Infective endocarditis remains, still one of the few dangerous conditions with a mortality rate of about 30 per cent in spite of the advent of so many antibiotics. The major cause for this high mortality is delay in diagnosis, because the clinical features in the early stage of the disease are unimpressive and more importantly inappropriate antibiotic therapy. The latter suppresses the fever but does not prevent the progression of the disease.

Nomenclature of Infective Endocarditis:

Since the infective agent is not always a bacteria, the term infective endocarditis is used in preference to bacterial endocarditis. With the advent of antibiotics, the clinical distinction between acute and subacute endocarditis has also become blurred.

Acute infective endocarditis — also termed as malignant endocarditis occurs is a setting of depressed host resistance and forms a part of generalised overwhelming infection. The onset is rapid with high swinging fever with rigor and sweats. Healthy valves are often affected. The duration is short and outcome often fatal.

Aetiology of Infective Endocarditis:

Subacute infective endocarditis occurs in any patient with a cardiac lesion, and who has a bacteraemia.

Predisposing Causes:

The valves or other structures that are affected are nearly always abnormal either as a result of rheumatic or congenital defect (Oram). Of the acquired defects, old rheumatic valvulitis accounts for 80% of cases. The most vulnerable lesions being minimal mitral and aortic regurgitation.

Severely damaged valves are less likely to be affected e.g. severe mitral stenosis, but in elderly subjects grossly sclerosed aortic valve can be affected. Of the congenital defects the important ones are persistent ductus arteriosus, bicuspid aortic valve, ventricular septal defects, coarctation of aorta, aneurysm of the sinuses of Valsalva, and arterio-venous fistula.

It is important to remember that ostium secundum types of atrial septal defects are not affected and the occurrence of infective endocarditis in ASD suggests that the defect must have been of the primum type. Other conditions where infective endocarditis might occur include pulmonary stenosis and hypertrophic obstructive cardiomyopathy.

Infection is rare on the right side of the heart but right-sided endocarditis is being increasingly recognised amongst drug addicts who use unsterile syringes.

Infective Agents:

In acute bacterial endocarditis – which is rare, the infective agents are strepto pyogenes and staphylococcus albus. These organisms may affect a normal valve, particularly after cardiac surgery and in drug addicts.

In subacute infective endocarditis, most infections are caused by organisms of relatively low virulence i.e. by those which are regarded as common sets. Prior to the advent of antibiotics i.e. penicillin strepto viridans used to account for 80% per cent of cases. The majority of the infective agents were strepto viridans, strepto haemolyticus, strepto faecalis, staph pyogenes and albus. Other organisms include various aerobic and anaerobic streptococci, Neisseria gonorrhoeae, Haemophylus influenzae, Brucella abortus and Bacillus proteus.

These organisms gain entrance into the body from the following sources:

1. Dental Extraction:

This procedure is the commonest cause of endocarditis. Bacteraemia with strep. Viridans often occurs after tooth extractions. Scaling and filling are occasionally responsible. Even chewing with infected teeth may produce bacteraemia.

2. Genito Urinary and Rectal Procedure:

Any stretching of tissue carrying commensal organisms can produce bacteraemia. Examples are urinary bladder catheterization, dilatation and curettage of the uterus and sigmoidoscopy. Strep, faecalis is the usual organism in these situations. But normal delivery is seldom a hazard.

3. Bedsores:

May be source of infection in the elderly or debilitated patients. The organisms are often penicillin resistant staphylococci.

4. Cardiac Surgery:

Including cardiac pacing and catheterisation may allow entrance of organism such as staph albus. In patients who have prior antibiotic cover there is also likelihood of fungus infection.

Rare infective agents include

Fungi — such as Candida, aspergillus, histoplasmosis, torulosis

Rickettsia burnetti (Q. fever)

Chlamydia type B.

Pathology of Infective Endocarditis:

The hallmarks of infective endocarditis are vegetations which are formed on the surface of damaged valves. The vegetations are comprised of irregular deposits of platelets white cells, red cells, and fibrin enclosing bacteria which are deeply embedded. “There is paucity of granulation tissues and cellular reaction and there is no walling off of the infection”. Presumably the bacteria may be brought to the valve by blood vessels of the valve itself. This may explain why severely scarred valves are not affected (Oram).

The vegetations are larger than those found in rheumatic endocarditis. These are friable and get easily dislodged forming emboli. The vegetations may extend into the chordae and along the wall of atria and ventricles. In congenital heart disease the site of vegetation depends on the direction of blood flow for example in VSD with L-R shunt these are found on right side of the septum and the opposite wall of right ventricle.

Emboli from vegetations may cause infarction of kidney, spleen, brain and gut. An infected embolus may produce local arteritis of the occluded vessel, causing weakness of the arterial wall and thus forming mycotic aneurysm. Mycotic aneurysm may also be formed in the valve cusp, in the sinuses of valsalva, in the ventricular septum aorta and peripheral vessel, Rupture of the mycotic aneurysm may cause fatal haemorrhage. The septic emboli may cause abscesses.

Many of the manifestations of infective endocarditis which were formerly believed to be due to microembolism are now thought to be due to deposition of complexes of antigen, antibody and compliment. Microscopical examination of skin lesions, such as petechia, splinter haemorrhages, and Osier’s node has always shown evidences of vasculitis but not of embolism.

Both focal and diffuse glomerulitis occur in kidneys. The renal lesions are due to deposition of immune complex in the basement membrane of glomerulus. Neurological manifestations are due to vasculitis. Heart failure in infective endocarditis is due to rupture of valve or chordae.

Clinical Features of Infective Endocarditis:

The disease may occur in young adults of either sex. In recent years there has been an h^ increased proportion of elderly patients with infective endocarditis.

A history of dental sepsis, tooth extraction or genito-urinary instrumentation may be obtained in about 50 per cent of cases.

The onset is gradual. The early symptoms comprise of malaise, anorexia and low grade pyrexia with intermittent sweats. Fever is some­times difficult to detect. Subacute episodes of fever may alternate with afebrile periods.

There is weight loss and progressive pallor. The classical description of cafe-au-lait comple­xion about the face and back of hand is a late sign and virtually non-existent now.

Finger clubbing and toe clubbing occur in about 50 per cent of cases and are diagnostic. It is important to remember that clubbing takes some 3-6 weeks to develop.

The spleen is usually palpable but rarely large. It is non-tender. Sudden enlargement of spleen with tenderness and appearance of splenic rub suggest infarction.

Cardiac Signs:

In a great majority of cases evidences of heart disease were already present. In absence of any cardiac involvement it is difficult to sustain the diagnosis. The alteration in the intensity and character of murmurs are strong confirmatory evidence in support of the diagnosis. The appearance of new aortic diastolic or mitral systolic murmurs is highly suggestive. The features of acute valvular incompetence differ considerably from those of this usual established disease because there is no time for compensatory ventricular dilatation and hypertrophies. As a result, pulmonary oedema will occur with little cardiac enlargement.

Embolic Phenomenon:

Frank emboli from vegetation on the infected valve may appear in any part of the circulation and may present as cardiac infarction, cerebrovascular accident, sudden loin pain and haematuria indicating renal infarction, and occlusion of the arteries of limbs. In right-sided endocarditis recurrent pulmonary emboli produce difficult diagnostic problems.

Minor emboli in the skin cause painful nodules in the pulp of the fingers. Osier’s nodes are larger subcutaneous emboli (5 mm in diameters). These are pathognomonic. Emboli may occur in the retina and appear as exudate surrounded by haemorrhage.

Mycotic aneurysm involving cerebral vessels may produce subarachnoid haemorrhage.

Diffuse vascular change affecting small vessels may be part of an excessive immune process rather than of embolic origin and may manifest as petichiae splinter haemorrhages (Horder’s line), haematuria due to glomerular lesion and generalised cerebral disturbances leading to a confusional state.

Investigations:

Anaemia is normocytic and normochromic. White cell count is not of great value in the diagnosis but the ESR is high; a fall of more than 50 mm in the 1st hour is unusual. A normal ESR, however, does not exclude the diagnosis.

Proteinuria common. Microscopy of urine for red cells is a good confirmatory evidence. If a spun specimen is examined, it is almost invariably positive.

High plasma gamma globulin levels are seen and may produce a positive latex fixation test.

Blood culture is mandatory for diagnosis and management. Culture of bone marrow may sometimes prove positive in the presence of negative blood culture.

Differential Diagnosis of Infective Endocarditis:

Any cause of pyrexia of uncertain origin must be considered. Sometimes it is difficult to differentiate between reactivations of rheumatic process and the features of infective endocarditis in a patient with pre-existing chronic rheumatic valvular disease. Left atrial myxoma may be confused with infective endocarditis because of identical clinical features.

The former however is more common in female, (vide differential diagnosis of mitral stenosis). Systemic lupus erythematosus with verrucous endocarditis of mitral valve may simulate clinically because of arthralgia and heart murmur but embolic manifestation is very rare.

Management of Infective Endocarditis:

Although most cases caused by strepto viridans infection respond to a standard treatment with Penicillin, the problem of antibiotic treatment is so great that in subacute infection it is usually wisest to delay antibiotic treatment until the causative organism has been identified. The best antibiotic regimen for the particular infection can then be outlined. Positive blood culture is needed to establish the diagnosis. It is a gross error to treat with inappropriate antibiotics an undiagnosed fever in a cardiac patient.

Blood cultures should be taken with aseptic precaution. In subacute disease and with a good laboratory, no advantage is achieved by taking more than three cultures within 24 hours. In potentially complicated cases as in drug addicts or after cardiac surgery it is wise to collect six cultures within 12 to 24 hours. There is no advantage in timing the blood culture in relation to the body temperature or by taking samples of arterial blood.

Negative cultures usually result from ineffective antibiotic treatment or due to presence of fastidious organisms requiring special techniques for culture. Persistently, negative culture suggests fungi, Q fever or psittacosis. Serological tests are necessary for their diagnosis.

If the clinical situation seems urgent and in any addicts, where rapid progression may be quickly fatal it is wise to start empirical treatment immediately after taking six sets of blood culture over one to one and half hour period before antibiotics are administered. The culture provides a valuable guide to the effectiveness of treatment.

Choice of Antibiotics:

The sensitivities of the organism to bactericidal antibiotics singly or in combination must be assessed by the bacteriologist in order to decide on appropriate treatment.

Bactericidal antibiotics such as Penicillin, Ampicillin, Cephalosporins and aminoglycosides must be used alone or in combination.

Bacteriostatic antibiotics such as sulphonamides, tetracycline, and chloramphenicol suppress the infection but do not eradicate it. Erythromycin and novobiocin may be helpful in combination with other drugs. Cotrimoxazole has been found to be useful. Penicillin is safe because it can be given in high concentration without toxic effect. Probenecid although boosting the penicillin level carries the risk of drug reaction, e.g. skin rash.

More resistant infection responds well to penicillin and streptomycin. This regime of ampicillin and streptomycin are usually effective against strep, faecalis.

Staphylococcal infection may produce penicillinase and requires treatment with methicillin, cloxacillin or cephaloridine. Strepto viridans usually responds to penicillin but as it may take several days to establish sensitivities it is best to begin with four million units, six hourly I.V. and reduce the dose later and change to intramuscular regime if the organism is sensitive.

Effectiveness of Therapy:

Clinical assessment is most important but wherever possible level of serum antibiotic level may be measured.

Penicillin Allergy:

If the patient is allergic to penicillin it may be possible to use an alternative antibiotic.

Considering the fact that penicillin is often the best agent it is wise to give a test dose to confirm the patient’s sensitivities. Desensitisation is a time-consuming process and steroids can conven­iently be used before beginning treatment.

Duration of Treatment:

The protective effect of the immune response requires prolonged therapy. It is best to stick to the classical recommendation of treatment for six weeks. The shorter course although successful at times is associated with a high rate of relapse and relapses are difficult to manage. Careful observation for several weeks is needed after the course of treatment has been completed, as failure may occur when the damaged valves starts shrinking.

Surgery in Infective Endocarditis:

If severe valvular incompetence occurs urgent mitral or aortic valve replacement may be necessary.

Prophylactic Treatment:

In susceptible individuals, infective endocarditis must be prevented by effective bactericidal antibiotic before undertaking any procedure which might lead to a bacteraemia. All patients with known valvular lesions and congenital heart disease must be protected in this way.