Infective Endocarditis Lecture (1) - New Mansoura University

New Mansoura University Faculty of Pharmacy Pharm D Program __________________________________________________________ _________________ pharmacotherapy II Infective endocarditis Lecture(1) ...

New Mansoura University Faculty of Pharmacy Pharm D Program __________________________________________________________ _________________ pharmacotherapy II Infective endocarditis Lecture(1)  Course Objectives By the completion of this course, the student should be able to know the clinical presentation, diagnostic criteria, classification criteria and latest evidence-based management guidelines of the various and most common infectious diseases.  Infective Endocarditis Sexually Transmitted Diseases Bacterial Meningitis Intra-Abdominal Infections Lower Respiratory Tract Infections Fungal Infections Upper Respiratory Tract Infections Human Immunodeficiency Virus Infection Gastrointestinal Infections Tuberculosis Urinary Tract Infections  Endocarditis is an inflammation of the endocardium, the membrane lining the chambers of the heart and covering the cusps of the heart valves. Infective endocarditis (IE) refers to infection of the heart valves by microorganisms, primarily bacteria. Endocarditis is often referred to as either acute or subacute depending on the clinical presentation. Acute bacterial endocarditis is a fulminating infection associated with high fevers (39.4°C or more), systemic toxicity, and death within days to weeks if untreated. Subacute infectious endocarditis is a more indolent infection, usually occurring in a setting of prior valvular heart disease.  Etiology Some of the most important risk factors include the following: ✓ Highest risk: presence of a prosthetic valve or previous IE ✓ Congenital heart disease (CHD), chronic intravenous (IV) access, acquired valvular dysfunction (eg, rheumatic heart disease), cardiac implantable device, chronic heart failure, mitral valve prolapse with regurgitation, IV drug abuse (IVDA), HIV infection, and poor dentition and/or oral hygiene. Three groups of organisms cause most cases of IE: staphylococci, streptococci, and enterococci. Staphylococci (S. aureus and coagulase-negative staphylococci; S. epidermidis) are the most common cause of prosthetic valve endocarditis (PVE) within the first year after valve surgery, and S. aureus is common in those with a history of IVDA. Some fungi and gram-negative bacteria; HACEK organisms (e.g., Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella) are less commonly involved in IE.  Clinical presentation The clinical presentation of patients with IE is highly variable and nonspecific. Fever is the most common finding (more than 90% of patients). The mitral and aortic valves are most often affected. IE usually begins insidiously and worsens gradually. Patients may present with non-specific findings such as fever, chills, weakness, dyspnea, cough, night sweats, weight loss, or malaise. Important clinical signs, especially prevalent in subacute illness, may include the following peripheral manifestations (“stigmata”) of endocarditis: Osler nodes, Janeway lesions, splinter hemorrhages, petechiae, clubbing of the fingers, Roth spots, and emboli. The patient may also have a heart murmur (sometimes new or changing), congestive heart failure, cardiac conduction abnormalities, cerebral manifestations, embolic phenomenon, and splenomegaly. Without appropriate antimicrobial therapy and surgery, IE is usually fatal. With proper management, recovery can be expected in most patients. Factors associated with increased mortality include: congestive heart failure, culture-negative endocarditis, endocarditis caused by resistant organisms such as fungi and gram-negative bacteria, left-sided endocarditis caused by Staphylococcus aureus, PVE.  Diagnosis Ninety to 95% of patients with IE have a positive blood culture. The hallmark laboratory finding is continuous bacteremia; three sets of blood cultures from 3 different sites should be collected within 1 hour (over 24 hours). Anemia, leukocytosis, and thrombocytopenia may be present. The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) may be elevated in approximately 60% of patients. Urinalysis may reveal proteinuria and microscopic hematuria. Transesophageal echocardiography is important in identifying and localizing valvular lesions in patients suspected of having IE. It is more sensitive for d ete c t i n g ve getat i o n s ( 9 0 % – 1 0 0 % ) , c o m p a re d w i t h t ra n st h o ra c i c echocardiography (40%–65%). The Modified Duke criteria, encompassing major findings of persistent bacteremia and echocardiographic findings and other minor findings, are used to categorize patients as “definite IE” or “possible IE”.  Non-pharmacological therapy Surgical intervention to remove the infectious foci and repair valves and/or valvular structures is an important adjunct in the management of both NVE (native valve endocarditis) and PVE (prosthetic valve endocarditis). In most cases, valvectomy and valve replacement are performed to remove infected tissues and restore hemodynamic function. Indications for surgery include heart failure, persistent bacteremia, persistent vegetation, an increase in vegetation size, or recurrent emboli despite prolonged antibiotic treatment, paravalvular extension (eg, abscess), or endocarditis caused by resistant organisms.  Pharmacological therapy Goals of Treatment: relieve the signs and symptoms of disease. Decrease morbidity and mortality associated with infection. Eradicate the causative organism with minimal drug exposure. Provide cost-effective antimicrobial therapy. Prevent IE in high risk patients with appropriate prophylactic antimicrobials. The most important approach to treatment of IE is isolation of the infecting pathogen and determination of antimicrobial susceptibilities, followed by initiating in the hospital high-dose, parentral bactericidal antibiotics for an extended period. Outpatient antimicrobial therapy should be considered early in the treatment of IE, after the patient is stable clinically and responds favorably to initial antibiotics. β-Lactam antibiotics, such as nafcillin (or oxacillin), penicillin G (or ceftriaxone), and ampicillin, remain the drugs of choice for staphylococcal, streptococcal, and enterococcal endocarditis, respectively.  Pharmacological therapy v STAPHYLOCOCCAL ENDOCARDITIS Endocarditis is most commonly caused by staphylococci, in particular S. aureus, mainly because of increased IVDA, more frequent use of peripheral and central venous catheters, and increased frequency of valve replacement surgery. Coagulase-negative staphylococci (usually S. epidermidis) are prominent causes of PVE. The recommended therapy for patients with left-sided IE caused by methicillin- susceptible S. aureus (MSSA) is 6 weeks of nafcillin or oxacillin. If a patient has a mild, delayed allergy to penicillin, first-generation cephalosporins (such as cefazolin) are effective alternatives but should be avoided in patients with an immediate-type hypersensitivity reaction.  Pharmacological therapy v STAPHYLOCOCCAL ENDOCARDITIS In a patient with a positive penicillin skin test or a history of immediate hypersensitivity to penicillin, vancomycin is an option. Penicillin-allergic patients who fail on vancomycin therapy should be considered for penicillin desensitization. Vancomycin (plus rifampin) is the drug of choice for methicillin- resistant staphylococci because most methicillin-resistant S. aureus (MRSA) and most coagulase-negative staphylococci are susceptible (sometimes, an aminoglycoside is added). Daptomycin is a recommended alternative.  Pharmacological therapy v STREPTOCOCCAL ENDOCARDITIS Streptococci are a common cause of IE, with most isolates being viridans group streptococci. Most viridans group streptococci are highly sensitive to penicillin G with MICs of 0.12 mcg/mL or less. Recommended therapy in the uncomplicated case caused by fully susceptible strains in native valves is 4 weeks of either high-dose penicillin G or ceftriaxone, or 2 weeks of combined penicillin G or ceftriaxone therapy plus gentamicin. Approximately 10%–20% are moderately susceptible (MIC 0.12–0.5 mcg/mL). For patients with complicated infection or when the organism is relatively resistant (MIC = 0.12–0.5 mcg/mL), combination therapy with an aminoglycoside and penicillin (higher dose) or ceftriaxone for the first 2 weeks is recommended followed by penicillin or ceftriaxone alone for an additional 2 weeks.  Pharmacological therapy v STREPTOCOCCAL ENDOCARDITIS When a patient has a history of an immediate-type hypersensitivity to penicillin, vancomycin should be chosen for IE caused by viridans group streptococci. When vancomycin is used, the addition of gentamicin is not recommended (Why??). In patients with endocarditis of prosthetic valves or other prosthetic material caused by viridans streptococci and Streptococcus bovis, treatment courses are extended to 6 weeks.  Pharmacological therapy v ENTEROCOCCAL ENDOCARDITIS Enterococci are the third leading cause of endocarditis and are noteworthy for the following reasons: (1) no single antibiotic is bactericidal (combinations of a cell wall–active agent, such as a penicillin or vancomycin, plus an aminoglycoside are necessary for killing); (2) MICs to penicillin are relatively high (1–25 mcg/mL); and (3) they are intrinsically resistant to all cephalosporins and relatively resistant to aminoglycosides. Enterococcal endocarditis ordinarily requires 4–6 weeks of high-dose penicillin G or ampicillin, plus gentamicin for cure. Ampicillin plus ceftriaxone is as effective as ampicillin plus gentamicin and should be considered as a treatment option. In addition to isolates with high-level aminoglycoside resistance, β-lactamase–producing enterococci (especially Enterococcus faecium) are increasingly reported. If these organisms are discovered, use of vancomycin or ampicillin–sulbactam in combination with gentamicin should be considered.  Evaluation of therapeutic outcomes The evaluation of patients treated for IE includes assessment of signs and symptoms, blood cultures, microbiologic tests (eg, MIC, or serum bactericidal titers), serum drug concentrations, and other tests to evaluate organ function. Persistence of fever beyond 1 week may indicate ineffective antimicrobial therapy, emboli, infections of intravascular catheters, or drug reactions. In some patients, fever may persist even with appropriate antimicrobial therapy. With effective therapy, blood should sterilize with negative cultures within a few days, although microbiologic response to vancomycin may be unusually slower. After the initiation of therapy, blood cultures should be rechecked until they are negative. If bacteria continue to be isolated from blood beyond the first few days of therapy, it may indicate that the antimicrobials are inactive against the pathogen or that the doses are not producing adequate concentrations at the site of infection. For all isolates from blood cultures, MICs should be determined.  Prevention of endocarditis Antimicrobial prophylaxis is used to prevent IE in patients believed to be at high risk. The use of antimicrobials for this purpose requires consideration of the types of patients who are at risk; the procedures causing bacteremia; the organisms that are likely to cause endocarditis; and the pharmacokinetics, spectrum, cost, and ease of administration of available agents. Q1: Which of the following antibiotics is commonly used as empiric therapy for native valve infective endocarditis caused by Gram-positive cocci? A) Ciprofloxacin B) Vancomycin C) Amoxicillin D) Azithromycin Q2: For infective endocarditis caused by Streptococcus viridans, which of the following antibiotics is commonly prescribed as first- line therapy in a patient without penicillin allergy? A) Metronidazole B) Doxycycline C) Penicillin G D) Rifampin Q3: What is the typical duration of antibiotic therapy for infective endocarditis caused by Staphylococcus aureus involving a prosthetic valve? A) 1 week B) 2 weeks C) 4-6 weeks D) 6-12 months Q4: In patients with infective endocarditis due to methicillin- sensitive Staphylococcus aureus (MSSA), which antibiotic is the preferred treatment? A) Vancomycin B) Cefazolin C) Gentamicin D) Clindamycin Q5: Which of the following adjunctive therapies is typically recommended for treating infective endocarditis involving a prosthetic valve caused by Staphylococcus aureus? A) Daptomycin alone B) Vancomycin with rifampin and gentamicin C) Amoxicillin-clavulanate D) Azithromycin Q6: For penicillin-allergic patients with infective endocarditis caused by Enterococcus species, which antibiotic regimen is preferred? A) Daptomycin and ciprofloxacin B) Vancomycin and gentamicin C) Ampicillin-sulbactam and metronidazole D) Ceftriaxone and doxycycline Q7: Which of the following is a key reason for using combination therapy (e.g., gentamicin with beta-lactam antibiotics) in treating infective endocarditis caused by Enterococcus? A) To reduce the risk of renal toxicity B) To improve the penetration of the drug into biofilms C) To minimize the side effects of antibiotics D) To reduce the development of resistance Q8: Which antibiotic is the treatment of choice for methicillin- resistant Staphylococcus aureus (MRSA) infective endocarditis in a patient with normal renal function? A) Linezolid B) Vancomycin C) Penicillin G D) Ceftriaxone Q9: In infective endocarditis caused by HACEK organisms (e.g., Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella), which of the following is the recommended antibiotic therapy? A) Vancomycin B) Ciprofloxacin C) Ampicillin-sulbactam D) Ceftriaxone Q10: For infective endocarditis caused by methicillin-resistant Staphylococcus aureus (MRSA) that is vancomycin-resistant, which of the following antibiotics is an alternative? A) Daptomycin B) Amoxicillin C) Penicillin G D) Cefuroxime Q11: Which of the following is the most common causative organism of native valve infective endocarditis in intravenous drug users? A) Streptococcus viridans B) Staphylococcus aureus C) Enterococcus faecalis D) Pseudomonas aeruginosa Q12: Which of the following clinical features is most commonly associated with infective endocarditis? A) Bradycardia B) Painless jaundice C) Fever D) Hemoptysis Q13: Which diagnostic test is most sensitive for detecting vegetations in infective endocarditis? A) Transthoracic echocardiogram (TTE) B) Electrocardiogram (ECG) C) Chest X-ray D) Transesophageal echocardiogram (TEE) Q14: In infective endocarditis caused by Streptococcus viridans, what is the most appropriate first-line treatment for a patient with no known drug allergies? A) Vancomycin B) Penicillin G C) Linezolid D) Azithromycin thank you