内科学课件：Infective Endocarditis

1、Case,At midnight on July 2, your first night on call as an intern, you got a call from the micro lab. One of the patients your colleague admitted earlier that day, one set of the blood cultures is positive, growing gram positive cocci. The patient is a 40 y.o. female with a history of asthma. One da

2、y PTA, she was seen in the ER with several days of low grade fevers, and the initial work up was unrevealing. Blood cultures were drawn and she was sent home. She came back with persistent low grade fevers, and now has pleuritic chest pain and some shortness of breath. What is the diagnosis? What sh

3、ould do next,Infective Endocarditis（IE,Outline,Definition Epidemiology Pathogenesis Clinical Manifestations Diagnosis Complications Treatment (emphasis on early surgery) Antibiotic prophylaxis Prognosis,Definitions,Infection of endocardial surfaces of the heart Any area causing high pressure jet may

4、 be involved Valves are most common affected formation of bulky fibrin mass called vegetation laden with microorganisms,A changing Epidemiology,Exact incidence difficult to measure ranges 310 episodes/100 000 person-years is increasing as the at-risk population grows Age distribution is changing mea

5、n age of patient is up to 55 years the peak incidence was 14.5 episodes/100 000 person-years in patients between 70 and 80 Male:Female = 2-9:1,Epidemiology,young adults with previously well-identied valve disease ( rheumatic) 、congenital heart disease older patients who more often develop IE as the

6、result of health care-associated procedures（chronic haemodialysis in severe kidney disease ，catheter，intravascular devices） or in patients with prosthetic valves Diabetes mellitus Intravenous drug abuse,Epidemiology,Mitral valve alone 28-45% Aortic valve alone 5-36% Both mitral and aortic valve 0-36

7、% Tricuspid 0-6% Pulmonic valve 1,Classification-time course,Acute: fulminant，rapid progression of symptoms Less than 6 weeks duration Significant systemic signs/symptoms Fever Elevated systemic WBC/ left shift with few immunologic signs. Central nerve system complications in 30-50% common pt with n

8、o underling heart disease Subacute: Slower, chronic progression of symptoms Low grade fevers Vague clinical signs/symptoms weakness, anorexia, malaise,etc,Etiology：Common,85% of all IE is positive blood cultures Causative microorganisms are most often： Viridans streptococci Staphylococcus aureus ent

9、erococci,According to AHA Scientific Statement 2005 and ESC guideline 2009,Etiology： Viridans Streptococci,30-65% of native valve endocarditis Typical agents of classic “SBE” common after dental procedure, tonsillectomy, bronchoscopy. almost always susceptible to penicillin G,Etiology： Staphylococci

10、,Coagulase Positive (Staph. aureus) a major causative agent 2540% case typically produces “acute” IE most often susceptible to oxacillin Coagulase Negative (Staph. epi, et al) Major cause of PVE， 3-8% of NVE with oxacillin resistance,Etiology：Uncommon,Strep pneumoniae: 1-3% cases , usually in those

11、with immune suppression(DM and Ethanolism) Group B ，C；D Streptococci（Streptococcus bovis） Staph. Epidermidis（ PVE，SBE ，in neonates） Brucella Fungi (e.gAspergillus ，Candiada ） H. influengae Coxiella burnetii (Q fever,Etiology ：HACEK organisms,Hemophilus, Actinobacillus, Cardiobacterium, Eikenella, Ki

12、ngella Fastidious gram negative bacilli Large vegetation, high likelihood of embolization. Slow growing: hold cultures for 3 weeks. Traditionally sensitive to beta lactams, now some produce beta lactamase,Etiology ：Fungi,Commonly encountered agents: Candida, Torulopsis, Aspergillus Predispositions P

13、rosthetic valves IVDA Immunosupression Hyperalimentation Prolonged abx treatment Large vegetations and frequent embolic events,Risk factors,Structure heart disease -rheumatic, congenital, aging -prosthetic heart valve Injected drug use Invasive procedure Indwelling vascular device Other infection wi

14、th bacteremia (pneumonia, menigitis) History of IE,Pathogenesis,Multiple independent pathophysiological processes : 3 key features “Trauma” of the heart surfaces Platelet/fibrin deposition over traumatized tissue (NBTE ：non-bacterial thrombotic endocarditis) “Bacteremia” subsequent infection of the

15、platelet/fibrin deposition (Bacterial endocarditis) Bacterial multiplication (10 9,10 cfu/gram of tissue,Pathogenesis- endothelial damage,turbulent blood ow (MVP, bicuspid AV，PV） Electrodes，leads or catheters Inammation： rheumatic carditis，IVDA degenerative changes Extracellular matrix proteins expo

16、sure tissue factor ，thromboplastin triggering coagulation NBTE,Pathogenesis-Transient bacteraemia,invasive procedures： intravascular，dental procedures， respiratory tract procedures（Bronchoscopy）, gastrointestinal or genitorurinary procedures, dermatological or musculoskeletal procedures spontaneous

17、bacteraemia：chewing and tooth brushing Leading to the concept of prophylaxis,PathogenesisCardiac Complications,Valvular abscess, perforation of a leaflet, rupture of chordae, papillary muscle or the septum Fistula into myocardium or the pericardial sac Valvular stenosis or insufficiency Myocardial i

18、nfarction Conduction disturbances,infectious endocarditis,vegetation,Pathogenesis,Vascular:embolism Renal : renal infarction. Immune system: glomerulonephritis. arthritis,Clinical Features,Case (back to the patient,You decided that you want to get more hx She tells you that 2 week prior to admission

19、, she had removed a splinter from her foot. Over the past week, she has low grade fevers, malaise, and generalized weakness, but no pulmonary/GI/GU symptom or signs,What is the most common symptom associated with endocarditis,Shortness of breath Chest pain Fatigue Low grade fever Chills Anorexia,Cli

20、nical manifestations： Subacute IE,with great variability Nonspecific prolong low grade fever with afternoon elevation, chills, rigors or night sweats, fatigue, myalgia, arthralgia, headache, nausea and vomiting Symptoms usually persist and worsen intermittently over several weeks or months Strept. v

21、iridans- fever39(102F) and progressive muddy pallor is common,Clinical manifestations： Acute Infective Endocarditis,Embolic events are common acute severe onset of hectic fever, rigors and prostration leading the patient very much sick within few days to less than weeks. Cardiac and renal failure de

22、velop rapidly Staphylococcus- high fever(39 40 / 102 104 F,History,IE should be suspected when a patient has an unexplained persistent fever with following conditions: - congenital or rheumatic heart disease, a prosthetic valve. - predisposing factor like- Dental, urinary or intestinal investigative

23、 manipulation or surgery, recent IV catheter. - IV drug use,Clinical manifestations：Signs,General examination - Acutely or chronically ill， Recent wt loss - Pallor ， digital clubbing - Tachycardia and Tempreture Skin lesion: appear late - Petechiae: Common both AIE、SIE due to vasculitis. - Splinter

24、hemorrhages, Conjunctival hemorrhage - Oslers nodes：Tender, pea-sized intradermal erythematous nodules in pads of fingers and toes, palms and soles. Painful, immune complex deposition - Janeway lesion- septic emboli of bacteria, Painless, flat, small(5mm), irregular erythematous lesions in palms and

25、 soles,Clinical manifestations：Signs,Cardiac findings: - Signs of underlying heart disease. - Developments of new murmur or a change in character of the existing murmur. Eye lesions: -Conjuctive petechiae and hemorrhage. - Roth spots- Retinal hag with a white or yellow center surrounded by a red irr

26、egular halo from microinfarction of retinal vessels caused by emboli,Clinical manifestations：Signs,Splenomegaly: -Mild to moderate. - If Splenic infarct- spleen may be painful and tender and friction rub heard over it. - Renal lesions: - Hematuria, renal abscess, acute glomerulonephritis. Metastatic

27、 infection: - Arthritis, meningitis, mycotic arterial aneurysm, pericarditis, abscesses, septic pulmonary emboli,Lab Investigations,Anemia of Chronic Disease in 70-90% ESR “almost always” elevated 90% Urinalysis gross or microscopic hematuria casts in glomerulonephritis bacteriuria and pyuria Elevat

28、ed BUN and Creatinine C-reactive protein,Lab Investigations,ECG Evidence of underlying heart disease or conduction defect (due to abscess formation) or infarction due to embolism. Culture from other site Cutaneous lesion, urine, synovial fluid, abscess and CSF. Immunoglobulin and complements Serum I

29、G increased Total complements and C3 decreased RF may be positive 50,Diagnosis： Lab Investigations,ECHO and Blood cultures ：cornerstone of diagnosis Valvular lesion and an organism Blood cultures negative in 10% cases due to antibiotics in prior 2 weeks due to fastidious organisms which may not grow

30、 well in media used,Blood cultures,Always before starting antibiotics Always triple samples aerobe, anaerobe and mycotic , 10 ml each Three sets of samples should be taken 30 min intervals in 1st 24 hours If HACEK group suspected hold 4 wks. Prior antibiotics within 2 wks lower sensitivity,Echocardi

31、ography,Transthoracic (TTE) and transoesophageal (TEE) fundamental importance in diagnosis, management, and follow-up Should be performed as soon as the IE is suspected Sensitivity of TEE is higher than TTE (vs 90-100% vs. 40-63% ) TEE is first choice to find IE complications,Echocardiography,Echoca

32、rdiographic findings in IE Vegetation Abscess Pseudoaneurysm Perforation Fistula Valve aneurysm Dehiscene of prosthetic valve,Role of other imaging,Multislice CT: abscess, pseudoaneurysms, perivalvular extension, fistula, concomitant pulmonary disease CMR: cerebral lesions Nuclear imaging: SPECT/CT

33、and PETCT Radiolabelled white blood cell SPECT Id start her on vancomycin STAT 2. draw one more set of blood cultures to be sure, and start her on vancomycin 3. draw 2 more sets of blood cultures, and start her on vancomycin 4. could be a contaminant; Id draw 2 more sets of blood cultures and hold o

34、ff on abx 5. its probably a contaminant (coag negative staph); hold off on abx, order tylenol STAT, and go back to bed,What is your next step to confirm the diagnosis of endocarditis,1. order EKG 2. draw more blood cultures 3. order echo 4. call infectious disease consult 5. call cardiology consult,

35、Alternative diagnoses,chronic infection rheumatological and autoimmune disease malignancy,Complications,Congestive heart failure Most common complication Main indication to surgical treatment 60% of IE patients Uncontrolled infection Persisting infection Perivalvular extension in infective endocardi

36、tis Systemic embolism Brain, spleen and lungs 30% of IE patients May be the first symptom,Complications - continued,Neurologic events Acute renal failure Rheumatic problems Myocarditis,Treatment basics,Sucess relies on eradication of pathogen Bactericidal regiment should be used Drug choice due to p

37、athogen Surgery is used mainly to cope with structural complications,Principles of Antimicrobial Treatment,Bacteriacidal antibiotics Antibiotics with good tissue penetration High concentrations to ensure diffusion into the valvular vegetations(MIC,MBC) Long term treatment (4-6 weeks) Synergistic com

38、binations, Early Optimal regimen is based on susceptibility testing Be vigilant for adverse drug effects,Treatment basics - continued,NVE standard therapy - it takes 2-6 weeks to eradicate the pathogen PVE longer regime is necessery over 6 weeks In Streptococcal IE shorter, 2 week course, can be use

39、d when combining -laktams with aminoglycosides Most widely used drugs amoxycylin, gentamycin In case of -laktams alergy - vancomycin,Antimicrobial treatment of oral streptococci and streptococcus,Antimicrobial treatment of oral streptococci and streptococcus,Antibiotic treatment to Staphylococcus sp

40、p,Antibiotic treatment to Staphylococcus spp,Antimicrobial treatment of Enterococcus,Antibiotic regimens for initial empirical treatment in acute severely ill patients,Monitoring during treatment,Blood culture to document clearing of bacteria. Daily physical examination for new or changing murmurs a

41、nd evidence on embolization. Fever may persist for 5-7 days despite of adequate therapy. ESR- checked weekly. Repeat blood culture after completion of treatment,Indications for Surgery,the presence of HF, locally uncontrolled infection, large (10 mm)and mobile vegetations indicates early surgery in

42、patients with NVE. Fungal endocarditis. Annular or aortic abscess. Sinus or aortic aneurysm. Persistent bacteremia and valve dysfunction After 7-10 days of appropriate antibiotics,Timing of surgery,Emergency: perform within 24hrs; urgent: within few days Elective: after 1-2 weeks of antibiotics ther

43、apy,Timing of surgery,Prophylaxis,First and most important proper oral hygiene Regular dental review Antibiotics only in high-risk group patients Prosthetic valve or foreign material used for heart repair History of IE Congenital heart disease Cyanotic without correction or with residual lickeage CH

44、D without lickeage but up to 6 months after surgery Use amoxycilin or ampicylin 30-60 min prior to intervention,Prognosis,One of the most serious of all infections.”* Is uniformly fatal if untreated Pre-antibiotic era - a death sentence Continues to have a high case fatality rate even in antibiotic era. Mortality 20-25% despite of adequate treatment Serious morbidity : 50-60% female may have a worse prognosis,Pathologic Basis of Disease