Infective endocarditis

Pharmacotherapeutics of Infective Endocarditis

1. Dr. V. S. Swathi Assistant Professor INFECTIVE ENDOCARDITIS

2. Definition Infective Endocarditis (IE) is an inflammation of the endocardium, the membrane lining the chamber of the heart and covering the cups of heart valves. Most commonly it refers to infection of heart valves by various microbes

3. Epidemiology In the world, 3-7.5 people per 1, 00,000 in a year are affecting with Infective Endocarditis In India, native valve endocarditis due to streptococcus species observed in 30-65% of population

4. Acute Fulminating form High fever and systemic toxicity is observed Mostly occurs due to Staphylococcus aureus If not untreated, it leads to death Sub acute infection Indolent form Mostly occurs due to Viridians streptococci Usually occurs in persons with pre existing valvular disease Prosthetic Valve Endocarditis (PVE) Infection to the endocardium occurs following insertion of prosthetic heart valve Cardiac Device Infective Endocarditis (CDIE) Infection to endocardium occurs following insertion of cardiac implantable electronic device

5. Risk factors Presence of prosthetic valve Previous Endocarditis Health care related exposure Congenital heart disease Chronic IV access Diabetes mellitus Acquired valvular dysfunction Cardiac implantation device Chronic heart failure Mitral valve prolapse with regurgitation Intravenous drug abuse

6. Etiology Staphylococci species Streptococci species Enterococci species Gram negative aerobic bacilli Fungi Miscellaneous bacteria

7. Pathophysiology

8. General Stigmata of Endocarditis Fever Chills Weakness Dyspnoea Night sweats Weight loss Malaise Osler’s nodes Janeway’s lesions Splinter haemorrhages Petechiea Clubbing of fingers Roth’s spots Flank pain with hematuria (Renal artery Emboli) Abdominal pain (Splenic artery emboli) Hemiplegia with altered mental status (cerebral artery emboli) Clinical presentation

9. Complications Acute heart failure Pulmonary abscess Abscess in brain, kidney and spleen Glomerularnephritis Aneurysms Cerebral infarction Skin manifestations

10. Diagnosis Clinical presentation Lab tests Echocardiography Duke’s diagnostic criteria

11. Duke’s Criteria Major criteria: 1 . Blood culture positive At least two positive cultures of blood samples drawn greater than 12hours apart Single positive blood culture for coxiella burnetii Antiphase 1 immunoglobulin G antibody titre greater than 1: 800 2. Evidence of endocardial involvement Transesophageal echocardiography or transthorasic echocardiography shows evidence of oscillating intracardiac mass on valve or supporting structures or abscess or new partial dehiscence of prosthetic valve

12. Minor criteria: 1. Predisposing heart problem 2. Injection drug use 3. Fever greater than 100.4 ͦ F 4. Vascular phenomenon Major arterial emboli Septic pulmonary infarcts Mycotic aneurysms Intracranial hemorrhage Conjuctival hemorrhage Janeway’s lesions 5. Immunological phenomenon Glomerularnephritis Osler’s nodes Roth’s spots Rheumatoid factor 6. Microbial evidence of positive blood culture but does not meet above major criteria (HACEK) Haemophilus species Aggregate species Cardiobacterium Eikenella species Kingella species

13. Duke’s criteria Interpretation Definitive 2 major criteria or 5 major criteria or 1 major criteria + 3 minor criteria Possible 1 major criteria + 3 minor criteria or 3 minor criteria Rejected If not met above criteria or Resolution of Infective Endocarditis with antibiotic therapy within 4 days or No pathological evidence

14. Non Pharmacological Treatment Valvectomy and valvular replacement to remove infected tissue

15. Treatment Algorithm of Infective Endocarditis

16. Drugs used in Treatment of Infective Endocarditis Drug Category Mode of Action Dose Adverse Effects Pencillin G Pencillins Inhibit bacterial cell wall synthesis 3 million units-IV-for every 4-6 hours Pseudomembranous colitis Maculopapular eruption Urticaria Serum sickness reaction Jarisch-Herxheimer reaction Ampicillin Pencillins Inhibit bacterial cell wall synthesis 2g-IV-for every 4 hours Erythema multiforme Urticaria Black hairy tongue Pseudomembranous colitis Seizures Oxacillin Pencillins Inhibit bacterial cell wall synthesis 2g-IV-for every 4 hours Diarrhea Rashes Fever Eosinophilia Hepatotoxicity

17. Ceftrioxone Cephalosporin Inhibit bacterial cell wall synthesis 2g-IV-for every 12 hours Injection site reactions Eosinophilia Diarrhhea Thrombocytosis Transaminitis Cefepime Cephalosporin Inhibit bacterial cell wall synthesis 2g-IV-for every 8 hours Rashes Erythema Diarrhhea Transaminitis Hypophosphotemia Gentamicin Aminoglycoside Inhibit bacterial protein synthesis 3mg/kg-IV-for 24 hours Vertigo Ataxia Increased creatinine levels Edema Erythema

18. Vancomycin Glycopeptides Inhibit bacterial cell wall synthesis 15-20mg/kg for every 12-24 hours Hypersensitivity SJS reaction Increased creatinine levels Vertigo Pseudomembranous colitis Daptomycin Lipopeptides Inhibit bacterial protein, DNA, RNA synthesis ≥8mg/kg-IV for every 24 hours Insomnia Throat pain Chest pain Abdominal pain Edema Rifampin Antitubercular drug Inhibit DNA dependent RNA polymerase which inhibit RNA transcription 300 mg IV or po every 8 hours Transaminitis Rashes Epigastric distress Anorexia Pseudomembranous colitis Linezolid Mislleaneous antibiotic Inhibit protein synthesis in bacteria 600 mg IV or po every 12 hours Diarrhea Taste alteration Discoloration of tongue Fungal infections Transaminitis

19. Resources https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4943430/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4971993/pdf/ACA-19-551.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5106088/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5067387/pdf/main.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6116710/pdf/main.pdf