2.  Inflammation of the endocardium  More commonly endocarditis is the infection of the heart valves by various microorganisms  can be classified as infective or noninfective endocarditis depending on whether a microorganism is the source of the problem or not.

3.  Endocarditis can be broken down into the following categories:  Native valve (acute and subacute) endocarditis  Prosthetic valve (early and late) endocarditis  Endocarditis related to intravenous drug use

4.  Acute bacterial endocarditis(ABE)  fulminating form  high fevers  systemic toxicity   virulent organisms, such as Staphylococcus aureus  If it is left untreated death can occur within few days to weeks.

5.  Subacute endocarditis (SBE)  indolent  less invasive organisms such as viridans streptococci  usually occurring in pre-existing vulvular heart disease  death can occur within 6 weeks to 3 months.

6.  Early prosthetic valve endocarditis  occurs within 60 days of valve implantation.  Staphylococci, gram-negative bacilli, and Candida species are the common infecting organisms.

7.  Late prosthetic valve endocarditis  occurs 60 days or more after valve implantation.  Alpha-hemolytic streptococci, enterococci, and staphylococci are the common causative organisms.

8.  Endocarditis related to intravenous drug use  commonly involves the tricuspid valve.  S. aureus is the most common causative organism

9.  US-incidence of IE is 1.4-4.2 cases per 100,000 people per year.  common in older adults.  The median age of onset is about 50 yrs.  The male or female ratio is approximately 2:1

10.  Increased mortality rates  increased age  infection involving the aortic valve  congestive heart failure  CNS complications, and underlying disease.  also vary with the infecting organism.

11.  Mortality rates in native valve disease range from 16-27%.  Mortality rates in patients with prosthetic valve infections are higher.  More than 50% of these infections occur within 2 months after surgery.

12.  Gram positive cocci predominate.  Streptococci or styphylococci cause 80% of IE on native valves.  Among the streptococci, alpha- haemolytic streptococci from the mouth cause most cases of SBE.  Others are gram negative aerobic bacilli, fungi, rickettsia, Chlamydia etc.

13.  Endothelial surface of the heart is damaged.  Platelet and fibrin deposited at the damaged site forming the nonbacterial thrombotic lesions(sterile lesions).  The vegetations of (NBTE) are friable masses, usually situated along the lines of valve closure.  They vary greately in size sometimes being rather large and causing infarctions when they embolize.

14.  attachment of microorganisms circulating in the bloodstream onto an endocardial surface especially NBTE.  bacteria multiply rapidly because the vegetation provides an ideal environment for the growth of microbial colonies.  Formation of an abscess is one of the most important complications of valvular infection  Developed by direct extention of valvular infection into the fibrous cardiac skeleton supporting the valves and it is mostly seen in case of ABE.

15.  Pathogenesis of early PVE  surgery may directly inoculate the valve with bacteria from patients skin or operating room personnel.  The recently placed nonendothelialized valve is more susceptible to bacterial colonization than native valves.  Bacteria also may colonize the new valve from contaminated bypass pumps, cannulas and pacemakers and from a nosocomial bacteremia subsequent with an intravascular catheter.

16. Symptoms of SBE  fever  chills  rigors  night sweats  general malaise  anorexia, fatigue, weight loss and weakness.  Headaches and musculoskeletal complaints, including myalgias, arthralgias and back pain are common

17.  Symptoms of ABE  hectic fevers and rigors leading to hospitalization within a few days.  Symptoms of cardiac failure may develop or worsen suddenly in either acute or subacute disease.  IE should be considered in any patient who presents with the classic triad of fever, anemia and murmur. Important physical signs of IE include heart failure, spleenomegaly, signs of embolization and peripheral signs

18.  One or more classic signs of infective endocarditis are found in as many as 50% of patients. They include the following:  Petechiae - Common but nonspecific finding  Splinter hemorrhages - Dark red linear lesions in the nail beds  Osler nodes - Tender subcutaneous nodules usually found on the distal pads of the digits  Janeway lesions – Hemorrhagic, painless plaques on the palms and soles  Roth spots - Retinal hemorrhages with small, clear centers; rare and observed in only 5% of patients.

19.  Laboratory abnormalities  Anemia (normocytic, normochromic) of chronic disease is common in subacute endocarditis  Leukocytosis is observed in acute endocarditis.  Thrombocytopenia  Elevated WBC count (ABE)

20.  Elevated ESR while not specific, is elevated in more than 90% of cases.  Proteinuria and microscopic hematuria are present in approximately 50% of cases  Elevated CRF

21.  BLOOD CULTURE  More than 90% of patients with IE have positive blood cultures.   Venous blood samples for these should be drawn several hours apart, before antibiotic therapy is started.  If the patient has ABE indicating that antibiotic therapy must be started immediately, the three sets should be drawn with short delay.

22.  ECHOCARDIOGRAPHY  It can detect vegetations, valve ring abscess, myocardial abscess etc  negative echocardiogram does not rule out IE.  This test is particularly indicated with culture- negative cases, such as in fungal endocarditis.  The disappearance or persistence of vegetations on echocardiograms during treatment are not reliable for the success or failure of antibiotic therapy but enlargement during therapy can indicate treatment failure.

23.  CHEST RADIOGRAPHY:  Provide more diagnostic information especially in a patient with right sided endocarditis.  Pulmonary embolic phenomena strongly suggest tricuspid disease.  ECG  Reveal heart block suggesting extension of the infection.

24.  CT SCANNING AND MRI:  This can reveal cerebritis, embolic infarction or hemorrhage in brain and infarcts or abscess formation in the spleen or other sites.  CARDIAC CATHETERIZATION  Indicated to determine the degree of valvular damage. It is especially useful when surgery is being considered or when antibiotic treatment seems to be failing.

25.  Duke Criteria  Definite Case of Endocarditis  Must have 2 major criteria or  1 major criteria & 3 minor criteria or 5 minor criteria  Possible Case of Endocarditis  Patient appears to have endocarditis but does not have the necessary number of major and minor criteria  Rejected Possibility of Endocarditis  While possibility considered initially an alternative diagnosis established or pathologic diagnosis not established

26.  Duke - Major Criteria  Positive blood culture  – Typical pathogen frequently associated with endocarditis  – Multiple positive cultures (75-100% of cultures positive)  – Positive cultures obtained throughout the day

27.  Evidence of endocardial involvement  --Echocardiogram positive  -- Vegetation present  -- Evidence of intra-cardiac abscess  -- Dehiscence of prosthetic valve  -- New evidence of valve regurgitation  Positive serology

28.  Duke - Minor Criteria  Fever >38 C (100.4 F)  predisposing heart disease  Positive Blood culture but not typical pathogen  Echo not meeting major criterion

29.  Immununological phenomena  --Glomerulonephritis, RF +ve, osler nodes, roth spots.  Vascular phenomena  – arterial emboli, Janeway lesion, septic pulmonary infarcts, intracranial hemorrhage

30.  Goals of the therapy  To relieve the signs and symptoms of the disease.  To decrease the morbidity and mortality associated with infection.  To eradicate the causative organism with minimal drug exposure  To provide cost effective antimicrobial therapy.  To prevent IE from occurring or recurring in high risk patients with appropriate prophylactic antimicrobials.

31.  N0N PHARMACOLOGIC TREATMENT  Surgery is an important adjunct in the management of endocarditis.  In most surgical cases, valvectomy and valve replacement are performed to remove infected tissue and to restore hemodynamic functions.  Persistent vegetations or an increase in the vegetation size after prolonged antibiotic treatment, valve dysfunction, perivalvular extention (eg: abscess) etc suggests surgery  It may also be considered in case of PVE endocarditis caused by resistant organisms ( eg: fungi or gram negative bacteria), or if there is persistent bacteremia.

32.  Penicillin G:  DOC for streptococcal infection.  Interferes with cell-wall mucopeptide synthesis of the microorganism.  Nafcillin :  Provides coverage for penicillinase-producing staphylococci.  Use to initiate therapy in any patient in whom a penicillin G–resistant staphylococcal infection is suspected.

33.  Gentamicin:  Offers synergistic benefit with penicillins in the treatment of gram-positive cocci.  Vancomycin:  Used for penicillin-resistant streptococci, methicillin-resistant staphylococci (eg, S epidermidis ), and enterococci. Potent antibiotic directed against gram-positive organisms and is active against enterococci.

34.  Rifampin:  Used synergistically in the treatment of staphylococcal infections associated with a foreign body, such as a prosthetic heart valve.  Inhibits DNA-dependent RNA polymerase activity in susceptible cells.

35.  SUSCEPTIBLE VIRIDANS STREPTOCOCCI AND STREPTOCOCCUS BOVIS Antibiotic Dosage and route Duration(wks)Aqueous crystalline penicilllin G sodium Or ceftriaxone 12-18 million U/d IV continuously or in 6 equally divided doses 2 gm once daily IV or IM 4 Aqueous crystalline penicilllin G sodium With gentamycin sulfate 12-18 million U/d IV continuously or in 6 equally divided doses 1 mg/kg IV or IM every 8 hrly 2 Vancomycin30 mg/kg/d IV in two equally divided doses 4

36.  Antibiotic Aqueous crystalline penicilllin G sodium With gentamycin sulfate Dosage and route 18 million U/d IV continuously or in 6 equally divided doses 1 mg/kg IV or IM every 8 hrly Duration(wks) 4 2 Vancomycin30 mg/kg/d IV in two equally divided doses 4

37.  THERAPY FOR ENDOCARDITIS DUE TO STAPHYLOCOCCUS IN THE ABSENCE OF PROSTHETIC MATERIAL

38.  Antibiotic Dosage and route Duration(w ks Methicillin susceptible Saphylococci Regimens for non beta lactam allergic patients Nafcillin or oxacillin sodium With optional addition of gentamycin sulfate 2 gm IV every 4 hrly 1 mg/kg IV or IM every 8 hrly 4-6 3-5 days Regimens for beta lactam allergic patients Cefazolin With optional addition of gentamycin sulfate 2 gm IV every 8 hrly 1 mg/kg IV or IM every 8 hrly 4-6 3-5 days Vancomycin30 mg/kg/d IV in two equally divided doses 4-6 Methicillin resistant Saphylococci Vancomycin 30 mg/kg/d IV in two equally divided doses 4-6

39.  Antibiotic Dosage and route Duration(w ks Regimens for Methicillin resistant Saphylococci Vancomycin With Rifampicin and with and with gentamycin sulfate 30 mg/kg/d IV in two equally divided doses 300 mg orally every 8 hrly 1 mg/kg IV or IM every 8 hrly >/=6 2 Regimens for Methicillin susceptible Saphylococci Nafcillin or oxacillin sodium With Rifampicin and with gentamycin sulfate 2 gm IV every 4 hrly 300 mg orally every 8 hrly 1 mg/kg IV or IM every 8 hrly >/=6 2

40. Antibiotic Dosage and route Duration(wks Aqueous crystalline penicilllin G sodium with gentamycin sulfate 18-30million U/d IV continuously or in 6 equally divided doses 1 mg/kg IV or IM every 8 hrly 4-6 4-6 Ampicillin sodium with gentamycin sulfate 12 gm/24 h continuously or in 6 equally divided doses 1 mg/kg IV or IM every 8 hrly 4-6 Vancomycin with gentamycin sulfate 30 mg/kg/d IV in two equally divided doses 1 mg/kg IV or IM every 8 hrly 4-6

41. AntibioticDosage and routeDuration(wks Ceftriaxone2 gm once daily IV or IM 4 Ampicillin sodium with gentamycin sulfate 12 gm/24 h continuously or in 6 equally divided doses 1 mg/kg IV or IM every 8 hrly 4

42.  CULTURE NEGATIVE ENDOCADITIS  Due to prior antibiotic therapy or unusual microorganisms such as Legionela species, Bartonella species, Coxiella burnetti or fungi.In this condition patients can be treated empirically with benzylpenicillin plus gentamycin as for enterococcal endocardtis.   Fungi cause between 2% - 4% of endocarditis cases. When fungal IE is identified the combined medical- surgical approach is recommended. Amphotericin B can be used with the possible addition of Flucytosin.  In case of Legionella IE prolonged parenteral therapy with either doxycycline or erythromycin, with prolonged oral therapy(6- 17 mnths) elicited cure in some patients

43.  CONCLUSION :  Endocarditis is the inflammation of the endocardium, which mainly affects the heart valves.  It is mainly caused by certain gram positive cocci. Large doses of parenteral antimicrobials usually are necessary to achieve bactericidal concentrations in the vegetations.  An extended duration of therapy is required even for susceptible pathogens because organisms are enclosed with in valvular vegetations and fibrin deposits. Appropriate therapy should be initiated, if left untreated it is fatal.