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Cimmino, G.; Bottino, R.; Formisano, T.; Orlandi, M.; Molinari, D.; Sperlongano, S.; Castaldo, P.; D’elia, S.; Carbone, A.; Palladino, A.; et al. Infective Endocarditis. Encyclopedia. Available online: https://encyclopedia.pub/entry/43256 (accessed on 20 December 2025).
Cimmino G, Bottino R, Formisano T, Orlandi M, Molinari D, Sperlongano S, et al. Infective Endocarditis. Encyclopedia. Available at: https://encyclopedia.pub/entry/43256. Accessed December 20, 2025.
Cimmino, Giovanni, Roberta Bottino, Tiziana Formisano, Massimiliano Orlandi, Daniele Molinari, Simona Sperlongano, Pasquale Castaldo, Saverio D’elia, Andreina Carbone, Alberto Palladino, et al. "Infective Endocarditis" Encyclopedia, https://encyclopedia.pub/entry/43256 (accessed December 20, 2025).
Cimmino, G., Bottino, R., Formisano, T., Orlandi, M., Molinari, D., Sperlongano, S., Castaldo, P., D’elia, S., Carbone, A., Palladino, A., Forte, L., Coppolino, F., Torella, M., & Coppola, N. (2023, April 19). Infective Endocarditis. In Encyclopedia. https://encyclopedia.pub/entry/43256
Cimmino, Giovanni, et al. "Infective Endocarditis." Encyclopedia. Web. 19 April, 2023.
Infective Endocarditis
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This entry is adapted from the peer-reviewed paper 10.3390/life13020377

Infective endocarditis (IE) is a rare but potentially life-threatening disease, sometimes with longstanding sequels among surviving patients. The population at high risk of IE is represented by patients with underlying structural heart disease and/or intravascular prosthetic material. Taking into account the increasing number of intravascular and intracardiac procedures associated with device implantation, the number of patients at risk is growing too. If bacteremia develops, infected vegetation on the native/prosthetic valve or any intracardiac/intravascular device may occur as the final result of invading microorganisms/host immune system interaction. In the case of IE suspicion, all efforts must be focused on the diagnosis as IE can spread to almost any organ in the body. Unfortunately, the diagnosis of IE might be difficult and require a combination of clinical examination, microbiological assessment and echocardiographic evaluation. There is a need of novel microbiological and imaging techniques, especially in cases of blood culture-negative.

infection antibiotics imaging technique infective endocarditis

1. Introduction

Infective endocarditis (IE) is a rare disease involving the endocardial surface and mainly the heart valves. However, it should be considered a systemic disease, involving multiple organs such as the brain, lung, vertebral column and spleen, and the embolic phenomena might be the symptoms of the disease at presentation. Despite the availability of broad-spectrum antibiotics and the diffusion of more accurate diagnostic techniques, such as transoesophageal echocardiography and positron emission tomography, the mortality rate of IE still remains high at up to 18–25% in the first 3 months [1].

2. Epidemiological Impact

The incidence of IE is estimated to be around 3–7/100,000 person-years, which has apparently been increasing over the last decades [2]. The in-hospital mortality rate is high, ranging from 14 to 22% [3][4], with a high incidence of per year mortality (up to 15–30%) [2] and a five-year survival rate, similar or even worse, than some cancers [2][5]. Even if the incidence is higher in men (with a male/female ratio ≥ 2:1), females have a worse prognosis and apparently undergo valve repair less frequently [6][7]. The increasing incidence of IE in the last 30 years, in the absence of improvement in outcomes and mortality, makes it a disease with a high impact on public health resources in terms of hospitalization and treatment costs [8].
Rheumatic and congenital valvular heart diseases have been the most important risk factors for endocarditis development, especially in young patients [9]. In developed countries, the epidemiology of IE has undergone significant changes, with emerging risk factors such as the presence of intracardiac devices (defibrillators and pacemakers mainly) and degenerative valvular disease, thus shifting the incidence of IE towards an older age (≥65 years old) [10][11].
Moreover, the last opioid epidemic has considerably affected the current epidemiology of IE in developed countries, especially in the USA, where there is an increased incidence of tricuspid valve endocarditis due to injection drug use, mainly affecting women and young people [12][13][14][15].

3. Microbiological Burden of Infective Endocarditis

3.1. Cardiac Device Related-Infective Endocarditis

CIED-IE are characterized by a significant prevalence of staphylococcal infections, accounting for up to 65%. Compared to the past, there is a decline in coagulase-negative staphylococcus infections (27%), with the emergence of S. Aureus as the primary cause of CIED-IE (38%). The frequent infectious agents are other gram-positive cocci at 21% (mainly streptococci 12% and enterococci 5%) [16][17].

3.2. Prosthetic Valve Endocarditis

Staphylococci (32%), streptococci (25%) and enterococci (16%) are the main causes of prosthetic valve endocarditis (PVE). Transcatheter aortic valve implantation (TAVI) deserves a separate mention as the main isolated infectious agent is Enterococcus spp. (25–30%), especially for early or peri-procedural infections (30–35%) [18][19][20][21].

3.3. Right-Sided Infective Endocarditis

Right-sided IE accounts for 5 to 10% of all endocarditis cases. Compared with left-sided IE, it is more frequently associated with intravenous drug use, intracardiac devices and central venous catheters. Staphylococcus aureus is the predominant infectious agent (60–90% of cases). Streptococcal and coagulase-negative staphylococcal infections are also frequent causes of right-sided IE. A higher prevalence of Pseudomonas aeruginosa and other Gram-negative bacteria is described in right-sided IE [22].

3.4. Immunosuppressive Therapy in Solid Organ Transplantation

The spectrum of organisms causing IE is quite different in transplant recipients compared to the general population. Fifty percent of the infections were due to Aspergillus fumigatus (17%) or Staphylococcus aureus (30%), while the prevalence of viridans streptococci infections was lower (4%) than IE in immunocompetent patients. The Enterococcus species (11%) and Candida species (6%) represent other common agents. Fungal infections accounted for the most frequent etiologic agent within 30 days of transplantation (60%), while bacterial infections caused the majority of cases (80%) after this period [23][24][25][26].

4. Diagnosis of Endocarditis

The diagnosis of IE is based on clinical manifestations, the identification of the infective pathogen by blood cultures or other microbiologic tests and the detection of valvular vegetations or the infection’s structural complications using cardiac imaging. The accepted criteria for IE’s diagnosis are the 2000 modified Duke’s criteria, which classify IE as definite, possible or rejected [27][28]. The modified Duke’s criteria were developed for the evaluation of patients with left-sided native valve IE, and their diagnostic accuracy is lower in patients with suspected right-sided native valve IE, prosthetic valve IE and pacemaker or defibrillator lead IE, for which echocardiography can be normal or inconclusive [29]. The sensitivity of the Duke’s criteria can be improved by other imaging modalities including MR, CT, PET/CT and SPECT/CT, aiming at evaluating cardiac involvement and embolic events. The choice of a particular diagnostic modality will be guided by local availability and expertise [30].
Electrocardiography and chest radiography should always be performed as part of the initial evaluation of patients with suspected IE. The presence of heart block or conduction delay at baseline electrocardiography may be indicative of paravalvular extension of the infection. Moreover, the finding of myocardial ischemia may suggest the occurrence of septic emboli in the coronary arteries. Chest radiography may show the presence of septic pulmonary emboli or potential alternative causes of fever and systemic symptoms [30].

4.1. Left-Sided Native Valve Endocarditis

IE of the left-sided native valve should be suspected in patients with relevant cardiac risk factors (e.g., pre-existing valvular or congenital heart disease), prior IE and other predisposing conditions, including intravenous drug use, immunosuppression, recent dental or surgical procedure, an indwelling cardiac device or intravenous catheter. Positive blood cultures, clinical features and echocardiographic findings remain the cornerstones for left-sided native valve IE’s diagnosis. At least three sets of blood cultures should be obtained at 30 min intervals from separate venipuncture sites before starting antibiotic therapy [31][32]. Each set consists of one aerobic and one anaerobic bottle, each of which contains a volume of blood of 10 mL. Samples from peripheral veins using a meticulous sterile technique are preferred over central venous catheter due to the risk of contamination. As bacteremia is usually continuous in patients affected by IE, blood cultures can be collected at any time and not necessarily when fever or chills occur. Blood culture results should be interpreted according to the modified Duke’s criteria. Most clinically significant bacteremias are usually detected within 48 h; the pathogen members of the HACEK group can be identified after 5 days of incubation with modern detection systems [33]. Occasionally, false-positive blood cultures can occur, due to the presence of contaminants. Contamination likelihood is reduced when the microorganism is found in multiple blood cultures obtained from different venipuncture sites [34].

Echocardiography, either TTE or TOE, is the mainstay of cardiac imaging for IE diagnosis, and it must be performed as soon as IE is suspected [35]. It is considered positive for IE in the presence of vegetations and/or structural complications, including abscesses, leaflet perforation, aortic pseudoaneurysm and intracardiac fistula. Echocardiography is also useful to evaluate any associated mitral or aortic valve dysfunction and the underlying left ventricular function. Generally, TTE is the first diagnostic tool in patients with suspected IE, with a high specificity (close to 100%) and modest sensitivity (about 75%) [35]. In particular, false-negatives may be found if vegetations are small or have embolized. Therefore, the absence of vegetations on TTE does not exclude IE diagnosis, although the finding of a valve with normal morphology and function greatly reduces its probability [36]. TOE sensitivity is higher than TTE in detecting both vegetations and cardiac complications; thus, in most cases, TOE follows TTE in the diagnostic workup of IE [37][38]. TOE becomes necessary when TTE is negative (or the transthoracic window is poor) but the clinical suspicion of IE is high, a valve vegetation is found with concern of intracardiac complications (e.g., new conduction delay due to paravalvular abscess), and vegetation is associated with significant valvular regurgitation to be quantified before surgery. Conventional TOE may be completed by 3D analysis, which provides a more precise estimate of the vegetation’s size with a better prediction of the embolic risk [39].

4.2. Right-Sided Endocarditis

Right-sided IE should be suspected in the presence of injection drug use, CIED (in which infection usually spreads from the pocket to the insertion leads), other intravascular devices, such as a central line, intra-aortic balloon pump or ventricular assist device, and underlying right-sided cardiac anomaly. Modified Duke’s criteria diagnostic sensibility for right-sided/CIED-IE is lower, as audible murmurs, peripheral emboli and immunologic and vascular phenomena are usually absent [29]. However, intravenous drug use and septic pulmonary emboli, which fall within the minor criteria, are important clues for right-sided IE.

4.3. Prosthetic Valve Endocarditis

The diagnosis of prosthetic valve IE should be suspected in patients with history of valve replacement and positive blood cultures and/or evocative symptoms and/or new prosthetic valve dysfunction, particularly paravalvular regurgitation.
TTE is often the initial imaging test. However, TOE has higher sensitivity than TEE for detection of both the vegetation and paravalvular extension of infection, including abscess, fistula, leaflet perforation, pseudoaneurysm and paraprosthetic leak. Therefore, TOE should always be performed in patients with prosthetic valves and suspicion of IE. Even when a complete echocardiographic evaluation is performed, modified Duke’s criteria sensitivity remains lower for prosthetic than native valves. Therefore, when IE diagnosis is not definitely based on the modified Duke’s criteria but the clinical suspicion is strong, echocardiography should be repeated after 5–7 days.

5. Infective Endocarditis Treatment: A Gray Scale of Evidence

5.1. Antibiotic Therapy: General Principles

Bactericidal regimens are more effective than bacteriostatic therapy as host defenses are of little help [40][41]. The association of aminoglycosides (inhibitor of proteic synthesis) with cell-wall inhibitors is no longer recommended in staphylococcal native valve endocarditis (NVE) because of its undemonstrated clinical benefits and increased renal toxicity [42]. Aminoglycosides are still recommended for harder infections (i.e., staphylococcal PVE), given in a single daily dose to reduce nephrotoxicity [43], even if a recent meta-analysis highlights the paucity of clinical data to support this treatment regimen and suggests a downgrade of the indication due to the lack of benefit and the demonstrated nephron- and hepato-toxicity of adjunctive gentamicin or rifampin in staphylococcal PVE [44]. Treatment of NVE should last 2–6 weeks. PVE needs prolonged therapy (6 weeks) due to the antibiotic tolerance of the bacteria present in vegetation and biofilms. Bactericidal drug combinations are preferred to monotherapy against tolerant organisms. In NVE that needs a valve replacement during antibiotic therapy, the postoperative antibiotic regimen should be the same one recommended for NVE and not for PVE. Rifampin should be used only in foreign body infections, such as PVE, after 3–5 days of effective antibiotic therapy once the bacteremia has been cleared. In HACEK-related species, third-generation cephalosporins and quinolones are suggested as some HACEK group bacilli are beta-lactamases producers [45].

5.2. Empirical Therapy

Empirical therapy should be started as soon as possible after collecting at least three sets of blood cultures. The choice of the antibiotics depends on the kind of valve affected (native or prosthetic), the time from surgery in the case of prosthetic valves (early or late), the place of infection (community, nosocomial or non-nosocomial healthcare-associated IE) and, in the case of non-community IE, the local prevalence of multidrug-resistant microorganisms. NVE and late PVE regimens should cover staphylococci, streptococci and enterococci. Early PVE or healthcare-associated IE regimens should cover methicillin-resistant staphylococci, enterococci and, ideally, non-HACEK Gram-negative pathogens.

5.3. Cardiac Device-Related IE

Cardiac device-related IE (CDR-IE) is an infection that involves electrode leads, cardiac valve leaflets or the endocardial surface. It is distinct from local device infection which is limited to the pocket of the cardiac device [46]. CDR-IE must be treated using prolonged antibiotic therapy and complete hardware removal, preferably by transvenous lead extraction [46]. Most CDR-IE infections are secondary to staphylococcal species (often methicillin-resistant) [47] so empirical therapy should include vancomycin. Daptomycin, approved for right-side IE and bacteremia attributable to S. aureus [48], is a valid molecule to treat CDR-IE [49].

5.4. Surgical Treatment

Surgery is necessary in up to 50% of patients with IE [50][51]. Most patients do not undergo surgery because the prohibitive surgical risk due to comorbidities, age or IE complications or, in a minor percentage of cases, the infection heals with medical therapy alone [52]. The ESC/AHA/AACT guidelines give recommendations on surgery with a level of evidence B (or C) [2][53][54], given the lack of evidence due to the ethical issue of patient selection in randomized trials. The aim of a surgical procedure is the removal of the infected or damaged valve tissue, the cleansing of any abscesses and the repair of a fistula or false aneurysm. If possible, the valve is spared; otherwise, it is replaced with a biological or mechanical prosthesis.

6. Prophylaxis

Prophylaxis is recommended in patients considered at a high risk of IE [55], who undergo dental procedures requiring manipulation of the gingival or periapical region of the teeth or perforation of the oral mucosa. Patients considered at the highest risk of IE are patients with a prosthetic valve/prosthetic material used for valve repair [56], patients with previous IE [57] and patients with untreated cyanotic congenital heart disease and those with CHD who have postoperative palliative shunts, conduits or other prostheses [58][59]. After surgical repair with no residual defects, LGs recommend prophylaxis for the first 6 months after the procedure [58][60].

7. Conclusions

Infective endocarditis is an evolving disease also because of the growth in mini-invasive cardiac procedures in the last few years. An up-to-date management should require (1) a preventive strategy to reduce the burden of morbidity and mortality especially in high risk patients; (2) improved diagnoses with early echocardiographic evaluation, rapid microbiological results and advanced imaging techniques when required; and (3) optimal therapeutical strategies based on the Endocarditis Team’s discussion, early risk stratification, tailored antibiotic therapy, early surgery if indicated and the management of complications.

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Subjects: Cardiac & Cardiovascular Systems
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register : Giovanni Cimmino , Roberta Bottino , Tiziana Formisano ,
Massimiliano Orlandi
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Daniele Molinari
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Simona Sperlongano
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Pasquale Castaldo
, Saverio D’Elia , Andreina Carbone ,
Alberto Palladino
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Lavinia Forte
, Francesco Coppolino ,
Michele Torella
, Nicola Coppola
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Update Date: 21 Apr 2023
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