1. Endocarditis Lobna AL Juffali December2013

2. Introduction 3-4 cases per 100,000 population per year 3-4 cases per 100,000 population per year Platlet – fibrin complex becomes infected with microorganisms (vegetation) Platlet – fibrin complex becomes infected with microorganisms (vegetation)

3. Definition Endocarditis is an inflammation of the endocardium, the membrane lining the chambers of the heart and covering the cusps of the heart valves. Endocarditis is an inflammation of the endocardium, the membrane lining the chambers of the heart and covering the cusps of the heart valves. Infective endocarditis (IE) refers to infection of the heart valves by microorganisms, primarily bacteria. Infective endocarditis (IE) refers to infection of the heart valves by microorganisms, primarily bacteria.

4. Pathogenisis

5. Pathogenesis

6. Pathophysiology Infective endocarditis generally occurs as a consequence of nonbacterial thrombotic endocarditis, which results from turbulence or trauma to the endothelial surface of the heart. Infective endocarditis generally occurs as a consequence of nonbacterial thrombotic endocarditis, which results from turbulence or trauma to the endothelial surface of the heart. Transient bacteremia then leads to seeding of lesions with adherent bacteria, and infective endocarditis develops. Transient bacteremia then leads to seeding of lesions with adherent bacteria, and infective endocarditis develops. Pathologic effects due to infection can include local tissue destruction and embolic phenomena. Pathologic effects due to infection can include local tissue destruction and embolic phenomena. In addition, secondary autoimmune effects, such as immune complex glomerulonephritis and vasculitis, can occur. In addition, secondary autoimmune effects, such as immune complex glomerulonephritis and vasculitis, can occur.

7. Risk factors Presence of a prosthetic valve (highest risk) Presence of a prosthetic valve (highest risk) Previous endocarditis (highest risk) Previous endocarditis (highest risk) Complex cyanotic congenital heart disease (e.g., single ventricle states) Complex cyanotic congenital heart disease (e.g., single ventricle states) Surgically constructed systemic pulmonary shunts Surgically constructed systemic pulmonary shunts Acquired valvular dysfunction (e.g., rheumatic heart disease) Acquired valvular dysfunction (e.g., rheumatic heart disease) Hypertrophic cardiomyopathy Hypertrophic cardiomyopathy Mitral valve prolapse with regurgitation Mitral valve prolapse with regurgitation IV drug abuse IV drug abuse

8. Clinical Presentation Symptoms fever, chills, weakness, dyspnea, night sweats, weight loss, and/or malaise. fever, chills, weakness, dyspnea, night sweats, weight loss, and/or malaise.Signs Fever Fever heart murmur heart murmur The patient may or may not have embolic phenomenon, The patient may or may not have embolic phenomenon, splenomegaly, splenomegaly,

9. Clinical Presentation (skin manifestations) Osler ’ s nodes

10. Clinical Presentation (skin manifestations) Splinter hemorrhage

11. Laboratory Findings The hallmark laboratory finding The hallmark laboratory finding  is continuous bacteremia; (+ve blood culture)  three sets of blood cultures should be collected over 24 hours. Leukocytosis Leukocytosis Anemia (normocytic, normochromic) Anemia (normocytic, normochromic) ESR ESR C-reactive protein C-reactive protein altered urinary analysis (proteinuria/microscopic hematuria altered urinary analysis (proteinuria/microscopic hematuria

12. Duke criteria for the diagnosis of infective endocarditis and proposed modifications Pathological criteria Pathological criteria –Microorganisms demonstrated by culture or histological in a vegetation –Active endocarditis demonstrated by histological examination Major criteria Major criteria –Positive blood cultures –Evidence of endocardial involvement

13. Duke criteria for the diagnosis of infective endocarditis and proposed modifications Minor criteria predisposing heart disease predisposing heart disease fever >38°C fever >38°C vascular phenomena vascular phenomena immunological phenomena immunological phenomena microbiological evidence (no major criterion) microbiological evidence (no major criterion) suspect echocardiography (no major criterion suspect echocardiography (no major criterion

14. Duke criteria for the diagnosis of infective endocarditis and proposed modifications Categories CategoriesDefinite: Pathological criteria positive Pathological criteria positive or 2 major criteria positive or 2 major criteria positive or 1 major and 2 minor criteria positive or 1 major and 2 minor criteria positive or 5 minor criteria positive or 5 minor criteria positivePossible: All cases which cannot be classified as definite or rejected  1 major and 1 minor criterion positive  3 minor criteria positive Rejected: Alternative diagnosis Alternative diagnosis Resolution of the infection with antibiotic treatment for 4 days Resolution of the infection with antibiotic treatment for 4 days No histological evidence No histological evidence

15. Other diagnostic tests An electrocardiogram, An electrocardiogram, chest radiograph, chest radiograph, echocardiogram (valvular vegetations) echocardiogram (valvular vegetations)

16. Causitive microorganism Streptococci Streptococci  Viridans  Other streptococci Staphylococci Staphylococci  Coagulase positive  Coagulase negative Enterococci Enterococci Gram-negative aerobic bacilli Gram-negative aerobic bacilli Fungi Fungi Miscellaneous bacteria Miscellaneous bacteria Mixed infections Mixed infections “ Culture negative ” “ Culture negative ” 60 – 80 30 – 40 15 – 25 20 – 35 10 – 27 1 – 3 1 – 3 5 – 18 1.5 – 13 2 – 4 <5 1 – 2 <5 – 24 %

17. DESIRED OUTCOME Relieve the signs and symptoms of disease. Relieve the signs and symptoms of disease. Decrease morbidity and mortality associated with infection. Decrease morbidity and mortality associated with infection. Eradicate the causative organism with minimal drug exposure. Eradicate the causative organism with minimal drug exposure. Provide cost-effective antimicrobial therapy. Provide cost-effective antimicrobial therapy. Prevent IE in high-risk patients with appropriate prophylactic antimicrobials. Prevent IE in high-risk patients with appropriate prophylactic antimicrobials.

18. Factors associated with increased mortality include the following: Congestive heart failure Congestive heart failure Culture-negative endocarditis Culture-negative endocarditis Endocarditis caused by resistant organisms such as fungi and gram- negative bacteria Endocarditis caused by resistant organisms such as fungi and gram- negative bacteria Left-sided endocarditis caused by Staphylococcus aureus Left-sided endocarditis caused by Staphylococcus aureus Prosthetic valve endocarditis (PVE) Prosthetic valve endocarditis (PVE)

19. GENERAL PRINCIPLES The most important approach to treatment of IE includes The most important approach to treatment of IE includes  isolation of the infecting pathogen  determination of antimicrobial susceptibilities  followed by high-dose, bactericidal antibiotics for an extended period. Treatment usually is started in the hospital, but in selected patients, it may be completed in the outpatient setting. Treatment usually is started in the hospital, but in selected patients, it may be completed in the outpatient setting.

20. GENERAL PRINCIPLES Large doses of parenteral antimicrobials usually are necessary to achieve bactericidal concentrations within vegetations. Large doses of parenteral antimicrobials usually are necessary to achieve bactericidal concentrations within vegetations. An extended duration of therapy is required, even for susceptible pathogens, because microorganisms are enclosed within valvular vegetations and fibrin deposits. An extended duration of therapy is required, even for susceptible pathogens, because microorganisms are enclosed within valvular vegetations and fibrin deposits.

21. Nonpharmamcological Therapy Surgery is an important adjunct to management of endocarditis in certain patients. Surgery is an important adjunct to management of endocarditis in certain patients. valvectomy and valve replacement valvectomy and valve replacement The most important indications for surgical intervention in the past have been The most important indications for surgical intervention in the past have been –heart failure in left-sided IE – persistent infections in right-sided IE.

22. Treatment Duration wks Recommeded Therapy organism mild, delayed allergy to penicillin Immedate type hyppersensitivity reaction to peniciilin 42424 Penicillin G Penicillin G + gentamicin Ceftriaxone Ceftriaxone +gentamicin Vancomycin Viridans streptococci (with penicillin MIC <0.12mcg/ml) 4 wk + 2Wk 4 Penicillin G + gentamicin Ceftriaxone +gentamicin Vancomycin Viridans streptococci (with penicillin MIC >0.12mcg/ml) In patients with endocarditis of prosthetic valves or other prosthetic material caused by viridans streptococci and Streptococcus bovis, treatment courses are extended to 6 weeks

23. Treatment The following conditions should all be present to consider a 2-week treatment regimen The isolate is penicillin sensitive. There are no cardiovascular risk factors. No evidence of thrombotic disease. Native valve infection. No vegetation greater than 5 mm diameter. Clinical response is evident within 7 days.

24. Staphylococci endocarditis Staphylococci endocarditis Endocarditis caused by staphylococci is becoming more prevalent,mainly because of Endocarditis caused by staphylococci is becoming more prevalent,mainly because of – increased IVDA –more frequent use of peripheraland central venous catheters – increased frequency of valve replacement surgery. Staphylococcus aureus is the most common organism causing IE among those with IVDA and persons with venous catheters. Staphylococcus aureus is the most common organism causing IE among those with IVDA and persons with venous catheters. Coagulase-negative staphylococci (usually S. epidermidis) are prominent causes of PVE Coagulase-negative staphylococci (usually S. epidermidis) are prominent causes of PVE

25. Is the organism methicillin resistant? Is the organism methicillin resistant? Should combinationtherapy be used? Should combinationtherapy be used? Is the infection on a native or prosthetic valve? Is the infection on a native or prosthetic valve? Does the patient have a history of IVDA? Does the patient have a history of IVDA? Is the infection on the left or right side of the heart? Is the infection on the left or right side of the heart? Staphylococci endocarditis Staphylococci endocarditis

26. Treatment Duration wks Recommeded Therapy organism 666 Oxacillin or nafcillin Oxacillin or nafcillin +/- Gentamicin for 3-5days Plus rifampin in prosthetic valves Cefazolin Cefazolin +/- Gentamicin for 3-5days +/- Gentamicin for 3-5days Plus rifampin in prosthetic valves Vancomycin Vancomycin Plus rifampin in prosthetic valves Staphylococci- Methicillin sensitive 6 or more Vancomycin Vancomycin Plus rifampin in prosthetic valves Staphylococci- Methicillin resistant 2 Oxacillin or nafcillin + Gentamicin Oxacillin or nafcillin + Gentamicin Right sided Endocarditis in IDUs * In patients with endocarditis of prosthetic valves or other prosthetic material addition of aminoglycosides is must for the first two weeks

27. Duration wks Recommeded Therapy organism 4-66 Penicillin G or ampicillin Penicillin G or ampicillin+gentamicin Vancomycin +gentamicin Enterococci 6 Ampicillin/ Sulbactam or vancomycin +gentamicn Enterococci – penicillin resistant 8 or more LinezolidQuinupristin/dalfopristin E.Faecium – penicillin,amioglycoside, and vancomycin resistant 8 or more Imipenem/cliastatin+ampicillinCeftriaxone+ampicillin E.Faecialis penicillin,amioglycoside, and vancomycin resistant Treatment

28. HACEK Infective Endocarditis  Haemophilus spp.  Actinobacillus actinomycetemcomitans  Cardiobacterium hominis  Eikenella corrodens  Kingella kingae Slow growing, fastidious Gram negatives likely cause of Culture Negative Endocarditis

29. Treatment the treatment of HACEK infective endocarditis ceftriaxone ceftriaxone ampicillin-sulbactam ampicillin-sulbactam oral ciprofloxacin for selected patients oral ciprofloxacin for selected patients Treatment is usually for 4 weeks, but it should be extended to 6 weeks in PVE caused by one of these organisms. Treatment is usually for 4 weeks, but it should be extended to 6 weeks in PVE caused by one of these organisms.

30. Culture-Negative Endocarditis Sterile blood cultures are reported in 5% to 20% of patients with infective endocarditis if strict diagnostic criteria are used Sterile blood cultures are reported in 5% to 20% of patients with infective endocarditis if strict diagnostic criteria are used This type of infective endocarditis may occur as a result of unidentified subacute right-sided infective endocarditis, previous antibiotic therapy, slow-growing fastidious organisms, nonbacterial etiologies (e.g., fungi), and improperly collected blood cultures This type of infective endocarditis may occur as a result of unidentified subacute right-sided infective endocarditis, previous antibiotic therapy, slow-growing fastidious organisms, nonbacterial etiologies (e.g., fungi), and improperly collected blood cultures When blood cultures from patients suspected of infective endocarditis show no growth after 48 to 72 hours, the laboratory should be advised and cultures held for up to a month to detect growth of fastidious organisms When blood cultures from patients suspected of infective endocarditis show no growth after 48 to 72 hours, the laboratory should be advised and cultures held for up to a month to detect growth of fastidious organisms

31. Aminoglycosides and Endocarditis Aminoglycosides are ototoxic and nephrotoxic Aminoglycosides are ototoxic and nephrotoxic Want to limit therapy to as short a period of time as possible to avoid toxicity Want to limit therapy to as short a period of time as possible to avoid toxicity – Staphylococci < 5 days – Staphylococci < 5 days – Enterococci will require 4-6 weeks – Enterococci will require 4-6 weeks

32. Aminoglycosides and Endocarditis Control peak and trough concentrations Control peak and trough concentrations Elderly and/or renally impaired patients treated for extended periods of time are at greatest risk Elderly and/or renally impaired patients treated for extended periods of time are at greatest risk Maintain gentamicin Cpmax 3-5 mg/L & Cpmin < 1 mg/L Maintain gentamicin Cpmax 3-5 mg/L & Cpmin < 1 mg/L Present data would not support SDD Present data would not support SDD

33. Vancomycin Trough serum vancomycin concentrations are the most accurate and practical method for monitoring efficacy. Trough serum vancomycin concentrations are the most accurate and practical method for monitoring efficacy. just before the fourth dose just before the fourth dose trough level Above 15-20mg/dl trough level Above 15-20mg/dl Red neck syndrome Red neck syndrome Ototoxicity Ototoxicity nephrotoxicity nephrotoxicity

34. EVALUATION OF THERAPEUTIC OUTCOMES assessment of signs and symptoms assessment of signs and symptoms Persistence of fever beyond 1 week may indicate ineffective antimicrobial therapy, emboli, infections of intravascular catheters, or drug reactions. Persistence of fever beyond 1 week may indicate ineffective antimicrobial therapy, emboli, infections of intravascular catheters, or drug reactions. In some patients, low-grade fever may persist even with appropriate antimicrobial therapy. In some patients, low-grade fever may persist even with appropriate antimicrobial therapy.

35. EVALUATION OF THERAPEUTIC OUTCOMES blood cultures should be negative within a few days, although microbiologic response to vancomycin may be unusually slower. blood cultures should be negative within a few days, although microbiologic response to vancomycin may be unusually slower. blood cultures should be rechecked until they are negative. During the remainder of the therapy, frequent blood culturing is not necessary. blood cultures should be rechecked until they are negative. During the remainder of the therapy, frequent blood culturing is not necessary.

36. EVALUATION OF THERAPEUTIC OUTCOMES For all isolates from blood cultures, MIC should be determined. For all isolates from blood cultures, MIC should be determined. When aminoglycosides are used for endocarditis caused by gram-positive cocci with a traditional three-times daily regimen, peak serum concentrations are recommended to be on the low side of the traditional ranges (3 to 4 mcg/mL for gentamicin). When aminoglycosides are used for endocarditis caused by gram-positive cocci with a traditional three-times daily regimen, peak serum concentrations are recommended to be on the low side of the traditional ranges (3 to 4 mcg/mL for gentamicin). Serum concentrations of the antimicrobial should generally exceed the MBC of the organism; however, in practice this principle is usually not helpful in monitoring patients with endocarditis. Serum concentrations of the antimicrobial should generally exceed the MBC of the organism; however, in practice this principle is usually not helpful in monitoring patients with endocarditis.

37. Endocarditis prophylaxis Conditions in which prophylaxis is necessary Prosthetic cardiac valves Prosthetic cardiac valves Previous infective endocarditis Previous infective endocarditis Congenital heart disease (CHD) Congenital heart disease (CHD) Unrepaired cyanotic CHD Unrepaired cyanotic CHD Completely repaired congenital heart defect with prosthetic material or device, during the first 6 months after the procedure Completely repaired congenital heart defect with prosthetic material or device, during the first 6 months after the procedure Repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device Repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device Cardiac transplantation recipients who develop cardiac valvulopathy Cardiac transplantation recipients who develop cardiac valvulopathy

38. Prophylaxis in Dental procedures Endocarditis prophylaxis is recommended for all dental procedures that involve manipulation of the gingival tissue of the periapical region of teeth or perforation of the oral mucosa. Endocarditis prophylaxis is recommended for all dental procedures that involve manipulation of the gingival tissue of the periapical region of teeth or perforation of the oral mucosa. When antibiotic prophylaxis is appropriate, a single 2-g dose of amoxicillin for adult patients at risk, given 30 to 60 minutes before undergoing procedures associated with bacteremia. When antibiotic prophylaxis is appropriate, a single 2-g dose of amoxicillin for adult patients at risk, given 30 to 60 minutes before undergoing procedures associated with bacteremia.

39. Other procedures that require prophylaxis Respiratory tract: Respiratory tract:  Tonsillectomy and or adenoidectomy  Surgical operations that involve an incision or biopsy of the respiratory mucosa

40. Case T.S. is a 48-year-old man who presents to the emergency department complaining of fever, chills, nausea/vomiting, anorexia, lymphangitis in his right hand, and lower back pain. He has no significant medical history except for kidney stones 4 years ago. He has no known drug allergies. He is homeless and an IV drug abuser (heroin) for the past year but quit 2 weeks ago. On physical examination, he is alert and oriented, with the following vital signs: temperature 100.8 º F (38 º C); heart rate 114 beats/minute; respiratory rate 12 breaths/minute; and blood pressure 127/78 mm Hg. He has a faint systolic ejection murmur, and his right hand is erythematous and swollen.

41. Case His laboratory values were all within normal limits. He had an HIV test done a year ago, which was negative. One blood culture was obtained that later grew MSSA. Two more cultures were obtained that are now growing gram-positive cocci in clusters. A transesophageal echocardiogram shows vegetation on the mitral valve.

42. Case Which one of the following therapeutic regimens is appropriate for T.S.? A. nafcillin IV therapy — antibiotic duration: 2 weeks. B. nafcillin IV plus rifampin therapy — antibiotic duration: ≥ 6 weeks. C. nafcillin IV plus gentamicin IV therapy — antibiotic duration: 2 weeks of both antibiotics. D. nafcillin IV plus gentamicin — antibiotic duration: 6 weeks (nafcillin) with first 3-5 days of gentamicin.