Continuing Education Activity

Infective endocarditis (IE) is an infection of the endocardial surfaces of the heart, which includes one or more heart valves. The incidence of infective endocarditis hospitalization in the United States is estimated at 12.7 per 100,000 annually. Most of the patients (57.7%) are male, and more than a third are 70 years and older. Several risk factors predispose patients to IE, such as structural heart disease (valvular disease or congenital heart disease), prosthetic heart valves, indwelling cardiovascular device, an intravascular catheter, chronic hemodialysis, human immunodeficiency virus infection, diabetes, or history of infective endocarditis. In addition, infective endocarditis may present as acute or subacute infection. Acute infections present as a rapidly progressive disease with high fevers, rigors, and sepsis. On the other hand, subacute bacterial endocarditis diagnosis is often delayed and presents with non-specific symptoms such as weight loss, fatigue, and dyspnea over several weeks to months. There are several differences between subacute bacterial endocarditis and acute bacterial endocarditis. Most cases of subacute bacterial endocarditis are caused by penicillin-sensitive Streptococcus viridans, while Staphylococcus aureus causes most cases of acute bacterial endocarditis. This activity reviews the prophylaxis of subacute endocarditis and highlights the role of the interprofessional team approach.

Objectives:

• Describe the patient presentation of subacute bacterial endocarditis.
• Outline the risk factors for contracting subacute bacterial endocarditis.
• Explain the antibiotic prophylactic techniques used to minimize the risk of subacute bacterial endocarditis.
• Summarize the interprofessional team members' involvement in prophylactically treating subacute bacterial endocarditis.

Indications

Infective endocarditis (IE) is an infection of the endocardial surfaces of the heart, which includes one or more heart valves. The incidence of infective endocarditis hospitalization in the United States is estimated at 12.7 per 100,000 annually. Most of the patients (57.7%) were male, and more than a third were 70 years and older.[1] Several risk factors predispose patients to IE, such as structural heart disease (valvular disease or congenital heart disease), prosthetic heart valves, indwelling cardiovascular device, an intravascular catheter, chronic hemodialysis, human immunodeficiency virus infection, diabetes, or history of infective endocarditis. Other risk factors include males older than 60 years, male gender, intravenous (IV) drug use, poor dentition, or dental infection. Infective endocarditis may present as acute or subacute infection.[2] 

Acute infections present as a rapidly progressive disease with high fevers, rigors, and sepsis. On the other hand, subacute bacterial endocarditis diagnosis is often delayed and presents with non-specific symptoms such as weight loss, fatigue, and dyspnea over several weeks to months. There are several differences between subacute bacterial endocarditis and acute bacterial endocarditis. Most cases of subacute bacterial endocarditis are caused by penicillin-sensitive Streptococcus viridans, while Staphylococcus aureus causes most cases of acute bacterial endocarditis.[3] Subacute bacterial endocarditis mostly happens in pre-existing heart disease, while acute bacterial endocarditis mostly happens in healthy hearts. After treatment, subacute bacterial endocarditis rarely leads to severe cardiac damage; however, most patients who survive acute bacterial endocarditis often die of cardiac failure within weeks or months.[3]

As the incidence of infective endocarditis continues to rise in the United States, healthcare providers must make appropriate decisions regarding antibiotic prophylaxis to prevent further complications. Antibiotic prophylaxis before procedures, especially dental procedures, used to be widely utilized to prevent infective endocarditis despite a lack of established evidence to support this practice. In guidelines published by the American Heart Association (AHA) in 2007, the recommended indications to use antibiotics for endocarditis prophylaxis were significantly restricted.[4] There were several reasons for this change. Firstly, infective endocarditis was more likely to occur with everyday activities such as teeth brushing and flossing rather than with a single medical or dental procedure. Secondly, it was felt that prophylaxis with antibiotics for dental procedures prevented very few IE cases. The cost of antibiotic therapy and the risk of adverse events, and the risk of promoting antibiotic resistance significantly outweighed the benefit of such prophylaxis. Thirdly, consistently good oral hygiene is considered more beneficial in preventing IE than a single dose of antibiotics.[4]

Mechanism of Action

The rationale for prophylactic antibiotic therapy for subacute bacterial endocarditis is the following:

1. Infective endocarditis is a fatal disease, and prevention is preferable to treatment of established infection.
2. Specific cardiac conditions predispose to infective endocarditis.
3. Reduce the incidence of bacteremia associated with invasive dental, oral, gastrointestinal (GI), and genitourinary (GU) tract procedures.
4. There is evidence that antimicrobial prophylaxis effectively prevents infective endocarditis in animal studies.
5. In humans, antimicrobial prophylaxis effectively prevents infective endocarditis in high-risk dental, oral, GI, or GU tract procedures.[5]

Infective endocarditis is fatal if untreated or unrecognized. It causes significant morbidity and mortality, despite present-day advances in antimicrobial therapy and surgical treatment. As a result, the prevention of infective endocarditis is necessary. Some animal studies have shown antibiotic prophylaxis may prevent infective endocarditis, but the data on humans is still lacking. Therefore, current guidelines in the United States still recommend using antimicrobial prophylaxis for patients undergoing several procedures at risk for infective endocarditis.

The American Heart Association currently recommends antibiotic prophylaxis only in patients with the following high-risk cardiac conditions:

Patients with prosthetic cardiac valves

Patients with previous infective endocarditis

Cardiac transplant recipients with valve regurgitation due to a structurally abnormal valve

Patients with congenital heart disease with:

• Unrepaired cyanotic congenital heart disease, including palliative shunts and conduits
• A totally repaired congenital heart defect, repaired with prosthetic material or device that has been placed by surgery or catheter intervention during the first six months after the procedure.
• Repaired congenital heart disease with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device

Patients with these high-risk conditions should receive antibiotics for the following procedures:

1. Dental procedures involve manipulating gingival tissue, manipulating the periapical region of teeth, or perforating the oral mucosa. This does not include routine anesthetic injections through noninfected tissue, dental radiographs, placement or adjustment of orthodontic devices, or trauma to the lips and teeth.[4][6]
2. The 2007 AHA guidelines also recommended prophylaxis for invasive respiratory tract procedures that involve incision or biopsy of the respiratory mucosa (e.g., tonsillectomy, adenoidectomy). Antibiotic prophylaxis has not been recommended for bronchoscopy unless the procedure involves an incision of the respiratory tract mucosa.[4]
3. Procedures of infected skin, skin structures, or musculoskeletal tissue.[4]

Administration

The most common bacteria to cause IE for dental and respiratory procedures are the various Streptococcus viridans species. The recommended prophylactic antibiotic is amoxicillin 2 grams orally 1 hour before the procedure. If the patient needs intravenous (IV) medication, ampicillin or ceftriaxone may be used. Cephalexin or azithromycin may be used in patients with a penicillin allergy. There is new penicillin resistance of the Streptococcus viridian; therefore, the prescribing physician must consider the resistance in their practice area when prescribing the appropriate antibiotic. In cases where Staphylococcus aureus is suspected, antistaphylococcal penicillin or vancomycin is recommended.[7] Antibiotics are usually given 

Recent American Heart Association guidelines suggest that clindamycin is no longer recommended as an alternative antibiotic regimen for patients undergoing dental procedures, given more severe adverse drug reactions associated with this clindamycin.[5]

Usually, antibiotics need to be administered 30 to 60 minutes before the planned procedure. However, only intravenous vancomycin needs to be administered two hours before the planned procedure. As per the 2013 guidelines for preoperative antimicrobial prophylaxis of infective endocarditis, the desired timing for antibiotic administration is within 60 minutes before surgery. However, if the antibiotic prophylaxis is accidentally not administered before the dental procedure, it can be administered up to two hours after a performed procedure.[8]

Adverse Effects

The most frequently reported adverse drug reaction with amoxicillin are nausea, vomiting, and headache. The incidence of serious adverse drug reactions such as hives, angioedema, and anaphylaxis is low.[9] Similarly, fatal anaphylaxis from a single dose of a cephalosporin in patients with no history of allergy is estimated to be less than one per one million doses. Clindamycin may cause more frequent and severe reactions such as clostridium difficile-associated diarrhea, and recent American Heart Association guidelines no longer recommend its use.[5]  

Doxycycline is an alternative for patients who cannot tolerate penicillin, cephalosporin, or macrolide. A serious reaction from a single dose of doxycycline is infrequent. There is a risk of a serious cardiovascular event, especially torsades des pointes with ventricular tachycardia, from azithromycin use in patients with a prolonged QTc interval of >450 milliseconds as detected by ECG. Therefore, azithromycin should be used with caution in patients with a prolonged QTc interval.[10] 

Clinicians should prescribe antibiotics for prophylaxis as per patient age, risk factors, comorbid conditions, and concomitant medicines. Amoxicillin is contraindicated in patients with hypersensitivity or anaphylactic reactions to penicillin antibiotics. Doxycycline use is contraindicated in pediatric patients and pregnant women. Macrolides are contraindicated in patients with existing cardiac arrhythmia and concomitant drugs that can prolong QTc interval.

Contraindications

Prophylaxis against IE is not recommended in patients at risk of IE for other non-dental procedures, such as a transesophageal echocardiogram, esophagogastroduodenoscopy, colonoscopy, or cystoscopy, in the absence of active infection. There is no indication for dental, gastrointestinal, or genitourinary procedural prophylaxis for patients with implantable cardiovascular devices. However, prophylaxis with an anti-staphylococcal antibiotic is indicated at the time of cardiovascular device implantation and any subsequent manipulation of the surgically created device pocket.[11][12]

For patients who have undergone coronary artery bypass graft surgery, antibiotic prophylaxis is not needed for dental procedures, as there is no increased risk of long-term infection.  Similarly, antibiotic prophylaxis is not needed for dental procedures for patients with coronary artery stents.[13] Further studies to evaluate the efficacy of antimicrobial prophylaxis in the prevention of infective endocarditis are needed.[14]

Enhancing Healthcare Team Outcomes

Subacute infective endocarditis is a lethal disorder if not treated. Healthcare professionals, including the nurse practitioner, dentist, pharmacist, primary care provider, internist, and cardiologist, should be familiar with the latest ACA and AHA guidelines on prophylaxis of patients at risk for IE. Prophylaxis against IE is not recommended in patients at risk of IE for other non-dental procedures, such as a transesophageal echocardiogram, esophagogastroduodenoscopy, colonoscopy, or cystoscopy, in the absence of active infection. In addition, for patients who have undergone coronary artery bypass graft surgery, antibiotic prophylaxis is not needed for dental procedures, as there is no increased risk of long-term infection. Similarly, antibiotic prophylaxis is not needed for dental procedures for patients with coronary artery stents.[5]

Subacute bacterial endocarditis (IE) is an infection that is a rare event and a challenge to diagnose. If the diagnosis is made early, outcomes are improved. All healthcare team members should be diligent in considering the possibility of IE in at-risk patients, as early treatment will improve outcomes. As mentioned above, subacute bacterial endocarditis prophylaxis requires close monitoring and communication, and follow-up monitoring requires coordination between clinicians, specialists, nurses, specialty-trained nurses, dentists, and pharmacists. An interprofessional team approach for the patients will translate to better patient outcomes, maximize efficacy and minimize adverse drug reactions. [Level 5]