Infectious Disease I Infective Endocarditis Courses in Therapeutics

Infectious Disease I: Infective Endocarditis Courses in Therapeutics and Disease State Management Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Learning Objectives (Slide 1 of 3) • List patient populations at increased risk for developing infective endocarditis (IE) • Delineate bacteria that commonly cause IE as well as situations where certain bacteria are more likely • Describe the sequential steps necessary to develop hematogenous spread of IE • Identify the clinical manifestations of the disease, including physical findings, laboratory abnormalities, blood cultures, and other diagnostic test (e. g. , echocardiography) • Argue the importance of correctly obtained blood cultures and state situations that may lead to “culture-negative” IE Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Learning Objectives (Slide 2 of 3) • Justify the rationale for high-dose parenteral, bactericidal, extendedduration antibiotics for IE treatment • Summarize the role of nonpharmacologic approaches (i. e. , surgery) in the treatment of IE and identify situations where this approach is preferred • Design drug regimens for the following types of infective endocarditis: streptococci, staphylococci, enterococci, the HACEK microorganisms, and “culture-negative” IE • Describe why β-lactam antibiotics are preferred for the treatment of IE and classify situations where vancomycin is appropriate • Evaluate the role of penicillin skin tests in patients with a documented penicillin allergy Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Learning Objectives (Slide 3 of 3) • Outline specific monitoring parameters during IE treatment, including signs and symptoms, blood cultures, microbiologic tests, serum drug concentrations, and tests that evaluate organ function • Identify patients who should receive antimicrobials for IE prophylaxis as well as bacteremia-causing procedures that can lead to IE in predisposed individuals • In high-risk groups receiving bacteremia-causing procedures, devise a prophylactic antimicrobial regimen and list alternative regimens in those with an immediate-type penicillin allergy Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Required Reading • Veverka A, Crouch MA, Odle BL. Chapter 89. Infective Endocarditis. In: Di. Piro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 9 e. New York, NY: Mc. Graw-Hill; 2014. • Baddour LM, Wilson WR, Bayer AS, et al. Infective endocarditis in adults: diagnosis, antimicrobial therapy, and management of complications: a scientific statement for healthcare professionals from the American Heart Association. Circulation. 2015; 132: 1435– 86. • Gerber MA, Baltimore RS, Eaton CB, et. Al. Prevention of rheumatic fever and diagnosis and treatment of acute Streptococcal pharyngitis: a scientific statement from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young, the Interdisciplinary Council on Functional Genomics and Translational Biology, and the Interdisciplinary Council on Quality of Care and Outcomes Research. Circulation. 2009; 119: 1541– 15 Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Overview • Serious infection involving the lining and valves of the heart • Acute Disease • High fevers • Elevated WBC counts • Systemic toxicity • Sub-acute Disease • • Slower and more subtle presentation Low grade fevers Night sweats Fatigue Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Risk Factors • Presence of a prosthetic valve (highest risk) • Previous endocarditis (highest risk) • Congenital heart disease (CHD) • Chronic IV access • Diabetes mellitus • Healthcare-related exposure • Acquired valvular dysfunction • Cardiac implantable device • Chronic heart failure • Mitral valve prolapse with regurgitation • IV drug abuse Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Pathophysiology • Hematogenous spread is the most common pathway • Endothelial surface of the heart must be damages • Platelet and fibrin depositions occur on the damaged epithelial surface • Bacteremia gives organisms access to and results in colonization of the endocardial surface • After colonization of the endothelial surface, a “vegetation” of fibrin, platelets, and bacteria forms • Implantation of prosthetic values or other cardiac hardware that has been contaminated with pathogens is another pathway for endocarditis Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Pathophysiology: Most Common Pathogens Agent Percentage of Cases Staphylococci 30– 70 • Coagulase positive • Coagulase negative Streptococci • Viridans streptococci • Other streptococci Enterococci Gram-negative aerobic bacilli Fungi Miscellaneous bacteria Mixed infections “Culture negative” 20– 68 Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved 3– 26 9– 38 10– 28 3– 14 5– 18 1. 5– 13 1– 9 <5 1– 2 <5– 17

Clinical Presentation (Slide 1 of 3) Symptoms • Fever • Chills • Night Sweats • Weakness • Dyspnea • Weight Loss • Myalgia or arthralgia Signs • Fever • New or changing heart murmur • Embolic Phenomena • Skin manifestations • Clubbing of extremities Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Clinical Presentation (Slide 2 of 3) Laboratory Tests • WBC count normal or elevated • Anemia • Elevated C-reactive protein (CRP) • Elevated erythrocyte sedimentation rate (ESR) • Altered urinary analysis • Blood Cultures Diagnostic Tests • Electrocardiogram • Chest radiograph • Echocardiogram • Transthoracic (TTE) • Transesophogeal (TEE) Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Clinical Presentation (Slide 3 of 3) • The signs and symptoms of infective endocarditis are not specific, and the diagnosis is often unclear • The Duke diagnostic criteria integrate clinical, laboratory, and echocardiographic findings to identify the likelihood a patient has endocarditis • Patients are grouped into one of three categories • Definite infective endocarditis • Possible infective endocarditis • Infective endocarditis rejected Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Modified Duke Criteria: Major Criteria (Slide 1 of 2) • Blood culture positive for IE • Typical microorganisms consistent with IE from 2 separate blood cultures: Viridans streptococci, Streptococcus bovis, HACEK group, Staphylococcus aureus; or community-acquired enterococci in the absence of a primary focus; or • Microorganisms consistent with IE from persistently positive blood cultures defined as follows: At least 2 positive cultures of blood samples drawn 12 h apart; or all of 3 or a majority of 4 separate cultures of blood (with first and last sample drawn at least 1 h apart) • Single positive blood culture for Coxiella burnetii or anti–phase 1 Ig. G antibody titer >1: 800 Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Modified Duke Criteria: Major Criteria (Slide 2 of 2) Evidence of endocardial involvement Echocardiogram positive for IE (TEE recommended for patients with prosthetic valves, rated at least “possible IE” by clinical criteria, or complicated IE paravalvular abscess; TTE as first test in other patients) defined as follows: oscillating intracardiac mass on valve or supporting structures, in the path of regurgitant jets, or on implanted material in the absence of an alternative anatomic explanation; or abscess; or new partial dehiscence of prosthetic valve; new valvular regurgitation (worsening or changing or preexisting murmur not sufficient) Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Modified Duke Criteria: Minor Criteria • Predisposition, predisposing heart condition, or IVDA • Fever, temperature >38°C • Vascular phenomena, major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhages, and Janeway’s lesions • Immunologic phenomena: glomerulonephritis, Osler’s nodes, Roth’s spots, and rheumatoid factor • Microbiological evidence: positive blood culture but does not meet a major criterion as noted above* or serological evidence of active infection with organism consistent with IE Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Modified Duke Criteria: Diagnostic Scoring (Slide 1 of 2) • Definite Infective Endocarditis • Pathological criteria • Microorganisms demonstrated by culture or histological examination of a vegetation, a vegetation that has embolized, or an intracardiac abscess specimen • Pathological lesions; vegetation or intracardiac abscess confirmed by histological examination showing active endocarditis • Clinical criteria • 2 major criteria • 1 major criterion and 3 minor criteria • 5 minor criteria Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Modified Duke Criteria: Diagnostic Scoring (Slide 2 of 2) • Possible IE • 1 major criterion and 1 minor criterion • 3 minor criteria • Rejected • Firm alternative diagnosis explaining evidence of IE; or • Resolution of IE syndrome with antibiotic therapy for 4 days; or • No pathological evidence of IE at surgery or autopsy, with antibiotic therapy for 4 days; or • Does not meet criteria for possible IE as above Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Goal Outcomes • Relieve the signs and symptoms of the disease • Decrease morbidity and mortality associated with the infection • Eradicate the causative organism with minimal drug exposure • Provide cost-effective antimicrobial therapy determined by the likely or identified pathogen, drug susceptibilities, hepatic and renal function, drug allergies, and anticipated drug toxicities • Prevent infective endocarditis from occurring or recurring in high -risk patients with appropriate prophylactic antimicrobials Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Treatment Overview • Empiric antibiotic treatment until an infecting pathogen is isolated • High dose, parenteral, bactericidal pathogen specific antibiotics for an extended period • A minimum of 4 to 6 weeks of antibiotic therapy is generally required Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Nonpharmacological Treatment • Surgical removal, repair, and/ or replacement of infected valves or cardiac hardware • Support of vital functions Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Pharmacological Treatment • β-Lactam antibiotics, such as penicillin G (or ceftriaxone), nafcillin, and ampicillin, remain the drugs of choice • The use of synergistic antimicrobial combinations may be required for certain pathogens to obtain a bactericidal effect • Once the infecting pathogen is identified, there are detailed guidelines for the treatment of each specific bacteria Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Pathogen Specific Therapies (Slide 1 of 7) Native Valve Endocarditis caused by highly penicillin- susceptible (MIC≤ 0. 12 mcg/m. L) viridans group streptococci and Streptococcus gallolyticus (bovis) Regimen Duration (weeks) Adult Dose Aqueous crystalline penicillin G sodium 4 12 -18 million units/24 hours Ceftriaxone 4 2 grams/24 hours Vancomycin 4 Trough goal 10 -15 Aqueous crystalline penicillin G sodium plus Gentamicin (traditional dosing peak of 3 -4 mcg/ml) 2 12 -18 million units/24 hours Ceftriaxone plus Gentamicin (traditional dosing peak of 3 -4 mcg/ml) 2 2 grams/24 hours Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Pathogen Specific Therapies (Slide 2 of 7) Native Valve Endocarditis caused by Streptococcus gallolyticus (bovis) and viridans group streptococci relatively resistant to penicillin (MIC> 0. 12 mcg/m. L) Regimen Duration (weeks) Aqueous crystalline penicillin G sodium 4 Adult Dose 24 million units/24 hours Plus Gentamicin (traditional dosing peak of 3 -4 mcg/ml) 2 Vancomycin 4 Trough goal 10 -15 Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Pathogen Specific Therapies (Slide 3 of 7) Prosthetic Valve Endocarditis caused by highly penicillin- susceptible (MIC≤ 0. 12 mcg/m. L) viridans group streptococci and Streptococcus gallolyticus (bovis) Regimen Duration (weeks) Adult Dose Aqueous crystalline penicillin G sodium 6 12 -18 million units/24 hours Ceftriaxone 6 2 grams/24 hours Vancomycin 6 Trough goal 10 -15 Aqueous crystalline penicillin G sodium plus Gentamicin (traditional dosing peak of 3 -4 mcg/ml) 6 12 -18 million units/24 hours Ceftriaxone plus Gentamicin (traditional dosing peak of 3 -4 mcg/ml) 6 2 2 grams/24 hours 2 Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Pathogen Specific Therapies (Slide 4 of 7) Prosthetic Valve Endocarditis caused by Streptococcus gallolyticus (bovis) and viridans group streptococci relatively resistant to penicillin (MIC> 0. 12 mcg/m. L) Regimen Duration (weeks) Aqueous crystalline penicillin G sodium 6 Adult Dose 24 million units/24 hours Plus Gentamicin (traditional dosing peak of 3 -4 mcg/ml) 2 Ceftriaxone 6 2 grams/24 hours Plus Gentamicin (traditional dosing peak of 3 -4 mcg/ml) 2 Vancomycin 4 Trough goal 10 -15 Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Pathogen Specific Therapies (Slide 5 of 7) Native Valve Endocarditis caused by Staphylococci Regimen Duration (weeks) Adult Dose Oxacillin or Nafcillin 6 12 g/24 hours Cefazolin 6 6 gm/24 hours Vancomycin 6 Trough goal 10 -20 Daptomycin 6 ≥ 8 mg/kg/dose MSSA MRSA Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Pathogen Specific Therapies (Slide 6 of 7) Prosthetic Valve Endocarditis caused by Staphylococci Regimen Duration (weeks) Adult Dose Oxacillin or Nafcillin 6+ 12 g/24 hours Plus Rifampin 6+ 900 mg/24 hours Plus gentamicin 2 Traditional dosing Peak goal 3 -4 mcg/ml Vancomycin 6+ Trough goal 10 -20 Plus Rifampin 6 + 900 mg/24 hours Plus gentamicin 2 Traditional dosing Peak goal 3 -4 mcg/ml MSSA MRSA Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Pathogen Specific Therapies (Slide 7 of 7) Prosthetic or Native Valve Endocarditis caused by Enterococci Regimen Duration (weeks) Adult Dose Ampicillin 4 -6 12 g/24 hours Plus gentamicin 4 -6 Traditional dosing Peak goal 3 -4 mcg/ml Aqueous crystalline penicillin G sodium 4 -6 18 -30 million units/24 hours Plus gentamicin 4 -6 Traditional dosing Peak goal 3 -4 mcg/ml Ampicillin 4 -6 12 g/24 hours Plus Ceftriaxone 4 -6 2 gm IV Q 12 H Vancomycin 4 -6 Trough goal 10 -15 Plus gentamicin 4 -6 Traditional dosing Peak goal 3 -4 mcg/ml OR OR OR Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Pathogen Specific Therapies Native and Prosthetic Valve Endocarditis caused by HACEK Microorganisms Regimen Duration (weeks) Adult Dose Ceftriaxone 4 -6 12 g/24 hours Ampicillin 4 -6 6 gm/24 hours Ciprofloxacin 4 -6 400 mg IV Q 12 H Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Endocarditis Culture Negative Therapies (Slide 1 of 2) • A patient with an acute clinical presentation of native valve infection should be started on antibiotic coverage for S aureus, β-hemolytic streptococci, and aerobic Gram negative bacilli • A patient with an subacute clinical presentation of native valve infection should be started on antibiotic coverage for S aureus, viridans group streptococci, HACEK, and enterococci Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Endocarditis Culture Negative Therapies (Slide 2 of 2) Regimen Duration Culture-Negative Endocarditis, Native Valve Ampicillin–sulbactam plus gentamicin Vancomycin plus gentamicin plus ciprofloxacin • 4– 6 Culture-Negative Endocarditis, Early (<1 Year) Prosthetic Valve Vancomycin plus cefepime plus rifampin plus gentamicin • 6 • 2 Culture-Negative Endocarditis, Late (>1 Year) Prosthetic Valve Ampicillin–sulbactam plus gentamicin plus rifampin • 6 Vancomycin plus gentamicin plus ciprofloxacin plus rifampin • 6 Suspected Bartonella, Culture-Negative Ceftriaxone plus gentamicin with or without doxycycline Culture-Positive Bartonella Doxycycline plus gentamicin Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved • 6 • 2

Overall Monitoring of Infective Endocarditis • Fever usually subsides within 1 week of initiating therapy • Echocardiography should be completed after completion of antibiotic therapy to establish a new baseline heart function • Blood cultures should be negative within a few days of starting antibiotic therapy Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Patients at Highest Risk of Endocarditis • Prosthetic cardiac valve or prosthetic material used for cardiac valve repair • Previous infective endocarditis • Congenital heart disease (CHD) • Unrepaired cyanotic CHD, including palliative shunts and conduits • Completely repaired congenital heart defect with prosthetic material or device, whether placed by surgery or by catheter intervention, during the first 6 months after the procedure† • Repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device (which inhibit endothelialization) • Cardiac transplantation recipients who develop cardiac valvulopathy Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Prophylaxis of Infective Endocarditis Highest Risk Cardiac Conditions Presence of a prosthetic heart valve Prior diagnosis of infective endocarditis Cardiac transplantation with subsequent valvulopathy Congenital heart disease (CHD)a Types of procedures Antimicrobial Options Any that require perforation of the oral mucosa or manipulation of the periapical region of the teeth of gingival tissue Adult Dosesb Pediatric Dosesb (mg/kg) Oral amoxicillin 2 g 50 IM or IV ampicillinc 2 g 50 IM or IV cefazolin or ceftriaxonec, d, e 1 g 50 Oral cephalexind, e, f 2 g 50 Oral clindamycine 600 mg 20 Oral azithromycin or clarithromycine 500 mg 15 IV or IM clindamycinc, e 600 mg 20 Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Summary • Endocarditis typically presents as fever • Antibiotic treatment durations differ significantly when treating native vs. prosthetic valve infections • There are specific guidelines for each pathogen causing endocarditis • Patients at the highest risk of infective endocarditis should receive prophylactic antibiotic therapy Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

References • Veverka A, Crouch MA, Odle BL. Chapter 89. Infective Endocarditis. In: Di. Piro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 9 e. New York, NY: Mc. Graw-Hill; 2014. • Baddour LM, Wilson WR, Bayer AS, et al. Infective endocarditis in adults: diagnosis, antimicrobial therapy, and management of complications: a scientific statement for healthcare professionals from the American Heart Association. Circulation. 2015; 132: 1435– 86. • Gerber MA, Baltimore RS, Eaton CB, et. Al. Prevention of rheumatic fever and diagnosis and treatment of acute Streptococcal pharyngitis: a scientific statement from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young, the Interdisciplinary Council on Functional Genomics and Translational Biology, and the Interdisciplinary Council on Quality of Care and Outcomes Research. Circulation. 2009; 119: 1541– 15 Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved