Infective Endocarditis
1. Osmonova Gulnaz Zhenishbaevna
2. Adeel
3. Marif Ali
(1. Teacher, International Medical Faculty, Osh State University, Osh, Kyrgyz Republic.
2. Student, International Medical Faculty, Osh State University, Osh, Kyrgyz Republic.
3. Student, International Medical Faculty, Osh State University, Osh, Kyrgyz Republic.)
Abstract
Infective endocarditis (IE) is an infectious inflammation of the endocardium and is a rare but highly morbid disease with a high mortality rate. Fever is the predominant clinical manifestation of the disease. The most common risk factors in pediatric patients are congenital heart disease and cardiac manipulation. Patients with IE with previously normal cardiac strucstures have increased in recent years. The dominant pathogen of IE is gram-positive cocci, the most common of which are Staphylococcus aureus and Streptococcus viridans. The gold standard for the diagnosis of IE is the modified Duke criteria, which are based on clinical manifestations and laboratory tests. In recent years, the applications of new methods have also helped a lot in the early diagnosis and treatment of IE. The safety and efficacy of early surgery have been confirmed. At present, the prevention strategy of IE is antibiotic prophylaxis that is only for high-risk patients, and the specific plan and the effect of prevention are still debatable and need further validation.
Keywords: Infective Endocarditis, Diagnosis, Treatment, Prevention
1. Introduction
Infective endocarditis (IE) refers to infectious inflammation of the heart valves, heart, or great-vessel endocardium, commonly caused by bacteria, fungi, or rickettsiae. Clinical manifestations frequently include fever (89 %), hepatosplenomegaly, changing heart murmurs, and skin petechiae or purpura; common complications are heart failure (45 %) and vascular embolism (22 %). The annual incidence of IE in children is approximately 3–10 per 100 000, with similar rates in boys and girls and an overall mortality of 15 %–30 %. It is a relatively uncommon but life-threatening disease. Because of the lack of high-level evidence, IE management still relies mainly on expert consensus. This review discusses recent advances in the pathogenesis, diagnosis, treatment, and prevention of IE.
2. Pathogenesis
The major risk factor for IE in children is congenital heart disease. Certain types of congenital heart disease create turbulent blood flow that damages endothelial cells, promoting deposition of platelets and fibrin and leading to nonbacterial thrombotic endocarditis (NBTE). The congenital heart defects most prone to IE are ventricular septal defect, tetralogy of Fallot, and patent ductus arteriosus, whereas patent foramen ovale or mild pulmonary artery branch stenosis does not increase risk. Other risk factors include cardiac surgery, intracardiac devices (pacemakers, prosthetic valves), and prolonged central venous catheter use. Li et al. showed that children with congenital heart disease have a significantly elevated IE risk within 6 months after central venous catheter placement, cardiac catheterization, open-heart surgery, valve surgery, or shunt procedures.
After NBTE forms, bacteria introduced by transient bacteremia during invasive procedures adhere to the thrombus or normal endocardium, proliferate, and form vegetations, causing valve destruction, perivalvular abscess, or pseudoaneurysm. In addition, most IE patients have high levels of circulating immune complexes and rheumatoid factor, together with immunologic phenomena such as Osler nodes, Roth spots, and glomerulonephritis, indicating that the immune response triggered by the pathogen also plays an important role.
In recent years the proportion of IE in children without underlying heart disease has risen (12 %–26 %); most cases occur in premature infants or those with chronic illness. Compared with children who have congenital heart disease, symptom-to-diagnosis time is markedly longer (18 days vs. 31 days), and these patients are more likely to require surgery. Therefore, prolonged unexplained fever, anemia, or new heart murmur in previously healthy children should prompt heightened suspicion for IE and prompt investigation.
3. Etiology
The predominant pathogens in pediatric IE are gram-positive cocci, including viridans group streptococci (e.g., Streptococcus sanguinis, S. mitis group, mutans group), staphylococci (Staphylococcus aureus, coagulase-negative staphylococci), β-hemolytic streptococci, and enterococci. A global systematic review of 105 studies encompassing 33 214 IE cases across all ages found S. aureus to be the most common organism (45.4 % of cases); in pediatric cohorts the order was S. aureus, viridans streptococci, coagulase-negative staphylococci, Candida, and enterococci. U.S. data from 2000–2010 showed staphylococci in 43.1 % and streptococci in 39.5 %. Similar Chinese data indicate gram-positive cocci in 87 % of cases (S. aureus 31 %, viridans streptococci 19 %), gram-negative bacteria 9 %, and fungi 5 %.
Viridans streptococci predominate in patients with underlying heart disease (32.7 %), whereas in infants and children with normal cardiac structures IE is most often caused by S. aureus, frequently involving the aortic and mitral valves. S. aureus causes more destructive valve damage than viridans streptococci and therefore has a higher surgical requirement. The increase in S. aureus IE is attributed to improved survival of complex congenital heart disease patients after corrective surgery, widespread use of new intracardiac materials, and rising numbers of transcatheter procedures.
Fungal endocarditis is far less common (≈1.1 % of IE) but carries high mortality, predominantly affecting infants. Risk factors include prematurity, congenital heart disease, central venous catheters, total parenteral nutrition, prolonged broad-spectrum antibiotics, and use of vascular patches during congenital heart surgery.
4. Diagnostic Methods
Diagnosis of IE relies on clinical features and laboratory findings. The gold standard remains the modified Duke criteria (2 major or 1 major + 3 minor or 5 minor criteria), which offer good specificity and sensitivity.
Major criteria
A. Positive blood culture: (1) Two separate cultures positive for typical IE organisms (viridans streptococci, HACEK group, S. aureus, community-acquired enterococci); (2) persistently positive cultures (≥2 cultures >12 h apart, or majority of ≥3–4 cultures with first and last drawn ≥1 h apart, or single Coxiella burnetii culture or phase-1 IgG titer >1:800).
B. Evidence of endocardial involvement: (1) Positive echocardiography showing vegetation, abscess, or new partial dehiscence of prosthetic valve; (2) new valvular regurgitation.
Minor criteria
Predisposing heart condition or intravenous drug use; 2. Fever ≥38.0 °C; 3. Vascular phenomena (major arterial emboli, septic pulmonary infarcts, intracranial hemorrhage, conjunctival hemorrhages, Janeway lesions); 4. Immunologic phenomena (glomerulonephritis, Osler nodes, Roth spots, positive rheumatoid factor); 5. Microbiologic evidence not meeting major criteria or serologic evidence of active infection.
5. Auxiliary Examinations
5.1 Etiologic Examination
5.1.1 Traditional culture techniques (blood culture, excised tissue culture)
Repeated blood cultures are essential. In children with unexplained fever and pathologic murmurs or a history of heart disease/endocarditis, three sets from different sites should be drawn on day 1; if negative, 2–3 additional sets on day 2. For subacute culture-negative cases, antibiotics may be withheld 48 h (if clinically safe) before repeat cultures. In acute cases, two sets are drawn immediately, followed by a third at least 1 h later, and empiric therapy started. Culture of surgically excised vegetations or valves can identify the pathogen even after preoperative antibiotics, as organisms may persist in infected tissue for weeks.
5.1.2 Molecular and proteomic techniques (blood pathogen metagenomic detection, excised-tissue gene detection)
These methods are minimally affected by prior antibiotics and offer rapid, sensitive, high-throughput detection. Specific real-time PCR and proteomic assays can identify species and resistance genes (e.g., mecA in MRSA). They are particularly useful for culture-negative, slow-growing, or surgically indicated IE and guide postoperative therapy. A systematic review by Reza et al. found PCR and qPCR on blood or excised tissue yielded higher positivity rates than culture, with tissue PCR showing the best sensitivity and specificity. Blood-culture negativity rates vary widely (5 %–70 %) and are higher in developing countries. Direct blood or tissue PCR improves pathogen detection and is an effective strategy for early etiology confirmation.
5.2 Imaging
Echocardiography is central to diagnosis and management; additional modalities such as multislice computed tomography (MSCT) and ¹⁸F-FDG PET-CT can further increase detection rates.
5.2.1 Transthoracic echocardiography (TTE
Inexpensive, rapid, and non-invasive; it quickly identifies vegetations and complications and is usually sufficient for most cases.
5.2.2 Transesophageal echocardiography (TEE)
Vegetation detection rate approaches 90 %. TEE is markedly superior to TTE for prosthetic-valve infection, perivalvular abscess, and fistulas and is preferred for aortic-root abscess, prosthetic-valve IE, chest-wall deformity, or obesity.
5.2.3 MSCT
Excellent for detecting cardiac abscesses or pseudoaneurysms and for delineating the extent of perivalvular extension; anatomic detail of pseudoaneurysms, abscesses, and fistulas is comparable to TEE. Contrast-enhanced MSCT also clearly demonstrates splenic or other distant abscesses.
5.2.4 Nuclear medicine imaging
¹⁸F-FDG PET-CT exploits increased metabolic activity in infectious/inflammatory foci. It is valuable for suspected IE, especially with intracardiac devices, and can detect peripheral emboli and metastatic infection.
6. Treatment
Antibiotic and surgical therapy are the cornerstones of IE management and determine prognosis. Both the 2014 AHA and 2015 ESC guidelines recommend a multidisciplinary “Endocarditis Team” including cardiologists, infectious-disease specialists, cardiac surgeons, neurologists, microbiologists, intensivists, and support from echocardiography, radiology, and anesthesiology.
6.1 Antibiotic Therapy
Bactericidal rather than bacteriostatic agents are required. Organisms within vegetations and biofilms grow slowly and are tolerant to antibiotics, necessitating prolonged therapy. Principles are early initiation, full dose, adequate duration, and pathogen-specific bactericidal drugs. Combination intravenous therapy is generally superior to monotherapy for synergy and to reduce resistance. Recommended duration is at least 4 weeks, usually 4–6 weeks, depending on organism and presence of prosthetic material; serial blood cultures until negative help assess response.
The 2015 AHA pediatric IE guidelines tailor regimens to pathogen, prosthetic valve status, time since implantation, and catheter-related infection:
Staphylococci: oxacillin/nafcillin + rifampin (or vancomycin + rifampin for MRSA); add gentamicin for first 2 weeks if prosthetic valve.
Streptococci: penicillin G or ceftriaxone (most viridans/non-enterococcal); gentamicin + penicillin/ampicillin for enterococci.
Gram-negative enteric bacilli: third- or fourth-generation cephalosporin + aminoglycoside per susceptibility.
HACEK: ceftriaxone, cefotaxime, or ampicillin-sulbactam.
Fungi: surgical debridement + amphotericin B (± flucytosine); if inoperable, amphotericin B + fluconazole/itraconazole/voriconazole.
Culture-negative: ampicillin-sulbactam + gentamicin (± vancomycin) for native or late prosthetic valves; add rifampin for early prosthetic valves.
Recent adult studies have explored shorter hospitalizations (e.g., 2-week therapy for uncomplicated oral-streptococcal or methicillin-sensitive S. aureus IE, or early switch to high-bioavailability oral agents), which may inform future pediatric strategies.
6.2 Surgical Treatment
Vegetations promote further platelet/fibrin deposition, shielding bacteria from host defenses and reducing antibiotic efficacy once mature. Surgery is required to remove infected material. Reported surgical mortality is low (≈5 %), with excellent long-term survival (1-, 5-, and 25-year rates ≈98 %, 90 %, and 80 %) and low recurrence (95 % recurrence-free at 25 years), although reoperation rates reach 45 % at 25 years. Main risk factors for surgical death include age, prosthetic valve, coagulase-negative staphylococci, prolonged preoperative antibiotics, shock, and aortic-valve replacement.
Early surgery (during index admission or within 30 days of diagnosis) reduces in-hospital mortality, septic emboli, and recurrence and is now recommended. Optimal timing remains under study. Current indications (largely extrapolated from adult guidelines) include congestive heart failure, progressive valvular dysfunction, and embolic events.
7. Prevention
7.1 Antibiotic Prophylaxis
Owing to cost, adverse effects, and limited evidence, prophylaxis is now restricted to high-risk patients only (ESC recommendations):
Any prosthetic valve or prosthetic material used for valve repair;
Previous IE;
Unrepaired cyanotic congenital heart disease or repaired CHD with residual palliative shunts/conduits or other prosthetic material (first 6 months post-procedure).
The AHA additionally recommends prophylaxis for cardiac-transplant recipients who develop valvulopathy. All moderate- and high-risk patients should maintain excellent dental and skin hygiene regardless of prophylaxis.
7.1.1 Dental procedures
Prophylaxis is limited to high-risk patients undergoing gingival, periapical, or oral-mucosal perforation procedures. There is no strong evidence linking respiratory, gastrointestinal, genitourinary, or musculoskeletal procedures to IE, and routine antibiotic prophylaxis is not recommended except for clearly infected sites (e.g., abscess drainage). Patients with prior IE face higher risks of heart failure, valve replacement, and death if IE recurs, so prophylaxis is advised for dental work in this group.
7.1.2 Cardiac surgery
IE risk rises within 6 months after cardiac surgery or catheterization, especially shunt procedures, mainly because of prosthetic material. Perioperative antibiotic prophylaxis and meticulous postoperative care are important risk-reduction measures.
Because IE is rare yet potentially fatal and most pediatric cases have identifiable high-risk factors, continued research into optimal prophylaxis regimens and their effectiveness remains essential.
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