Infective EndocarditisEdit

Infective endocarditis (IE) is a serious infection that affects the endothelial surface of the heart, most often involving one or more heart valves. The disease is driven by bacteremia or fungemia that seeds damaged or prosthetic endocardium, leading to the formation of vegetations—complex aggregates of microorganisms, inflammatory cells, fibrin, and platelets. IE can cause valve destruction, heart failure, systemic embolization, and septic complications. Advances in antimicrobial therapy, improved imaging, and surgical techniques have reduced mortality, but IE remains a life-threatening condition that requires prompt, specialized care.

Predisposing heart conditions, intravascular devices, and exposure to infectious organisms from the community or healthcare settings contribute to risk. Common predisposing factors include prior valvular disease, congenital heart lesions, prosthetic cardiac valves, history of endocarditis, poor dental or skin health with episodes of bacteremia, and, in many regions, intravenous drug use. Healthcare-associated IE, often related to indwelling catheters, prosthetic material, or invasive procedures, has become an increasingly important portion of cases.

Epidemiology

IE occurs worldwide, with incidence typically estimated at a few cases per 100,000 person-years in developed countries and higher rates in regions with prevalent rheumatic heart disease or limited access to healthcare. It shows a male predominance and shifts in age distribution toward older adults in many high-income countries. The etiologic organisms and microbiology of IE reflect patient risk factors: native valve IE in community settings is often caused by oral flora such as streptococci, whereas hospital- and device-associated IE more frequently involves skin flora such as staphylococci. Prosthetic valve endocarditis (PVE) often presents with more aggressive courses and a distinct microbial spectrum, including coagulase-negative staphylococci and skin-adapted organisms.

Rising use of intravascular devices and longer survival with chronic heart disease have influenced the epidemiology, increasing the proportion of healthcare-associated IE and emphasizing the importance of infection control, device management, and timely diagnosis.

Pathophysiology

The pathophysiology of IE begins with endothelial injury to the cardiac surface, which may be due to rheumatic disease, degenerative changes, congenital defects, prosthetic material, or turbulent flow from abnormal valves. Bacteremia or fungemia allows organisms to adhere to the damaged surface, aided by nonbacterial thrombotic endocarditis that provides a scaffold of fibrin and platelets. Microorganisms then proliferate within the developing vegetation, where the immune response and antibiotic penetration are limited by biofilm formation and the vegetative matrix. This combination contributes to persistent infection, potential embolization to the brain, kidneys, spleen, lungs, or limbs, and progressive valvular dysfunction.

Different clinical contexts influence the microbiology and pathophysiology. Native valve endocarditis (NVE) typically arises from community-acquired organisms, with oral streptococci and Staphylococcus aureus among common culprits. Prosthetic valve endocarditis (PVE) often involves skin flora and device-associated organisms, and culture-negative cases can occur when prior antibiotics obscure culture results or when fastidious pathogens are involved. The presence of a prosthetic valve creates a nidus for infection that can be more challenging to eradicate and may necessitate longer therapy or surgical intervention.

Microbiology

The organism profile of IE varies by setting, patient risk factors, and valve status. Common causes include:

Staphylococcus aureus, including methicillin-susceptible and methicillin-resistant strains, which often drive acute and rapidly progressive disease, particularly in NVE and PVE with healthcare exposure.
Streptococcus species from the viridans group and other oral streptococci, frequently implicated in community-acquired NVE following transient bacteremia.
Enterococcus species, which can be associated with urinary tract or gastrointestinal sources and may require combination therapy.
Coagulase-negative staphylococci, especially in PVE or infection related to prosthetic material.
Culture-negative endocarditis, seen when prior antibiotics suppress growth or when fastidious organisms (e.g., certain intracellular bacteria) are involved.

Diagnosis and management rely on identifying the causative organism via blood cultures and tailoring therapy to susceptibility patterns. See Duke criteria for the diagnostic framework, and consult local microbiology resources for organism-specific guidance.

Clinical features

IE presents with a spectrum of symptoms and signs reflecting infection, inflammation, and valvular disruption. Classic features include:

Fever and chills, often persistent.
New or changing heart murmurs due to valvular involvement.
Fatigue, night sweats, malaise, and weight loss.
Embolic phenomena, which can cause neurologic deficits, splenic infarcts, renal impairment, or limb ischemia.
Signs of systemic infection such as bacteremia-related symptoms, septic shock in severe cases, and, on exam, specific cutaneous findings (e.g., petechiae, Janeway lesions, Osler nodes in some patients).
Heart failure symptoms if there is significant valvular destruction or regurgitation.

The clinical course can be acute or subacute, depending on the organism and the patient’s underlying cardiac status. Timely recognition hinges on a combination of clinical suspicion, positive blood cultures, and imaging studies.

Diagnosis

Diagnosis integrates microbiology, imaging, and clinical findings. Central elements include:

Blood cultures: multiple sets obtained before starting antibiotics to identify the causative organism and guide therapy.
Echocardiography: transthoracic echocardiography (TTE) is often initial; transesophageal echocardiography (TEE) provides higher sensitivity, particularly for detecting vegetations, abscesses, prosthetic valve infection, or perforation.
Duke criteria: a structured framework that combines major criteria (positive blood cultures for typical IE organisms; evidence of endocardial involvement by imaging) with minor criteria (predisposing heart condition, fever, vascular or immunologic phenomena, microbiologic evidence not meeting major criteria, echocardiographic findings not meeting definite endocarditis criteria). See Duke criteria for details.
Additional imaging and tests: imaging of embolic events or complications (e.g., brain imaging for neurologic symptoms) and targeted laboratory studies for organ dysfunction and source control. In culture-negative cases, broader microbiologic testing and serologies may be used.

Therapeutic decisions, including the consideration of surgical intervention, are guided by the organism, valve involvement, patient stability, and evidence of complications such as heart failure, uncontrolled infection, or progressive valvular damage.

Management

Management centers on eradication of infection with appropriately chosen antimicrobial therapy and, when indicated, surgical intervention to address valve destruction, heart failure, or persistent infection.

Antimicrobial therapy

Native valve IE: initial empiric intravenous antibiotics are tailored based on culture results and susceptibility. Common themes include coverage for Staphylococcus aureus, streptococci, and Enterococcus species, with regimens adjusted to local resistance patterns.
Prosthetic valve IE: management is more aggressive and often requires a combination of agents (for example, regimens that address coagulase-negative staphylococci and other prosthetic-associated organisms) and longer durations of therapy.
Duration and route: most episodes require prolonged intravenous therapy, typically in the range of 4–6 weeks, with the exact duration determined by organism, site of infection, and patient response.
Guidelines and stewardship: practitioners consult current guidelines from major bodies such as the American Heart Association and the European Society of Cardiology to select agent choices, durations, and considerations for combinations (including agents like rifampin in select prosthetic cases). Antibiotic stewardship remains important to minimize adverse effects and resistance.

Surgical intervention

Surgery is considered when medical therapy alone is unlikely to control infection or when there is: - Refractory heart failure due to severe valvular dysfunction. - Uncontrolled bacteremia or abscess formation. - Severe valvular destruction with risk of further complications. - Large, highly mobile vegetations with embolic risk, or infection with difficult-to-treat organisms. - Prosthetic valve endocarditis with structural complications.

Decision-making is multidisciplinary, involving cardiology, infectious disease, and cardiothoracic surgery teams. See Valve replacement and Valve repair for related considerations.

Monitoring and follow-up

Serial blood cultures to document clearance of bacteremia.
Serial imaging to assess valve function and detect complications.
Monitoring for drug toxicity, especially with prolonged IV therapy.
Adjustment of therapy based on culture results, patient tolerance, and response to treatment.

Controversies and debates

IE management encompasses several areas with ongoing discussion and evolving evidence. Approaches are guided by patient risk, organism, and institutional expertise, and practice varies by region and by center.

Antibiotic prophylaxis for dental and invasive procedures: guidelines have shifted toward selective prophylaxis for high-risk individuals rather than universal prophylaxis. Proponents argue targeted prophylaxis reduces the incidence of IE in vulnerable patients, while skeptics question the magnitude of benefit and worry about promoting antimicrobial resistance. See discussions around antibiotic prophylaxis and related guideline statements.
Indications and timing for surgery: while surgical intervention can be lifesaving in select cases, the optimal timing remains debated, balancing surgical risk against the benefits of source control and improved hemodynamics. Some centers advocate earlier operation for specific patterns of valve destruction or persistent infection, while others emphasize antibiotic therapy first when feasible.
Duration of therapy: the standard 4–6 weeks of IV antibiotics is based on organism and site of infection, but some studies explore shorter courses in selected patients or alternative regimens. Decisions are individualized and guided by guidelines from major societies.
Role of rifampin in prosthetic valve endocarditis: rifampin can enhance biofilm penetration, but concerns about drug interactions and resistance development mean its use is carefully considered and typically reserved for specific prosthetic infections in consultation with infectious disease specialists.
Outpatient parenteral antimicrobial therapy (OPAT): shifting suitable patients to OPAT can reduce hospital stays and costs, but requires robust outpatient infrastructure and monitoring to ensure safety and adherence.
Culture-negative endocarditis: when cultures do not yield a pathogen, management relies on broad-spectrum empiric therapy and repeated evaluation to identify occult organisms or noninfectious mimics, with ongoing research into rapid diagnostics and tailored approaches.