Infective Endocarditis

By | 2013-06-07

Infective endocarditis (IE) is a life-threatening disorder that results from microorganisms that colonize the cardiac endocardium, which commonly causes destruction of valves or other structures within the heart. Bacteremia is by far the most common etiology, with the mitral and aortic valve most frequently affected. Vegetation may cause thromboembolism or metastatic infections, which involve multiple body organs and produce a large variety of clinical signs which makes diagnosis difficult. The incidence of infective endocarditis in necropsied dogs has been reported to range from 0.06% to 6.6%. Evaluation of clinical data from university animal hospitals points to infective endocarditis as a comparably rare condition with incidences ranging from 0.04% to 0.13%. Medium to large breed, mainly purebred, middle-aged male dogs are reported to be predisposed. The incidence in cats, based on clinical experience, is considered to be 7 to 10 times lower than in dogs. Animals with congenital heart disease have a low incidence of infective endocarditis”, but associations have been reported with subaortic stenosis and occasionally with PDA. infective endocarditis has not been found to have any association with chronic mitral valve insufficiency in dogs.

Infective Endocarditis: Pathology

Vegetation associated with by infective endocarditis mainly affects the left heart with the highest incidence involving the mitral valve. Involvement of the right heart or mural endocardium is uncommon. Pathologic findings vary and depend on the virulence of the infecting organism, the duration of infection, and the immunologic response. Intracardiac vegetation consists of different layers of fibrin, platelets, bacteria, red and white cells, and is often covered by an intact endothelium. Bacteria may continue to grow despite antibiotic therapy owing to the location deep within the vegetation and a slow metabolic rate. Necrosis and destruction of the valve stroma or chordae tendineae proceed rapidly in peracute or acute infective endocarditis, which causes valvular insufficiency and cardiac failure.

Infective Endocarditis: Etiology and Pathogenesis

Transient or persistent bacteremia is a prerequisite for the development of infective endocarditis. A large number of bacteria have been associated with bacteremia (see section on Blood Culture below) and some are known to cause infective endocarditis. Most bacteria require predisposing factors to cause infective endocarditis, such as depression of the immunosystem or endothelial damage, sometimes with depositions of platelet-fibrin complexes, to adhere to the valve and create infective endocarditis. The origin of the bacteremia may be active infection localized somewhere within the body. A proportion of cases with infective endocarditis has no clinically detectable source of infection. Possible routes for bacteria to reach and infect the endocardium are by direct contact with the surface endothelium via the bloodstream or from capillaries within the valve (vasculitis).

The consequences of infective endocarditis depend on several factors: virulence of the infective agent; site of infection; degree of valvular destruction; influence of vegetation on valvular function; production of exo- or endotoxins; interaction with the immunosystem with the formation of immunocomplexes; and development of thromboembolism and metastatic infections. Gram-negative bacteremia results often in a peracute or acute clinical manifestation, whereas gram-positive bacteremia typically results in a subacute or chronic condition. The vegetation may cause valvular insufficiency or obstruction. The destruction of valvular tissue is caused by the action of bacteria or the cellular response from the immunologic system. Deposition of immunocomplexes in different organs may cause glomerulonephritis, myositis, or polyarthritis. Septic embolization that produces clinical signs is uncommon but 84% of affected dogs had evidence of systemic embolization at necropsy and glomerulonephritis was reported in 16% of 44 dogs with infective endocarditis.

Infective Endocarditis: Case History and Clinical Signs

The diagnosis of infective endocarditis can easily be overlooked because the case history and clinical signs are not specific and there may be an absence of predisposing factors to raise the suspicion of infective endocarditis. Clinical signs are variable and occur in different combinations. Commonly reported signs include lethargy, weakness, fever (sometimes recurrent), anorexia, weight loss, GI disturbances, and lameness. Stiffness and pain originating from joints or muscles may be caused by immunomediated responses and abdominal pain may be caused by secondary renal or splenic infarction, septic embolization, or abscess formation. If the condition leads to severe valvular damage, especially of the aortic valve, signs of cardiac failure and syncope from arrhythmias may occur. Predisposing factors that in combination with the clinical signs above, should raise the suspicion of infective endocarditis are immunosuppressive drug therapy, such as cortico-steroids; aortic stenosis; recent surgery, especially in conjunction with trauma to mucosal surfaces in the oral or genital tract and infections in these body regions, especially prostatitis; indwelling catheters, infected wounds, abscesses, or pyoderma.

Physical Examination

Most clinical signs lack specificity for infective endocarditis. However, fever, heart murmur (particularly if newly developed), and lameness are considered classical signs. Fever is reported to occur in 80% to 90% in dogs with infective endocarditis. Absence of fever is reported to be more common in cases with aortic valve involvement but may also be attributed to treatment with antibiotics or corticosteroids.

Since aortic insufficiency is otherwise uncommon in dogs, the finding of a diastolic murmur and bounding peripheral pulse should raise the suspicion of infective endocarditis of the aortic valve. Systolic murmurs may be caused by destruction of the mitral valve, which results in mitral regurgitation or vegetations that obstruct the aortic outflow tract, which leads to stenosis. These murmurs are, in contrast to diastolic murmurs, poor indicators of infective endocarditis since they frequendy occur in dogs with other conditions, such as chronic mitral valve insufficiency and aortic stenosis. It should be noted that 26% of dogs with infective endocarditis are reported to lack audible murmurs. Lameness is also an inconsistent finding in infective endocarditis with an incidence of 34% in one study. A range of other physical findings may be present, depending on which organs are affected by circulating immunocomplexes or septic embolization. Possible findings are pain reactions from muscles or abdomen (spleen, intestines, or kidneys), cold extremities, cyanosis, and skin necrosis from severe embolization and a variety of neurologic disturbances if the central nervous system is affected.

Blood Culture

Positive blood cultures are crucial evidence of infective endocarditis. The theory that bacteremia from infective endocarditis is intermittent has changed in recent years to the opinion that, if existent, it is continuous. Thus negative or intermittent positive cultures are unusual when collection and handling of samples is conducted properly. The time for sampling is probably not critical, but a constant finding through repeat samplings is valuable to exclude sample contamination. The technique for obtaining samples aseptically and anaerobically is important and described in detail below. In cases of positive blood culture, it is important to evaluate if the microorganism is consistent with the diagnosis of infective endocarditis.

Microorganisms known to cause infective endocarditis in dogs are, in order of reported incidence, Stapkylococcus aureus, E. coli, betahemolytic streptococci, Pseudotnonas aeroginosa, Corynebacterium spp., Erysipelothrix rhusiopathiae (tonsillarium), and Bartonella irinsonii. B. vinsonii and related proteobacteria has recently been recognized as a potential cause for endocarditis in dogs. They have been found in dogs with cardiac arrhythmias, endocarditis, or myocarditis. Bartonella spp. are also a potential cause for infective endocarditis in cats. Furthermore, Bartonella spp. have been reported to occasionally cause infective endocarditis in immunocompromised (but also immunocompetent) humans, with the cat serving as the major reservoir (cat scratch disease). The recommended antibiotic therapy when the resistance is unknown is erythro-mycin or doxycycline. Immediate antibiotic therapy of humans after significant dog or cat bites may furthermore be motivated as commensals, such as Capnocytophaga canimorsus, in the saliva of dogs and cats have been reported to occasionally cause septicemia with a mortality as high as 30%. Negative blood cultures are fairly common and may be due to antibiotic therapy, chronic situations with “incapsulated” infections, noninfective infective endocarditis (only platelets and fibrin in vegetation), or failure to grow organisms from samples. Some bacteria may grow slowly and samples should not be regarded as definitely negative until they have been incubated for 10 days. More common is a rapid growth of microorganisms with 90% of cultures positive within 72 hours of incubation.

Obtaining Blood Cultures

The referral laboratory should be contacted concerning the preferred type of preprepared vials before obtaining a sample; special additives are available if the patient has been on antibiotics. Pediatric vials are useful because less blood is required but volumes in the range of 20 to 30 mL increase the chance for growth. To avoid contamination, strictly aseptic sampling should be observed which includes thorough shaving and disinfection of the sampling site and strict use of sterile gloves. Three samples with adequately filled vials from different puncture sites should be collected. If samples are collected with a syringe, suction should cease before withdrawal of the needle from the patient to avoid contamination with skin bacteria and a new sterile needle should be used for the transfer of blood into the bottles. The bottles should be prewarmed to 37° C and, after sampling, incubated at the same temperature. Sampling through indwelling catheters should be avoided but may be used as a second choice. The former recommendation to draw samples over 24-hour periods has changed, since multiple simultaneously drawn samples in humans have been shown to be equally sensitive.

Electrocardiographic Findings

Arrhythmia is reported to occur in 50% to 75% of dogs with infective endocarditis.sn.86 Ventricular premature beats and tachyarrhythmias are the most commonly encountered arrhythmias, but they are usually not life threatening. Deviation in the ST-segment suggests myocardial hypoxia and may indicate coronary artery embolism or ischemia from heart failure. Evidence of chamber enlargement may occur in chronic infective endocarditis. All the mentioned ECG abnormalities are, however, nonspecific.

Radiogrophic Findings

Radiography often does not add any information specific for infective endocarditis. In cases of chronic infective endocarditis with aortic or mitral insufficiency, left-sided cardiac enlargement may be detected. Calcified deposits on the valve leaflets are occasionally observed in chronic cases.

Echocardiographic Findings

Echocardiography has significantly improved the possibility of diagnosis and monitoring of animals with infective endocarditis. Valvular vegetations may be detected using two-dimensional echocardiography, although minor lesions may be difficult to distinguish from myxomatous lesions. M-mode can be used to measure secondary changes in cardiac size and to detect abnormal mitral valve motion such as fluttering from aortic regurgitation. Mitral or aortic regurgitation may be detected using continous or color-flow Doppler echocardiography.

Other Laboratory Findings

Mild anemia is found in 50% to 60% of cases with infective endocarditis. The anemia is similar to those from other infections, usually being normocytic and normochromic. Leukocytosis is found in about 80% of dogs with infective endocarditis, usually due to neutrophilia and monocy-tosis (left shift). Other findings that may be encountered include elevated blood urea nitrogen (BUN) due to embolization, metastatic infection, heart failure, or immune-mediated disease.

Urine analysis may reveal pyuria, bacteriuria, or proteinuria. Elevated serum alkaline phosphatase may be found, probably caused by circulating endotoxins and reduced hepatic function, which may cause hypoalbuminemia. The serum glucose concentration may be decreased and serologic tests for immuno-mediated disease, such as Coombs test, may be positive.

Diagnosis of Infective Endocarditis

Since the clinical signs of infective endocarditis are often a result of complications, rather than reflecting the intracardiac infection, the diagnosis may easily be overlooked. Major criteria for infective endocarditis are positive blood cultures with typical microorganisms for infective endocarditis from two separate samples plus evidence of cardiac involvement. The localization and severity of cardiac lesions is confirmed by echocardiographic visualization of vegetations. In the absence of positive cultures, a tentative diagnosis of infective endocarditis can be made if there is clinical and laboratory evidence of systemic infection, such as fever and leukocytosis plus cardiac involvement and possibly signs of embolization.

Management of Infective Endocarditis

The goal of therapy is to eradicate the infective microorganism and to treat all secondary complications. A successful outcome of the therapy is based on early diagnosis and immediate and aggressive treatment. Only bactericidal antibiotics capable of penetrating fibrin should be considered. The antibiotic concentration in serum and deep within vegetations should exceed the organisms minimal inhibitory concentration (MIC), but preferably also the minimum bactericidal concentration (MBC), continuously or throughout most of the interval between doses. Treatment should continue for at least 6 weeks to eradicate dormant microorganisms.

Management of Cases with Tentative Diagnosis of infective endocarditis

A blood culture (see section above) and an antibiotic sensitivity profile should be obtained. While results from cultures and sensitivity tests are awaited, intravenous treatment with a high dosage of bactericidal antibiotic IV, such as cephalosporins (second generation), should be initiated. Alternatives to cephalosporins are combinations of ampicillin or amoxicillin for gram-positive organisms and gentamicin or amikacin for gram-negative organisms. An alternative to gentamicin and amikacin, which are potentially toxic and only recommended to be used for at most one week, is enrofloxacin for suspected gram-negative infective endocarditis. Enrofloxacin is bactericidal and may penetrate myocardium and heart valves and is also indicated for treating Bartonella infections. Choice of antibiotic should preferably depend on the suspected source of infection and the estimated resistance pattern for the primary infection. Practitioners should try to identify the source of infection and treat it as aggressively as possible, such as use of surgical drainage or debridement. Possible secondary problems should be identified, such as heart or renal failure that need therapy or may impair the prognosis.

For dogs with heart failure from aortic regurgitation, hydralazine titered to an adequate reduction of arterial blood pressure is effective and should be considered as a part of medical therapy. When results are available from blood cultures, appropriate antibiotics are selected and aggressive IV treatment continued for 5 to 10 days while renal function is monitored. If results from cultures are negative, the decision to continue antibiotic therapy should be based on clinical improvement. Depending on the early outcome of therapy, subcutaneous administration may substitute a 5 to 10 days IV treatment, and later be superseded by oral preparations. The duration of therapy should be at least 6 weeks on the effective antibiotic. Frequent clinical examinations, blood screening, and urine analyses should be performed during that period.

Prognosis of Infective Endocarditis

Factors that indicate a poor prognosis include late diagnosis and late start of therapy; vegetations on valves (especially the aortic); gram-negative infections, heart or renal failure that do not respond to therapy; septic embolization or metastatic infection; elevation of serum alkaline phosphatase and hypoalbuminemia (70% mortality is reported if this is found in cases with infective endocarditis); concurrent treatment with corticosteroids, regardless if antibiotics are given simultaneously; treatment with bacteriostatic antibiotics or premature termination of antibiotic therapy. Factors that indicate a more favorable prognosis include only mitral valve involvement (47% of dogs are reported to survive); gram-positive infections, origin of infection being the skin, abscesses, cellulitis, or wound infections.

Prevention of Infective Endocarditis

Prophylactic antibiotics may be indicated 1 to 2 hours before and 12 to 24 hours after diagnostic or surgical procedures when turbulent blood flow is suspected to have damaged the endocardium, such as aortic stenosis, patent ductus arteriosus (PDA), or ventral septal defect (VSD). In these cases, early treatment of all manifest infections is important to avoid bacteremia and reduce the risk for infective endocarditis, and caution should be observed when bleeding or infection is anticipated or evident in the oral, urogenital, intestinal, or respiratory tract. Amoxicillin may be the first choice, but other antibiotics, such as clindamycin or cephalosporins, may also be considered depending on the organ system involved and site of infection.