Endocarditis: Symptoms, Causes & Treatment

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Endocarditis is a serious and potentially life-threatening inflammation of the endocardium, the thin inner lining of the heart. It is usually caused by an infection from bacteria, fungi, or other microorganisms. Although the condition is not common, affecting about 3 to 10 people per 100,000 each year worldwide, it has high health risks. Even with treatment, 15% to 30% of patients may die, depending on the type of organism involved and how quickly treatment begins. Endocarditis is most likely to develop in people who already have heart problems, such as damaged or artificial heart valves, congenital (present from birth) heart defects, or a history of previous heart infections.

Symptoms often start with general, flu-like signs such as fever, chills, night sweats, and tiredness. Other common symptoms include shortness of breath, cough, muscle or joint pain, weight loss, and tiny blood spots under the skin or fingernails. A new or changing heart murmur, a sound caused by turbulent blood flow, may suggest the infection is affecting the heart valves. Severe cases can lead to complications such as stroke, heart failure, or blockages caused by infected clots traveling through the bloodstream.

Endocarditis occurs when germs enter the bloodstream and attach to the heart’s inner surface, forming clumps called vegetations. This is more likely in people with abnormal or artificial heart valves, which provide surfaces where germs can stick more easily. Major risk factors include congenital heart defects, implanted heart devices, injecting drugs with unsterile needles, previous episodes of endocarditis, and medical or dental procedures that allow bacteria to enter the blood.

Treatment usually requires long courses of intravenous (IV) antibiotics, typically lasting 4 to 6 weeks. Common antibiotics include vancomycin, gentamicin, ceftriaxone, and penicillin G, depending on the specific organism causing the infection. Fungal endocarditis, although rare, may require antifungal drugs such as amphotericin B or echinocandins. Surgery may be needed to repair or replace damaged heart valves or remove infected tissue if complications arise.

Prevention focuses on lowering the chance of germs entering the bloodstream, especially in people at high risk. Good oral hygiene, regular dental care, avoiding the use of unsterile needles, and ensuring sterile procedures during medical care are key measures. For certain high-risk individuals such as those with artificial heart valves or a history of endocarditis, preventive antibiotics before specific dental procedures may be recommended to reduce the risk of infection.

Classification of Endocarditis

The condition is classified in several ways, including by cause, location, type of heart tissue involved, and clinical presentation. 

Types of Endocarditis

There are several types of endocarditis, primarily distinguished by cause and location:

  • Infective Endocarditis (IE): Infective endocarditis is the most common and clinically significant form. It occurs when bacteria, fungi, or occasionally other microorganisms enter the bloodstream and adhere to the endocardium or heart valves, forming infectious growths called vegetations. Common causative organisms include Staphylococcus aureus, Streptococcus viridans, Enterococcus species, and, less frequently, fungi such as Candida or Aspergillus. Infective endocarditis can damage heart valves, lead to systemic emboli, and cause severe complications such as stroke or heart failure. It is further subdivided based on the type of microorganism, the valve involved (native vs. prosthetic), and the mode of acquisition (community-acquired, healthcare-associated, or injection drug use–related).
  • Non-infective Endocarditis: Non-infective endocarditis refers to sterile, non-microbial inflammation or deposition of tissue on the heart valves. A key example is Libman–Sacks endocarditis, which occurs in autoimmune conditions such as systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). In these conditions, immune complexes and fibrin deposits accumulate on the heart valves, forming vegetations that resemble those of infective endocarditis but without active microbial infection. Another form, non-bacterial thrombotic endocarditis (NBTE), can develop in patients with advanced malignancy or chronic wasting diseases due to hypercoagulability. Although non-infective forms do not involve pathogens, they can still cause embolic events and may become infected secondarily.
  • Prosthetic Valve Endocarditis: Prosthetic valve endocarditis occurs in individuals with artificial (mechanical or bioprosthetic) heart valves. It accounts for 10–30% of all endocarditis cases and is associated with a higher risk of complications due to the foreign material. PVE is classified as: Early-onset PVE, occurring within the first 60 days after valve surgery and commonly caused by hospital-acquired organisms such as coagulase-negative staphylococci, Staphylococcus aureus, or Gram-negative bacteria. Late-onset PVE, occurring after 60 days and typically caused by community-acquired organisms similar to those seen in native valve endocarditis. Prosthetic valve infections often require combined medical and surgical management because antibiotics may not fully eradicate bacteria adhering to artificial materials.
  • Device-related Endocarditis: Device-related endocarditis involves infections associated with implanted cardiac devices such as pacemakers, implantable cardioverter defibrillators (ICDs), and intracardiac leads. These infections commonly arise from skin flora like Staphylococcus aureus and Staphylococcus epidermidis, which can colonize the device pocket or leads. Device-related endocarditis frequently necessitates complete removal of the device in addition to antibiotic treatment, as microorganisms can form biofilms that protect them from antimicrobial therapy.

Acute vs. Subacute Forms

Endocarditis manifests in acute or subacute forms depending on onset and severity.

  • Acute Endocarditis: Acute endocarditis develops rapidly, often within days, and is typically caused by highly virulent (aggressive) microorganisms, most notably Staphylococcus aureus. Patients often present with sudden, severe symptoms such as high fever, shaking chills, marked toxicity, and rapid progression to complications like acute heart failure. Because of its aggressive course, acute endocarditis carries a high risk of mortality and requires immediate medical intervention, often including hospitalization, intravenous antibiotics, and in some cases emergency surgery.
  • Subacute Endocarditis: Subacute endocarditis has a slower, more insidious onset, unfolding over weeks to months. It is usually caused by less aggressive organisms, such as Streptococcus viridans, which commonly originate from the mouth. Symptoms tend to be milder and more nonspecific, including fatigue, low-grade fever, weight loss, and progressive weakness. Subacute endocarditis is more frequently associated with underlying heart defects such as congenital abnormalities or previously damaged valves. Although symptoms are less dramatic than in acute cases, delayed diagnosis can lead to significant complications if untreated.

Etiology and Risk Factors

Endocarditis results from the interaction between certain infectious agents, bodily conditions, and medical risk factors. The causes include both microbial infections and non-infective triggers. Medical history can significantly influence susceptibility.

Infective Agents

The majority of endocarditis cases are caused by bacterial microorganisms that enter the bloodstream (a process known as bacteremia) and subsequently adhere to the endocardium or heart valves. The most common bacterial pathogens include:

  • Staphylococcus aureus – the leading cause worldwide, responsible for both acute and healthcare-associated endocarditis. It is especially common among intravenous drug users and patients with intravascular catheters.
  • Streptococcus viridans group – often associated with poor oral hygiene or dental procedures, and a typical cause of subacute endocarditis.
  • Enterococcus species – frequently linked to infections of the gastrointestinal or genitourinary tract, particularly in older adults.

These organisms typically gain access to the bloodstream through skin breaches, dental extractions, periodontal disease, surgical wounds, contaminated needles, or insertion of vascular access devices. Once in circulation, they adhere to damaged or irregular cardiac surfaces and begin forming vegetations, which are masses of microbes, inflammatory cells, fibrin, and platelets.

Fungal pathogens, though much less common, can cause severe and highly destructive forms of endocarditis. Species such as Candida and Aspergillus are most often encountered in immunocompromised individuals, including transplant recipients, patients on chemotherapy, and those receiving long-term intravenous nutrition. Fungal vegetations tend to be large and more prone to embolization, increasing the risk of stroke and systemic complications.

Non-Infective Causes

Non-infective endocarditis encompasses several conditions in which sterile vegetations form on the heart valves without microbial involvement. These vegetations are typically composed of fibrin and platelets and can serve as a nidus for later bacterial infection.

A prominent type is Libman–Sacks endocarditis, which occurs in autoimmune disorders such as systemic lupus erythematosus (SLE) and antiphospholipid syndrome. In these conditions, immune complex deposition and inflammatory injury to the endocardium promote vegetation formation. Although often clinically silent, these lesions can lead to embolic events, valvular dysfunction, or secondary infective endocarditis.

Another form, non-bacterial thrombotic endocarditis (NBTE) also known as marantic endocarditis, occurs mainly in individuals with advanced malignancies, chronic inflammatory disorders, or severe wasting diseases. These states induce hypercoagulability, increasing the likelihood of fibrin deposition on the valves. Trauma to endothelial surfaces from catheterization or turbulent blood flow can also trigger non-infective vegetations.

While these lesions are sterile, they can cause significant complications

Predisposing Medical Conditions

Certain pre-existing heart abnormalities significantly elevate the risk of developing endocarditis. These conditions create abnormal blood flow or damaged surfaces that facilitate microbial attachment. Major cardiac risk factors include:

  • Congenital heart defects, such as ventricular septal defects, bicuspid aortic valves, or patent ductus arteriosus.
  • Prosthetic (artificial) heart valves, which provide surfaces that are highly susceptible to microbial colonization.
  • Rheumatic heart disease, particularly in regions where rheumatic fever remains prevalent.
  • History of previous endocarditis, which greatly increases recurrence risk due to residual valvular damage.

In addition to cardiac factors, numerous medical and behavioral conditions predispose individuals to endocarditis. These include:

  • Intravenous drug use, especially with non-sterile needles, which introduces bacteria directly into the bloodstream.
  • Invasive cardiac procedures, such as catheterization, valve replacement, or implantable device insertion.
  • Presence of indwelling intravascular catheters, commonly used in oncology or critical care settings.
  • Immunosuppressed states, including HIV infection, chronic steroid use, chemotherapy, and post-transplant therapy, which reduce the body’s ability to clear infections.

Elderly patients, individuals with chronic kidney disease on hemodialysis, and those with poor oral hygiene also face increased risk due to frequent bacteremia from gum disease or repeated vascular access.

Pathophysiology

Endocarditis is characterized by infection and inflammation of the endocardium, particularly the heart valves, and progresses through a series of interconnected pathological events. These events include microbial entry into the bloodstream, adherence to damaged endocardial surfaces, formation of vegetations, and the dissemination of infectious material throughout the body.

Mechanisms of Infection

Endocarditis typically begins when microorganisms, most commonly bacteria and less frequently fungi, enter the bloodstream and find an environment suitable for attachment and proliferation. This process requires two essential conditions: transient or persistent bacteremia and a surface within the heart that supports microbial colonization.

Damage to the endocardium, whether from mechanical stress, congenital malformation, degenerative valvular disease, rheumatic inflammation, or prosthetic material, exposes underlying extracellular matrix proteins. This exposure allows platelets and fibrin to accumulate on the injured surface. The initial deposition of these components forms a sterile thrombus, also referred to as nonbacterial thrombotic endocarditis (NBTE) when it occurs without infection. These thrombi serve as an ideal foundation or nidus, for microbial attachment.

Microorganisms such as Staphylococcus aureus, Streptococcus viridans, and Enterococcus species possess specialized proteins called adhesins, which allow them to bind to fibrin, fibronectin, and other matrix components. Once attached, these organisms multiply within the protective environment of the thrombus. The immune system often struggles to clear these microbes because the vegetative mass lacks blood supply, limiting immune cell access. Certain pathogens, such as S. aureus, also possess toxins and enzymes that promote tissue destruction and dissemination, leading to aggressive infection.

The reduced vascularity of the valve leaflets, unlike other tissues in the body, imposes additional barriers to immune surveillance. This anatomical feature, combined with microbial virulence factors, explains why infective endocarditis can persist even in the presence of bacteremia and why it often requires prolonged, high-dose antimicrobial therapy.

Formation of Vegetations

A hallmark feature of infective endocarditis is the development of vegetations, which are complex, multilayered masses consisting of fibrin, platelets, microorganisms, and inflammatory cells. These vegetations form primarily on the heart valves, especially in regions exposed to turbulent or high-velocity blood flow, such as the mitral and aortic valves in left-sided disease or the tricuspid valve in intravenous drug users.

Vegetations can vary greatly in size, morphology, and mobility. Larger or more friable (easily broken) vegetations pose a higher risk for embolization. Their structural characteristics, particularly the lack of vascularization, mean that antibiotics penetrate poorly, allowing the embedded microbes to remain metabolically active and protected within the matrix.

Histologically, vegetations display layered deposits of fibrin interspersed with dense clusters of bacteria. The absence of blood vessels and the presence of biofilm-like environments contribute to persistent infection. This mechanism explains the clinical necessity for 4–6 weeks of parenteral antibiotics, ensuring adequate drug levels in the bloodstream to suppress bacterial proliferation long enough for the immune system to aid in clearing the infection.

Vegetations also cause mechanical problems, such as restricting valve movement or causing valve leaflets to fail to close properly, resulting in valvular regurgitation. Over time, this can lead to progressive volume overload and heart failure, one of the most serious complications of endocarditis.

Embolic Complications

Embolization occurs when fragments of vegetations break loose and travel through the bloodstream as septic emboli, carrying living microorganisms to distant organs. Embolic events contribute significantly to the morbidity and mortality associated with endocarditis. The risk of embolization is highest in infections caused by virulent organisms, such as S. aureus, and in cases with large (>10 mm), mobile vegetations.

The destination of emboli depends on the side of the heart affected:

  • Left-sided endocarditis (mitral or aortic valve involvement) sends emboli into the systemic circulation. These emboli may occlude arteries in the brain, causing ischemic stroke or intracerebral hemorrhage; the spleen, leading to splenic infarction or abscess; the kidneys, resulting in renal infarcts or nephritis; or peripheral arteries, causing limb ischemia.
  • Right-sided endocarditis (typically tricuspid valve involvement) produces emboli that travel to the lungs, resulting in septic pulmonary emboli. These can manifest as chest pain, cough, hemoptysis, cavitary lung lesions, or acute respiratory distress.

Embolization not only spreads infection but can also seed new sites for abscess formation. For example, cerebral emboli can initiate mycotic aneurysms, which are infected arterial wall outpouchings with a risk of rupture and intracranial hemorrhage. Embolic complications frequently prompt consideration of surgical intervention, especially when vegetations remain large despite appropriate antibiotic therapy.

Clinical Presentation

Endocarditis often presents with a mix of systemic and cardiovascular symptoms. Its manifestations can vary based on the infection’s duration and the causative organism.

Common Signs and Symptoms

Fever is the most frequent clinical feature of endocarditis, occurring in the majority of cases. It may be high-grade in acute infections, particularly those caused by Staphylococcus aureus or low-grade and intermittent in subacute disease associated with organisms like Streptococcus viridans. Fever is often accompanied by systemic inflammatory symptoms such as chills, rigors, night sweats, and profound fatigue. Many patients describe a persistent sense of malaise or weakness that gradually interferes with daily activities, reflecting the chronic inflammatory state and cytokine release.

Unintentional weight loss and anorexia are also common, particularly in subacute cases in which symptoms evolve over weeks. Musculoskeletal symptoms including arthralgia, myalgia, and sometimes back pain, may appear due to immune-complex deposition or septic emboli. Cardiopulmonary symptoms depend on the progression of valvular dysfunction. As the infection destroys valve tissue, regurgitation can develop, leading to dyspnea on exertion, orthopnea, and, in severe cases, symptoms of acute pulmonary edema. Patients may also present with a persistent cough or chest discomfort when heart failure or septic pulmonary emboli occur.

Embolic manifestations are a major part of the clinical picture. Fragmentation of vegetation can send emboli to virtually any organ system. Cerebral embolization may result in acute neurological deficits such as sudden weakness, speech difficulties, altered mental status, or stroke. Emboli to the spleen can cause left upper-quadrant pain and splenic infarction, while renal emboli may lead to flank pain or hematuria. Cutaneous or mucosal petechiae, tiny pinpoint hemorrhages, often reflect microvascular embolization and are a classic but nonspecific feature.

Physical Examination Findings

Physical examination is a crucial diagnostic tool in suspected endocarditis. One of the most important findings is a new or changing heart murmur. This typically reflects valvular destruction, regurgitation, or perforation caused by the infection. The nature of the murmur depends on which valve is affected, for example, a holosystolic murmur at the apex suggests mitral regurgitation, while a diastolic murmur along the left sternal border may indicate aortic insufficiency.

Peripheral stigmata of endocarditis, although less common in modern clinical practice due to earlier diagnosis, remain highly characteristic when present. Splinter hemorrhages appear as thin, linear reddish-brown streaks under the nails and represent small-vessel emboli. Janeway lesions, painless, flat, erythematous or hemorrhagic macules on the palms and soles, are associated with septic microemboli. In contrast, Osler nodes are tender, raised nodules on the fingertips or toes, thought to result from immune-complex deposition. These lesions provide important diagnostic clues, especially when combined with systemic symptoms.

Ophthalmologic findings may also be encountered. Roth spots, which are retinal hemorrhages with pale centers, can be detected during fundoscopic examination and reflect microvascular injury. Although not pathognomonic, their presence supports the diagnosis in the appropriate clinical context.

Signs of heart failure are especially important due to the risk of rapid clinical deterioration. These include peripheral edema, jugular venous distension, hepatomegaly, and pulmonary crackles on auscultation. Patients with right-sided endocarditis, often linked to intravenous drug use, may present with symptoms related to septic pulmonary emboli such as pleuritic chest pain, hemoptysis, or respiratory distress. In severe cases, cardiogenic shock may occur due to acute valvular destruction or perforation.

Other physical findings may point to systemic embolization or immune-mediated complications. Skin examination may reveal petechiae on the conjunctivae, buccal mucosa, or lower extremities. Neurological examination may show focal deficits in patients with cerebral emboli, while abdominal tenderness may suggest splenic or renal involvement. Because the presentation can be extremely diverse, clinicians must carefully interpret these findings in conjunction with laboratory and imaging studies.

Diagnosis

Endocarditis diagnosis involves combining clinical findings, laboratory tests, and imaging studies. Accurate identification relies on structured criteria and exclusion of other conditions presenting with similar symptoms.

Diagnostic Criteria

The Duke criteria are the most widely used for diagnosing infective endocarditis. These criteria include major and minor elements such as positive blood cultures, evidence of endocardial involvement on echocardiography, fever, vascular phenomena, and predisposing heart conditions.

Major criteria:

  • Positive blood cultures with typical microorganisms
  • Evidence of endocardial involvement via imaging

Minor criteria:

  • Predisposing heart conditions or intravenous drug use
  • Fever over 38°C
  • Vascular and immunologic phenomena like emboli or glomerulonephritis

Diagnosis is definite when two major, one major plus three minor, or five minor criteria are met.

Laboratory Investigations

Blood cultures remain essential to isolate the causative pathogen. At least three sets should be obtained from different sites over 24 hours before antibiotics are administered.

Elevated inflammatory markers such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) support inflammation but are nonspecific. Complete blood count often shows leukocytosis.

Serologic tests may help identify organisms that are difficult to culture, such as Coxiella burnetii or Bartonella species. Cultures should be repeated if initial samples are negative but clinical suspicion remains high.

Imaging Modalities

Transthoracic echocardiography (TTE) is the first-line imaging tool. It detects vegetations, abscesses, and valve dysfunction. However, its sensitivity is limited, especially in obese patients or prosthetic valves.

Transesophageal echocardiography (TEE) offers higher resolution and better visualization of prosthetic valves or intracardiac complications. TEE is recommended when TTE results are inconclusive or suspicion remains high.

Additional imaging such as cardiac MRI or CT scans may assess complications like abscesses or embolic phenomena but are not routine diagnostic tools.

Differential Diagnosis

Several conditions mimic infective endocarditis clinically and echocardiographically. These include sterile thrombotic endocarditis, rheumatic heart disease, and cardiac tumors like myxomas.

Febrile illnesses such as lupus or vasculitis may also present with similar signs. Non-infectious causes require exclusion through blood cultures, serology, and imaging.

Identifying the correct diagnosis avoids inappropriate antibiotic use and guides proper management strategies.

Microbiology

The microbiology of endocarditis is central to understanding its pathogenesis, clinical course, and optimal treatment strategies. Endocarditis arises when microorganisms colonize the cardiac endocardium, particularly damaged or prosthetic valves, forming vegetations composed of fibrin, platelets, inflammatory cells, and microbial clusters.

Bacterial Pathogens

Bacteria account for the vast majority of infective endocarditis cases. Staphylococcus aureus remains the most common and most virulent etiologic agent, particularly in acute endocarditis. It is strongly associated with intravenous drug use, intravascular catheters, hemodialysis, and healthcare-associated infections. S. aureus has a remarkable ability to adhere to intact endothelium—unlike many other pathogens requiring pre-damaged surfaces—which explains its aggressive tissue destruction and rapid progression to valve perforation, abscess formation, and septic embolization. Methicillin-resistant S. aureus (MRSA) is increasingly encountered in both community and hospital settings, complicating antimicrobial therapy.

Streptococcus viridans, part of the normal oral flora, remains an important cause of subacute endocarditis. These organisms typically enter the bloodstream through dental caries, gingival inflammation, or dental procedures. Because they are less virulent than S. aureus, infections tend to progress more indolently. The organisms preferentially adhere to pre-existing valvular abnormalities, such as those caused by rheumatic heart disease or congenital defects. Other streptococci, including Streptococcus bovis (now Streptococcus gallolyticus), are also implicated and are notable because their isolation often warrants evaluation for colorectal malignancy or polyps.

Enterococci, particularly Enterococcus faecalis and Enterococcus faecium, cause endocarditis primarily in older adults and individuals with genitourinary or gastrointestinal tract manipulation. These organisms possess intrinsic resistance to several antibiotics and frequently demonstrate multidrug resistance, complicating treatment. Enterococcal endocarditis often requires combination therapy, and relapse is not uncommon due to their ability to persist in vegetations.

A subset of endocarditis cases involve HACEK organisms (Haemophilus species, Aggregatibacter, Cardiobacterium, Eikenella corrodens, and Kingella). These are fastidious, gram-negative bacilli associated with subacute disease. They are part of the normal oropharyngeal flora and may follow dental infections or procedures. HACEK organisms typically grow slowly and may require prolonged incubation periods, historically leading to culture-negative results, although modern automated culture systems have improved detection. Despite their low virulence, they can cause significant structural damage when diagnosis is delayed.

Less common bacterial causes include Corynebacterium species, Propionibacterium acnes (especially in prosthetic valve infections), and Staphylococcus lugdunensis, which behaves more aggressively than other coagulase-negative staphylococci. Zoonotic organisms such as Brucella and Coxiella burnetii cause highly specialized forms of endocarditis with unique diagnostic challenges.

Fungal Endocarditis

Fungal endocarditis represents a small but highly lethal subset of cases. It primarily affects immunocompromised individuals, those with HIV/AIDS, neutropenia, prolonged corticosteroid use, or hematologic malignancies, as well as patients with long-term central venous catheters or prosthetic valves. Among fungal pathogens, Candida species, particularly Candida albicans, are the most frequent culprits. They form bulky, friable vegetations prone to embolization and are often associated with prosthetic valve involvement.

Aspergillus species form the second major group of fungal pathogens. Unlike Candida, Aspergillus rarely causes positive blood cultures, making diagnosis extremely difficult. Patients may present with massive embolic events due to the large vegetations these fungi produce. Aspergillus endocarditis is strongly associated with intravenous drug use, immunosuppression, and prior cardiac surgery.

Fungal vegetations are dense and poorly penetrated by antifungal drugs. Consequently, effective management typically requires a combination of prolonged high-dose antifungal therapy and surgical valve replacement. Without surgery, mortality rates remain exceedingly high.

Culture-Negative Cases

Culture-negative endocarditis presents a major diagnostic challenge and accounts for approximately 5–31% of cases, depending on the population and diagnostic techniques available. In many cases, cultures are negative because patients have received antibiotics before blood cultures were obtained, suppressing bacterial growth. However, true culture-negative cases are often caused by fastidious organisms that do not grow in standard culture media.

Coxiella burnetii, the agent responsible for Q fever, is a classic cause of culture-negative endocarditis. This organism frequently affects individuals with exposure to livestock and can cause chronic, indolent infection that preferentially targets prosthetic or previously damaged valves. Diagnosis relies on serologic testing, particularly detection of high titers of phase I IgG antibodies.

Bartonella species, especially Bartonella henselae and Bartonella quintana, are increasingly recognized etiologic agents. Risk factors include homelessness, body lice infestation, and close contact with cats. These organisms cause subacute or chronic endocarditis and often require polymerase chain reaction (PCR) or serologic testing for detection.

Tropheryma whipplei, the bacterium responsible for Whipple disease, can occasionally cause endocarditis, often in middle-aged men. Blood cultures are typically negative, and diagnosis relies on PCR from blood or valvular tissue. Symptoms may include weight loss, arthralgia, and gastrointestinal disturbances.

Other rare causes of culture-negative endocarditis include Legionella, Mycoplasma, and geographically restricted organisms such as Coxiella-like agents, Rickettsia, and certain fungi. Modern molecular techniques, PCR, 16S rRNA sequencing, and metagenomic next-generation sequencing, have significantly increased the ability to identify causative organisms in patients with negative cultures.

Management and Treatment

Effective management of endocarditis involves targeted antimicrobial therapy, potential surgical intervention, and comprehensive supportive care. Treatment aims to eradicate infection, prevent complications, and maintain cardiac function.

Antimicrobial Therapy

Antimicrobial therapy remains the cornerstone of endocarditis management. Treatment consists of prolonged, high-dose, intravenous antibiotics designed to achieve bactericidal activity against pathogens embedded within vegetations. These vegetations are often poorly vascularized, requiring sustained drug exposure to penetrate fibrin and platelet layers. Accordingly, standard therapy typically ranges from 4 to 6 weeks, though longer durations may be required for complicated infections, prosthetic valve involvement, or fungal etiologies.

Initial therapy is often empiric, broad-spectrum antibiotic coverage initiated before culture results are available, especially in critically ill patients. Empiric regimens commonly include combinations such as vancomycin plus gentamicin, with or without a broad-spectrum beta-lactam (e.g., ceftriaxone, cefepime, or piperacillin-tazobactam) depending on patient risk factors and local resistance patterns.

Once the causative organism is identified, treatment is narrowed based on culture and sensitivity results:

  • Viridans streptococci: typically treated with penicillin G or ceftriaxone, often combined with gentamicin for synergistic activity in severe cases.
  • Staphylococcus aureus: Methicillin-sensitive strains (MSSA) respond to nafcillin, oxacillin, or cefazolin. Methicillin-resistant strains (MRSA) require vancomycin or daptomycin.
  • Enterococci: usually managed with combination therapy such as ampicillin plus gentamicin or ampicillin plus ceftriaxone for synergistic killing.
  • HACEK organisms: typically treated with ceftriaxone or fluoroquinolones like ciprofloxacin.

Fungal endocarditis, although rare, is difficult to treat and often life-threatening. Therapy generally includes high-dose antifungal agents such as amphotericin B, liposomal amphotericin B, or echinocandins (e.g., caspofungin, micafungin) in conjunction with early surgical intervention.

Surgical Interventions

Surgical management plays a pivotal role in endocarditis, especially in complicated or advanced cases. Approximately 50% of patients with infective endocarditis ultimately require surgery at some point during their treatment. Surgery is primarily used to remove infected material, restore functional valve structure, and prevent catastrophic complications such as heart failure or systemic embolization.

The most common surgical procedures include valve repair or valve replacement, depending on the extent of tissue destruction. Prosthetic valve endocarditis often requires replacement of the infected device, while native valves may sometimes be reconstructed if tissue damage is limited.

Indications for surgery include:

  • Heart failure resulting from severe valvular regurgitation or obstruction.
  • Persistent infection despite adequate antimicrobial therapy, evidenced by ongoing fevers, positive blood cultures, or enlarging vegetations.
  • Large vegetations (typically ≥10–15 mm) with high embolic risk, particularly after embolic events.
  • Paravalvular abscess, fistula formation, or other structural complications.
  • Prosthetic valve infection, especially when accompanied by dehiscence or regurgitation.

The timing of surgery is individualized but may range from emergent intervention in cases of cardiogenic shock to early surgery within days for severe valvular dysfunction or uncontrolled infection.

Supportive Care

Cardiovascular support focuses on optimizing heart function. This may involve diuretics for fluid overload, vasodilators to reduce afterload, or inotropic agents in cases of severe heart failure. Patients with arrhythmias or conduction defects may require temporary or permanent pacemaker placement.

Anticoagulation management is approached cautiously. While some patients with prosthetic valves require anticoagulation, its use may increase the risk of hemorrhagic stroke, especially in those with cerebral emboli or mycotic aneurysms. Decisions are individualized based on risk-benefit assessment.

Monitoring for embolic events, including neurological assessments, abdominal examinations, and respiratory evaluations, is essential due to the ongoing risk during early treatment. Serial echocardiography helps assess vegetation size, valve function, and response to therapy.

Nutritional support becomes important for patients with significant weight loss, reduced appetite, or increased metabolic demands. In severe cases, dietitian-guided supplementation is recommended.

Management of comorbid conditions, such as diabetes, chronic kidney disease, or immunosuppressive states, is also crucial because these factors influence prognosis and susceptibility to complications.

Complications

Endocarditis can lead to several serious complications affecting the heart and other organs. These complications often result from infection damage or emboli traveling through the bloodstream. 

Heart Failure

Heart failure is not only the most common but also the most dangerous cardiac complication of infective endocarditis, occurring in up to 50–60% of patients. It results primarily from structural damage to the cardiac valves, which interferes with their ability to maintain unidirectional blood flow. When vegetations enlarge or infection erodes the valve leaflets, the result is acute or worsening regurgitation. This sudden increase in volume load on the heart, especially the left ventricle, precipitates pulmonary congestion, shortness of breath, orthopnea, and reduced exercise tolerance.

The severity of valve damage depends on the causative organism. Virulent pathogens such as S. aureus or Streptococcus pneumoniae can destroy valve tissue within days, leading to rapid hemodynamic collapse. In contrast, infections caused by viridans streptococci may progress more slowly. Mechanical obstruction can also occur when bulky vegetations impede proper valve opening, further reducing cardiac output.

Over time, chronic regurgitation causes dilation of the cardiac chambers, thickening of the ventricular walls, and eventual systolic dysfunction. If left untreated, acute heart failure associated with endocarditis is frequently fatal. Surgical intervention is often required, particularly for severe aortic or mitral regurgitation, uncontrolled infection, or recurrent embolization. In many cases, valve replacement is the only means of restoring functional hemodynamics.

Systemic Embolization

Systemic embolization is another major and potentially devastating complication, occurring in approximately 20–50% of endocarditis cases. It arises when fragments of vegetations detach from infected valves and travel through the bloodstream. The embolization risk is highest in the first two weeks of antimicrobial therapy, especially when vegetations are large (≥10 mm), mobile, or caused by aggressive organisms such as S. aureus or Candida species.

Cerebral embolization is the most common manifestation, accounting for nearly 65% of embolic events. It can result in ischemic stroke, intracerebral hemorrhage, brain abscess, or meningitis. Patients may present with sudden neurological deficits such as weakness, aphasia, visual disturbances, or altered consciousness.

Emboli traveling to the spleen can cause splenic infarcts or abscesses, presenting with left upper quadrant abdominal pain, fever, and leukocytosis. Renal embolization may manifest as flank pain, hematuria, renal infarction, or acute kidney injury. In right-sided endocarditis, typically associated with intravenous drug use, emboli travel to the lungs, causing septic pulmonary emboli that lead to pleuritic chest pain, hemoptysis, and cavitary lung lesions visible on imaging.

Despite effective antibiotic therapy, the risk of embolization does not fully disappear until vegetations stabilize or shrink. In cases of persistent large vegetations or recurrent embolic events, surgical removal of infected valve tissue becomes necessary to prevent further systemic complications.

Paravalvular Abscess

Paravalvular abscess occurs when infection extends beyond the valve leaflets into the surrounding annular or myocardial tissue. This complication is particularly common in aortic valve endocarditis and prosthetic valve infections, occurring in approximately 10–40% of such cases. The abscess cavity forms as pus accumulates in the infected tissues, weakening structural integrity and interfering with both mechanical and electrical function of the heart.

Clinically, paravalvular abscess may present with persistent fever despite antibiotic therapy, new conduction abnormalities, or worsening heart failure. One of the hallmark signs is atrioventricular (AV) block, which occurs when the infection erodes tissue near the conduction pathways, an especially characteristic finding in aortic root abscesses. Progression may lead to complete heart block requiring immediate temporary or permanent pacemaker insertion.

Diagnostic tools such as transesophageal echocardiography (TEE) are crucial for early detection, as transthoracic echocardiography often misses these lesions. In some cases, cardiac CT or MRI may be required to fully delineate the extent of infection.

Paravalvular abscesses rarely respond fully to antibiotics alone due to poor drug penetration and a high microbial burden within the necrotic tissue. Therefore, surgical debridement and valve replacement are generally indicated. Without timely intervention, abscesses can rupture, leading to fistula formation, severe valvular insufficiency, or fatal cardiac tamponade.

Additional Complications

While heart failure, embolization, and abscess formation are the most common, several other serious complications deserve emphasis due to their clinical significance:

Conduction Abnormalities

Damage to the conduction pathways can lead to arrhythmias such as:

  • atrioventricular blocks
  • bundle branch blocks
  • atrial fibrillation (often secondary to atrial dilation)

These abnormalities can precipitate syncope, hemodynamic instability, or sudden cardiac death.

Mycotic Aneurysms

These arise when infected emboli lodge in arterial walls, causing localized weakening and aneurysm formation. They may occur in cerebral, mesenteric, or peripheral arteries. A ruptured mycotic aneurysm can cause catastrophic hemorrhage or stroke.

Metastatic Infections

Septic emboli can seed distant tissues, leading to:

  • spinal epidural abscess
  • vertebral osteomyelitis
  • septic arthritis
  • liver abscess

These manifestations often complicate the clinical picture and require prolonged therapy or surgical drainage.

Renal Complications

Renal dysfunction in endocarditis may arise from:

  • embolic infarction
  • immune complex–mediated glomerulonephritis
  • antibiotic toxicity
  • septic shock–induced acute tubular necrosis

Hematuria, proteinuria, or progressive renal insufficiency may occur over time.

Septic Shock

In aggressive infections, the overwhelming inflammatory response may induce septic shock, characterized by hypotension, multi-organ dysfunction, and the need for vasopressor support.