1. Infective Endocarditis

2. DR ALIREZA AHMADI Assistant Professor of Medical University of Isfahan

3.  Infective endocarditis (IE) is an infection of the endocardium and/or heart valves that involves thrombus formation (vegetation), which may damage the endocardial tissue and/or valves.  Although uncommon in children, it is important to identify and treat IE because of its significant morbidity and mortality.  Prompt diagnosis, rapid treatment, and recognition of complications are imperative for optimal patient outcomes.

5.  The incidence of endocarditis is approximately 1 case per 1000 pediatric hospital admissions.  In a review of several published studies between 1986 and 1995, the estimated incidence in children was 0.3 per 100,000 children per year with a mortality of 11.6%  The distribution of etiologies has shifted. Rheumatic heart disease, which was once common, is now a rare cause of endocarditis. Rheumatic heart disease

6.  In contrast, the advent of sophisticated cardiac procedures and  Early intervention has led to an increase in the incidence of endocarditis in children with congenital heart disease.

7.  Preexisting cardiac abnormalities are found in approximately 75-90% of children with bacterial endocarditis.  Endocarditis is rare in infancy;  in this age group,it usually follows  open heart surgery or is associated with a central venous line.

8.  The overall mortality rate for endocarditis in pediatric patients is approximately 16-25%.  Improved general health care,  improved dental care,  early treatment, and  antibiotic prophylaxis have decreased the mortality rate.  Mortality is mostly due to secondary congestive heart failure (CHF).

9.  Infective endocarditis can also occur in children without any abnormal valves or cardiac malformations.  Patients with congenital heart lesions where there is turbulent blood flow due to a hole or stenotic orifice, especially if there is a high pressure gradient across the defect, are most susceptible to endocarditis.

11.  This turbulent flow traumatizes the vascular  endothelium, creating a substrate for deposition of fibrin and platelets, leading to the formation of a nonbacterial thrombotic embolus (NBTE) that is thought to be the initiating lesion for infective endocarditis.  The development of transient bacteremia then colonizes this NBTE or biofilm, leading to proliferation of bacteria within the lesion.

13.  Given the heavy colonization of mucosal surfaces (the oropharynx, or gastrointestinal, vaginal, or urinary tracts) by potentially pathogenic bacteria, these surfaces are thought to be the origin of this transient bacteremia.

16.  Transient bacteremia has been reported  to occur in 20-68% of patients after tooth brushing.  Maintenance of good oral hygiene may be a more important factor in decreasing the frequency and magnitude of bacteremia.

17.  prosthetic cardiac valves or other  prosthetic material used for cardiac valve repair,  unrepaired cyanotic CHD (including those palliated with shunts and conduits),  completely repaired defects with prosthetic material or device during the 1st 6 mo after repair, * repaired CHD with residual defects at or adjacent to the site of a prosthetic patch

18.  previous infective endocarditis.  Patients with high velocity blood flow lesions such as ventricular septal defects and aortic stenosis are also at high risk.  In older patients, congenital bicuspid aortic valves and mitral valve prolapse with regurgitation pose additional risks for  endocarditis.

19.  Surgical correction of CHD may reduce but does not eliminate the risk of endocarditis, with the exception of repair of a simple atrial septal defect or patent ductus arteriosus without prosthetic material.

20.  High risk 1. Prosthetic valves 2. Previous episode of endocarditis 3. Complex cyanotic CHD(e.g., single ventricle,TGA,TOF) 4. Surgically constructed systemic artery“to“pulmonary artery shunts 5. Injection drug use 6. Indwelling central venous catheters

21.  Moderate risk Uncorrected PDA Uncorrected VSD Uncorrected ASD (other than secundum) Bicuspid aortic valve MVP with regurgitation Rheumatic mitral or aortic valve disease Other acquired valvar diseases Hypertrophic cardiomyopathy

22.  In ",30% of patients with infective endocarditis, a predisposing factor is presumably recognized.  Although a preceding dental procedure may be identified in 10-20% of patients, the time of the procedure may range from 1 to 6 mo prior to the onset of symptoms.  Primary bacteremia with Staphylococcus aureus is thought to be another risk for endocarditis.

23.  Viridans-type streptococci (a-hemolytic streptococci) and  Staphylococcus aureus remain the leading causative agents for endocarditis in pediatric patients.  Other organisms cause endocarditis less frequently and,  in =6% of cases, blood cultures are negative for any organisms.

24.  No relationship exists between the infecting organism and the type of congenital defect,  the duration of illness, or  the age of the child.  Staphylococcal endocarditis is more common in patients with no underlying heart disease;

25.  viridans group streptococcal infection is more common after dental procedures;  group D enterococci are seen more often after lower bowel or genitourinary manipulation;  Pseudomonas aeruginosa  or Serratia marcescens is seen more frequently in intravenous drug users;

26.  fungal organisms are encountered after open heart surgery.  Coagulase-negative staphylococci are common in the presence of an indwelling central venous catheter.

27.  COMMON: NATIVE VALVE OR OTHER CARDIAC LESIONS  Viridans group streptococci (Streptococcus mutans, Streptococcus sanguinis,  Streptococcus mitis)  Staphylococcus aureus  Group D streptococcus (enterococcus) (Streptococcus bovis, Streptococcus  Faecalis)

28.  Streptococcus pneumoniae  Haemophilus influenzae  Coagulase-negative staphylococci  Coxiella burnetii (Q fever)'  Neisseria gonorrhoeae  Brucella *  Chlamydia psittaci*  Chlamydia trachomatis*  Chlamydia pneumoniae*  Legionella*  Bartonella *

29.  Streptobacillus moniliformis*  Pasteurella multocida*  Campylobacter fetus  HACEKgroup includes Haemophilus species (H. paraphrophilus, H. parainfluenzae, H.  aphrophilus), Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella speciesCulture negative (6% of cases)

30.  Staphylococcus epidermidis  Staphylococcus aureus  Viridans group streptococcus  Pseudomonas aeruginosa  Serratia marcescens  Diphtheroids  Legionella species"  HACEK qroup'  Fungi

31.  Prior congenital or rheumatic heart disease  Preceding dental, urinary tract, or intestinal procedure  Intravenous drug use  Central venous catheter  Prosthetic heart valve

32.  Fever  Chills  Chest and abdominal pain  Arthralgia, myalgia  Dyspnea  Malaise, weakness  Night sweats  Weight loss  CNS manifestations (stroke, seizures, headache)

33.  Elevated temperature  Tachycardia  Embolic phenomena (Roth spots, petechiae, splinter nail bed hemorrhages, Osler  nodes, CNS or ocular lesions)  Janeway lesions  New or changing murmur

34.  Splenomegaly  Arthritis  Heart failure  Arrhythmias  Metastatic infection (arthritis, meningitis, mycotic arterial aneurysm, pericarditis,  abscesses, septic pulmonary emboli)  Clubbing

37.  Early manifestations are usually mild, especially when viridans group streptococci are the infecting organisms.  Prolonged fever without other manifestations (except, occasionally, weight loss) that persists for as long as several months may be the only  symptom.

38.  Alternatively, the onset may be acute and severe, with  high, intermittent fever and prostration.  The symptoms are often nonspecific and consist of low-grade fever with afternoon  elevations, fatigue, myalgia, arthralgia, headache, and,  chills, nausea, and vomiting.

39.  Symptoms NVE (%) (n = 60) PVE (%) (n = 30)  Fever 75 87  Weight loss 52 20  Skin lesions 51 47  New murmur 33 33  Splenomegaly 20 20

40.  New or changing heart murmurs are common, particularly with associated heart failure.  Splenomegaly and petechiae are relatively common.  Serious neurologic : embolic strokes, cerebral abscesses, mycotic aneurysms, and hemorrhage are most often associated with staphylococcal disease and may be late manifestations.

42.  Meningismus,  increased intracranial pressure,  altered sensorium,  and focal neurologic signs are manifestations of these complications.

43.  Myocardial abscesses may occur with staphylococcal disease and may damage the cardiac conducting system, causing  heart block, or  may rupture into the pericardium and produce purulent pericarditis. * Pulmonary and other systemic emboli are  infrequent, except with fungal disease

44.  Many of the classic skin findings develop late in the course of the disease; they are seldom seen in appropriately treated patients.  include Osler nodes (tender, pea-sized intradermal nodules in the pads of the fingers and toes),  Janeway lesions (painless small erythematous or hemorrhagic lesions on the palms and soles),  and splinter hemorrhages (linear lesions beneath the nails).  These lesions may represent vasculitis produced by circulating antigen-antibody complexes.

48.  Identification of infective endocarditis is most often based on  a high index of suspicion during evaluation of an infection in a  child with an underlying risk factor.

52.  Positive blood culture  Elevated erythrocyte sedimentation rate; may be low with heart or renal failure  Elevated C-reactive protein  Anemia  Leukocytosis

53.  Immune complexes  Hypergammaglobulinemia  Hypocomplementemia  Cryoglobulinemia  Rheumatoid factor  Hematuria  Renal failure: azotemia, high creatinine (glomerulonephritis

54.  The critical information for appropriate treatment of infective endocarditis is obtained from blood cultures.  Blood specimens for culture should be obtained as promptly as possible, even if the child feels well and has no other physical findings.  Three to five separate blood collections should be  obtained after careful preparation of the phlebotomy site.

55.  The timing of collections is not important because bacteremia can be expected to be relatively constant.  In 90% of cases of endocarditis, the causative agent is recovered from the 1st 2 blood cultures.  The laboratory should be notified that endocarditis is suspected so that, if necessary, the blood can be cultured on enriched media for longer than usual (>7 days) to detect nutritionally deficient and fastidious bacteria or fungi.

56.  Antimicrobial pretreatment of the patient reduces the yield of blood cultures to 50-60%.  Other specimens that may be cultured include scrapings from cutaneous lesions, urine, synovial fluid, abscesses, and, in the presence of manifestations of meningitis, cerebrospinal fluid.

57.  Serologic diagnosis or  PCR of resected valve tissues is necessary in patients with unusual or fastidious microorganisms.

59.  Chest radiograph: bilateral infiltrates, nodules, pleural effusions  Echocardiographic : valve vegetations, prosthetic valve dysfunction or leak, myocardial abscess, new-onset valve insufficiency

61.  The combination of transthoracic and transesophageal echo cardiography enhances the ability to diagnose endocarditis.  Two-dimensional echocardiography can identify the size, shape, location, and mobility of the lesion; when combined with Doppler studies, the  presence of valve dysfunction (regurgitation, obstruction) can be determined and its effect on left ventricular performance.

63.  Echo is helpful in predicting embolic complications, given that lesions >1 cm and fungating masses are at greatest risk for embolization. * The absence of vegetations does not exclude endocarditis, and vegetations are often not visualized in the early phases of the disease or in patients with complex congenital heart lesions.

64.  The Duke criteria help in the diagnosis of endocarditis.  Major criteria include:  (1) positive blood cultures  (2 separate cultures for a usual pathogen, 2 or more for less typical pathogens), and  (2) evidence of endocarditis on echocardiography (intracardiac mass on a valve or other site,  regurgitant flow near a prosthesis,  abscess,  partial dehiscence of prosthetic valves, or  new valve regurgitant flow).

65.  include predisposing conditions,  fever,  embolic-vascular signs,  immune complex phenomena  (glomerulonephritis, arthritis, rheumatoid factor, Osler  nodes, Roth spots),  a single positive blood culture or serologic evidence of infection, and  echo cardiographic signs not meeting the major criteria.

66.  Two major criteria, or  one major + three minor, or  five minor criteria suggest definite endocarditis.

67.  The following minor criteria are added to those above list:  the presence of newly diagnosed clubbing,  splenomegaly,  splinter hemorrhages, and  petechiae;  a high ESR;  a high CRP;  and the presence of central nonfeeding lines, peripheral lines,  and microscopic hematuria.

70.  Antibiotic therapy should be instituted immediately once a definitive diagnosis is made.  When virulent organisms are responsible, small delays may result in progressive endocardial damage and are associated with a greater likelihood of severe complications.

71.  Empirical therapy before the identifiable agent is recovered may  be initiated with vancomycin plus gentamicin in patients without a prosthetic valve and when there is a high risk of S. aureus  enterococcus or viridans streptococci (the 3 most common organisms).

72.  A total of 4-6 wk of treatment is usually recommended.  Depending on the clinical and laboratory responses, antibiotic therapy may require modification  and, in some instances, more prolonged treatment is required.

73.  With highly sensitive viridans group streptococcal infections,shortened regimens that include oral penicillin for some portion have been recommended.  In nonstaphylococcal disease, bacteremia  usually resolves in 24-48 hr, whereas fever resolves in 5-6 days with appropriate antibiotic therapy.  Resolution with staphylococcal disease takes longer.

74.  Surgical intervention for infective endocarditis is indicated for severe aortic or mitral valve involvement  with intractable heart failure.

79.  Oral Amoxicillin 2g,(50 mg/kg)

81. AgeFrequencyPercent < 2 years730% 2-6 years730% 7 -12 years520% 13-18 years520% Total24100%

83. FrequencyPercent Staph negative coagulase440% Staph aureus220% Hemophilus110% Ecoli110% Pesudomonas110% Fungal110% Total10100%

84. Thank you