKING ANTIBIOTICS

If a patient is on a long-term antibiotic regimen with an antibiotic that is also recommended for infective endocarditis prophylaxis for a dental procedure, the patient should be given an antibiotic from a different class rather than simply increasing the dosage of the current antibiotic. Cephalosporins should be avoided because of possible cross-resistance of viridans group streptococci. If possible, dental procedures should be delayed at least 10 days after completion of the antibiotic regimen so that there is enough time for the usual flora to be reestablished.

Patients who are taking parenteral antibiotics for infective endocarditis may need to have a dental procedure during therapy, particularly if the patient is planning to have cardiac valve replacement surgery. In these circumstances, parenteral antibiotics should be continued and dosage timing adjusted so that the drug is taken 30 to 60 minutes before the dental procedure.

PATIENTS TAKING ANTICOAGULANTS

Intramuscular injections for infective endocarditis prophylaxis should not be given to patients taking anticoagulants. Oral antibiotics should be given instead, if possible.

PATIENTS UNDERGOING CARDIAC SURGERY

A dental examination before cardiac surgery is recommended so that dental treatment can be completed before the procedure. Patients who undergo surgery for prosthetic heart valves or intravascular or intracardiac materials are at risk of infection. Because morbidity and mortality associated with these infections are high, perioperative antibiotic prophylaxis is recommended.

Early-onset prosthetic valve endocarditis is most often caused by S. aureus, coagulasenegative staphylococci, or diphtheroids. No antibiotic regimen is effective against all of these microorganisms. Antibiotic prophylaxis at the time of surgery should be against staphylococci and should be of short duration. A first-generation cephalosporin is typically used; however, antibiotic choice should take into account the antibiotic susceptibility patterns of the patient's hospital. Most nosocomial coagulase-negative staphylococci are methicillin resistant. Even so, antibiotic prophylaxis with a first-generation cephalosporin is recommended for these patients.

In hospitals with a high prevalence of methicillin-resistant strains of Staphylococcus epidermidis, antibiotic prophylaxis with vancomycin may be beneficial, but has not been found superior to cephalosporins. Prophylaxis should be started immediately before the operation, repeated during prolonged operations (to maintain serum concentrations), and continued for up to 48 hours after the operation (to minimize resistant microorganisms).

Other Considerations

Because coronary artery bypass graft surgery is not associated with a long-term risk of infection, antibiotic prophylaxis for dental procedures is not needed in persons who have undergone such surgeries. Antibiotic prophylaxis also is not recommended for persons with coronary artery stents who undergo a dental procedure.

Although patients who have had a heart transplant are at risk of acquired valvular dysfunction, there is insufficient evidence to support specific recommendations for this population. Infective endocarditis that occurs in these patients is associated with a high risk of adverse outcomes; therefore, antibiotic prophylaxis in patients who have had a heart transplant and who undergo dental procedures may be beneficial, but its usefulness is not well established.

A summary of the major changes in these updated recommendations for prevention of infective endocarditis compared with previous AHA guidelines is shown in Table 3.