immunodeficiency or immunosuppression, malignancy, diabetes mellitus, and excessive alcohol use. dental operations in the past, one in eight cases of infective endocarditis was because of bacteremia caused by dental procedures (in most cases due to streptococcus viridans, which reside in the oral cavity), such as cleaning or extraction of a tooth. this was thought to be more clinically significant than it actually was. however, it is important that a dentist or a dental hygienist be told of any heart problems before commencing treatment. antibiotics are administered to patients with certain heart conditions as a precaution, although this practice has changed in the us, with new american heart association guidelines released in 2007, and in the uk as of march 2008 due to new nice guidelines. everyday tooth brushing and flossing will similarly cause bacteremia, so a high standard of oral health should be adhered to at all times. although there is little evidence to support antibiotic prophylaxis for dental treatment, the current american heart association guidelines are highly accepted by clinicians and patients. pathogenesis drawing of endocarditis. damaged valves and endocardium contribute to the development of infective endocarditis. specifically, the damaged part of a heart valve forms a local blood clot, a condition known as non-bacterial thrombotic endocarditis (nbte). the platelet and fibrin deposits that form as part of the blood clotting process allow bacteria to take hold and form vegetations. as previously mentioned, the body has no direct methods of combating valvular vegetations because the valves do not have a dedicated blood supply. this combination of damaged valves, bacterial growth, and lack of a strong immune response results in infective endocarditis. damage to the valves and endocardium can be caused by: altered, turbulent blood flow. the areas that fibrose, clot, or roughen as a result of this altered flow are known as jet lesions. altered blood flow is more likely in high pressure areas, so ventricular septal defects or patent ductus arteriosus can create more susceptibility than atrial septal defects. catheters, electrodes, and other intracardiac prosthetic devices. solid particles from repeated intravenous injections. chronic inflammation. examples include auto-immune mechanisms and degenerative valvular lesions. the risk factors for infective endocarditis provide a more extensive list of conditions that can damage the heart. diagnosis vegetation on the tricuspid valve by echocardiography. arrow denotes the vegetation. in general, the duke criteria should be fulfilled in order to establish the diagnosis of endocarditis. although the duke criteria are widely used, they have significant limitations. for example, the sensitivity of the duke criteria for detecting infective endocarditis decreases when prosthetic heart valves are present. as the duke criteria rely heavily on the results of echocardiography, research has addressed when to order an echocardiogram by using signs and symptoms to predict occult endocarditis among people who inject drugs and among non drug-abusing patients. however, this research is over twenty years old and it is possible that changes in the epidemiology of endocarditis and bacteria such as staphylococci make the following estimates incorrect. the blood tests c reactive protein (crp) and procalcitonin have not been found to be particularly useful in helping make or rule out the diagnosis. ultrasound echocardiography is the main type of diagnostic imaging used to establish the diagnosis of infective endocarditis. there are two main types of echocardiography used to assist with the diagnosis of ie: transthoracic echocardiography (tte) and transesophageal echocardiography (tee). the transthoracic echocardiogram has a sensitivity and specificity of approximately 65% and 95% if the echocardiographer believes there is 'probable' or 'almost certain' evidence of endocarditis. however, in endocarditis involving a prosthetic valve, tte has a sensitivity of approximately 50%, whereas tee has a sensitivity exceeding 90%. the tee also has an important diagnostic role when the tte does not reveal ie but diagnostic suspicion remains high, since tee is more sensitive for infective endocarditis and is better able to characterize infection-related damage to the heart valves and surrounding tissues. guidelines support the initial use of tte over tee in people with abnormal blood cultures, a new heart murmur, and suspected infective endocarditis. tee is the preferred initial form of imaging in people with suspected infective endocarditis who have a moderate to high pretest probability of infective endocarditis, including people with prosthetic heart valves, blood cultures growing staphylococcus, or have an intracardiac device (such as a pacemaker). modified duke criteria established in 1994 by the duke endocarditis service and revised in 2000, the duke criteria are a collection of major and minor criteria used to establish a diagnosis of infective endocarditis. according to the duke criteria, diagnosis of infective endocarditis can be definite, possible, or rejected. a diagnosis of infective endocarditis is definite if either the following pathological or clinical criteria are met: one of these pathological criteria: histology or culture of cardiac vegetation, embolized vegetation, or intracardiac abscess from the heart finds microorganisms active endocarditis one of these combinations of clinical criteria two major clinical criteria one major and three minor criteria five minor criteria diagnosis of infective endocarditis is possible if one of the following combinations of clinical criteria is met: one major and one minor criteria three minor criteria are fulfilled major criteria positive blood culture with typical ie microorganism, defined as one of the following: typical microorganism consistent with ie from two separate blood cultures, as noted below: viridans-group streptococci, or streptococcus bovis including nutritional variant strains, or hacek group, or staphylococcus aureus, or community-acquired enterococci, in the absence of a primary focus microorganisms consistent with ie from persistently positive blood cultures defined as: two positive cultures of blood samples drawn >12 hours apart, or three or a majority of ≥four separate blood cultures (with first and last sample drawn at least one hour apart) coxiella burnetii detected by at least one positive blood culture or igg antibody titer for q fever phase 1 antigen >1:800. this was previously a minor criterion evidence of endocardial involvement with positive echocardiogram is defined as 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 or new valvular regurgitation (worsening or changing of preexisting murmur not sufficient) minor criteria predisposing factor: known cardiac lesion, recreational drug injection fever >38 °c vascular phenomena: arterial emboli, pulmonary infarcts, janeway lesions, conjunctival hemorrhage immunological phenomena: glomerulonephritis, osler's nodes, roth's spots, rheumatoid factor microbiologic evidence: positive blood culture (that doesn't meet a major criterion) or serologic evidence of infection with organism consistent with ie but not satisfying major criterion risk among people who do not use intravenous drugs and have a fever in the emergency department, there is a less than 5% chance of occult endocarditis. mellors in 1987 found no cases of endocarditis nor of staphylococcal bacteremia among 135 febrile patients in the emergency room. the upper confidence interval for 0% of 135 is 5%, so for statistical reasons alone, there is up to a 5% chance of endocarditis among these patients. in contrast, leibovici found that among 113 non-selected adults admitted to the hospital because of fever there were two cases (1.8% with 95%ci: 0% to 7%) of endocarditis. among people who do use intravenous drugs and have a fever in the emergency department, there is about a 10% to 15% prevalence of endocarditis. this estimate is not substantially changed by whether the doctor believes the patient has a trivial explanation for their fever. weisse found that 13% of 121 patients had endocarditis. marantz also found a prevalence of endocarditis of 13% among such patients in the emergency department with fever. samet found a 6% incidence among 283 such patients, but after excluding patients with initially apparent major illness to explain the fever (including 11 cases of manifest endocarditis), there was a 7% prevalence of endocarditis. among people with staphylococcal bacteremia (sab), one study found a 29% prevalence of endocarditis in community-acquired sab versus 5% in nosocomial sab. however, only 2% of strains were resistant to methicillin and so these numbers may be low in areas of higher resistance. prevention not all people with heart disease require antibiotics to prevent infective endocarditis. heart diseases have been classified into high, medium and low risk of developing ie. those falling into high risk category require ie prophylaxis before endoscopies and urinary tract procedures. diseases listed under high risk include: prior endocarditis unrepaired cyanotic congenital heart diseases completely repaired congenital heart disease in their first 6 months prosthetic heart valves incompletely repaired congenital heart diseases cardiac transplant valvulopathy following are the antibiotic regimens recommended by the american heart association for antibiotic prophylaxis: oral amoxicillin one hour before the procedure intravenous or intramuscular ampicillin one hour before the procedure in patients allergic to penicillins azithromycin or clarithromycin orally one hour before the procedure cephalexin orally one hour before the procedure clindamycin orally one hour before the procedure in the uk, nice clinical guidelines no longer advise prophylaxis because there is no clinical evidence that it reduces the incidence of ie and there are negative effects (e.g. allergy and increased bacterial resistance) of taking antibiotics that may outweigh the benefits. antibiotics were historically commonly recommended to prevent ie in those with heart problems undergoing dental procedures (known as dental antibiotic prophylaxis). there is, however, insufficient evidence to support whether antibiotics are effective or ineffective at preventing ie when given prior to a dental procedures in people at high risk. they are less commonly recommended for this procedure. in some countries e.g. the us, high risk patients may be given prophylactic antibiotics such as penicillin or clindamycin for penicillin-allergic people prior to dental procedures. prophylactics should be bactericidal rather than bacteriostatic. such measures are not taken in certain countries e.g. scotland due to the fear of antibiotic resistance. because bacteria are the most common cause of infective endocarditis, antibiotics such as penicillin and amoxicillin (for beta lactamase-producing bacteria) are used in prophylaxis. treatment high-dose antibiotics are the cornerstone of treatment for infective endocarditis. these antibiotics are administered by the intravenous (iv) route to maximize diffusion of antibiotic molecules into vegetation(s) from the blood filling the chambers of the heart. this is necessary because neither the heart valves nor the vegetations adhering to them are supplied by blood vessels. antibiotics are typically continued for two to six weeks depending on the characteristics of the infection and the causative microorganisms. antibiotic treatment lowers the risk of embolic complications in people with infective endocarditis. in acute endocarditis, due to the fulminant inflammation, empirical antibiotic therapy is started immediately after the blood has been drawn for culture to clarify the bacterial organisms responsible for the infection. this usually includes vancomycin and ceftriaxone iv infusions until the infecting organism is identified and the susceptibility report with the minimum inhibitory concentration becomes available. once this information is available, this allows the supervising healthcare professional to modify the antimicrobial therapy to target the specific infecting microorganism. the routine use of gentamicin to treat endocarditis has fallen out of favor due to the lack of evidence to support its use (except in infections caused by enterococcus and nutritionally variant streptococci) and the high rate of complications. in cases of subacute endocarditis, where the person's hemodynamic status is usually stable, antibiotic treatment can be delayed until the causative microorganism can be identified. viridans group streptococci and streptococcus bovis are usually highly susceptible to penicillin and can be treated with penicillin or ceftriaxone. relatively resistant strains of viridans group streptococci and streptococcus bovis are treated with penicillin or ceftriaxone along with a shorter two-week course of an aminoglycoside during the initial phase of treatment. highly penicillin-resistant strains of viridans group streptococci, nutritionally variant streptococci like granulicatella sp., gemella sp., abiotrophia defectiva, and enterococci are usually treated with a combination therapy consisting of penicillin and an aminoglycoside for the entire duration of 4–6 weeks. some people may be treated with a relatively shorter course of treatment (two weeks) with benzyl penicillin iv if infection is caused by viridans group streptococci or streptococcus bovis as long as the following conditions are met: endocarditis of a native valve, not of a prosthetic valve a mic ≤ 0.12 mg/l a complication such as heart failure, arrhythmia, or pulmonary embolism occurs no evidence of extracardiac complication like septic thromboembolism no vegetations > 5 mm