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Infective Endocarditis: Epidemiology, Diagnosis and Management Holger P. Salazar, MD, FACC Stern Cardiovascular Foundation No financial relation to disclose.

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Presentation on theme: "Infective Endocarditis: Epidemiology, Diagnosis and Management Holger P. Salazar, MD, FACC Stern Cardiovascular Foundation No financial relation to disclose."— Presentation transcript:

1 Infective Endocarditis: Epidemiology, Diagnosis and Management Holger P. Salazar, MD, FACC Stern Cardiovascular Foundation No financial relation to disclose

2 Epidemiology of Infective Endocarditis

3 Annual incidence in USA 10,000-20,000 new cases, stable over past 30 years Annual incidence in USA 10,000-20,000 new cases, stable over past 30 years Prosthetic valve endocarditis accounts for 15% of cases Prosthetic valve endocarditis accounts for 15% of cases Mortality is about 20%, due to CHF, valvular dysfunction, or uncontrolled infection Mortality is about 20%, due to CHF, valvular dysfunction, or uncontrolled infection 50% over the age of 50 50% over the age of 50

4 Valvular Involvement in Infective Endocarditis Valve Percent of Cases Mitral 28-45% Aortic 5-36% Aortic + Mitral 0-35% Tricuspid 5% Combined right and left 0-4%

5 Most Common Underlying Cardiac Lesions In Infective Endocarditis Mitral valve prolapse Mitral valve prolapse Degenerative valvular lesions Degenerative valvular lesions Calcified mitral annulus Calcified mitral annulus Valve nodules Valve nodules Bicuspid Aortic Valve Bicuspid Aortic Valve Prosthetic Valve Prosthetic Valve

6 Risk of Infective Endocarditis for Selected Groups Risk Factor Incidence* Injection Drug Use Rheumatic heart disease 440 Bioprosthesis 383 Prior endocarditis Mechanical prosthesis 308 VSD (Medical therapy) 220 * Cases per 10 5 patient-years

7 Classification of Infective Endocarditis

8 Infective Endocarditis: Classification Native Valve (75-90% of cases) Acute -- ˃ 1 to 2 weeks Acute -- ˃ 1 to 2 weeks Subacute-- >2 week Subacute-- >2 week Prosthetic Valve (10-25% of cases) Early Onset-- ˃ 12 months Early Onset-- ˃ 12 months Late Onset-- > 12 months Late Onset-- > 12 months

9 Two Flavors of Infective Endocarditis: Native and Prosthetic Valves

10 Clinical Manifestations of Endocarditis

11 Infective Endocarditis: Symptoms (%) Fever80 Chills40 Weakness40 Dyspnea40 Sweats25 Weight loss25 Malaise25 Stroke20 Skin lesions20 Headache20 Achiness20 Chest pain15 Altered mental status10-15 Back pain10

12 Native Valve Endocarditis: Signs (%) Fever90 Murmur85 New 3-5 Changing 5-10 Emboli50+ Splenomegaly Metastatic20 infection Retinal lesions 20 Skin manifestations18-50 Petechiae Petechiae Splinters 15 Oslers nodes Janeway lesions <10

13 Cutaneous Findings of Endocarditis Oslers nodes are small raised, swollen, painful erythematous lesions the size of a pea, on pads of fingers or toes Janeway lesions are nontender macular lesions most commonly involving the palms and soles and are caused by septic emboli Splinter hemorrhages

14 Roths Spots and Endocarditis Round or oval retinal hemorrhages with white spots seen in the retina early in the course of IE, caused by complex mediated vasculitis

15 Microbiology of Endocarditis

16 Microbiology of Native Valve Endocarditis OrganismPercent of Cases Viridans streptococci30-40% Other streptococci15-25% Staphylococcus aureus10-27% Enterococcus species 5-18% Gram negative bacilli 2-13%

17 Microbiology of Prosthetic-Valve Endocarditis Organism Percentage of Cases Early Onset Late Onset (> 12 m) Coagulase negative staph30-35%15% Staphylococcus aureus17-23%20% Gram negative bacilli10%5% Streptococci 5-10%33% Fungi 10% 2%

18 Causes of Culture-Negative Endocarditis Coxiella burnetti (Q fever) Coxiella burnetti (Q fever) Bartonella species (cat scratch disease) Bartonella species (cat scratch disease) HACEK organisms* HACEK organisms* Legionella species Legionella species Aspergillus species Aspergillus species Lactobacillus species Lactobacillus species * Haemophilus species; Actinobacillus actinomycetemcomitans; Cardiobacteriumhominis; Eikenella corrodens; and Kingella kingae

19 Echocardiography and Diagnosis of Endocarditis

20 Transthoracic Echocardiography and Endocarditis No technological advance has had as much impact on approach to patients with IE No technological advance has had as much impact on approach to patients with IE Rapid, non-invasive and specific for vegetations (98%) Rapid, non-invasive and specific for vegetations (98%) May be inadequate in 20% of patients because of obesity, COPD, or chest-wall deformities May be inadequate in 20% of patients because of obesity, COPD, or chest-wall deformities TTE should be used in the evaluation of those with suspected native valve IE who are good candidates for imaging TTE should be used in the evaluation of those with suspected native valve IE who are good candidates for imaging

21 Transesophageal Echocardiography and Endocarditis More costly and invasive but increases the sensitivty (from 75% to 95%) while maintaining specificity (85-98%) More costly and invasive but increases the sensitivty (from 75% to 95%) while maintaining specificity (85-98%) More sensitive for defining perivalvular extension, perforation of valves, and myocardial abscess More sensitive for defining perivalvular extension, perforation of valves, and myocardial abscess A negative TEE has a negative predictive value for IE of > 92% A negative TEE has a negative predictive value for IE of > 92%

22 TTE or TEE or Both? Recent guidelines suggest that among patients with suspected endocarditis appropriate use of echocardiography depends on prior probability of IE Recent guidelines suggest that among patients with suspected endocarditis appropriate use of echocardiography depends on prior probability of IE If this probability is < 4%, a negative TTE is cost effective and satisfactory in ruling out IE If this probability is < 4%, a negative TTE is cost effective and satisfactory in ruling out IE If this probability is 4 to 60%, initial use of TEE is more cost effective and efficient than initial TTE followed by TEE (if former negative) If this probability is 4 to 60%, initial use of TEE is more cost effective and efficient than initial TTE followed by TEE (if former negative) Mylonakis & Calderwood NEJM 2001;345:1318

23 Limitations of Echocardiography in the Diagnosis of Endocarditis Falsely negative early in disease Falsely negative early in disease False positive diagnosis with thickened valve leaflets, valve nodules or tumors False positive diagnosis with thickened valve leaflets, valve nodules or tumors Inability to distinguish healed from active vegetations Inability to distinguish healed from active vegetations Lower sensitivity in those with mechanical prostheses Lower sensitivity in those with mechanical prostheses Blood cultures remain the test of choice for patients with suspected endocarditis Blood cultures remain the test of choice for patients with suspected endocarditis

24 Duke Criteria for Diagnosis of Endocarditis

25 Duke Criteria for Diagnosis of Infective Endocarditis: Major Criteria Positive blood culture for typical organism (from 2 separate cultures or Staphylococcus aureus or enterococcal bacteremia without a primary focus) or Positive blood culture for typical organism (from 2 separate cultures or Staphylococcus aureus or enterococcal bacteremia without a primary focus) or Persistent bacteremia for any organism > 12 hrs apart or Persistent bacteremia for any organism > 12 hrs apart or All of 3 or majority of 4 BC positive drawn > 1 hr apart All of 3 or majority of 4 BC positive drawn > 1 hr apart Echocardiographic criteria Echocardiographic criteria - Oscillating mass, abscess or new dehiscence of prosthesis - Oscillating mass, abscess or new dehiscence of prosthesis - New valvular regurgitation - New valvular regurgitation

26 Duke Criteria for Diagnosis of Infective Endocarditis: Minor Criteria Predisposing heart condition or injection drug use Predisposing heart condition or injection drug use Fever greater than or equal to 38 o C Fever greater than or equal to 38 o C Immunologic phenomena: GN, Oslers nodes, Roth Spots, RF Immunologic phenomena: GN, Oslers nodes, Roth Spots, RF Echo consistent, but not meeting major criteria Echo consistent, but not meeting major criteria Vascular phenomena: arterial embolism, septic PE, mycotic aneurysm, intracranial hemorrhage, Janeway lesions Vascular phenomena: arterial embolism, septic PE, mycotic aneurysm, intracranial hemorrhage, Janeway lesions Microbiologic evidence: positive BC not meeting major criteria or serology indicating active infection with consistent organism Microbiologic evidence: positive BC not meeting major criteria or serology indicating active infection with consistent organism

27 Duke Criteria for Diagnosis of Infective Endocarditis Definite endocarditis: Pathologic criteria Organisms by culture or histology in vegetation, embolus, or cardiac abscess or Organisms by culture or histology in vegetation, embolus, or cardiac abscess or Pathologic lesion such as vegetation or cardiac abscess Pathologic lesion such as vegetation or cardiac abscess Clinical criteria 2 major, or 1 major plus 3 minor, or 5 minor criteria 2 major, or 1 major plus 3 minor, or 5 minor criteria

28 Right Sided Endocarditis in Injection Drug Users

29 Right-sided Endocarditis in Injection Drug Users 46 y/o man injection drug user (heroin) with fevers, sweats and right sided pleuritic chest pain. Blood cultures grew penicillin- susceptible S. aureus and echocardiogram showed 1 mm Tricuspid valve vegetation. HIV negative and in hospital for 7 days with oxacillin and gentamicin followed by 21 days of outpatient ceftriaxone (2 gms/ day). Multiple peripheral septic emboli with cavitation

30 Right-Sided Endocarditis in Injection Drug Users Common complication with overall favorable prognosis Common complication with overall favorable prognosis Vegetations > 2 cm associated with higher mortality (33% vs 1.3%) Vegetations > 2 cm associated with higher mortality (33% vs 1.3%) S. aureus most common pathogen (>80%) than Viridans streptococci S. aureus most common pathogen (>80%) than Viridans streptococci >50% with septic emboli on chest radiographs >50% with septic emboli on chest radiographs Hecht SR and Berger M Ann Int Med 1992;117:560

31 Right Sided Endocarditis in Injection Drug Users: Treatment Two week regimen (nafcillin or oxacillin + gentamicin) for susceptible isolates Two week regimen (nafcillin or oxacillin + gentamicin) for susceptible isolates Oral therapies still controversial Oral therapies still controversial Exclusion to short-course protocol: Exclusion to short-course protocol: Extracardiac complications of IE Extracardiac complications of IE Fever for > 7 days Fever for > 7 days HIV infection HIV infection Vegetation > 1-2 cm Vegetation > 1-2 cm Chambers HF Ann Intern Med 1988;109:619

32 AHA Guidelines for Treatment of Endocarditis

33 Aortic Versus Mitral Valve Endocarditis Aortic ~55% ~75% Mitral~85%~40% Pulmonary~1% Tricuspid~20% Acute aortic regurgitation is poorly tolerated because the LV is less compliant than the LA resulting higher LV wall stress! Watch out for abrupt deterioration! Overall incidence Surgical Patients

34 AHA Guidelines for Antibiotic Therapy in Native Valve Endocarditis OrganismRegimenWeeks PCN-sensitive PCN G MI qd or4 Ceftriaxone 2 g qd or 4 Ceftriaxone 2 g qd + 2 Gentamicin 3 mg/kg qd or Vancomycin 1 g bid4 PCN-insensitivePCN G 18 MI qd + 4 Gentamicin 1 mg/kg tid 2 or Vancomycin 1 g bid4 Doses assume normal renal function

35 AHA Guidelines for Antibiotic Therapy in Native Valve Endocarditis OrganismRegimenWeeks MSSAOxacillin or Nafcillin 2 g q4h4-6 or Cefazolin 2 g tid4-6 both +/- Gentamicin 1 mg/kg tid 3-5d or Vancomycin 1 g bid +/- Gent MRSAVancomycin 1 g bid4-6 +/- Gentamicin 1 mg/kg tid4-6 Doses assume normal renal function

36 AHA Guidelines for Antibiotic Therapy in Native Valve Endocarditis Organism RegimenWeeks Enterococci (VSE)PCN + Gentamicin or 6 Vancomycin + Gentamicin 6 as above HACEKCeftriaxone 2 g qd or 4 Ampicillin 2 g q4h + 4 Gentamicin 1 mg/kg tid 4 Doses assume normal renal function

37 AHA Guidelines for Antibiotic Therapy in Prosthetic Valve Endocarditis OrganismRegimenWeeks MSSA or MSSEOxacillin or Nafcillin 2 g q4h6+ + Gentamicin 1 mg/kg tid 2 + Rifampin 300 mg tid6+ MRSA or MRSEVancomycin 1 g bid6+ + Gentamicin 1 mg/kg tid2 + Rifampin 300 mg tid6+ Doses assume normal renal function

38 Steel: Often the Best Antimicrobial Agent In Treating Infective Endocarditis

39 Medical versus Surgical therapy Surgery is always in addition to medical therapy Surgery is always in addition to medical therapy The vast majority of the operated patients would die if not operated The vast majority of the operated patients would die if not operated Some medically treated patients are inoperable Some medically treated patients are inoperable

40 Surgical Indications in Endocarditis Refractory CHF Refractory CHF > 1 serious embolic event > 1 serious embolic event Uncontrolled infection Uncontrolled infection Physiologically significant valve dysfunction by echo Physiologically significant valve dysfunction by echo Fungal endocarditis Fungal endocarditis Ineffective antimicrobial therapy Ineffective antimicrobial therapy Mycotic aneurysm Mycotic aneurysm Most cases of PVE due to antibiotic resistant pathogens Most cases of PVE due to antibiotic resistant pathogens Local cardiac suppurative complications Local cardiac suppurative complications

41 Echocardiographic Features Predicting Need for Surgery in Endocarditis Persistent vegetations after a major embolus Persistent vegetations after a major embolus Large (> 1 cm) mitral valve vegetation Large (> 1 cm) mitral valve vegetation Increasing vegetation size after 4 weeks of antimicrobial therapy Increasing vegetation size after 4 weeks of antimicrobial therapy Acute mitral insufficiency Acute mitral insufficiency Valve perforation or rupture Valve perforation or rupture Periannular extension of infection Periannular extension of infection AHA Committee on Endocarditis

42 Homograft or Prosthetic Valve Replacement for Aortic Valve IE There are no and probably will be no randomized studies! There are no and probably will be no randomized studies! Good results are possible to obtain with either Good results are possible to obtain with either However, an increasing number of publications favor homografts However, an increasing number of publications favor homografts Technically easier and safer Technically easier and safer Lower risk of heart block Lower risk of heart block Lower infection and re-infection rate Lower infection and re-infection rate Homograft does not require anticoagulation Homograft does not require anticoagulation Limited supply of homografts Limited supply of homografts Limited durability of homograft Limited durability of homograft

43 Timing of Surgery 30% require surgery in the acute phase another 20-40% will require surgery later Main principle: Dont postpone an indicated operation, however: Main principle: Dont postpone an indicated operation, however: Pts with strokes: Postpone surgery, if possible 1-3 weeks, particularly if evidence of hemorrhage Pts with strokes: Postpone surgery, if possible 1-3 weeks, particularly if evidence of hemorrhage If valve repair is planned: 1 week of preop antibiotic treatment If valve repair is planned: 1 week of preop antibiotic treatment Re-infection rate is lower after surgery for healed endocarditis Re-infection rate is lower after surgery for healed endocarditis

44 Early Surgery Versus Conventional Treatment for IE Kaplan–Meier Curves for Cumulative Probabilities of Death and Composite End Point at 6 Months Kang DH, et al: NEJM 2012; 366:2466

45 Early Surgery Versus Conventional Treatment for IE Clinical End Points Kang D et al. N Engl J Med 2012;366: Kang DH, et al: NEJM 2012; 366:2466 Early Surgery Versus Conventional Treatment for Infective Endocarditis

46 Special Surgical Considerations Related to Location Aortic valve IE: Be aggressive! Aortic valve IE: Be aggressive! Acute aortic regurgitation is poorly tolerated Acute aortic regurgitation is poorly tolerated Mitral valve IE: Repair whenever possible, consider risk of embolism Mitral valve IE: Repair whenever possible, consider risk of embolism Right-sided IE: Be conservative! Right-sided IE: Be conservative! Repair, excision, (replacement) Repair, excision, (replacement) Pulmonary valve IE is very uncommon Pulmonary valve IE is very uncommon

47 Aortic Root Endocarditis With Vegetation and Fistula to Right Atrium

48 The infection penetrates through to the floor of the Right atrium just about to destroy the A-V node

49 Ventricular Assist Device Associated Endocarditis

50 LVAD and Endocarditis

51 Endocarditis and Ventricular Assist Devices Patients with VADs are at high risk for nosocomial bloodstream infections Patients with VADs are at high risk for nosocomial bloodstream infections Incidence of VAD associated IE may be as high as 13% (relapsing bacteremia/fungemia common) Incidence of VAD associated IE may be as high as 13% (relapsing bacteremia/fungemia common) At least 24 cases in literature (33% Candida 20% Enterococcus) with 50% associated mortality At least 24 cases in literature (33% Candida 20% Enterococcus) with 50% associated mortality Difficult to visualize inflow and outflow conduits by echocardiography Difficult to visualize inflow and outflow conduits by echocardiography Treatment: tranplantation! Device exchange high rate of failure/death Treatment: tranplantation! Device exchange high rate of failure/death Gordon and McCarthy in Advanced Therapy Cardiac Surgery 2002

52 Pacemaker Associated Endocarditis

53 Pacemaker-Associated Endocarditis >2 million people (including 1 million Americans) use pacemakers >2 million people (including 1 million Americans) use pacemakers Infections uncommon but difficult to eradicate without device removal (generator + leads via laser extraction if possible) Infections uncommon but difficult to eradicate without device removal (generator + leads via laser extraction if possible) Pacemaker endocarditis can be difficult diagnosis to make on clinical grounds Pacemaker endocarditis can be difficult diagnosis to make on clinical grounds TEE sensitive in finding suspicious lesions on pacemaker TEE sensitive in finding suspicious lesions on pacemaker Chua J et al Ann Int Med 2000;133:644

54 Pacemaker-Associated Endocarditis

55 Prophylaxis to Prevent Endocarditis

56 Endocarditis Prophylaxis Class I: No class I indications. Class I: No class I indications. Class IIa: Reasonable for pts at highest risk for adverse outcomes from IE having dental procedures that involve manipulation of either gingival tissue or the periapical region of the teeth or perforation of the oral mucosa Class IIa: Reasonable for pts at highest risk for adverse outcomes from IE having dental procedures that involve manipulation of either gingival tissue or the periapical region of the teeth or perforation of the oral mucosa - Pts with prosthetic cardiac valves or prosthetic - Pts with prosthetic cardiac valves or prosthetic material used for valve repair material used for valve repair - Pts with previous IE - Pts with previous IE - Pts with CHD: unrepaired cianotic CHD including - Pts with CHD: unrepaired cianotic CHD including paliative shunts and conduits paliative shunts and conduits ACC/AHA 2008 Guideline Update on Valvular Heart Disease: JACC 2008; 676

57 Endocarditis Prophylaxis Class IIa (cont): Class IIa (cont): - Complete repaired CHD fixed with prosthetic material - Complete repaired CHD fixed with prosthetic material or device, whether placed surgically or by catheter or device, whether placed surgically or by catheter intervention, during first 6 months after procedure intervention, during first 6 months after procedure - Repaired CHD with residual defects at the site or - Repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or device adjacent to the site of a prosthetic patch or device - Cardiac transplant pts with valve regurgitation due - Cardiac transplant pts with valve regurgitation due to structurally abnormal valve to structurally abnormal valve Class III: Prophylaxis not recommended against nondental procedures: TEE, EGD or colonoscopy Class III: Prophylaxis not recommended against nondental procedures: TEE, EGD or colonoscopy ACC/AHA 2008 Guideline Update on Valvular Heart Disease: JACC 2008; 676

58 Endocarditis Prophylaxis Prophylaxis accepted in high risk pts: Prophylaxis accepted in high risk pts: - Incision of the respiratory tract mucosa, such - Incision of the respiratory tract mucosa, such as tonsillectomy and adenoidectomy as tonsillectomy and adenoidectomy - Infections of the GI or GU tract - Infections of the GI or GU tract - Pts undergoing elective cistoscopy or other - Pts undergoing elective cistoscopy or other urinary tract manipulation who have urinary tract manipulation who have enterococcal UTI enterococcal UTI ACC/AHA 2008 Guideline Update on Valvular Heart Disease: JACC 2008; 676

59 Procedures Not Requiring Prophylaxis in At Risk Patients Dental restoration Dental restoration Adjustment of braces Adjustment of braces Flexible bronchoscopy Flexible bronchoscopy GI endoscopy GI endoscopy C-section deliveries C-section deliveries Cardiac catheterization Cardiac catheterization Urethral catheterization (sterile urine) Urethral catheterization (sterile urine)

60 ACC/AHA Guidelines for Prevention of Bacterial Endocarditis Oral: Amoxicillin 2g min before oral procedure Oral: Amoxicillin 2g min before oral procedure Unable to take PO: Ampicillin 2g IM or IV, or cefazolin or Unable to take PO: Ampicillin 2g IM or IV, or cefazolin or ceftriaxome IV 1g IM or IV min before procedure ceftriaxome IV 1g IM or IV min before procedure Allergic to PCN – oral: clindamycin 600mg, Allergic to PCN – oral: clindamycin 600mg, azithromycin or clarithromycin 500mg min before azithromycin or clarithromycin 500mg min before procedure procedure Allergic to PCN and unable to take PO: clindamycin 600mg IM or IV or cefazolin or ceftriaxone 1g IM or IV (do not use if anaphylaxis, angioedema, urticaria with PCN Allergic to PCN and unable to take PO: clindamycin 600mg IM or IV or cefazolin or ceftriaxone 1g IM or IV (do not use if anaphylaxis, angioedema, urticaria with PCN ACC/AHA 2008 Guideline Update on Valvular Heart Disease: JACC 2008; 676


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