Overview of management of infective endocarditis in adults

INTRODUCTION — The management of infective endocarditis (IE) includes prompt diagnosis, treatment with antimicrobial therapy, and in some cases of complicated IE, surgical management. Preventive measures including antimicrobial prophylaxis may reduce the risk of initial and recurrent IE for patients with relevant risk factors.

This topic will discuss the management of IE in adults. Details regarding antimicrobial therapy and surgery for IE are discussed separately, as are issues related to prevention of IE. (See "Prevention of endocarditis: Antibiotic prophylaxis and other measures" and "Antimicrobial therapy of left-sided native valve endocarditis" and "Antimicrobial therapy of prosthetic valve endocarditis" and "Surgery for left-sided native valve infective endocarditis" and "Surgery for prosthetic valve endocarditis" and "Right-sided native valve infective endocarditis".)

Clinical manifestations, diagnosis, complications, and outcomes of IE are discussed separately. (See "Clinical manifestations and evaluation of adults with suspected left-sided native valve endocarditis" and "Prosthetic valve endocarditis: Epidemiology, clinical manifestations, and diagnosis" and "Nonbacterial thrombotic endocarditis" and "Complications and outcome of infective endocarditis".)

IMPORTANCE OF PROMPT DIAGNOSIS — The diagnosis of IE is relatively straightforward in some patients but can be quite challenging in patients who present early in the course of infection and/or patients with nonspecific symptoms.

IE should be suspected in patients with fever (with or without bacteremia) and/or relevant cardiac risk factors (prior IE, presence of a prosthetic valve or cardiac device, history of valvular or congenital heart disease) or noncardiac risk factors (intravenous drug use, indwelling intravenous lines or cardiac devices, or a recent dental or surgical procedure).

Delay in diagnosis and treatment may be associated with complications, including valvular regurgitation, heart failure (HF), embolic events, and sepsis.

The accepted criteria for diagnosis of IE are the 2023 Duke-ISCVID IE Criteria [1]. Diagnostic tools within these criteria include blood cultures (two to three sets of blood cultures obtained from separate venipuncture sites before initiation of empiric antibiotic therapy), non-culture based microbiologic methods for fastidious organisms, and imaging with echocardiography, cardiac computed tomography (CT), or 18F-fluorodeoxyglucose positron emission tomography-CT. Issues related to diagnosis of IE are discussed further separately. (See "Clinical manifestations and evaluation of adults with suspected left-sided native valve endocarditis" and "Prosthetic valve endocarditis: Epidemiology, clinical manifestations, and diagnosis".)

GENERAL APPROACH — Patients with IE should receive multidisciplinary care by infectious disease, cardiology, and cardiac surgery specialists to optimize clinical evaluation as well as antibiotic and surgical treatment [2].

Management of IE includes the following components [3]:

●Prompt diagnosis and institution of effective antimicrobial therapy to reduce the risk of complications and development of indications for surgery. (See 'Importance of prompt diagnosis' above and 'Antimicrobial therapy' below.)

●Management of antithrombotic therapy. Neither anticoagulant therapy nor antiplatelet therapy is indicated to reduce the risk of thromboembolic complications in IE. (See 'Role of antithrombotic therapy' below.)

●Assessment of need for removal of any infected implanted devices or arteriovenous fistula or graft. (See 'Role of device or AV shunt removal' below.)

●Identification of patients with an indication for early valve surgery. (See 'Role of valve surgery' below.)

●Monitoring response to antibiotic therapy with confirmation that bacteremia resolves.

●Monitoring of hemodynamic and cardiac status, including surveillance electrocardiograms to evaluate for new conduction abnormalities.

●Follow-up and prevention of recurrent IE (including good dental hygiene, antimicrobial prophylaxis, and closure of patent ductus arteriosus or ventricular septal defect, if present). (See 'Follow-up' below and 'Prevention' below.)

ANTIMICROBIAL THERAPY

General principles — In general, antibiotic therapy for IE should be targeted to the organism isolated from blood cultures.

The duration of therapy should be calculated from the first day of negative blood cultures. Issues related to duration of therapy for patients requiring valve surgery are discussed below. (See 'For patients requiring valve surgery' below.)

Empiric antibiotic therapy

●Indications – For patients with suspected IE who present without acute symptoms, empiric therapy is not always necessary and can be deferred until blood culture results are available, particularly since accurate microbiologic diagnosis is a critical first step in planning the treatment strategy.

For acutely ill patients with signs and symptoms strongly suggestive of IE, empiric therapy may be necessary. Such empiric therapy should be administered only after at least two (preferably three) sets of blood cultures have been obtained from separate venipunctures and ideally spaced over 30 to 60 minutes.

●Selection – The choice of empiric therapy should take into consideration the most likely pathogens. In general, empiric therapy should cover staphylococci (methicillin-susceptible and methicillin-resistant), streptococci, and enterococci.

The appropriate empiric regimen varies depending on the nature of the involved valve (eg, native versus prosthetic valve); this is discussed separately. (See "Antimicrobial therapy of left-sided native valve endocarditis", section on 'Empiric therapy' and "Right-sided native valve infective endocarditis", section on 'Empiric antibiotic therapy' and "Antimicrobial therapy of prosthetic valve endocarditis", section on 'Empiric therapy'.)

For native valve IE — Issues related to antimicrobial therapy for native valve endocarditis (NVE) are discussed in detail separately. (See "Antimicrobial therapy of left-sided native valve endocarditis".)

The duration of antibiotic therapy for NVE typically ranges from four to six weeks. Factors that compel extended courses include left-sided vegetations (which tend to have higher bacterial densities), presence of drug-resistant organisms, and use of slowly bactericidal antibiotics such as vancomycin [4,5].

For prosthetic valve IE — Issues related to antimicrobial therapy for prosthetic valve endocarditis (PVE) are discussed in detail separately. (See "Antimicrobial therapy of prosthetic valve endocarditis".)

Treatment of PVE is more difficult than treatment of NVE and may require surgical replacement of the prosthesis in addition to antibiotic therapy. The typical duration of antimicrobial therapy is six weeks [4,5].

For IE in people who inject drugs — Issues related to IE in people who inject drugs (PWID) are discussed in detail separately. (See "Right-sided native valve infective endocarditis".)

In general, antimicrobial therapy for treatment of IE in PWID is dictated by the infecting pathogen and its antimicrobial susceptibility pattern. Studies have evaluated short-course or alternative therapeutic regimens for treatment of IE patients with a history of injection drug use; data for oral regimens are sparse.

For patients requiring valve surgery — In patients with an indication for early valve surgery (ie, surgery prior to completion of antimicrobial therapy), the timing of surgery is based upon balancing the urgency of indications for surgery against risk factors or contraindications for surgery, generally irrespective of the duration of preoperative antibiotic therapy. If the infected valve is resected and operative valve cultures are positive, an entire postoperative antibiotic course is advised. If operative cultures are negative and blood cultures prior to surgery are negative, the original planned duration of therapy should be completed.

Treatment of specific pathogens — Issues related to treatment of IE due to staphylococci, streptococci, enterococci, HACEK organisms (Haemophilus aphrophilus [subsequently called Aggregatibacter aphrophilus and Aggregatibacter paraphrophilus]; Actinobacillus actinomycetemcomitans [subsequently called Aggregatibacter actinomycetemcomitans]; Cardiobacterium hominis; Eikenella corrodens; and Kingella kingae) and some gram-negative organisms are discussed separately, as are issues related to treatment of culture-negative IE. (See "Antimicrobial therapy of left-sided native valve endocarditis" and "Antimicrobial therapy of prosthetic valve endocarditis".)

Issues related to treatment of IE due to other uncommon pathogens are discussed separately. (See "Candida endocarditis and suppurative thrombophlebitis" and "Treatment and prevention of invasive aspergillosis" and "Pseudomonas aeruginosa bacteremia and endocarditis" and "Endocarditis caused by Bartonella".)

Echo monitoring during therapy — During the course of antibiotic therapy, repeat echocardiogram (transthoracic echocardiography [TTE] and/or transesophageal echocardiography [TEE]) may be warranted if a new complication of IE is suspected.

Clinical indications for repeat TTE and/or TEE may include new murmur, embolic complications, new or progressive heart failure, and development of atrioventricular block. In addition, patients with persistent fever or persistent bacteremia (eg, longer than five to seven days) warrant repeat echocardiography to evaluate for abscess. If considering a change from parenteral to oral antibiotic regimen for the completion of a therapeutic course, repeat echocardiography should be performed to rule out abscess or other indication for surgery.

There is no role for repeat echocardiography for evaluation of vegetation size, and the approach to repeat echocardiogram does not differ based on the pathogen. (See "Complications and outcome of infective endocarditis" and "Role of echocardiography in infective endocarditis".)

Issues related to follow-up echocardiography following completion of therapy are discussed below. (See 'Follow-up' below.)

ROLE OF ANTITHROMBOTIC THERAPY — Patients with IE are at high risk for embolic events, including embolic stroke, and at high risk for bleeding complications, including intracerebral hemorrhage. The available limited data suggest that neither anticoagulant therapy nor aspirin reduces the risk of embolism in patients with IE. Therefore, neither anticoagulant therapy nor antiplatelet therapy is indicated to reduce the risk of thromboembolic complications in IE. Patients with IE frequently have one or more coexistent conditions that pose a risk of thrombotic complications separate from IE; in such patients, we weigh the risk of withholding antithrombotic therapy against the risk of receiving antithrombotic therapy. These issues are discussed further separately. (See "Antithrombotic therapy in patients with infective endocarditis".)

ROLE OF DENTAL CARE — Patients with IE due to common oral organisms should undergo a thorough dental evaluation; the examination should focus on periodontal inflammation, pocketing around teeth, and caries that may result in pulpal infection and subsequent abscess [4]. A full series of intraoral radiographs allows identification of caries, periodontal disease, and other disease (ie, tooth fracture) not evident from clinical examination. If possible, corrective dental care should be done while the patient is still receiving antibiotics. All active sources of oral infection should be eradicated. (See 'Follow-up' below.)

ROLE OF COLONOSCOPY — For patients with IE due to Streptococcus bovis/Streptococcus equinus complex (formerly group D streptococci), colonoscopy is warranted given the association between these organisms and colonic neoplasm. (See "Infections due to Streptococcus bovis/Streptococcus equinus complex (SBSEC; formerly group D streptococci)".)

For patients with IE due to E. faecalis with unknown source who are in the age range for screening colonoscopy (eg, ≥45 years) (see "Screening for colorectal cancer: Strategies in patients at average risk"), colonoscopy is reasonable [6,7]. In one retrospective study including 154 patients with IE due to E. faecalis, 109 had an unknown source; 61 underwent colonoscopy; of those, neoplasm was observed in 31 patients (four were carcinomas, the rest were adenomas) [6].

ROLE OF DEVICE OR AV SHUNT REMOVAL

Removal of intravascular catheters — In patients with an intravascular catheter who develop IE, catheter removal is warranted. (See "Intravascular non-hemodialysis catheter-related infection: Treatment".)

Removal of cardiac devices — Complete cardiac implantable electronic device (CIED) removal (including the leads and pulse generator) is warranted in the following circumstances (see "Infections involving cardiac implantable electronic devices: Treatment and prevention", section on 'Device removal versus retention'):

●Transesophageal echocardiography demonstrating valve or lead vegetation.

●Positive blood culture for S. aureus or Candida species.

●High-grade bacteremia (defined as multiple [two or more] separate positive blood cultures drawn ≥1 hour apart) with coagulase-negative staphylococci or Cutibacterium (formerly Propionibacterium) species.

●Other high-grade bacteremia without alternative source (especially due to an organism that commonly causes endocarditis, such as alpha-hemolytic streptococci, beta-hemolytic streptococci, or enterococci).

●CIED pocket infection.

Surgical excision of AV fistula for hemodialysis — In cases of suspected fistula or graft infection, imaging with ultrasonography, computed tomography, or magnetic resonance imaging may identify a local fluid collection or abscess for drainage or debridement. Although bacteremia may have originated from hemodialysis access, excision of the arteriovenous (AV) fistula or graft is not needed in most cases. In rare cases complicated by septic emboli from the graft or fistula, excision may be warranted. Treatment of AV fistula or graft infection should be individualized, as patients will still require other vascular access for hemodialysis, including a possible central venous catheter. (See "Arteriovenous fistula creation for hemodialysis and its complications", section on 'Infection' and "Arteriovenous fistula creation for hemodialysis and its complications" and "Arteriovenous graft creation for hemodialysis and its complications".)

ROLE OF VALVE SURGERY — In patients with IE treated with antibiotic therapy, a number of complications are associated with poor prognosis and may warrant early surgical therapy (ie, surgery performed prior to completion of antimicrobial therapy).

When early surgery is indicated, it should not be delayed except for patients with major cerebrovascular complications (eg, hemorrhagic stroke) or those with high operative risk or poor long-term prognosis due to other medical problems. Patients who experience embolic events in the central nervous system without hemorrhage or major neurologic impairment may still undergo cardiac surgery with reasonable risk, but surgical delay for at least four weeks is appropriate for patients with hemorrhagic stroke.

For native valve IE

For left-sided native valve IE — Patients with left-sided native valve endocarditis (NVE) frequently require early valve surgery due to the presence of one or more complications (eg, IE-associated valve dysfunction complicated by HF, intracardiac abscess, difficult-to-treat pathogen, and/or persistent infection) [8]. Indications for surgery for left-sided NVE are discussed separately. (see "Surgery for left-sided native valve infective endocarditis")

For right-sided native valve IE — Indications for surgery in right-sided NVE include very large vegetations (≥20 mm in diameter), recurrent septic pulmonary emboli, highly resistant organisms, or persistent bacteremia [4]. HF is not a common indication for early surgery in right-sided NVE, since severe tricuspid valve regurgitation is better tolerated (from a hemodynamic standpoint) than severe left-sided regurgitation. Severe tricuspid regurgitation causing right HF that is poorly responsive to medical therapy is a less common indication for surgery [4,9]. In such cases, valve repair is generally preferred to valve replacement, particularly in PWID [4,10]. (See "Right-sided native valve infective endocarditis", section on 'Management'.)

For people who inject drugs — The indications for surgery in patients with IE and concurrent injection drug use are generally the same as for other patients with IE. IE in PWID most commonly affects the tricuspid valve, but can involve left-sided valves and prosthetic valves [11,12].

Difficult ethical and practical problems arise when patients who are actively abusing injection drugs develop recurrent IE and need valvular surgery. (See "Right-sided native valve infective endocarditis", section on 'Management'.)

For prosthetic valve IE — Early surgery for prosthetic valve endocarditis is indicated for IE complications similar to native valve endocarditis (eg, HF due to prosthetic valve dysfunction, paravalvular regurgitation, or intracardiac fistula; annular abscess, difficult-to-treat pathogen, persistent infection). (See "Surgery for prosthetic valve endocarditis".)

FOLLOW-UP — After completion of antibiotic therapy for IE, the intravenous catheter used for antibiotic administration should be removed promptly.

At the end of antibiotic therapy, a TTE should be performed to serve as a new baseline reference for valve appearance, severity of valvular regurgitation, and quantitation of left ventricular function. Complete resorption of valvular vegetations by the end of antimicrobial therapy is uncommon, even with successful treatment [13]. In addition, laboratory tests (white cell count, erythrocyte sedimentation rate, and C-reactive protein) should be performed to serve as a new baseline reference [4,5].

Subsequently, the frequency of monitoring depends upon the baseline evaluation, including the presence and severity of valvular regurgitation. At a minimum, patients should receive follow-up monitoring according to standard recommendations for chronic valve regurgitation, if present. (See "Chronic secondary mitral regurgitation: General management and prognosis", section on 'Evaluation and monitoring' and "Natural history and management of chronic aortic regurgitation in adults", section on 'Echocardiography'.)

Patients should be counseled regarding the importance of daily dental hygiene, serial dental evaluation, and the role of antibiotic prophylaxis prior to specific types of procedures including certain types of dental work. (See 'Prevention' below.)

In the absence of clinical symptoms of infection, there is no role for routine surveillance blood cultures. Blood cultures are warranted for patients with recurrence of fever or signs of infection.

PREVENTION — Patients who have been cured of IE are at a higher risk of recurrent IE. All patients with prior IE should be educated about possible symptoms and signs of IE, and the need for prompt medical care if these occur, including the importance of obtaining blood cultures prior to administration of antibiotics [4]. Clinical evaluation including echocardiography should be performed if signs or symptoms of IE recur or if signs or symptoms of worsening valve disease develop.

Measures for prevention of IE, including antibiotic prophylaxis, are discussed separately. (See "Prevention of endocarditis: Antibiotic prophylaxis and other measures".)

In addition, predisposing factors for IE or bacteremia should be addressed. Patients who use injection drugs should be offered and enrolled in addiction treatment programs and counselling. If possible, patients with central venous access, particularly those with catheter-based hemodialysis, should receive other vascular access (eg, hemodialysis arteriovenous access via constructed native AV fistula or AV prosthetic graft) to reduce exposure to the risk of catheter infection.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Cardiac valve disease" and "Society guideline links: Treatment and prevention of infective endocarditis" and "Society guideline links: Outpatient parenteral antimicrobial therapy".)

SUMMARY AND RECOMMENDATIONS

●Importance of prompt care – Patients with infective endocarditis (IE) should receive prompt multidisciplinary care by infectious disease, cardiology, and cardiac surgery specialists to optimize clinical evaluation as well as antibiotic and surgical treatment. Early diagnosis and treatment of IE are required to reduce the high risk of morbidity and mortality associated with this disease. (See 'Importance of prompt diagnosis' above.)

●Management of IE – Management of IE includes prompt institution of effective antimicrobial therapy, monitoring of response to therapy and valve function, management of any indicated antithrombotic therapy, assessment of potential sources of infection and need for removal of any infected implanted devices or atrioventricular access, identification of patients with an indication for valve surgery, follow-up, and prevention of recurrent IE. (See 'General approach' above.)

●Role of valve surgery – When early surgery is indicated, it should not be delayed except for patients with major cerebrovascular complications (eg, hemorrhagic stroke) or those with high operative or poor long-term prognosis due to other medical problems. (See 'Role of valve surgery' above.)

•Native valve endocarditis – Patients with left-sided native valve endocarditis (NVE) frequently require early valve surgery due to the presence of one or more complications (eg, IE-associated valve dysfunction complicated by heart failure [HF], intracardiac abscess, difficult-to-treat pathogen, or persistent infection). (See 'For native valve IE' above and "Surgery for left-sided native valve infective endocarditis".)

•Prosthetic valve endocarditis – Early surgery for prosthetic valve endocarditis is indicated for IE complications similar to NVE (eg, HF due to prosthetic valve dysfunction, paravalvular regurgitation, or intracardiac fistula; annular abscess; difficult-to-treat pathogen; or persistent infection). (See 'For prosthetic valve IE' above and "Surgery for prosthetic valve endocarditis".)