Updates to the Recommendations for the Prevention of Infective Endocarditis

The Therapeutic Guidelines: Antibiotic has recently updated their recommendations for the prevention of infective endocarditis.

Infective endocarditis refers to infection of the endocardial surfaces of the heart and is typically of bacterial origin. While a healthy endocardium is resistant to bacterial colonisation, infection can occur when endocardial injury coincides with bacteraemia. Endocardial injury may be related to turbulent flow (e.g. due to diseased valves), mechanical trauma (e.g. during insertion of intravascular catheters), or intravenous drug abuse (i.e. due to the repeated injection of particulate matter). The bacteraemia required for the development of infective endocarditis may be the result of oral flora introduced into the bloodstream (i.e. during dental procedures or daily oral hygiene activities) or from an established, distant source of infection.

While infective endocarditis is a relatively uncommon condition, it is associated with high morbidity and mortality. Therefore, antibiotic prophylaxis may be appropriate for certain individuals prior to procedures with a high risk of bacteraemia.

Key updates to the guidelines:

• Ventricular assist devices (VADs) added to the list of conditions warranting prophylaxis
• Clindamycin is no longer recommended for endocarditis prophylaxis prior to dental procedures
• Antibiotics with enterococcal activity should be considered for institutions with high rates of endocarditis following transcatheter aortic valve implantation (TAVI) or cardiac implantable electronic device (CIED) procedures using an inguinal approach.

Ventricular assist devices

Ventricular assist device-related infections have been reported to occur in between 18% and 59% of patients after implantation. This can include bloodstream infection, relapsing bacteraemia, sepsis, and endocarditis. When endocarditis occurs in these patients, the mortality rate has been reported to be 50%.

Due to this high risk and poor outcomes, VADs are now included among the conditions for which prophylaxis is recommended.

Clindamycin

Clindamycin is no longer recommended for endocarditis prophylaxis for dental procedures as it is associated with a higher frequency of severe adverse drug reactions (ADR) compared to other antibiotics.

A UK study looking at antibiotic prophylaxis found that clindamycin was associated with 13 fatal and 149 non-fatal ADR reports per million prescriptions. The majority of serious events were related to Clostridioides difficile infection. In contrast, amoxicillin was associated with zero fatal and 22.62 non-fatal ADR reports per million prescriptions.

Where endocarditis prophylaxis is indicated prior to dental procedures, amoxicillin is the first-line option. Cefalexin can be used for patients who have experienced a non-severe penicillin hypersensitivity reaction. For patients who have had a severe penicillin hypersensitivity reaction, doxycycline or azithromycin are the recommended alternatives.

Consideration must still be given to the potential for these alternative agents to cause adverse reactions. For example, doxycycline can cause oesophageal irritation and ulceration, and azithromycin can prolong the QT interval.

Enterococcal activity

A large international cohort study found high rates of postoperative infective endocarditis following TAVI. This study found Enterococcus spp. to be the most commonly isolated species in patients presenting with early peri-procedural infective endocarditis. While this pattern has not been observed in Australia, the updated guidelines recommend considering antibiotics with enterococcal activity in centres with high infection rates following TAVI and cardiac device implantation using an inguinal approach.

First and second generation cephalosporins do not have enterococcal activity. However, amoxicillin and ampicillin are active against enterococci. Oral doses should be administered 60 minutes before the procedure, intramuscular doses 30 minutes before, and intravenous doses 60 minutes before. Vancomycin or teicoplanin could be considered alternatives for patients with penicillin hypersensitivity. These agents should be administered in addition to any standard surgical prophylaxis required.

Conclusion

The current recommendations from the Therapeutic Guidelines: Antibiotic for the prevention of infective endocarditis are shown in Table 1. Prophylaxis is recommended for patients undergoing one of the procedures listed in column A if they also have a condition listed in column B.

Table 1. Indications for antibiotic prophylaxis for infective endocarditis (adapted from eTG)