What is the treatment for culture-negative endocarditis in a patient with a hypersensitivity reaction to doxycycline (antibiotic)?

From the Guidelines

For culture-negative endocarditis in a patient with doxycycline allergy, I recommend empiric therapy with vancomycin (15-20 mg/kg IV every 12 hours, adjusted to maintain trough levels of 15-20 μg/mL) plus ceftriaxone (2 g IV daily) for 4-6 weeks. This combination provides broad coverage against common endocarditis pathogens including streptococci, staphylococci, and HACEK organisms, as suggested by 1. If the patient has prosthetic valve endocarditis, consider adding gentamicin (3 mg/kg IV daily, divided into 3 doses) for the first 2 weeks. For patients with penicillin allergies, replace ceftriaxone with levofloxacin (750 mg IV/oral daily).

Key Considerations

• Monitor renal function, complete blood counts, and drug levels weekly, as recommended by 1.
• Blood cultures should be repeated after 48-72 hours of therapy to confirm clearance of bacteremia.
• Echocardiography should be performed to assess valve function and vegetation size.
• The combination of a cell-wall active agent (vancomycin or ceftriaxone) with an aminoglyoside provides synergistic bactericidal activity against many endocarditis-causing organisms, as noted in 1.

Therapy Options

• For native valve endocarditis, consider ampicillin-sulbactam 12 g per 24 h IV in 4 equally divided doses, plus gentamicin sulfate 3 mg per kg per 24 h IV/IM in 3 equally divided doses, as suggested by 1.
• For prosthetic valve endocarditis, consider vancomycin 30 mg per kg per 24 h IV in 2 equally divided doses, plus gentamicin sulfate 3 mg per kg per 24 h IV/IM in 3 equally divided doses, and cefepime 6 g per 24 h IV in 3 equally divided doses, as recommended by 1.

Patient Management

• Patients with culture-negative endocarditis should be treated in consultation with an infectious diseases specialist, as emphasized by 1.
• Patients with suspected or documented Bartonella endocarditis should be treated with ceftriaxone sodium 2 g per 24 h IV/IM in 1 dose, plus gentamicin sulfate 3 mg per kg per 24 h IV/IM in 3 equally divided doses, as suggested by 1.

From the FDA Drug Label

Vancomycin Hydrochloride for Injection, USP is effective in the treatment of staphylococcal endocarditis Vancomycin Hydrochloride for Injection, USP has been reported to be effective alone or in combination with an aminoglycoside for endocarditis caused by S. viridans or S. bovis. Vancomycin Hydrochloride for Injection, USP has been reported to be effective for the treatment of diphtheroid endocarditis Specimens for bacteriologic cultures should be obtained in order to isolate and identify causative organisms and to determine their susceptibilities to vancomycin

Treatment of culture negative endocarditis in a patient with an allergy to doxycycline may include vancomycin as an option, considering the drug's effectiveness in treating various types of endocarditis, including staphylococcal, S. viridans, S. bovis, and diphtheroid endocarditis 2. However, culture and susceptibility information should be obtained to guide the selection of therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

From the Research

Diagnosis of Culture-Negative Endocarditis

• The diagnosis of culture-negative endocarditis can be challenging, and it is often severe and difficult to diagnose 3.
• The condition can be categorized into three main categories: bacterial endocarditis with blood cultures sterilized by previous antibacterial treatment, endocarditis related to fastidious microorganisms, and "true" blood culture-negative endocarditis due to intracellular bacteria that cannot be routinely cultured in blood 3, 4.
• Diagnostic approaches involve thorough patient history, blood and serum testing, serological testing, and molecular techniques such as targeted and shotgun metagenomic sequencing 4, 5.

Treatment of Culture-Negative Endocarditis

• The treatment of culture-negative endocarditis depends on the likely causative agent and the presence of prosthetic material, with surgical intervention often required 4.
• The choice of antibiotic depends on the clinical setting, and in general, penicillin and gentamicin are indicated for a subacute onset, while flucloxacillin and gentamicin are indicated for an acute onset 6.
• For patients with a history of intravenous drug abuse or those who have recently had a prosthetic valve inserted, vancomycin is recommended, often in combination with other antibiotics such as rifampicin and gentamicin 6.

Considerations for Patients with Allergies

• For patients with an allergy to doxycycline, alternative antibiotics should be considered, taking into account the likely causative agent and the clinical setting.
• The treatment should be started without delay, even if the diagnosis is in doubt, and the choice of antibiotic should be guided by the clinical presentation and the results of diagnostic tests 6, 4.