Treatment of Blood Culture-Negative Endocarditis

Though treatment of endocarditis is tailored to each patient depending on history, epidemiology, risk factors, and comorbidities, empirical management is warranted. The American Heart Association (AHA) recommends treating patients empirically for acute BCNE with vancomycin and cefepime.1 For patients with subacute BCNE, AHA recommends vancomycin and ampicillin/sulbactam.6 These treatments are initiated while the specific pathogen for BCNE is being identified.

The HACEK group of organisms includes Haemophilus parainfluenzae, Aggregatibacter spp (aphrophilus and actinomycetemcomitans), Cardiobacterium hominis, Eikenella corrodens, and Kingella kingae. They are responsible for 1.5% to 2% of all infective endocarditis and are managed with third-generation cephalosporins such as ceftriaxone.7 The HACEK organisms are fastidious, gram-negative bacilli that require special growth medium or longer incubation times to be isolated. If patients with HACEK infective endocarditis are treated promptly, they have an 80% to 90% chance of survival.7

Tailoring treatment and patient management to the specific organism in BCNE results in a wide array of pharmacological choices as well as duration of therapy. Treatment times range from 3 months to greater than 18 months depending on the organism identified. Coxiella burnetii (Q fever) and Tropheryma whipplei are treated with doxycycline and hydroxychloroquine.2 Brucella spp are best managed with doxycycline, cotrimoxazole, and rifampin.2 The preferred approach to treatment of Bartonella spp includes doxycycline and gentamicin.2 Fungal endocarditis is best treated with amphotericin B.2 Again owing to the diversity of organisms associated with BCNE, the list of treatment recommendations for this diagnosis is extensive. Providers must use current and updated resources to select optimal pharmacological agent(s) and duration of treatment.

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If a patient with endocarditis is found to have a comorbidity thought to ultimately be responsible for the disease (ie, systemic lupus erythematous [SLE]), then referral to appropriate specialist is necessary.3

Prophylactic treatment may be warranted to prevent future complications that can arise from BCNE. Anticoagulation should be discussed as atrial fibrillation is a common complication of valvular vegetation. The AHA also recommends anticoagulation for BCNE patients with a prior history of atrial fibrillation, prosthetic valve, deep vein thrombosis, pulmonary embolism, and/or coronary artery disease.1 Surgery is indicated in a handful of circumstances as demonstrated in Table 3.6


Blood culture-negative endocarditis can be a challenging diagnosis to confirm. Primary care providers are on the frontline in the prompt identification of potential BCNE cases, allowing for prioritization of workup, management, and improved patient outcomes. A thorough history and physical examination are critical in the initial evaluation of patients with suspected BCNE. Blood culture-negative endocarditis warrants a multidisciplinary approach involving the primary care provider, cardiologist, cardiothoracic surgeon, and potentially other medical specialists (as appropriate for the patient/case) to achieve the goal of prompt and successful evaluation, management, and recovery.

Brittany Yacavone, PA-C, is scheduled to start the Piedmont Heart Advanced APP Fellowship Training Program in Advanced Cardiology at Piedmont Hospital in Atlanta, Georgia, in fall 2023; Elizabeth Prince-Coleman, MPA, PA-C, has been a practicing PA for almost 9 years with Augusta University Health. She also serves as the program director for the Augusta University PA Program.


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This article originally appeared on Clinical Advisor