Antibiotic Prophylactic Regimens for Endocarditis

AHA Guidelines

The American Heart Association (AHA) Guidelines for Prevention of Infective Endocarditis (see image below) were updated in 2007 and included numerous changes from the previous 1997 version. The guidelines were approved by the Council on Scientific Affairs of the American Dental Association has approved the guidelines as it relates to dentistry. Additionally, the guideline is endorsed by the Infectious Diseases Society of America and by the Pediatric Infectious Diseases Society.[1]

Acute bacterial endocarditis caused by Staphylococcus aureus with aortic valve ring abscess extending into myocardium. Courtesy of Janet Jones, MD, Laboratory Service, Wichita Veterans Administration Medical Center.

Major changes in the updated AHA guidelines include:

• Only an extremely small number of cases of infective endocarditis (IE) might be prevented by antibiotic prophylaxis for dental procedures even if such prophylactic therapy were 100% effective
• IE prophylaxis for dental procedures should be recommended only for patients with underlying cardiac conditions associated with the highest risk of adverse outcome from IE
• For patients with these underlying cardiac conditions, prophylaxis is recommended for all dental procedures that involve manipulation of gingival tissue or the periapical region of teeth or perforation of the oral mucosa
• Prophylaxis is not recommended based solely on an increased lifetime risk of acquisition of infective endocarditis
• Administration of antibiotics solely to prevent endocarditis is not recommended for patients who undergo a genitourinary or gastrointestinal tract procedure

The antibiotic prophylactic regimens recommended by the AHA are only for patients with underlying cardiac conditions associated with the highest risk of adverse outcome from infective endocarditis.[1]

High-risk cardiac conditions

Antibiotic prophylaxis is indicated for the following high-risk cardiac conditions:

• Prosthetic cardiac valve 
• History of infective endocarditis (see image below) 
• Congenital heart disease (CHD) (except for the conditions listed, antibiotic prophylaxis is no longer recommended for any other form of CHD): (1) unrepaired cyanotic CHD, including palliative shunts and conduits; (2) completely repaired congenital heart defect with prosthetic material or device, whether placed by surgery or by catheter intervention, during the first 6 months after the procedure; and (3) repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device (which inhibits endothelialization) 
• Cardiac transplantation recipients with cardiac valvular disease

AAOS Guidelines

A clinical practice guideline produced jointly by the American Academy of Orthopaedic Surgeons (AAOS) and the American Dental Association (ADA) was published in April 2013.[2] The recommendation proposes that the practitioner consider changing the long-standing practice of routinely prescribing prophylactic antibiotic for patients with orthopaedic implants who undergo dental procedures. The grade of recommendation is listed as limited, indicating there is unconvincing evidence. The previous guideline from 2003 was updated in 2009 and endorsed antibiotic prophylaxis before dental procedures for all patients with prosthetic joints, with no 2-year time limit.[3] The 2009 guideline position had been criticized for excessive and unwarranted antibiotic use.[4]

For further information on infective endocarditis, see Infective Endocarditis, Pediatric Bacterial Endocarditis, Infectious Endocarditis, and Neurological Sequelae of Infective Endocarditis.

For patients with high cardiac risk, antibiotic prophylaxis is recommended for all dental procedures that involve manipulation of gingival tissue or the periapical region of teeth or perforation of the oral mucosa.

The following dental procedures do not require endocarditis prophylaxis:

• Routine anesthetic injections through noninfected tissue

• Taking dental radiographs

• Placement of removable prosthodontic or orthodontic appliances

• Adjustment of orthodontic appliances

• Placement of orthodontic brackets

• Shedding of deciduous teeth

• Bleeding from trauma to the lips or oral mucosa

Antibiotic prophylaxis is recommended for invasive respiratory tract procedures that involve incision or biopsy of the respiratory mucosa (eg, tonsillectomy, adenoidectomy). Antibiotic prophylaxis is not recommended for bronchoscopy unless the procedure involves incision of the respiratory tract mucosa. For invasive respiratory tract procedures to treat an established infection (eg, drainage of abscess, empyema), administer an antibiotic that is active against Streptococcus viridans.

Patients with high cardiac risk who undergo a surgical procedure that involves infected skin, skin structure, or musculoskeletal tissue should receive an agent active against staphylococci and beta-hemolytic streptococci (eg, antistaphylococcal penicillin, cephalosporin).

If the causative organism of respiratory, skin, skin structure, or musculoskeletal infection is known or suspected to be Staphylococcus aureus, administer an antistaphylococcal penicillin or cephalosporin, or vancomycin (if patient is unable to tolerate beta-lactam antibiotics). Vancomycin is recommended for known or suspected methicillin-resistant strains of S aureus.

Antibiotics are no longer recommended for endocarditis prophylaxis for patients undergoing genitourinary or gastrointestinal tract procedures.

Several studies have tracked the incidence of viridans group streptococci infective endocarditis (VGS-IE) following the guideline changes in the United States and the United Kingdom instituted in 2007 and 2008 respectively.

In the United States, Desimone et al found no perceivable increase in the incidence of VGS-IE in a localized area of Minnesota since the publication of the 2007 AHA endocarditis prevention guidelines. Rates of incidence (per 100,000 person-years) during the intervals of 1999-2002, 2003-2006, 2007-2010, and 2011-2013 were 3.6, 2.7, 0.7, and 1.5, respectively, reflecting an overall significant decrease (P=.03 from Poisson regression). Likewise, nationwide estimates of hospital discharges with a VGS-IE diagnosis trended downward during 2000-2011, with a mean number per year of 15,853 and 16,157 for 2000-2003 and 2004-2007, respectively, decreasing to 14,231 in 2008-2011 (P=.05 from linear regression using weighted least squares method).[5, 6]

A large retrospective epidemiologic study of patients hospitalized with a first episode of IE was conducted to quantify trends in the incidence and etiologies of infective endocarditis in the United States was conducted in California and New York. IE cases from mandatory state databases between January 1, 1998 and December 31, 2013 were analyzed. Among 75,829 patients with first episodes of endocarditis, the standardized annual incidence was stable between 7.6 (95% CI, 7.4 to 7.9) and 7.8 (95% CI, 7.6 to 8.0) cases per 100 000 persons.[7]

Mitral valve prolapse affects approximately 2-3% of the general population. The first report of population-based incidence of IE in 896 patients with contemporary echocardiographic diagnosis of mitral valve prolapse (MVP) was analyzed based on the largest geographically-defined MVP community-cohort with longest follow-up available for this purpose. The study reports the incidence of IE in patients with echocardiographic MVP diagnosis to be approximately 87 cases per 100,000 person-years, which represents approximately 8 times the risk of IE in the general population. Prior studies reported wide variation in the estimated incremental relative risk of IE in MVP patients compared to nonMVP patients (2.9-8.2).[8]

The findings of one study supported the 2008 National Institute for Health and Clinical Excellence (NICE) in the United Kingdom guideline recommendations that antibiotic prophylaxis prior to invasive dental procedures was likely to not be of benefit in preventing infective endocarditis in patients with a history of rheumatic fever or a heart murmur. The authors did suggest though that patients at highest risk (eg, those with prosthetic valves) still might benefit.[9] Note that the study was conducted in England; therefore, a limitation of the study is the external generalizability of the findings to other countries.

Dayer et al investigated changes in the prescribing of antibiotic prophylaxis and the incidence of infective endocarditis in England since the introduction of the 2008 NICE guidelines. Although the data from the study did not establish a causal association, prescriptions of antibiotic prophylaxis have fallen substantially and the incidence of infective endocarditis has increased significantly in England since introduction of the 2008 NICE guidelines.[10] Thornhill et al also reported that since March 2008 there has been an increase in IE cases since the 2008 NICE guidelines.[11] The NICE Clinical Guidelines were updated in 2015 to address this research that reported an increase in IE cases, however, NICE did not change their recommendations and no longer recommended antibiotic prophylaxis in patients at high-risk of IE who are undergoing high-risk dental procedures.[12, 13] In 2015, The Task Force for the Management of Infective Endocarditis of the European Society of Cardiology (ESC) released their guidelines that continued to recommend antibiotic prophylaxis only for patients at the highest risk.[14]

A study by Thornhill et al that reviewed five years of English hospital admissions for conditions associated with increased infective endocarditis risk reported that the patients at highest risk of recurrence or death during an infective endocarditis admission were patients with a previous history of infective endocarditis. Risks were also high in patients with prosthetic valves and previous valve repair. Patients at moderate risk included patients with congenital valve anomalies. Congenital heart conditions repaired with prosthetic material were at lower risk and risk was also seen in patients with cardiovascular implantable electronic devices.[15]

The most common cause of endocarditis for dental, oral, respiratory tract, or esophageal procedures is S viridans (alpha-hemolytic streptococci). Antibiotic regimens for endocarditis prophylaxis are directed toward S viridans, and the recommended standard prophylactic regimen is a single dose of oral amoxicillin. Amoxicillin, ampicillin, and penicillin V are equally effective in vitro against alpha-hemolytic streptococci; however, amoxicillin is preferred because of superior gastrointestinal absorption that provides higher and more sustained serum levels.

All doses shown below are administered once as a single dose 30-60 min before the procedure.

Standard general prophylaxis

Amoxicillin

Adult dose: 2 g PO

Pediatric dose: 50 mg/kg PO; not to exceed 2 g/dose

Unable to take oral medication

Ampicillin

Adult dose: 2 g IV/IM

Pediatric dose: 50 mg/kg IV/IM; not to exceed 2 g/dose

Allergic to penicillin

Clindamycin

Adult dose: 600 mg PO

Pediatric dose: 20 mg/kg PO; not to exceed 600 mg/dose

Allergic to penicillin

Cephalexin or other first- or second-generation oral cephalosporin in equivalent dose (do not use cephalosporins in patients with a history of immediate-type hypersensitivity penicillin allergy, such as urticaria, angioedema, anaphylaxis)

Adult dose: 2 g PO

Pediatric dose: 50 mg/kg PO; not to exceed 2 g/dose

Azithromycin or clarithromycin

Adult dose: 500 mg PO

Pediatric dose: 15 mg/kg PO; not to exceed 500 mg/dose

Allergic to penicillin and unable to take oral medication

Clindamycin

Adult dose: 600 mg IV

Pediatric dose: 20 mg/kg IV; not to exceed 600 mg/dose

Cefazolin or ceftriaxone (do not use cephalosporins in patients with a history of immediate-type hypersensitivity penicillin allergy, such as urticaria, angioedema, anaphylaxis)

Adult dose: 1 g IV/IM

Pediatric dose: 50 mg/kg IV/IM; not to exceed 1 g/dose