D.BASEM ELSAID ENANYLECTURER OF CARDIOLOGY

AINSHAMS UNIVERSITY

Infective endocarditis

-- Staphylococci and streptococci account for the majority of cases.--S. aureusViridans group streptococci EnterococciCoagulase-negative staphylococciStreptococcus bovisOther streptococciNon-HACEK gram-negative bacteria Fungi 2%HACEK 2%; Organisms in this category include a number of fastidious gram-negative bacilli: Haemophilus aphrophilus; Actinobacillus actinomycetemcomitans; Cardiobacterium hominis; Eikenella corrodens; and Kingella kingae.--Culture negative endocarditis (8%).

--most common organism causing subacute native valve endocarditis-> Streptococcus viridians.--most common organism causing endocarditis in intravenous drug abusers (IVDA) Staphylococcus aureus.----most common organism causing early prosthetic valve endocarditis Staphylococcus infection, particularly S. epidermidis and S. aureus--E. faecalis endocarditis is often associated with malignancy or manipulation of the gastrointestinal orgenitourinary tract.--most common cause of culture-negative endocarditis prior use of antibiotics. Other causes include fastidious organisms (HACEK group, Legionella, Chlamydia, Brucella, certain fungal infections, etc.) and noninfectious causes=Techniques using the polymerase chain reaction (PCR) can detect and identify nonculturableorganisms. Limitations of PCR include lack of reliable application to whole blood samples, risk ofcontamination, false negatives due to the presence of PCR inhibitors in clinical samples, inability toprovide information concerning bacterial sensitivity to antimicrobial agents, and persistent positivity despite clinical remission.

**Factors predispose to the development of IE: injection drug use (IDU) The most common infecting organism is S. aureus, particularly in right-sided infection, prosthetic heart valves (type of prosthetic valve does not have an impact on the development of IE), and structural heart disease (rheumatic, prolapse, congenital: bicuspid aortic valves, patent ductus arteriosus, ventricular septal defect, coarctation of the aorta, and tetralogy of Fallot).**Chronic hemodialysis patients are at significant risk for IE intravascular access, calcific valvular disease, and immune impairment.**Other predisposing factors for IE include:HIVPregnancy Peritoneovenous shunts for the control of intractable ascites Ventriculoatrial shunts for the management of hydrocephalus

AHA 2014

Class IIa1. Prophylaxis against infective endocarditis (IE) is reasonable for the following patients at highestrisk for adverse outcomes from IE before dental procedures that involve manipulation of gingivaltissue, manipulation of the periapical region of teeth, or perforation of the oral mucosa ,(Level of Evidence: B): Patients with prosthetic cardiac valves; Patients with previous IE; Cardiac transplant recipients with valve regurgitation due to a structurally abnormalvalve; or Patients with CHD with:o Unrepaired cyanotic CHD, including palliative shunts and conduits;o Completely repaired congenital heart defect repaired with prosthetic material ordevice, whether placed by surgery or catheter intervention, during the first 6 monthsafter the procedure; oro Repaired CHD with residual defects at the site or adjacent to the site of a prostheticpatch or prosthetic device.

Class IIIProphylaxis against IE is not recommended in patients with VHD who are at risk of IE fornondental procedures (e.g., TEE, esophagogastroduodenoscopy, colonoscopy, or cystoscopy) inthe absence of active infection . (Level of Evidence: B)

==& Antibiotic prophylaxis is recommended for procedures on respiratory tract or infected skin, skin structures, or musculoskeletal tissue only for patients with underlying cardiac conditions associated with the highest risk of adverse outcome from IE.& Antibiotic prophylaxis solely to prevent IE is not recommended for GU or GI tract procedures.

--Libman-Sacks endocarditis is a form of nonbacterial thrombotic endocarditis seen in patients with systemic lupus erythematosus (SLE). Described in 1924, the vegetations most commonly occur on the mitral valve, although they can affect all four cardiac valves. The lesions are due to accumulations of immune complexes, fibrin, and mononuclear cells. Most lesions do not cause symptoms, although valvular regurgitation or stenosis can occasionally occur because of the lesions. Embolization of the lesions is rare.

HISTORY

--History of prior cardiac lesions and historical clues pointing toward a recent source of bacteremia, such as indwelling intravascular catheters or intravenous drug use.--With the rise in rates of IE due to S. aureus in the 21st century, IE is more often presents as acute rather than chronic disease.

PHYSICAL EXAMINATION

--Careful cardiac examination for signs of new regurgitant murmurs or heart failure.--Vigorous search should be undertaken for the classic clinical stigmata of endocarditis, including evidence of small and large emboli with special attention to the fundi, conjunctivae, skin, and digits. --A neurologic evaluation may reveal evidence of focal neurologic impairment; it can also be used as a baseline examination should such abnormalities appear later.--Associated peripheral cutaneous or mucocutaneous lesions of IE include petechiae, splinter hemorrhages, Janeway lesions, Osler's nodes, and Roth spots. --Petechiae are not specific for IE but are its most common skin manifestation (may be present on the skin, usually on the extremities, or on mucous membranes such as the palate or conjunctivae, the latter usually as hemorrhages best seen with eversion of either upper or lower eyelids).--Splinter hemorrhages, also nonspecific for endocarditis, are nonblanching, linear reddish-brown lesions found under the nail bed.

Petechiae

Splinter hemorrhages

--Janeway lesions, Osler's nodes, and Roth spots are more specific (but still not diagnostic) , less common, and Roth spots are rare.--Janeway lesions are macular, nonblanching, nonpainful, erythematous lesions on the palms and soles.--Osler's nodes are painful, violaceous nodules found in the pulp of fingers and toes and are seen more often in subacute than acute cases of IE.--Roth spots are exudative, edematous hemorrhagic lesions of the retina.

Janeway lesion

Osler's nodes

--Patients with IE may have involvement of other organs due to embolic events (eg, focal neurologic deficits, renal and splenic infarcts) or a systemic immune reaction (eg, glomerulonephritis, arthritis). --In right-sided endocarditis, septic pulmonary infarcts may be seen.

What factors (discussed in detail in the ESC guidelines on endocarditis)should raise the suspicion for endocarditis?- Bacteremia or sepsis of unknown cause- Fever- Constitutional symptoms such as unexplained malaise, weakness, arthralgias, and weight loss- Hematuria, glomerulonephritis, and suspected renal infarction- Embolic event of unknown origin- New heart murmur (primarily regurgitant murmurs)- Unexplained new atrioventricular (AV) nodal conduction abnormality (prolonged PR interval,heart block)- Multifocal or rapidly changing pulmonic infiltrates- Peripheral abscesses- Cutaneous lesions (Osler nodes, Janeway lesions)- Ophthalmic manifestations (Roth spots)

Blood cultures

--Should be obtained prior to antibiotic therapy.--A minimum of three blood cultures should be obtained over a time period based upon the severity of the illness: subacute, the patient is not critically ill preferable to delay therapy for one to three days while awaiting the results of blood cultures and other diagnostic tests. Acutely ill three blood cultures should be obtained over a one hour time span before beginning empiric therapy. --Almost all cases of bacterial IE are due to aerobic organisms; thus, culturing for anaerobes is rarely useful. --Additional blood cultures are occasionally useful in patients who have been treated recently with antibiotics.--Since many patients with bacterial endocarditis have low grade bacteremia, a minimum of 10 mL (and preferably 20 mL) of blood should be obtained from adults and 0.5 to 5 mL from infants and children. --Each set of cultures should be obtained from separate venipuncture sites.--Blood cultures can be taken at any time; they do not need to be obtained with the appearance of chills or fever since patients with IE typically have a continuous bacteremia.

The definition of persistent bacteremia varies with the likelihood that the organism is a cause of endocarditis:

For an organism likely to cause endocarditis (eg, S. aureus, viridans streptococci), two positive samples collected more than 12 hours apartFor an organism that is more commonly a skin contaminant, three or a majority of four or more separate blood cultures are positive and the first and last samples are collected at least one hour apart

Other laboratory tests

--Antiphase I IgG titer >1:800 for Coxiella burnetii.--An elevated erythrocyte sedimentation rate and/or an elevated level of C-reactive protein.--A normochromic normocytic anemia.--The white blood cell count may be normal or elevated in patients with subacute presentations of endocarditis; however, most patients with staphylococcal endocarditis have leukocytosis and some may have thrombocytopenia.--Hyperglobulinemia, cryoglobulins, circulating immune complexes, hypocomplementemia, elevated rheumatoid factor titers, and false positive serologic tests for syphilis all occur in some patients.--Most patients with endocarditis have an abnormal urinalysis, as manifested by microscopic or gross hematuria, proteinuria, and/or pyuria (lacks specificity). However, the presence of red blood cell casts on urinalysis is generally indicative of glomerulonephritis.

Electrocardiogram

--The presence or subsequent appearance of changes suggestive of ischemia or infarction on the electrocardiogram may provide useful clues to the presence of emboli to the coronary circulation.--The initial presence or new appearance of heart block or conduction delay may provide an important clue to extension of infection to the valve annulus and adjacent septum.

Chest radiograph

--Evidence of septic pulmonary emboli. In such cases, there may be a few or multiple focal lung infiltrates, which may reveal central cavitation. --Rarely, chest radiographs show calcification in a cardiac valve, which may raise suspicions of endocarditis in a febrile patient.

Multiple cavitating lung nodules due to septic pulmonary emboli

Echocardiography

--Evaluation of patients in settings in which endocarditis is suspected (such as persistent bacteremia without a known source or high clinical suspicion with negative cultures).--Detection and characterization of vegetations on valves and in other sites (as in patients with congenital heart disease).--Detection of valvular dysfunction and assessment of hemodynamic severity.--Detection of associated abnormalities such as shunts or abscesses.--Re-evaluation of patients in complex settings (such as those with virulent organisms, severe hemodynamic effects, persistent or recurrent fever or bacteremia, or clinical deterioration).**TTE has relatively low sensitivity for vegetation in IE (29 to 63 percent in different series) although the specificity approaches 100 percent. Thus, the absence of vegetation does not preclude the diagnosis and TEE is usually warranted.

--Reasonable to begin with TEE in selected settings:

*Limited transthoracic windows (eg, due to obesity, chest wall deformity, or mechanical ventilation)*Prosthetic valves, especially prosthetic aortic or mitral valves in which shadowing may make visualization difficult by TTE*A prior valvular abnormality (including previous endocarditis)*S. aureus bacteremia*Bacteremia due to an organism known to be a common cause of IE such as viridans streptococci

-- Some patients with abnormal on findings on TTE may require further evaluation by TEE ( have one or more of the following risk factors for perivalvular abscess):

*Conduction delay by ECG that is not known to be old*Persistent fever despite appropriate antimicrobial therapy*Aortic valve endocarditis

Diagnostic criteria for vegetations

** Valvular vegetation is defined as "a discrete mass of echogenic material adherent at some point to a leaflet surface and distinct in character from the remainder of the leaflet" based upon the following characteristics:

Texture — gray scale and reflectance of myocardiumLocation — upstream side of the valve in the path of the jet or on prosthetic materialCharacteristic motion — chaotic and orbiting; independent of valve motionShape — lobulated and amorphousAccompanying abnormalities - abscess and pseudoaneurysm, fistulae, prosthetic dehiscence, paravalvular leak, significant preexisting or new regurgitation

** Vegetations also characteristically prolapse into the upstream chamber: mitral vegetations into the atrium in systole and aortic vegetations into the left ventricular outflow tract during diastole. **Vegetations tend to flank the regurgitant jet. **Intracardiac foreign structures, such as pacemaker leads, must also be interrogated for the presence of a vegetation

**Characteristics of a mass not likely to be a vegetation include:

Texture — reflectance of calcium or pericardium (appears white)Location — outflow tract attachment, downstream surface of valveShape — stringy or hair-like strands with narrow attachmentLack of accompanying turbulent flow or regurgitation

**Some vegetations persist after bacterial cure has been achieved and remain stable in size for many years. However, chronic lesions are more echogenic than acute vegetations

Masses have also been analyzed according to four properties:

Size — established by the two largest orthogonal diametersMobility — defined as: grade 1, fixed; grade 2, fixed base free edge; grade 3, pedunculated; grade 4, prolapsingDensity — defined as: grade 1, calcified; grade 2, partially calcified; grade 3, denser than myocardium but not calcified; grade 4, equivalent to myocardiumExtent — defined as: grade 1, single; grade 2, multiple on a single leaflet; grade 3, multiple leaflets; grade 4, extending to extravalvular structures

Nonbacterial endocarditis

— There are a number of nonbacterial causes of endocarditis that may produce vegetations, these are also best evaluated with TEE. Other etiologies include various types of fungal infections, brucellosis, gonococcus, and noninfectious causes including Libman-Sacks endocarditis, Loffler's endocarditis, granulomatous diseases, and scleroderma.

False positive results in TEE

**They arise because small, previously invisible irregularities and degenerative processes are clearly seen in magnified format:

--Tiny mobile strands are frequently encountered on the valves; these strands probably represent a normal degenerative process and are known as Lambl's excrescences.--Strands, possibly from the same source, can also arise on the sewing ring of prosthetic valves. In addition, a free suture end can occasionally be visualized and may be mistaken for a pathologic finding.--Redundant chordae or false tendons in the left ventricle as well as Chiari's remnant in the right atrium may be mistaken for vegetative masses.--Chordal insertion into normal mitral valve margins may mimic a mass.

** Their dense fibrotic nature can best be appreciated by noting their bright nonvibratory nature on M-mode imaging.

** Repeat examination is important, particularly in patients at high risk for IE, such as those with a prosthetic valve or unexplained bacteremia.

--Preliminary data suggest that multislice CT may emerge as a useful tool for evaluation of IE.--Routine culture of heart valves removed at the time of surgery can lead to false positive results. -- Histologic demonstration of microorganisms, vegetations, or active endocarditis in cardiac valve tissue obtained at surgery is included in the Duke criteria and is considered to be a criterion of confirmed infective endocarditis. IE was characterized by microorganisms, vegetations, and significant neutrophil-rich inflammatory infiltrates with extensive neovascularization.-- Routine magnetic resonance imaging (MRI) may be useful in patients with definite or suspected IE.

Treatment

--Bactericidal, not bacteriostatic, therapy are effective in treating endocarditis.--Empiric therapy:*Therapy for IE should be targeted to the organism isolated from blood cultures.*Cultures are positive in over 90% of patients with IE. *For patients with suspected IE who present without acute symptoms, empiric therapy is not always necessary results of blood cultures are usually available within one to three days.*Acutely ill patients with signs and symptoms strongly suggestive of IE, empirical therapy may be necessaryONLY after at least two (preferably three) sets of blood cultures have been obtained from separate venipunctures.*Empirical therapy should cover staphylococci (methicillin-susceptible and resistant), streptococci and enterococci. Vancomycin (30 mg/kg per 24 h IV in two divided doses) is appropriate choice for initial therapy in most patients.

-- Most patients with IE become afebrile 3-5 days after treatment is begun with an appropriate antibiotic. Patients with S. aureus endocarditis may respond somewhat more slowly, remaining febrile for 5-7 days after the institution of therapy.--Initial microbiologic response to therapy should be assessed by obtaining repeat blood cultures 48 to 72 hours after antibiotics are begun. --Thereafter, regular careful serial examinations should be performed to search for signs of heart failure, emboli, or other complications.--Duration of therapy must be sufficient to eradicate microorganisms growing within the valvular vegetations.--Oral regimens should NOT be used as initial therapy.--When expertise is available to safely supervise desensitization protocols the health care provider should inform the patient who undergoes desensitization that the tolerance induced persists only as long as the patient continues to receive the drug. Once antibiotic therapy is stopped for a period of more than 24 hours, repeat desensitization is required if the particular drug is to be used again.

--Selected patients with native valve noncomplicated right-sided endocarditis due to S. aureus with no evidence of renal failure, extrapulmonary metastatic infections, or simultaneous left-sided valvular infection, may be successfully treated with two week regimens utilizing the combination of nafcillin and gentamicin

Culture-negative IE

*Defined as endocarditis without etiology following inoculation of three independent blood samples in a standard blood culture system with negative cultures after seven days of incubation and subculturing. *Cultures are negative in endocarditis for three major reasons:

Previous administration of antimicrobial agentsInadequate microbiological techniquesInfection with highly fastidious bacteria or nonbacterial pathogens (eg, fungi)

Prosthetic valve endocarditis

--All treatment for PVE should be initiated in the hospital, preferably in an institution where cardiac surgery is available. (6weeks)--Patients should remain hospitalized until fever resolves and it is clear that surgery can be safely avoided.--Patients presenting with hemodynamic instability or acute disease should receive empiric antibiotics promptly after three sets of blood cultures have been obtained. Empiric antibiotic therapy with three agents should be initiated: vancomycin, gentamicin, and either cefepime or a carbapenem. --The antimicrobials used to treat a specific pathogen causing PVE are generally the treatment used for that organism when it causes native valve endocarditis (NVE). Staphylococci, which commonly cause PVE, are an exception to this dictum.

Fungal PVE

--Most infectious disease specialists, recommend a combined approach that utilizes both antifungal agents and valve replacement. --Amphotericin B (daily doses ranging from 0.7 to 1.0 mg/kg per day) is the antimicrobial of choice for treatment of fungal PVE as the greatest clinical experience in treating fungal PVE is with this agent.--For the treatment of endocarditis caused by mycelial fungi, such as Aspergillus or Mucor species, somewhat larger doses are used (1.0 to 1.5 mg/kg per day). Some recommend for the treatment of fungal endocarditis, amphotericin B be combined with flucytosine (150 mg/kg per day divided into four doses with adjustments for renal dysfunction) in an attempt to achieve a synergistic effect. This initial phase of treatment is usually given for at least six weeks.--Since the potential for relapse is high in Candida PVE, even with surgical intervention, it is recommended along with most infectious disease specialists a suppressive second phase of oral therapy with fluconazole (200 to 400 mg daily or another triazole) for prolonged periods, if not indefinitely

CULTURE-NEGATIVE PVE

--In the absence of clinical clues to a specific etiology, the AHA recommend that treatment for culture-negative PVE, with onset within the first year following valve surgery, should include vancomycin, gentamicin, cefepime, and rifampin. The ESC recommendations for this group omit cefepime. --For initial therapy of PVE with onset greater than one year after surgery, the AHA and the ESC recommend treatment with ampicillin-sulbactam plus gentamicin or vancomycin, gentamicin and ciprofloxacin. The AHA recommends the addition of rifampin to these regimens. --For patients with the onset of disease 12 months or more after valve implantation where Bartonella is suspected, the AHA recommend treatment with ceftriaxone, gentamicin, and doxycycline. --Aggressive efforts must be made to identify a causative agent and specific therapy defined, since treatment regimens for the causes of true blood culture-negative endocarditis vary widely. --Epidemiologic considerations should be weighed carefully. As an example, in some regions of the world Coxiella burnetii is a common cause of culture-negative PVE. The possibility of fungal endocarditis should be considered, especially in patients with a complex perioperative course.--If unexplained fever persists in the face of empiric therapy, surgery to obtain a vegetation for microbiologic evaluation should be considered

Complications

--Complications and severe outcomes tend to occur with greater frequency among the elderly and patients with renal failure.--Complications can occur before, during and, rarely, even after the end of therapy (eg, ruptured mycotic aneurysm).--According to pathogenesis:Embolic (eg, cerebral infarct)Local spread of infection (eg, heart valve destruction)Metastatic infection (eg, vertebral osteomyelitis)Immune-mediated damage (eg, glomerulonephritis)

CARDIAC COMPLICATIONS

**Heart failure (HF) remains the most common cause of death due to IE.-Valvular insufficiency resulting from infection-induced valvular damage is the usual cause. Rarely, embolism of fragments of valvular vegetations or vegetation-induced stenosis of the coronary ostia can cause acute myocardial infarction and subsequent HF.**Perivalvular abscesses : about 30 to 40 percent. The aortic valve and its adjacent annulus are more susceptible.-Involvement of the conducting system is most common with infection of the aortic valve, especially when there is involvement of the valve ring between the right and non-coronary cusp.-Should be suspected when fever persists despite appropriate antimicrobial therapy and/or when conduction abnormalities appear on the ECG.-(TEE) has a much greater likelihood of detecting a myocardial abscess than (TTE).-Appear to have higher rates of systemic embolization and fatal outcomes.

**Other rare extravalvular cardiac complications of IE include:

--Pericarditis, which may be suppurative or nonsuppurative, can rarely cause pain or even cardiac tamponade.--Fistulous intracardiac connections (eg, aorta-atrial or aorta-ventricular) due to extension of infection from the valve to adjacent myocardium may rarely result in large aneurysms, a pseudoaneurysm if the aortic wall is involved or even myocardial perforation.--Aortic valve dissection.--Descending thoracic aorta intraluminal infectious masses.

EMBOLIZATION

--Systemic emboli most commonly complicate left-sided IE but rarely can occur in tricuspid valve endocarditis via a patent foramen ovale, appears to be more common with IE due to fungal pathogens.--Emboli to the lung with subsequent abscess formation occur frequently in patients with tricuspid endocarditis.--Emboli can produce:

StrokeBlindnessPainful ischemic or frankly gangrenous extremitiesUnusual pain syndromes (eg, due to splenic or renal infarction)Hypoxia (due to pulmonary emboli in right-sided endocarditis)Paralysis (due to embolic infarction of either the brain or spinal cord)Acute myocardial infarction--Risk of embolization tends to decline after the institution of effective antimicrobial therapy.--Vegetation size is generally a risk factor for embolization.--The initiation of aspirin after the diagnosis of IE is of no benefit and may be harmful.

NEUROLOGIC COMPLICATIONS

--Symptomatic cerebrovascular complications occur in about 35 percent of patients. Silent cerebrovascular complications (including ischemia and microhemorrhage) may occur in up to 80 percent of patients.--Neurologic complications may be the presenting symptom in patients with IE.--The mechanism for and types of neurologic complications are diverse and include:

Embolic strokeAcute encephalopathyMeningoencephalitisPurulent or aseptic meningitisCerebral hemorrhage (due to stroke or a ruptured mycotic aneurysm)Brain abscess or cerebritisSeizures (secondary to abscess or embolic infarction)

--RENAL : Renal infarction (due to emboli), drug-induced acute interstitial nephritis, glomerulonephritis (due to deposition of immunoglobulins and complement in the glomerular membrane) and, rarely, renal abscess can occur in patients with IE.--Rarely, metastatic abscesses develop in the kidneys, spleen, brain or soft tissues (eg, the psoas muscle) in the setting of IE. Persistent fever during or after treatment for IE and occasionally recurrent bacteremia after cure of the valvular infection may be the only clues to the presence of splenic abscess. Splenic abscesses are often diagnosed only at autopsy and generally require splenectomy for cure. Appropriate treatment, including drainage of abscesses, is needed not only to control the local infection but also to prevent ongoing bacteremia

--Mycotic aneurysms can occur in the cerebral or systemic circulation of patients with IE, usually at points of vessel bifurcation. (greatest affinity for the arterial wall and more likely to cause infected aneurysm=Staphylococcus spp and Salmonella spp. )--Classic presentation is a painful, pulsatile, and enlarging mass together with systemic features of infection, such as fever and malaise. The mass may be palpable or demonstrable only by imaging. In the setting of aneurysm involving the aorta, the patients may complain of back or abdominal pain may. Infected aneurysms can rupture presenting as expanding hematoma or if an intracerebral vessel is affected, as stroke or subarachnoid hemorrhage. --(CT) angiography definitively diagnoses the aneurysm:Saccular, eccentric aneurysm or multilobulated aneurysm.Soft tissue inflammation or mass around a vessel.Aneurysm with intramural air or air collection around the vessel.Perivascular fluid collection.--Prior to the availability of culture results, we favor treatment with a combination of vancomycin and an agent with activity against gram-negative organisms, especially Salmonella and enteric gram-negatives; reasonable choices include ceftriaxone, a fluoroquinolone, and piperacillin-tazobactam.--At extracranial sites in patients with an acceptable surgical risk, surgical excision of the aneurysm and wide debridement of infected tissues is the treatment of choice. Patients with a high surgical risk and at some anatomic sites (eg, nonruptured intracerebral) may be best managed with antibiotic therapy alone.--Endovascular techniques may be useful as a palliative measure for patients who refuse surgery, those with a prohibitive risk for surgery, and possibly for patients with ruptured infected aneurysm, as a means to contain the rupture, thus allowing definitive treatment under more elective circumstances. (does not remove the infected focus)

--Vertebral osteomyelitis is a well known but relatively rare complication of IE. Severe back pain in any patient with IE should alert the clinician to this possibility.--Acute septic arthritis, involving one or more joints, may be the first clue to the presence of IE:*When infections spontaneously arise in joints of the axial skeleton (eg, sacroiliac, pubic, or manubriosternal joints).*When organisms with a known propensity to cause IE (eg, S. aureus, viridans streptococci or non-group A beta-hemolytic streptococci) grow from a joint aspirate, particularly in patients without a history of recent surgery, joint infection, or trauma.*When multiple joints are infected.

COMPLICATIONS OF MEDICAL OR SURGICAL THERAPY

--Aminoglycoside-induced ototoxicity or nephrotoxicity--Secondary bacteremia due to central vascular lines--Mediastinitis or early postoperative prosthetic valve endocarditis--Intravenous catheter-associated phlebitis--Drug fever--Allergic or idiosyncratic reactions to various antimicrobial agents--Bleeding due to disturbances in coagulation caused by anticoagulants (in prosthetic valve endocarditis)

Predictors of death

Infection with S. aureusHeart failureDiabetes mellitus Embolic eventsPerivalvular abscessLarger vegetation size Female genderContraindication to surgery Low serum albumin Persistent bacteremia Abnormal mental status Poor surgical candidacy

Surgery in native valve endocarditis

--Surgery is warranted for patients with active native valve IE who have one or more of the following complications:

*Heart failure (HF), particularly if moderate to severe, that is directly related to valve dysfunction*Severe aortic or mitral regurgitation with evidence of abnormal hemodynamics such as premature closure of the mitral valve in patients with aortic insufficiency*Endocarditis due to fungal or other highly resistant organisms*Perivalvular infection with abscess or fistula formation*Several other complications are considered possible indications for surgery in selected patients with IE. These include:

-Embolic events while on an appropriate antibiotic regimen OR associated with a large vegetation (larger than 10 mm in diameter)-Vegetations larger than 10 mm in diameter, even without embolic events, if mobile and associated with other signs of more severe disease. -The European Guidelines cited also include isolated vegetation >15 mm in size as an indication for surgery although they acknowledge that the evidence for this recommendation is relatively weak.

--Antibiotics should be continued for at least the planned duration of therapy (four to six weeks) with longer therapy if cultures of the surgically-removed tissue are positive.--Surgery should not be delayed to complete antimicrobial therapy in patients with progressive HF or evidence of other complications.

Emergency surgery: surgery performed within 24 h, urgent surgery: within a few days, elective surgery: after at least 1 or 2 weeks of antibiotic therapy.

Surgery in prosthetic valve endocarditis

--The European Society of Cardiology recommends emergent or urgent surgery for PVE when there is severe valve dysfunction or fistula formation and refractory pulmonary edema, cardiogenic shock, or persisting heart failure. --Urgent surgery is also advised for uncontrolled infection (abscess, fistula), bacteremia persisting for 7 to 10 days, PVE caused by fungi or multiresistant organisms, and PVE caused by staphylococci or gram-negative bacilli (especially if onset is early after surgery). --Similarly, for prevention of emboli after a prior embolus, when there are other indications for surgery and vegetations are large (>10 mm), or perhaps very large vegetations (>15 mm) are present, urgent surgery is recommended. --Surgery to prevent emboli based on large vegetations alone is supported by expert opinion only and relatively controversial. --Surgery for dehiscent, dysfunctional prosthetic valves in the absence of heart failure can be elective.--Surgery is generally advised for PVE caused by S. aureus when accompanied by intracardiac complications, and also for fungi, gram-negative (nonHACEK) microorganisms (particularly P. aeruginosa), and multi-drug resistant enterococci.--Following valve replacement for active bacterial endocarditis, the Task Force on Infective Endocarditis of the (ESC) recommends another full course (six weeks) of antimicrobial treatment if the intraoperative valve culture is positive. If the culture is negative and pathology does not indicate acute necrotizing infection, ESC recommendes that the full treatment course be completed (counting the duration of preoperative antibiotics).--The rate of recurrent PVE after surgery is six to 15 percent.

Anticoagulant and antiplatelet therapy in patients with infective endocarditis

**Mechanical heart valves:--The 2008 ACCP Guidelines suggest that the vitamin K antagonist (VKA) should be discontinued in patients with an infected prosthetic valve who are taking the VKA at the time of initial presentation. Unfractionated heparin should be substituted for a VKA until it is clear that invasive procedures will not be required and the patient has stabilized without signs of central nervous system involvement (eg, intracranial bleeding due to a ruptured mycotic aneurysm or hemorrhagic transformation of a bland infarct). VKA therapy can be reinstituted when the patient is deemed stable without contraindications or neurologic complications.

**Patients with stroke:--Anticoagulation should be temporarily discontinued in all patients with a mechanical valve and IE who develop central nervous system symptoms compatible with embolism or stroke, despite the potential risk of further thromboembolism.--If there is a compelling need to reinstitute anticoagulant therapy during the first two weeks following the onset of stroke, serial brain imaging with CT or MRI should be performed to exclude hemorrhagic transformation or intraparenchymal hemorrhage.--Angiography, preferably noninvasive contrast angiography with CT, may be necessary to exclude a mycotic aneurysm in selected patients who have evidence of hemorrhage by routine brain imaging studies and who are candidates for definitive neurosurgical or embolization therapy. If CT angiography does not show a mycotic aneurysm in such patients, a conventional invasive angiogram is required as the definitive test. If a symptomatic mycotic aneurysm is detected by angiography, resumption of anticoagulation should be postponed until definitive treatment has been achieved.--Serial neuroimaging and angiography are not indicated for patients without hemorrhagic transformation who do not require anticoagulation.

**Native or bioprosthetic valves with cerebral embolism:--Anticoagulation is not routinely recommended because there is persuasive evidence of the risk of intracerebral hemorrhage without solid countervailing evidence of benefit.**An inferior vena caval filter is an option for selected patients with deep vein thrombosis who are not candidates for anticoagulation.**When there is increased concern about the risk of intracerebral bleeding, or for those patients requiring placement of central venous access or other procedures, heparin anticoagulation has the advantage of permitting more rapid reversal of anticoagulation.**Care must be taken with the use of warfarin in patients receiving antibiotics, as these may change the metabolism of this agent. As an example, rifampin induces cytochrome enzymes that accelerate the metabolism of warfarin. Thus, rifampin therapy will markedly increase the daily dose of warfarin required for effective anticoagulation, and the discontinuation of rifampin will necessitate a reduction in the daily dose.**It is not recommend: routine use of aspirin to prevent embolism in patients with IE.

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