Dr Babak Tamizi far MD. Assistant Professor Of Internal Medicine Al-Zahra Hospital Isfahan University Of Medical Sciences ١
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A 57-year-old man presents with new-onset fever, shortness of breath, lower extremity swelling, and weakness of his entire left side. If retinal examination is abnormal, which one of the following is a likely abnormality? a. Papilledema b. Sausage-shaped appearance of arterioles c. Fundal hemorrhage d. Background diabetic retinopathy e. Absence of red reflex ٤
ESSENTIALS OF DIAGNOSIS Preexisting organic heart lesion Fever New or changing heart murmur Evidence of systemic emboli Positive blood culture Evidence of vegetation on echocardiography ٥
GENERAL CONSIDERATIONS Important factors that determine the clinical presentation Nature of the infecting organism Which valve is infected Route of infection ٦
More virulent organisms, particularly Staphylococcus aureus, cause Rapidly progressive and destructive infection Acute febrile illnesses Early embolization Acute valvular regurgitation and myocardial abscess ٧
Subacute presentation Viridans strains of streptococci, enterococci, and other gram-positive and gram-negative bacilli, yeasts, and fungi Systemic and peripheral manifestations may predominate Patients may have underlying cardiac disease, but prevalence as a risk factor is decreasing The initiating event is colonization of the valve by bacteria during a transient or persistent bacteremia ٨
Native valve endocarditis Most commonly due to S aureus (~40%) Viridans streptococci (~30%) Enterococci (5 10%) ٩
Native valve endocarditis Gram-negative organisms and fungi account for a small percentage Injection drug users S aureus in at least 60% of cases and 80 90% of tricuspid valve infections Enterococci and streptococci comprise the balance in about equal proportion ١٠
Prosthetic valve endocarditis Early infections (within 2 months of valve implantation) are commonly caused by Staphylococci both coagulase-positive and coagulase-negative Gram-negative organisms and fungi Late prosthetic valve endocarditis Resembles native valve endocarditis Most cases caused by streptococci, though coagulase-negative staphylococci cause a significant proportion of cases ١١
Organisms Causing Major Clinical Forms of Endocarditis CommunityAcquired (n =1718) Health Care Associated (n =788) Streptococci 40 9 Pneumococci 2 Enterococci 9 13 Staphylococcus aureus 28 53 Coagulase-negative staphylococci 5 12 Fastidious gram-negative coccobacilli (HACEK group) 3 Gram-negative bacilli 1 2 Candida spp. <1 2 Polymicrobial/miscellaneous 3 4 Diphtheroids <1 Culture-negative 9 5 ١٢
DEMOGRAPHICS Injection drug use Underlying valvular disease ١٣
Clinical and Laboratory Features of Infective Endocarditis Feature Frequency % Fever 80 90 Chills and sweats 40 75 Anorexia, weight loss, malaise 25 50 Myalgias, arthralgias 15 30 Anemia 70 90 Back pain 7 15 Leukocytosis 20 30 Heart murmur 80 85 Microscopic hematuria 30 50 New/worsened regurgitant murmur 20 50 Arterial emboli 20 50 Splenomegaly 15 50 Clubbing 10 20 Neurologic manifestations 20 40 Peripheral manifestations (Osler's nodes, subungual hemorrhages, Janeway lesions, Roth's spots) 2 15 Petechiae 10 40 Laboratory manifestations Elevated erythrocyte sedimentation rate 60 90 Elevated C-reactive protein level >90 Rheumatoid factor 50 Circulating immune complexes 65 100 ١٤
Clinical Findings SYMPTOMS AND SIGNS Most present with a febrile illness that has lasted several days to 2 weeks Heart murmurs In most cases, heart murmurs are stable Changing murmur is significant diagnostically, but it is the exception rather than the rule ١٥
Clinical Findings SYMPTOMS AND SIGNS Characteristic peripheral lesions occur in up to 20 25% of patients Petechiae (on the palate or conjunctiva or beneath the fingernails) Subungual ("splinter") hemorrhages Osler nodes (painful, violaceous raised lesions of the fingers, toes, or feet) Janeway lesions (painless erythematous lesions of the palms or soles) Roth spots (exudative lesions in the retina) ١٦
Septic emboli with hemorrhage and infarction due to acute Staphylococcus aureus endocarditis ١٧
DIFFERENTIAL DIAGNOSIS Valvular abnormality without endocarditis Rheumatic heart disease Mitral valve prolapse Bicuspid or calcific aortic valve ١٨
DIFFERENTIAL DIAGNOSIS Flow murmur (anemia, pregnancy, hyperthyroidism, sepsis) Atrial myxoma Noninfective endocarditis, eg, systemic lupus erythematosus (Libman-Saks endocarditis), marantic endocarditis (nonbacterial thrombotic endocarditis) Hematuria due to other causes, such as Glomerulonephritis Renal cell carcinomaacute rheumatic fever - Vasculitis ١٩
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Diagnosis LABORATORY TESTS Blood culture Most important diagnostic tool To maximize the yield, obtain three sets of blood cultures at least 1 h apart before starting antibiotics ٢١
In acute endocarditis, leukocytosis is common In subacute cases, anemia of chronic disease and a normal white blood cell count are the rule Hematuria and proteinuria as well as renal dysfunction may result from emboli or immunologically mediated glomerulonephritis ٢٢
Duke criteria for the diagnosis Major criteria Two positive blood cultures for a typical microorganism of infective endocarditis Positive echocardiography (vegetation, myocardial abscess, or new partial dehiscence of a prosthetic valve) New regurgitant murmur ٢٣
Duke criteria for the diagnosis Minor criteria Presence of a predisposing condition Fever > 38 C Embolic disease Immunologic phenomena (Osler nodes, Roth spots, glomerulonephritis, rheumatoid factor) Positive blood cultures not meeting the major criteria or serologic evidence of active infection with an organism that causes endocarditis ٢٤
Duke criteria for the diagnosis A definite diagnosis is made with 80% accuracy if two major criteria, or one major criterion and three minor criteria, or five minor criteria are fulfilled Possible endocarditis is defined as the presence of 1 major and 1 minor criterion, or three minor criteria If these criteria thresholds are not met and either an alternative explanation for illness is identified or the patient has defervesced within 4 days, endocarditis is highly unlikely ٢٥
IMAGING STUDIES Chest radiograph may show findings indicating an underlying cardiac abnormality in right-sided endocarditis, pulmonary infiltrates Echocardiography Transthoracic echocardiography is 55 65% sensitive; it cannot rule out endocarditis but may confirm a clinical suspicion Transesophageal echocardiography is 90% sensitive in detecting vegetations is particularly useful for identifying valve ring abscesses, and pulmonary and prosthetic valve ٢٦ endocarditis
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DIAGNOSTIC PROCEDURES The ECG is nondiagnostic. Changing conduction abnormalities suggest myocardial abscess formation ٢٨
Treatment MEDICATIONS SURGERY
The diagnostic use of transesophageal and transtracheal echocardiography ٣٠
MEDICATIONS For penicillin-susceptible viridans streptococcal endocarditis (ie, MIC 0.1 mcg/ml) Penicillin G, 2 3 million units intravenously every 4 hours for 4 weeks Duration of therapy can be shortened to 2 weeks if gentamicin, 1 mg/kg intravenously every 8 hours, is used with penicillin (do not use 2 week regimen if symptoms are present for at least 3 months or there are complications such as myocardial abscess or extracardiac infection) ٣١
MEDICATIONS For penicillin-susceptible viridans streptococcal endocarditis (ie, MIC 0.1 mcg/ml) Ceftriaxone, 2 g once daily intravenously or intramuscularly for 4 weeks, is also effective therapy and is a convenient regimen for home therapy For the penicillin-allergic patient, vancomycin, 15 mg/kg intravenously every 12 hours for 4 weeks, is given ٣٢
For penicillin-resistant viridans streptococci (ie, MIC > 0.1 mcg/ml but 0.5 mcg/ml) Treat for 4 weeks Penicillin G, 3 million units intravenously every 4 hours, is combined with gentamicin, 1 mg/kg intravenously every 8 hours for the first 2 weeks In the patient with IgE-mediated allergy to penicillin, vancomycin alone, 15 mg/kg intravenously every 12 hours for 4 weeks, should be administered ٣٣
Vancomycin should be effective for endocarditis caused by strains resistant to penicillin Group A streptococcal infection can be treated with penicillin, ceftriaxone, or vancomycin for 4 6 weeks Groups B, C, and G streptococci Tend to be more resistant to penicillin than group A streptococci Some experts recommend adding gentamicin, 1 mg/kg intravenously every 8 hours, to penicillin for the first 2 weeks of a 4- to 6-week course ٣٤
enterococcal endocarditis Penicillin alone is inadequate; either streptomycin or gentamicin must be included Gentamicin is the aminoglycoside of choice, because streptomycin resistance is more common Ampicillin, 2 g intravenously every 4 hours, or penicillin G, 3 4 million units intravenously every 4 hours penicillin-allergic patient, vancomycin, + gentamicin, The recommended duration of combination therapy is 4 6 weeks ٣٥
methicillin-susceptible S aureus Nafcillin or oxacillin, 1.5 2 g intravenously every 4 hours for 6 weeks, is the preferred therapy Uncomplicated tricuspid valve endocarditis probably can be treated for 2 weeks with nafcillin or oxacillin alone For penicillin-allergic patients, cefazolin, 2 g intravenously every 8 hours, or vancomycin, 30 mg/kg intravenously divided in two or three doses, may be used For methicillin-resistant strains, vancomycin remains the preferred agent A combination of vancomycin, 30 mg/kg/d intravenously divided in two or three doses for 6 weeks, rifampin, 300 mg every 8 hours for 6 weeks, and gentamicin, 1 mg/kg intravenously every 8 hours for the first 2 weeks, is recommended for prosthetic valve infection ٣٦
endocarditis caused by HACEK organisms Ceftriaxone (or some other thirdgeneration cephalosporin), 2 g intravenously once daily for 4 weeks is treatment of choice Prosthetic valve endocarditis should be treated for 6 weeks In the penicillin-allergic patient, experience is limited, but trimethoprim-sulfamethoxazole, quinolones, and aztreonam should be considered ٣٧
Surgery required for optimal outcome Moderate to severe congestive heart failure due to valve dysfunction Partially dehisced unstable prosthetic valve Persistent bacteremia despite optimal antimicrobial therapy Lack of effective microbicidal therapy (e.g., fungal or Brucella endocarditis) S. aureus prosthetic valve endocarditis with an intracardiac complication Relapse of prosthetic valve endocarditis after optimal antimicrobial therapy ٣٨
Surgery to be strongly considered for improved outcome Perivalvular extension of infection Poorly responsive S. aureus endocarditis involving the aortic or mitral valve Large (>10-mm diameter) hypermobile vegetations with increased risk of embolism Persistent unexplained fever (>10 days) in culture-negative native valve endocarditis Poorly responsive or relapsed endocarditis due to highly antibiotic-resistant enterococci or gram-negative bacilli ٣٩
Timing of Cardiac Surgical Intervention in Patients with Endocarditis Timing Strong Supporting Evidence Emergent (same day) Acute aortic regurgitation plus preclosure of mitral valve Sinus of Valsalva abscess ruptured into right heart Rupture into pericardial sac Urgent (within 1 2 days) Valve obstruction by vegetation Unstable (dehisced) prosthesis Acute aortic or mitral regurgitation with heart failure (New York Heart Association class III or IV) Septal perforation Perivalvular extension of infection with/without new electrocardiographic conduction system changes Lack of effective antibiotic therapy Elective (earlier usually preferred) Progressive paravalvular prosthetic regurgitation Valve dysfunction plus persisting infection after antimicrobial therapy Fungal (mold) endocarditis 7 10 days of ٤٠
SURGERY Valvular regurgitation resulting in acute heart failure not resolve promptly after institution of medical therapy even if active infection is present, especially if the aortic valve is involved ٤١
SURGERY Infections that do not respond to appropriate antimicrobial therapy after 7 10 days (ie, persistent fevers, positive blood cultures despite therapy) are more likely to be eradicated if the valve is replaced Nearly always required for fungal endocarditis and is more often necessary with gram-negative bacilli ٤٢
SURGERY Infection involving the sinus of Valsalva or produces septal abscesses Recurrent infection with the same organism often indicates that surgery is necessary, especially with infected prosthetic valves Continuing embolization when the infection is otherwise responding may be an indication for surgery ٤٣
THERAPEUTIC PROCEDURES Colonoscopy should be performed to exclude colon cancer in patients with endocarditis caused by S bovis ٤٤
Outcome FOLLOW-UP Defervescence occurs in 3 4 days on average if infection is caused by Viridans streptococci Enterococci Coagulase-negative staphylococci Patients may remain febrile for a week or more if infection is caused by S aureus Pseudomonas aeruginosa ٤٥
COMPLICATIONS Destruction of infected heart valves Myocardial abscesses leading to conduction disturbances Systemic embolization Metastatic infections Mycotic aneurysms Right-sided endocarditis, leads to septic pulmonary emboli, ٤٦
PROGNOSIS Higher morbidity and mortality associated with nonstreptococcal etiology, aortic or prosthetic valvular infection ٤٧
WHEN TO REFER Infectious diseases consultation recommended Patients with signs of heart failure should be referred for surgical evaluation WHEN TO ADMIT Patients with evidence of heart failure Patients with a nonstreptococcal etiology For initiation of antimicrobial therapy in suspected, definite, or possible cases ٤٨
Thank you ٤٩
PREVENTION ٥٠
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