What is the management of infective endocarditis?

From the Guidelines

Endocarditis management requires prompt antibiotic therapy and potential surgical intervention, with the most recent guidelines from 2015 recommending an evaluation of epidemiological factors and consultation with an infectious diseases specialist for culture-negative endocarditis 1. The initial treatment involves empiric intravenous antibiotics, and the choice of antibiotics depends on the suspected causative organism.

• For patients with acute clinical presentations of native valve infection, coverage for S aureus, β-hemolytic streptococci, and aerobic Gram-negative bacilli is reasonable 1.
• For patients with a subacute presentation of NVE, coverage of S aureus, VGS, HACEK, and enterococci is reasonable 1. Once the causative organism is identified, therapy should be tailored accordingly.
• For Streptococcal endocarditis, penicillin G or ceftriaxone for 4-6 weeks is recommended 1.
• Staphylococcal endocarditis often requires nafcillin or oxacillin for methicillin-sensitive strains or vancomycin for resistant strains, typically for 6 weeks 1.
• Enterococcal infections usually need combination therapy with ampicillin plus gentamicin 1. Surgical intervention is indicated for heart failure, uncontrolled infection, prevention of embolic events, or valve dysfunction, with the 2008 guidelines recommending surgery for patients with infective endocarditis of a prosthetic valve who present with evidence of persistent bacteremia or recurrent emboli despite appropriate antibiotic treatment 1. Patients require close monitoring for complications including heart failure, embolic events, and adverse drug reactions.
• Antibiotic therapy must be completed fully even after symptom improvement, as premature discontinuation risks relapse 1.
• Endocarditis prophylaxis with amoxicillin is recommended for high-risk patients undergoing dental procedures 1. This aggressive management approach is necessary because endocarditis carries significant mortality if inadequately treated.
• Blood cultures should be repeated to confirm clearance of bacteremia, and echocardiography is recommended for all adult patients with bacteremia 1.

From the FDA Drug Label

The definition of right-sided infective endocarditis (RIE) used in the clinical trial was Definite or Possible Endocarditis according to the modified Duke criteria and no echocardiographic evidence of predisposing pathology or active involvement of either the mitral or aortic valve Complicated RIE comprised patients who were not intravenous drug users, had a positive blood culture for MRSA, serum creatinine ≥2.5 mg/dL, or evidence of extrapulmonary sites of infection. Patients who were intravenous drug users, had a positive blood culture for methicillin-susceptible S. aureus (MSSA), had serum creatinine <2. 5 mg/dL, and were without evidence of extrapulmonary sites of infection were considered to have uncomplicated RIE. The coprimary efficacy endpoints in the trial were the Adjudication Committee success rates at the Test of Cure visit (6 weeks after the last treatment dose) in the ITT and Per Protocol (PP) populations. Among patients with persisting or relapsing S. aureus infections, 8/19 daptomycin for injection-treated patients and 7/11 comparator-treated patients died Failure of treatment due to persisting or relapsing S aureus bacteremia/endocarditis may be due to reduced daptomycin susceptibility (as evidenced by increasing MIC of the S. aureus isolate) Most patients who failed due to persisting or relapsing S aureus infection had deep-seated infection and did not receive necessary surgical intervention [see Warnings and Precautions (5. 9)] .

Endocarditis Management with Daptomycin

• Daptomycin is used to treat right-sided infective endocarditis (RIE) and complicated RIE.
• The success rates of daptomycin in treating endocarditis were 44.2% in the ITT population and 54.4% in the PP population.
• The main causes of treatment failure were deep-seated infections and reduced daptomycin susceptibility.
• Surgical intervention may be necessary for patients with persisting or relapsing S. aureus infections.
• Daptomycin should be used with caution in patients with moderate to severe renal impairment, as clinical success rates were lower in these patients 2.

From the Research

Endocarditis Management Overview

• Endocarditis is a difficult-to-treat infectious disease, with various bacteria responsible for the infection, including staphylococci, streptococci, enterococci, and Gram-negative bacilli 3.
• The main objective of medical treatment is to sterilize the vegetative lesions characteristic of the disease, which requires identification of the causative organism, in vitro determination of its susceptibility, and the choice of a bactericidal treatment 4.

Treatment Strategies

• Empirical treatment, oral switch, and treatment duration are crucial aspects of endocarditis management 3.
• For staphylococcal endocarditis, anti-staphylococcal penicillins, such as cefazolin, and vancomycin are recommended 3.
• The use of aminoglycosides, such as gentamicin, has been reduced over the last 20 years, and should be administered once daily for no longer than 2 weeks 3.
• The optimal duration of antibacterial treatment is 4 weeks for most native valve endocarditis and 6 weeks for prosthetic-valve endocarditis 3, 5, 4.

Specific Treatment Regimens

• For enterococcal endocarditis, a combination of aqueous penicillin G and either streptomycin or gentamicin is recommended 5.
• Outpatient continuous-infusion benzylpenicillin combined with either gentamicin or ceftriaxone is an effective treatment regimen for enterococcal endocarditis 6.
• A dual beta-lactam therapy with ampicillin and ceftriaxone may provide a tolerable and equally efficacious option for treatment of Enterococcus faecalis infective endocarditis 7.

Treatment Monitoring and Duration

• Therapy must be monitored rigorously, and the duration of treatment must be sufficient to prevent failure or relapse 4.
• The oral switch is safe in patients stabilized after the initial intravenous course 3.
• Treatment failure and relapse rates vary depending on the treatment regimen and the causative organism 6, 7.