1	Endocarditis ד"ר מיכל חוברס היח' למחלות זיהומיות, בית חולים מאיר
2	"בת 82 שבוע תלונות של..." בת 82 שבוע תלונות של כאבים וכיחלון ב 2 אצבעות כף יד שמאל. ללא חום פרט לכך בדיקה פיזיקאלית תקינה עברה בירור לקרישויות יתר שהיה תקין. ס"ד אנמיה קלה, CRP-28.9 טופלה באיליופרוסט ללא הטבה CT אנגיו- ללא הצרויות בעורקי היד- ממצא לוואי חשד לאוטם בטחול
3	"שלשה ימים לאחר מכן נפילה..." שלשה ימים לאחר מכן נפילה +חבלה ברקה. מיד לאחר מכן צלולה. CT מח ללא עדות לדימום. מספר שעות לאחר מכן ישנוניות, מבולבלת, חום עד 39. הוחל טיפול בזינצף (לא נילקחו תרביות דם). ב21/11/07 החמרה CT מח חוזר תקין. בוצע LP: 100 תאים לבנים 85% סגמנטים, 80 כדוריות אדומות. גלוקוז 70 נילקחו 3 סטים של תרביות דם
4	"הוחל טיפול אנטיביוטי" הוחל טיפול אנטיביוטי ב6 בקבוקים Staph Aureus TTE לא נראו וגטציות TEE 2 מסות מוביליות היוצאות מבסיס משותף בעלה מיטרלי אחורי, נראות כוגטציות. גודלן 1.7 ס"מ. יתכן שיש פרפורציה בבסיס הממצא
5	Diagnosis A disease with variable presentation Host (old vs young) Bacteria (acute vs sub-acute) valve) Rt. vs Lt.)
6	Clinical suspicion!! Prolonged fever Embolic phenomena Fever in a patent with prosthetic valve, or previous endocarditis. Blood cultures
7	Optimal number of blood cultures One? 1. Does not maximize the chance of isolating an organism (99% with two) Volume is important-> 20ml/ set 2. Can not demonstrate the presence of continuous bacteremia 3. Can not distinguish contamination from true bacteremia Two to three in native valve Four in prosthetic valve (“colonizers” can be true pathogens)
8	Duke criteria Major: Microbiological criteria Echocardiography Minor Fever Major embolic events Non embolic vascular phenomena Underlying vascular disease Intermittent bacteremia
9	Modified Duke major microbiological criteria Typical microorganism from 2 separated blood cultures: Strep viridanse HACEK (Haemophilus, Actinobacillus, Cardibacterium, Eikenella, Kingella) Staph Aureus Community acquired Enterococcus Phase 1 IgG>1:800 C. burnetii
10	"Streptoccoci" Streptoccoci 60-80% viridans 30-40% enterococci 5-18% other 15-25% Staphylococci 20-35% aureus 10-27% coag-neg 1-3% Gram neg 1.5-13% Fungi 2-4% Culture neg 5- 24%
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14	Modified Duke major microbiological criteria Persistently positive blood cultures of any microorganism > 12h apart All 3 or most >3 separated blood cultures >1h apart (between 1^st to last)
15	Definite by Duke Two major One major + Three minor Five minor
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21	"Clinical suspicionà" Clinical suspicionà Empiric therapy Rapid diagnosisà Identify pt at high risk for complications who might need early surgery High suspicion and TTE negative proceed to TEE
22	Antibiotic therapy Blood culture should be obtained every 24-48h. Counting days of therapy from the first day of negative blood cultures. Maximal doses of antibiotics
23	Viridians group strep (α-hemolytic) Common cause of community acquired native valve endocarditis. Usually not on normal valve Sub-acute presentation Heterogeneous group S sanguis, S oralis, S salivarius S milleri (S anginosus)- tends to form abcesses Nutritionally variant strep (Abiotrophia defective, Granulicatella) more difficulte to grow in lab
24	Treatment based on MIC to penicillin Highly susceptible (MIC<0.12) 4 w of Pen G or Ceftriaxone 2 w of Pen G or Ceftriaxone+ Gent once daily (recommended only to low risk for AEs, not recommended to pt with extracardiac infection) MIC>0.12, <0.5 4 weeks of Pen G or Ceftriaxone+ 2w gent MIC> 0.5 Like Enterococcal endocarditis
25	S. aureus Endocarditis Endocarditis in 26% of patients with SAB May attack normal heart Frequently fulminant course (Lt side endocarditis) Mortality 20-65% Heart failure 20-50% Neurologic manifestations 30% Paravalvular abscesses are more common in S aureus IE- TEE for evaluation
26	"Most common pathogen in Rt..." Most common pathogen in Rt side endocarditis At risk population: IVDU Presentation: cough, pleuritic chest pain, dispnea Chest XR: Multiple rounded pulmonary infiltrate Better prognosis
27	S. Aureus Bacteremia Third of the pt with SAB develop complications Risk factors for metastatic dis.: Cardiac valvular dis Prostatic implants( 34% of SAB and PV, 45% of SAB and pacemaker, 34% of SAB and orthopedic devices developed infection of the device) Community – acquired Older age(>65 attributable mortality 14.5% vs. 6.3%
28	TEE in SAB Prosthetic valve Prolonged bacteremia Persistent symptoms New cardiac conductions abnormalities Community acquired SAB TTE non diagnostic
29	Treatment-MSSA Uncomplicated infection-native valve- 4 w of Orbenin 2grX6, or cefazolin 2grX3 (gent in the first 3-5 days) With complications (perivalvular abscess, septic emboli)- 6w of therapy. Prostetic valve – 6 weeks+ 2w gent
30	MRSA Increasing in hospitals Greater morbidity and mortality Lower rates of bacteriological cure Vancomycin –treatment of choice Poor outcome including with MIC within susceptible range (<4) Cure with MIC< 0.5 in 56% of pt MIC 1-2 in 9% of pt
31	"Combination with rifampin resulted in..." Combination with rifampin resulted in prolongation of bacteremia Combination with gent. resulted in increased nephrotoxicity
32	Enterococci Normal inhabitants of GI tract and urethra Usually a subacute presentation The mean duration of nonspecific symptoms (malaise, fatigue) was 140 days Affects older men Greater than 40% of pt have no underlying heart dis Intrinsically resistant bacteria
33	Treatment “Sensitive enterococci” Ampicillin 2grX6 + gent 80mgX3 (or streptomycin) for 4-6 weeks In 5y nationwide prospective a study from Sweden of 93 episodes of enterococcal endocarditis: overall cure rate of pt treated with 2-3 w of gent was comparable to longer treatment duration.
34	"Resistant to pen- Vanco+" Resistant to pen- Vanco+ gent for 6 w Enterococcus faecium resistant to pen+vanco+gent- Linezolid for >8w Enterococcus faecalis resistant to pen+vanco+gent- Ceftriaxon+ Ampicillin for> 8 w
35	“Culture Negative IE” Administration of Abx Rt sided IE, Mural, PVE Fastidious organism: Slow growing: HACEK Diagnosed by serology: Q fever, Bartonella Less: Mycoplasma, Legionella, Chlamidia, Brucella Diagnosis delayed- increased risk for valve destruction, higher mortality Fever resolved 1^st week 90% survival Fever continue; 50% survival
36	Q Endocarditis Cases evolving from acute Q to chronic: 12 of 1569 (7.6%) Median 6 months (1-18) from onset of acute disease All had preexisting valvular dis. 40% of pt with valvulopathy developed IE All pt with acute Q should be screened for h/o Pt with valvulopathy and fever should be screened for Q fever
37	Fungi Risk Groups IVDU Post reconstructive heart surgery Prolonged antibiotic therapy Candida predominated in the addicts Candida and Aspergillus in the non- addicts
38	Fungi Cure rate is poor (14.5%) Large bulky vegetations Tendency of myocardial invasion Widespread systemic septic emboli Poor penetration of drugs Low toxic to therapeutic ratio
39	"Historically:" Historically: Fungal endocarditis a stand-alone indication for surgery Ampho B is the drug of choice Reevaluation in order Mortality is high New drugs are available
40	Complicated Lt side endocarditis in adults-Risk classification for mortality Five baseline features independently associated with 6m mortality: Moderate to severe CHF Comorbidity (charlson score≥2) p=0.3 Abnormal mental status p=0.2 Bacterial etiology other than S viridans p<0.001 Medical therapy without surgery p=0.02
41	CHF In native valve occurs more often in aortic valves (29% vs 20% mitral) The degree of tolerance is valve dependent: acute aortic regurgitation being the least tolerant CHF irrespective of mechanism or course, predict a grave prognosis with medical therapy alone.
42	"A decision to delay surgery..." A decision to delay surgery to extend preoperative antibiotic treatment should be discouraged The incidence of re-infection of newly implanted valve in a pt with active endocarditis is 2-3%. Far less than the mortality for uncontrolled CHF
43	Embolization Systemic embolization occurs in 22-50% of IE Up to 65% of embolic events involve the CNS The highest incidence is seen in aortic and miteral valve IE caused by S Aureus Candida HACEK
44	"Most embolization occur within the..." Most embolization occur within the first 2w of therapy. Highest embolic rate (37%) vegetation on anterior mitral leaflet. Several studies showed higher embolic rate with Lt. side vegetation>1cm
45	"Healthy 49 year old male" Healthy 49 year old male 10 days fever Treated with rulid for two days without improvement. Day 1 On admission: appears well Fever 39.7 c. Systolic murmur on LSB Decreased breath sound on left lung Rest of the physical exam was normal Chest X ray was normal
46	"Lab results:" Lab results: WBC:12300, Hb:11.8, PLT:204000 Albumin:2.7 LFT: SGOT-76,SGPT-141,GGT-271, ALK PHOS.-165, Urea,creatinine-normal ECG: sinus rhythm ,1^o a-v block
47	"Blood culture were drawn" Blood culture were drawn Start I.V Augmentin Day 2 On Blood culture: (8/8) Streptococcus pneumonia
48	"TTE:" TTE: Thickened bicuspid aortic valve Mild to moderate AR Possible mild AS Small perimembranous VSD Trivial TR No vegetation seen What next?
49	"Day 3" Day 3 On the evening: sudden pain in right shoulder, dyspnea Pulmonary edema Transfer to cardiology unit, intubated. TEE performed
50	"On TEE:" On TEE: very thickened aortic valve. Severe AR Hypoecogenic mass at the base of aorta. (abscess?). Perivalvular abscess Membranous VSD Day 4:Transfer to emergency valve replacement Operation results: huge abscess at the root of aorta Septal perforation (false VSD)
51	Periannular extension of infection Predicts higher mortality rate, more frequent CHF, and more frequent cardiac surgery. Occurs in 10-40% of native valve IE In native aortic valve spread through the weakest portion of annulus- near AV node. Heart block is a frequent sequela. In prostetic valve IE occurs in 56-100%
52	"In a study of 51..." In a study of 51 episodes of IE and 24 perivalvular abscesses: among demographic, clinical, and echo findings the only significant correlate of abscess was the presence of AV block New block PPV- 88% for abcsees formation, but low sensitivity (45%) TTE misses up to 50% of abscesses detected by TEE
53	Micotic Aneurysm Septic embolization to arterial vasa vasorum or intraluminal space Occurs most frequently in intracranial arteries.
54	Intra Cranial MA Mortality rate among pt with ICMA is 60% Clinical presentation is highly variable Severe headache Altered sensorium Focal neurological deficits Some may leak and present with meningeal signs MRA or CTA have sensitivity and specificity of 90-95% for detecting ICMA
55	"ICMA can heal with medical..." ICMA can heal with medical therapy Monitor with serial neuroimaging Sign of enlargement or leakà consider intervention
56	Prophylaxis
57	Reasons for revision of Prophylaxis Guidelines IE is much more likely to result from bacteremias associated daily activities (X2d) Than bacteremias caused by dental GI or GU procedure (X2y) Prophylaxis may prevent a very small number of cases of IE The risk of antibiotic associated AE exeeds the benefits of prophylaxis
58	Cardiac conditions associated with HR of adverse outcome from IE (Prophylaxis for dental procedure reasonable) PV Previous Endocarditis Congenital Heart Diseases (Urepaired Cyanotic CHD, CHD with prostatic material (first 6m) Cardiac transplantation with valvulopathy
59	Regimens for dental procedure Single dose 30-60m before procedures Ampicillin 2gr Cefazolin 1gr Clinda 600mg Azithro/clarithro 500 mg