Infective Endocarditis for Primary Care Physicians

Transcription

1 Infective Endocarditis for Primary Care Physicians David N Gilbert, MD Disclosures Consultant to: Merck Pfizer Medicine Company Cempra 1

2 Introduction There are roughly 30,000 new cases of IE in the US each year. The annual number is increasing There is risk of mortality:e.g., 25% risk if the etiology is S.aureus In survivors, major complications include hematogenous osteomyelitis, CVA, and need for valve surgery Patient # 1 62 y.o. Caucasian male welder complains of progressive fatigue and an unintentional 20 lb. weight loss ROS negative PMH Takes no prescription meds No illicit drugs; No tobacco; Minimal alcohol Recent divorce; thinks he might be depressed 2

3 Patient # 1 (cont.) BP: 130/70, R 12/min, P 80 and regular Cursory exam. : no abnormalities H/H: 10 and 30 WBC: 10, 500 with 85% PMNs Multichemistry screen: unremarkable Diagnosis: anemia Plan: Iron studies, Check stool for occult blood Patient #1 (Cont.) Two days later call to office from ED Patient under evaluation for acute onset of left CVA pain and gross hematuria T 37.8 C, BP 120/ 55 Grade iii/vi systolic ejection murmur and faint early diastolic decrescendo murmur Blood cultures ordered Admitted and immediate TTE performed 3

4 Pathogenesis of Endocarditis Intracardiac Platelet Gram-pos turbulence fibrin cocci: vegetations (no PMNs) stick Stripping of endocardial cells Collagen exposure Do not stick: E. coli 4

5 Clinical Examples of Turbulent Flow Disrupted Endocardium Congenital: ventricular septal defect; mitral valve prolapse Post-rheumatic fever: mitral and /or aortic valve disease Calcific aortic stenosis (older patient) Intravenous drug use talc-induced trauma, esp. to tricuspid valve Prosthetic valve 5

6 Clinical Manifestations Variable symptoms ranging from acute chills, fever, and shock ( acute ) to minimal fever, night sweats and weight loss( subacute ) Complications may dominate: heart failure, emboli, skin lesions Gilbert Modification of Duke Criteria for Dx of IE Continuous bacteremia (3 sets) Murmur valvular insufficiency Major emboli (brain, coronary arteries, spleen, kidney) Demonstration of presence of vegetations by ECHO, or surgery, or autopsy Other findings are minor: normocytic anemia, skin/mucous membrane vasculopathy 6

7 Diagnosis Think of it Draw three blood cultures Look for emboli: brain, spleen, renal Image heart for vegetations (Trans-esophageal ECHO preferred) Microbial Etiology of Infective Endocarditis (IE)? Most common on native valves is grampositive cocci: Viridans streptococci, Staphylococcus aureus, Enterococcus faecalis On prosthetic valves: Staphylococcus epidermidis, rarely fungi, very rarely gram-neg bacilli So, what grew in our patient s blood cultures? 7

8 S.gallolyticus aka S.bovis Group D enterococcus that lives in GI tract Causes 6 % of IE in USA (EJCMID, 2005) Among S. bovis infected patients, median % with concomitant adenoma or carcinoma was 60 %(CID 2011; 53:870) Surface proteins & pili with great avidity for surface of colonic neoplasms Some suggest carcinogenic; data poor Patient #2: I need more pain medicine. 55 y.o.male construction worker is on permanent disability due back injury and subsequent ruptured disk surgeries Needs daily MS-Contin to perform ADL Now complains of progressively severe pain; asks primary care MD to provide more narcotic 8

9 Outpatient (or ED) Visit T 37.5 C, BP 125/85, P 84/min, R 18/min Physical exam: Fresh tracks both arms. Admits to use of street drugs to supplement Back exam: Pain, ROM similar previous exams. WBC: 13,000 with 85% neutrophils Stat ECHO cardiogram: vegetations on tricuspid valve; patient admitted Post-Admission Three Blood cultures ordered Empiric piperacillin-tazobactam plus vancomycin Chest X-Ray: Multifocal hematogenous/embolic pneumonia 12 hrs. later: all 3 blood cultures positive for S. aureus 9

10 Diagnosis: S.aureus Tricuspid Valve Endocarditis. Now what? Think about the source Complications: Emboli Seeding other tissues, organs THE NEXT DAY After 24 hrs of Vancomycin Patient suddenly unable to move his legs. Incontinent of urine and feces. Back MRI: T6-L1 epidural abscess with compression of the spinal cord Despite emergent surgery and ultimate cure of the bone/disk infections, permanent paraplegia Especially in adults with back pain, think about vertebral osteomyelitis/diskitis 10

11 Need to customize treatment for each individual patient because: Vegetations consist of fibrin, platelets and colonies of bacteria. Few, if any, phagocytic cells. So need bacteriocidal antibiotic therapy Further, bacterial colonies mature; not a lot of dividing bacteria; hence, beta-lactams have reduced number of targets Antibiotics do not penetrate vegetations well Bacteria can transform into spore like forms: e.g. Small colony variants S. aureus WHAT Have We Learned? 1. Need endocardial turbulence to produce platelet fibrin vegetations 2. GPCs responsible for over 75% of IE 3. Dx: Continuous bacteremia & TEE 4. Where did the bug come from? 5. Where did the bug go? 6. ID help to customize bactericidal therapy 11

12 ROTH SPOTS 12

13 Osler s Nodules Splinter hemorrhage Janeway Lesions Conjunc.Petechiae Main Points Understanding pathogenesis helps with diagnosis and management Once diagnosis is made, need to think about source of the etiologic bacteria and complications of the infection Treatment details make every patient an experiment: consultation advised 13

14 PLAN 2 or 3 example cases as springboard to discussion of: Pathogenesis Criteria for diagnosis Source and complications Principles of antimicrobial therapy 14

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16 IE Diagnostic Criteria Persistent bacteremia with a pertinent organism Source of turbulence: e.g., valvular heart disease Detection of platelet-fibrin vegetation Evidence of embolization of vegetations Detection of vegetations by transesophageal echocardiography 16

17 Risk Factors and Microbial Etiology Risk Factor Congenital heart disease, rheumatic valve damage, degenerative valvulopathy (e.g., calcific aortic stenosis) IV Drug Use Prosthetic Heart Valve Common Etiologic Organisms Viridans streptococci (e.g. S. mitis), Enterococcus faecalis/faecium Staphylococcus aureus Staphylococcus epidermitis, S. aureus Microbial Etiology of IE** S.aureus, 31% Viridans strepto., 17% Enterococci, 11% S.epidermidis, 11% **ArchIntMed 2009:169, 463 S.gallolyticus (bovis), 7% Other streptococci, 5% HACEK*, 2% Gram neg Bacilli, 2% *H: H.parainfluenza A: Aggregatibacter sp C: Cardiobacterium sp E: Eikenella sp K: Kingella sp 17

18 Streptococcus gallolyticus subsp.gallolyticus (formerly S. bovis) Microbiology: Next slide Implication: Source suggests important occult pathology Treatment: Discuss with patient # 2 18

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20 Enterococci and Cidal Therapy In vitro suscept/resist Suscept Pen. & Gent Suscept Pen; R to Gent Suscept Gent; R to Pen R to both Pen & Gent Primary Therapy Pen G + Gentamicin Pen G alone X months Vanco + Gent Linezolid (static) Alternative Therapy Vanco + Gentamicin Ceftriax. + Amp No clear alternative Ceftriax. + Amp Viridans Streptococci & Cidal Therapy Pen G, in vitro MIC ug/ml Primary Therapy </= 0.12 Pen G + Gent X 2 weeks 0.12-</= 0.5 Pen G + Gent X 4 wks > 0.5 Pen G + Gent X 6 wks Alternative Therapty Ceftriax + Gent X 2 wks Vanco X 4 wks Vanco + Gent X 6 wks 20