Gram-negative Bacterial Endocarditis in Adults: State-of-the-heart

Sania S Raza; Omer W Sultan; Muhammad R Sohail


Expert Rev Anti Infect Ther. 2010;8(8):879-885. 

In This Article



Historically, β-lactam antibiotics such as penicillin or ampicillin, with or without the addition of aminoglycoside, were considered the drugs of choice for HACEK endocarditis. However, more recent data suggest an increasing frequency of β-lactamase-producing pathogens in the HACEK group.[9,24] Current practice guidelines from the American Heart Association (AHA) recommend empiric treatment with a third-generation cephalosporin (e.g., ceftriaxone 2 g intraveously or intramuscularly every 24 h) or ampicillin–sulbactam (12 g every 24 h in four equally divided doses) as the first line of therapy for HACEK endocarditis.[9] The recommended duration of therapy is 4 weeks. Alternative treatment options include the use of fluoroquinolones (e.g., ciprofloxacin 500 mg orally every 12 h or 400 mg intravenously every 12 h) in patients who are allergic to or unable to tolerate cephalosporins and ampicillin. However, AHA guidelines caution that use of fluoroquinolones should be avoided in patients younger than 18 years of age.


Cardiac surgery has traditionally been recommended as a cornerstone of therapy for non-HACEK, especially Pseudomonas, endocarditis because of the high mortality associated with conservative medical management. However, in a more contemporary cohort of non-HACEK endocarditis reported by ICE-PCS investigators,[3] the mortality rate did not statistically differ between patients who received medical therapy alone compared with those receiving combined medical and surgical intervention. In their study, in-hospital mortality rate remained high (24%) despite higher rates of cardiac surgery (51%). Most patients (63%) received combined antibiotic therapy with a β-lactam plus aminoglycoside and/or fluoroquinolone, while 38% received monomicrobial treatment. Once again, there was no difference in outcome among patients receiving single as opposed to combination antibiotic therapy with aminoglycosides.[3] However, one major limitation of this investigation was the lack of follow-up and outcome data after hospital discharge.

We recommend a thorough evaluation of patients with non-HACEK Gram-negative endocarditis to assess the necessity of surgical intervention. Decision to treat medically versus combined medical and surgical treatment should be individualized and made on a case-by-case basis. Patients with TEE evidence of valve perforation, chordae tendineae rupture, intra-cardiac abscesses or paravalvular extension of infection should be promptly referred for surgical evaluation. In addition, traditionally described indications for valve surgery such as worsening heart failure, persistently positive blood cultures and isolation of multidrug-resistant Gram-negative bacteria may be additional considerations for cardiac surgery. Whether the large size of the vegetation (>1 cm) or location (anterior mitral leaflet) alone are indications for valve replacement surgery in bacterial endocarditis remains a subject of debate. Recurrent embolization during appropriate antimicrobial therapy also warrants surgical consultation.


For the last few decades, antimicrobial prophylaxis before invasive dental procedures was considered a crux of preventing bacterial endocarditis from oropharyngeal organisms, in particular the viridian group streptococci and HACEK organisms, in a variety of cardiac valvulopathies. However, these recommendations were based on small, uncontrolled studies and personal anecdotes. With more contemporary and better designed population-based studies, the routine use of antibiotic prophylaxis before dental procedures has come under question. A recent study by Lockhart et al. demonstrated a higher incidence of bacteremia from daily tooth brushing than after 'periodic' dental procedures.[25] Others have also demonstrated frequent bacteremias from activities of daily life such as chewing food, urinating, defecating and tooth brushing. Based on these data, the AHA revised their guidelines for endocarditis prophylaxis in a statement published in 2008.[26] Revised practice guidelines place greater emphasis on optimal oral hygiene over prophylactic antibiotics for dental procedure. Use of antimicrobial prophylaxis is now reserved for certain high-risk situations that include presence of prosthetic heart valves, previous history of infective endocarditis, uncorrected or recently corrected congenital cardiac defects and development of cardiac valvulopathy after cardiac transplantation. However, no clinical data or guidelines are available for prevention of non-HACEK Gram-negative bacilli endocarditis during GI or genitourinary procedures.