Clinical Pharmacy

 Infective endocarditis (IE), a microbial infection of the heart valves or other endocardial tissue, usually is associated with an underlying cardiac defect.  IE used to be classified as either “acute bacterial endocarditis” or “subacute bacterial endocarditis,” based on the clinical presentation and course of the untreated disease.  This classification system is nonspecific, however, and it does not account for many nonbacterial causes of endocarditis, such as chlamydiae, rickettsiae, and fungi.

 The pathogenesis of endocarditis involves a complex series of events that ultimately results in the formation of an infected platelet β fibrin thrombus on the valve surface. This thrombus is called a vegetation.  Endocarditis can result in life-threatening hemodynamic disturbances and embolic episodes. Without antimicrobial therapy and surgical intervention, IE is virtually 100% fatal.  Because of bacterial proliferation to high densities in the fibrin mesh protected from normal host defenses, cure of infection requires prolonged therapy of 4 to 6 weeks with relapse not uncommon.

 Overall, streptococci and staphylococci are identified as the cause of 80% to 90% of cases of IE. Historically, viridans streptococci have been the predominant causative pathogens in IE, accounting for 60% to 80% of all cases.  When comparing epidemiologic studies in the aggregate over the past decades, however, staphylococci have assumed increased importance as a cause of IE. Viridans streptococci remain the predominant cause of IE in children and in young women with isolated mitral valve involvement.

 Staphylococcus aureus is identified as the leading cause of IE (40%) in one US study and confirmed in another large multinational study at 32%.  Acquisition of IE in nearly half was presumed to be health care-related, supporting a low threshold to evaluate underlying IE in the setting of health care-related S. aureus bacteremia.  More importantly, strains exhibiting methicillin- resistance account for up to 40% of IE cases involving S. aureus.

 General  The clinical presentation of IE is highly variable and can involve almost any organ system.  Symptoms  Nonspecific Complaints from patients may include  Fever  Chills  Night sweats  Weakness  Dyspnea  Weight loss  Myalgia or arthralgias  Signs  Fever is the most common sign of IE.  New or changing heart murmur  Embolic phenomena (emboli affect the heart, lungs, abdomen, or extremities)  Skin manifestations (e.g., petechiae, splinter hemorrhages, Osler nodes, Janeway lesions)  Splenomegaly  Clubbing of extremities

 Modified Duke Criteria for IE depend on clinical presentation& Laboratory tests Blood Cultures  At least three sets of blood cultures collected by separate venipunctures should be obtained over the first 24 hours of presentation. Echocardiography  Echocardiograms are used for detecting the presence of vegetation. Either a transthoracic echocardiogram (TTE) or atransesophegeal echocardiogram (TEE) may be used

 General Principles  The avascular nature of the vegetation results in an environment that is devoid of normal host defenses (e.g., phagocytic cells and complement); this permits uninhibited growth of bacteria.  Therefore, to eradicate the causative organism, high doses of a parenterally administered, bactericidal antibiotic generally are administered for 4 to 6 weeks.

 For some infections, it may be necessary to use two antibiotics to achieve synergistic activity against the organism. For example, the addition of an aminoglycoside to penicillin results in a more rapid and complete bactericidal effect against enterococci.  Once an organism has been identified, its in vitro susceptibility pattern is determined by the minimum inhibitory concentration (MIC) for various antibiotics.

 The overall goal of therapy is to eradicate the infection and minimize/prevent any complications.  Patients with suspected IE should be evaluated for risk factors that may provide some indication as to the most likely organism causing the infection.  If no risk factors can be determined, empirical therapy primarily should cover gram-positive organisms.  Generally, if streptococci are suspected, empirical treatment should consist of penicillin plus gentamicin. However, if staphylococci or enterococci are suspected; empirical treatment should consist of vancomycin plus gentamicin.

 The American Heart Association recently published new guidelines for the management of IE, including specific treatment recommendations.  These guidelines include primary and alternative regimens, as indicated in the treatment tables under strength of recommendation.

 Surgical intervention has become an integral therapy in combination with pharmacologic management of IE. Valve replacement is the predominant intervention, and it is used in a minimum of 25% for all cases of IE.

 Negative blood cultures are present in about 5% to 10% of patients who meet strict criteria for the diagnosis of IE and have not recently received antibiotics. The prior administration of antimicrobials is thought to account for most cases of culture-negative endocarditis.  Slow-growing and fastidious organisms, such as gramnegative bacilli in the Haemophilus- Actinobacillus-Cardiobacterium-Eikenella- Kingella (HACEK) group, Brucella, Coxiella, chlamydiae, strict anaerobes, and fungi, should be pursued in culture-negative patients.

 Rationale and Recommendations  Because infective endocarditis is associated with significant mortality and long-term morbidity, prevention in susceptible patients is of paramount importance. Estimates are, however, that <10% of all cases are theoretically preventable.  Prophylactic antibiotics are thought to provide protection by decreasing the number of organisms reaching the damaged heart valve from a primary source. Thus, antibiotics theoretically prevent bacterial multiplication on the valve and interfere with bacterial adherence to the cardiac lesion.

 Indications and Choice of Agent  Presence of a prosthetic valve, valvular or congenital heart diseases while undergoing multiple tooth extractions places the patient at risk for developing endocarditis.

Drug Dose Dental or Upper Respiratory Tract ProceduresSingle Dose 30 to 60 Minutes Before Procedure Standard Regimen Amoxicillin (oral)Adult: 2 g Pediatric: 50 mg/kg Allergic to penicillin or ampicillin (oral) ClindamycinAdult: 600 mg orPediatric: 20 mg/kg Cephalexin b,c Adult: 2 g orPediatric: 50 mg/kg Azithromycin or clarithromycinAdult: 500 mg Pediatric: 15 mg/kg Unable to Take Oral Medications AmpicillinAdult: 2 g (IM) or (IV) Pediatric: 50 mg/kg IM or IV Allergic to penicillin or ampicillin ClindamycinAdult: 600 mg (IV) orPediatric: 20 mg/kg IV Cefazolin b Adult: 1 g IM or IV Pediatric: 50 mg/kg IM or IV