INFECTIVE ENDOCARDITIS



Infection of the endocardium, usually involving diseased cardiac valves, is termed infective en­docarditis. It is most frequently caused by bacteria but can also be caused by fungi. It is classified as acute or subacute depending on the clinical course of the disease. More virulent organisms (e.g., staphylococci, group A beta-hemolytic streptococci, and pneumococci) tend to produce the acute form of the disease with rapid progres­sion and death within a few weeks if untreated. Streptococcus viridans (alpha-hemolytic strep­tococci) causes approximately 50 per cent of all cases of endocarditis and usually follows a sub­acute course, also eventually fatal if untreated but lasting several months. It is commonly preceded by dental surgery. Other bacteria that cause en­docarditis relatively commonly include the en-terococci, gonococci, and Streptococcus bovis (a group D nonenterococcal streptococcus). Gram-negative organisms uncommonly cause infective endocarditis. Enterococcal and Streptococcus bovis endocarditis may occur after genitourinary or gastrointestinal surgery. The incidence of Streptococcus bovis endocarditis is increased in patients with carcinoma of the colon. Staphylo­coccal endocarditis, common in narcotic addicts, may follow wound infections or prosthetic car­diac valve surgery. Staphylococcus aureus usu­ally results in acute endocarditis, whereas Staph­ylococcus epidermidis endocarditis is usually subacute. Fungal endocarditis, rare but increasing in frequency, probably owing to more patients with valvular prostheses and drug addiction, is usually due to Candida albicans, Histoplasma capsulatum, or Aspergillus. A variety of other or­ganisms can rarely cause endocarditis.

Endocarditis is characterized by vegetations, consisting of infecting organisms embedded in platelet-fibrin thrombi with an inflammatory re­action mainly of mononuclear cells, usually lo­cated on the valvular leaflets. The valve tissue be­neath the vegetation undergoes destruction. Endocarditis occurs in the left more commonly than the right heart. The mitral valve is involved most frequently, followed by the aortic and tri­cuspid valves. Right-sided lesions such as on ap­parently normal tricuspid valves have become more common recently due to intravenous drug addiction.

The infection may cause rupture of the valve tissue itself or of its chordal structures, leading to either gradual or acute valvular regurgitation. Some virulent bacterial (for example, Staphylo­coccus aureus) or fungal vegetations may become large enough to obstruct the valve orifice or create a large embolus. Aneurysms of a sinus of Valsalva may occur and can rupture into the pericardial space. The infection may invade the interventri­cular septum, causing intramyocardial abscesses or septal rupture that can involve the conduction system of the heart. Peripheral septic emboli may occur with left-sided and septic pulmonary em­boli with right-sided endocarditis.

Patients with pre-existing valvular heart dis­ease are at particular risk for developing endo­carditis. Rheumatic heart disease, congenital heart disease, hypertrophic obstructive cardio­myopathy, mitral valve prolapse, degenerative changes in valves, and prosthetic valves are pre­disposing features. All these lesions are charac­terized by the production of turbulent flow. Once endothelium has been damaged and bacteremia has occurred, a vegetation may be established, usually on the valve surface toward the chamber of lower pressure (for example, on the atrial sur­face of an abnormal mitral valve). Infective en­docarditis in a patient with a patent ductus ar­teriosus occurs on the low pressure pulmonic side where more turbulence and eddying of blood occur. Atrial septal defects do not predispose to infective endocarditis because little turbulent flow is created from this defect. Dental, gastroin­testinal, and genitourinary manipulations are the most frequent sources of bacteremia causing en­docarditis. This transient bacteremia, in the pres­ence of pre-existing valvular lesions, is the most common predisposing factor to endocarditis, fol­lowed by intravenous drug addiction and cardiac surgery. In acute infective endocarditis, previ­ously normal valves may be involved in up to half of cases. Only a small number of these highly in­vasive bacteria appear to be required to initiate infection. On the other hand, in the subacute in­fection, sterile platelet-fibrin thrombi caused by the trauma of the jet from the turbulent hemo­dynamics are thought to precede and subse­quently become infected from the transient bac­teremia.

Males are affected more commonly than fe­males. Patients with subacute endocarditis are often minimally symptomatic, most commonly having nonspecific symptoms that may be over­looked such as fever, chills, sweats, malaise, an­orexia, or weight loss. Acute endocarditis pre­sents with a more dramatic illness and may include acute congestive heart failure or manifes­tations of pulmonary or systemic emboli (e.g., renal, splenic, retinal, coronary, or cerebral in­farction). Mycotic (infected) aneurysms can occur, especially in the cerebral circulation, giv­ing rise to subarachnoid hemorrhages.

Heart murmur and fever are the two major find­ings and are present in about 95 per cent of pa­tients. The heart murmurs are regurgitant, systolic if due to mitral or tricuspid infection, and dias­tolic if due to aortic regurgitation. Rarely obstruc­tive murmurs result. A murmur varying in dura­tion and intensity over time suggests endocarditis. The murmurs of the underlying cardiac disease may be present and sometimes confuse the di­agnosis. In patients with tricuspid endocarditis, a heart murmur may be absent. In addition, patients with acute endocarditis of the left heart may de­velop a murmur only during the course of therapy after the diagnosis has been made from positive blood cultures or a peripheral embolic phenomenon. A murmur usually appears at some time during the course or treatment of acute endocar­ditis.

Clinical and laboratory manifestations of en­docarditis are summarized in Table 10-1. Periph­eral stigmata are much less frequent than in the pre-antibiotic era and are thought to be caused by septic, embolic, and immunologic consequences of the infection. Chest x-ray findings are nonspe­cific and show evidence of any pre-existing car­diac disease in addition to signs of progressive ventricular failure from the endocarditis. Multi­ple pulmonary infiltrates may be a manifestation of septic pulmonary infarctions from right-sided endocarditis.

The most important laboratory evaluation is the blood culture. Three to six cultures should be ob­tained over a period of several hours. A small number of patients may have persistently negative blood cultures secondary either to infection with an organism difficult to culture (for example, fun­gal endocarditis) or to previous antibiotic therapy. Aerobic and anaerobic cultures should be ob­tained. If previous antibiotic therapy has been ad­ministered, cultures should be obtained over sev­eral days if possible.

Echocardiography may establish any underly­ing valvular abnormality predisposing the patient to endocarditis, or the complications of endocar­ditis such as flail mitral valve leaflet, intramy-ocardial abscess, or hemodynamic abnormalities. Vegetations may be identified directly if they ex­ceed approximately 3 mm in diameter. Smaller vegetations may not be noted, and therefore fail­ure to visualize vegetations does not exclude en­docarditis. Echocardiography can identify fungal vegetations most frequently because these vege­tations are generally large. In many patients the diagnosis is clear, and cardiac surgery may be per­formed without cardiac catheterization. If cath­eterization is done, one must be cautious not to dislodge a vegetation.

The differential diagnosis of infective endocar­ditis is broad and includes viral syndromes, acute rheumatic fever, atrial myxoma, connective tissue diseases such as lupus erythematosus, neurologic disorders, and occult neoplasms. Definitive di­agnosis usually relies on blood culture results. When cultures are negative, the diagnosis must be made indirectly by echocardiography and periph­eral stigmata. It is sometimes difficult to deter­mine in an elderly patient with a systolic murmur whether positive blood cultures represent endo­carditis or bacterial seeding of the blood from an­other source; at times, empirical treatment for en­docarditis without confirmation of the diagnosis may be required.

Endocarditis on a prosthetic valve usually pre­sents similarly to native valve endocarditis. The organisms causing prosthetic valve endocarditis in the early postoperative period are usually those involved in infected surgical wounds (e.g., staph­ylococci) and in pulmonary and urinary tract in­fections. Endocarditis in the late postoperative pe­riod commonly involves organisms that occur in bacteremia related with dental, gastrointestinal,or genitourinary procedures as does native en­docarditis.
The natural history of untreated endocarditis is universally fatal, although the time course for acute and subacute forms is different. Despite the availability of antibiotic and surgical therapy, the mortality and morbidity are still high. Patients who are older, have more virulent organisms, have a longer duration of illness before the insti­tution of therapy, have extensive valvular dam­age, congestive heart failure, renal involvement, or other complications such as myocarditis, my­ocardial abscess, mycotic aneurysms, or emboli­zation are more likely to have an unfavorable out­come.

Bactericidal antibiotics that have been dem­onstrated to be effective toward the specific or­ganism isolated should be employed. Dosage should be followed by measuring the antibacterial activity of the patient’s serum against the organ­ism, and dilutions of at least 1:8 of the patient’s serum should inhibit bacterial growth. The du­ration of therapy is controversial but is usually recommended to be six weeks for most infecting organisms. Initial treatment can be delayed until identification of the infecting organism in patients with subacute endocarditis but must be instituted empirically immediately after obtaining cultures in patients with acute endocarditis. Antibiotics are usually administered intravenously. Strepto­coccus viridans responds to penicillin G; strep­tomycin or gentamicin is sometimes added to the regimen because of in vitro synergy. Vancomycin can be substituted in individuals allergic to pen­icillin. Enterococcal endocarditis must be treated with penicillin or vancomycin, plus an amino­glycoside. Streptococcus bovis is sensitive to pen­icillin, and therapy is the same as for viridans streptococci. Staphylococci are treated with pen­icillin G if they are non-penicillinase-producing or with semisynthetic penicillins such as nafcil-lin, oxacillin, or methicillin if they produce pen­icillinase or if that fact is unknown. Methicillin-resistaht strains have been identified for which vancomycin must be used. Therapy for gram-neg­ative bacteria should be guided by antibiotic sen­sitivity testing and may include drugs such as car-benicillin and/or aminoglycosides. Fungal endocarditis is treated with amphotericin B, sometimes with flucytosine added. Fungal en­docarditis usually requires surgical intervention.

Heart failure is treated conventionally with dig­italis, diuretics, and afterload reduction. Regur­gitant mitral or aortic valve lesions may respond to afterload therapy with intravenous nitroprus-side as a temporizing measure. Severe heart fail­ure must be treated with valve replacement, wait­ing until the infection has been effectively treated if possible, but in the presence of active infection with concomitant! antibiotic therapy if necessary. Indications for surgery in infective endocarditis include heart failure not responding to medical management; recurrent infection despite appar­ently adequate medical therapy; infections on most prosthetic valves, especially if prosthetic valve malfunction is present; infections with orheart valves are at particularly high risk. Alpha-hemolytic (viridans) streptococci are the most common causes of endocarditis following dental procedures, and antibiotic prophylaxis should be directed at these organisms, whereas prophylaxis after gastrointestinal/genitourinary procedures must include antibiotics to treat enterococcal in­fections. Antibiotic regimens are described in.