Wall-July PV-Review - VetLearn.com

CE 

614 Vol. 24, No. 8 August 2002 

Article #3 (1.5 contact hours) 

Refereed Peer Review 

KEY FACTS 

■ Bacteremia, either transient or 

permanent, must occur in order 

for infective endocarditis (IE) to 

develop. 

■ Echocardiography is the best 

diagnostic tool for confirming IE. 

■ Early diagnosis followed 

immediately by aggressive 

antibiotic therapy is critical 

for long-term survival of 

dogs with IE. 

Comments? Questions? 

Email: compendium@medimedia.com 

Web: VetLearn.com • Fax: 800-556-3288 

Infective Endocarditis 

in Dogs 

University of Georgia 

Michelle Wall, DVM 

Clay A. Calvert, DVM, DACVIM 

Craig E. Greene, DVM, MS, DACVIM 

ABSTRACT: Infective endocarditis (IE) most often affects young to middle-aged, large-breed 

dogs with no history of heart disease. Coagulase-positive staphylococci and streptococci are 

the most commonly associated bacteria. Clinical findings indicative of IE include fever, an 

inflammatory leukogram, a heart murmur of recent onset, and lameness; but these findings 

are not consistently present. Echocardiography and blood cultures are important aspects of 

the diagnostic database. The aortic or mitral valve is involved in almost 100% of cases; 

involvement of the aortic valve is most common. The echocardiographic appearance of aortic 

valve IE is pathognomonic. A diastolic murmur of aortic regurgitation is common and highly 

suggestive of IE. The femoral pulses associated with advanced aortic valve IE are bounding 

and quick. Long-term (6 to 8 weeks or longer), high-dose, bactericidal antibiotic therapy is 

required to treat IE. Intravenous therapy should be maintained as long as possible (at least 2 

weeks) and followed by subcutaneous administration. Combination therapy using clindamycin 

plus enrofloxacin is recommended. IE may be difficult to recognize, often imitates immunemediated 

or rickettsial diseases, and is usually lethal. Congestive heart failure is the usual outcome, 

especially with aortic valve IE. 

Endocarditis denotes inflammation of the endocardial surface of the 

heart. 1–11 Infective endocarditis (IE), also referred to as vegetative or bacterial 

endocarditis, is the invasion by an infective microbe of the endothelial 

surface of the heart, usually the valves. 1–14 

When infectious microbes colonize a heart valve, they not only produce proliferative 

lesions (vegetations) but also destroy valvular tissue. 7,8 The vegetations 

are of variable size and shape, from small warty nodules to large cauliflower-like 

masses (Figure 1). The vegetations are comprised of three layers 7–11 : 

• A large inner layer of platelets, fibrin, red blood cells (RBCs), white blood 

cells, and bacteria 

• A middle layer of bacteria 

• An outer layer of fibrin 

BACTEREMIA AND ADHERENCE 

Bacteremia, either transient or permanent, must occur in order for IE to 

develop. 5,7,12 Culmination into IE involves the endothelium, hemostatic mecha- 

www.VetLearn.com

Compendium August 2002 Infective Endocarditis 615 

Figure 1—Gross pathology specimen demonstrating the aortic 

valve of a dog with IE. One of the valve leaflets was pale, cauliflower-like, 

firm on palpation, and appeared to be calcified. 

nisms, the host’s immune system, surface properties of 

the microorganisms, and peripheral events that initiate 

bacteremia. 7,8 Resistance of the intact endothelium to 

infection can be deduced from the relative infrequency 

of IE compared with the known frequency of bacteremias. 

8,13 Although phagocytic cells remove 

Factors Predisposing Dogs to Bacteremia 

and Infective Endocarditis 

Bacterial infections 

Prostatitis 

Diskospondylitis 

Pyoderma 

Infected wounds/abscesses 

Stomatitis/gingivitis 

Invasive procedures 

• Protracted surgery 

• Infected tissue manipulation 

• Indwelling catheters 

Immunosuppression 

• Exogenous corticosteroid administration 

• Drugs 

• Neoplasia 

Congenital heart defect (subaortic stenosis) 

microbes from the blood, platelet-fibrin depositions 

may occur spontaneously; microorganisms may adhere 

to these sites and initiate IE before the immune system

616 Small Animal/Exotics Compendium August 2002 

can obliterate the infection. 8 

Chronic, low-grade microbemia predisposes dogs to 

IE. 7,13,14 Infective microorganisms in the blood must be 

capable of adhering to a platelet-fibrin matrix. 7,8,15 

Within this matrix, not only are white blood cells 

unable to phagocytize bacteria, but the bacteria are very 

concentrated. 7,8,15 Very few granulocytes are within the 

vegetation; and layers of fibrin, platelets, and RBCs 

protect the microorganisms. 7,8 

VALVE INVOLVEMENT 

Heart valves are subject to constant trauma as they 

open and close. 7,8 The incidence of IE appears to be 

directly related to the force placed upon each valve. 16,17 

The mitral and aortic valves are most commonly 

infected, and the tricuspid and pulmonic valves are seldom 

involved. 2,4,6,9–16,18,19 In a study of 45 dogs, 22 had 

aortic involvement, 16 had mitral, 1 had both aortic 

and mitral, and only 1 had tricuspid involvement. 6 

During the past 10 years, our experience is that approximately 

90% of infections involve the aortic valve. 

EPIZOOTIOLOGY 

The prevalence of IE is much lower than that of 

dilated cardiomyopathy and myxomatous mitral valve 

degeneration. The incidence rates at two referral institutions 

were both approximately five cases per year. 6,10 

During the last 10 years, two to five dogs with IE have 

been recognized annually at the University of Georgia. 

Typically, affected dogs are 4 to 8 years of age and 

medium to large sized (less than 10% weigh less than 

10 kg). 6,10 Affected dogs are seldom younger than 2 or 

older than 10 years of age. German shepherds, boxers, 

golden retrievers, Labrador retrievers, and rottweilers 

may be overrepresented. 1–4,6,9–11 Males are affected more 

often; a 2:1 ratio, possibly due to chronic bacterial prostatitis, 

has been reported. 6 

PREDISPOSING FACTORS 

There are numerous factors predisposing dogs to the 

development of IE. A common misconception is that IE 

is associated with structural heart disease. It is interesting 

that dogs with the highest incidence of advanced 

myxomatous mitral valve degeneration (older, smallbreed 

dogs) have a very low incidence of IE. Furthermore, 

IE is seldom associated with congenital heart diseases 

in dogs, with the exception of subvalvular aortic 

stenosis (SAS). 1–4,6,19 With SAS, turbulent, high-velocity 

blood flow in the left heart may produce microtrauma 

on the valve leaflets and facilitate microbe colonization. 

9,10,19,20 Boxers, rottweilers, and golden retrievers 

have relatively high incidences of both IE and 

SAS. 2,3,6,19,20 Less than 10% of dogs with SAS develop IE, 

www.VetLearn.com 

and possibly less than 10% of dogs with IE have 

SAS. 2,3,6,19,20 Establishing or eliminating an ultrasonographic 

diagnosis of SAS with aortic valve IE can be difficult 

because the vegetation may obscure the SAS lesion. 

Predisposing factors for platelet–fibrin–RBC deposition 

on the endocardium include procedures involving 

the gingiva, oropharynx, gastrointestinal tract, or 

infected tissues and intravenous (IV) catheters. 6,8,9,12,21–23 

Although gingivitis/stomatitis may be associated with 

bacteremia and IE, dogs with the highest incidence of 

this condition (older, small-breed dogs) seldom develop 

IE. 2,3,6 Hypercoagulability associated with malignancies, 

disseminated intravascular coagulation, hypercortisolemia, 

or immune-mediated diseases may predispose 

dogs to IE. 7,8,24 Any abnormality that either is associated 

with chronic bacteremia (e.g., gingivitis, urinary or prostatic 

infection, pyoderma, wounds) or impairs host 

defenses (e.g., neoplasia, diabetes mellitus, hyperadrenocorticism, 

exogenous corticosteroids or other 

immunosuppressive therapies) increases the risk for 

IE. 5,8,12,13 However, dogs most prone to hyperadrenocorticism 

have a low incidence of IE, and we have rarely 

identified the two conditions in the same dog. The 

source of infection may be suspected but is proven in 

less than 50% of cases. 6,12,13 

Damaged endothelium exposes the extracellular polysaccharide 

dextran, which facilitates the attachment of 

some bacterial species. 25,26 Because of the limited species 

of microbes that account for the vast majority of IE 

cases, it can be deduced that certain organisms (e.g., 

coagulase-positive staphylococci and some streptococci) 

have an increased ability to colonize the endocardium. 

2,3,6–8,15 Fibronectin can be produced by 

endothelial cells and platelets in response to vascular 

injury, and receptors for fibronectin are present on the 

surface of some bacteria, including coagulase-positive 

staphylococci and some streptococci. 26 Fibronectin may 

even facilitate the adherence of some bacteria, including 

staphylococci, to intact endothelium. 15,26 

Corticosteroids 

Dogs affected with IE often have a history of receiving 

corticosteroids. 6 In some instances, corticosteroids 

were administered in the weeks preceding the development 

of IE to treat an illness associated with unrecognized 

bacteremia, skin disease, or presumed immunemediated 

disease. Survival rates of dogs with mitral 

valve IE that received corticosteroids were lower than 

those that did not receive them. 6 

Infective Microbes 

The vast majority of IE cases are the result of bacteria; 

rickettsial agents are occasionally identified, but fungal


IE is rare in dogs. 2,4–6,12,14,27,28 More than 50% of infections 

in dogs are the result of coagulase-positive staphylococci 

and streptococci. 2,6,10–12,29,30 Bartonella, Brucella, 

Coxiella, and Chlamydia have been identified as causative 

agents in culture-negative IE cases in humans. 31–34 Factors 

predisposing humans to fungal infections (e.g., prosthetic 

valve replacement, IV drug abuse, chronic 

immunosuppressive therapy, chronic broad-spectrum 

antibiotic usage 8,27 ) are less common in dogs. 

PATHOPHYSIOLOGY 

Aside from the constitutional signs of infection, 

which are mediated by cytokines, the clinical manifestations 

of IE are the result of valvular destruction, 

embolic phenomena, and immune-complex disease. 3,6–8 

Congestive heart failure (CHF) is the usual outcome in 

dogs with aortic valve IE. 2,4,6,9–12 

Embolization leads to organ infarction and metastatic 

infection. 6–9,24 Embolization is a frequent cause of clinical 

signs and clinical deterioration. Even in the absence 

of clinical evidence, dogs almost always have systemic 

emboli at necropsy, and the kidneys are almost always 

infarcted. 9–11 Emboli are usually present in many organs 

and tissues. 2,4,6,10,12 

Persistent bacteremia stimulates both cell-mediated 

and humeral immune systems. 7–10 Circulating immune 

complexes containing IgG, IgA, IgM, and complement 

may be deposited subendothelially along glomerular 

basement membranes, in joint capsules, and in blood 

vessels, leading to glomerulonephritis, arthritis, and vasculitis. 

3–5,7,8,10,35–40 Clinical signs of IE frequently mimic 

those of immune-mediated disorders, and positive 

immune-test results (e.g., Coombs test, antinuclear antibody 

test) can occur because of antigen–antibody–complement 

interaction. 6,35 Rheumatoid factor, antinuclear 

Clinical Findings That May Be Associated with 

Infective Endocarditis 

Heart murmur 

• Recent onset 

• Diastolic component 

Fever 

Inflammatory leukogram 

Systemic embolic phenomena 

• Saddle thrombus 

• Limb edema 

• Lameness 

Arthropathy 

• Joint swelling 

• Pain 

• Lameness 


antibodies, and circulating immune complexes contribute 

to the development of polyarthritis, renal disease, 

and myocarditis. 6–9,35–40 

CLINICAL FINDINGS 

Clinical signs and diagnostic abnormalities associated 

with IE are often nonspecific and often include 

extracardiac manifestations. The interval between the 

initiating bacteremic event and diagnosis of IE is usually 

uncertain, and a predisposing factor is not always 

evident. 6 Occasionally, there is a history of an illness 

that, in retrospect, may have initiated bacteremia 1 to 

3 months before the diagnosis of IE. 6 Affected dogs 

often have signs of systemic infection, including fever 

and leukocytosis. Septic or sterile embolization/infarction, 

metastatic infections, and organ failure are 

responsible for many of the clinical signs. 6–8,12 Clinical 

signs associated with IE are diverse and misleading, 

and IE has frequently been called “the great imitator.” 

10 Owners variably report lethargy, depression, 

weakness, anorexia, weight loss, lameness, neurologic 

signs, and signs consistent with CHF. 2–4,6,12,19 Fever, 

either current or a history thereof, is not always present 

and may be easily overlooked. 3,6,12 Fever is often 

absent at the time of diagnosis because the bacteremia 

is low grade or there was previous therapy with antibiotics, 

steroids, or NSAIDs. 6,12 

Heart Murmurs 

Cardiac sequelae of IE include valvular insufficiency 

because infection destroys the valvular tissue and interferes 

with function. 7–10 The severity of destruction varies 

with chronicity and the virulence of the organism. 7–10 IE 

is the most common cause of a murmur of aortic regurgitation 

(the aortic valve is the most commonly 

infected 2,6 ), which can be detected over the left heart 

base or on the right thoracic wall midway between the 

tricuspid valve area and the manubrium. Systolic murmurs 

result from mitral regurgitation or aortic valve vegetation–generated 

systolic flow turbulence. A murmur 

of recent onset, especially with a diastolic component, 

accompanied with fever is very suggestive of IE. 2,6 The 

femoral pulses associated with mitral valve endocarditis 

are typically normal but may be weak if left-sided CHF 

is present. 2–4,6 The femoral pulses associated with aortic 

valve endocarditis may be normal or hyperdynamic and 

bounding. 2 The systolic pulse pressure with aortic regurgitation 

is often increased because of volume overload 

and resultant increased stroke volume. Diastolic pressure 

may be low because of arterial blood runoff back into 

the left ventricle during diastole; thus not only may the 

diastolic pressure be low, but the systolic pressure wave 

duration may be shortened.


Lameness 

Lameness due to IE is an occasional finding rarely 

caused by septic emboli but usually the result of 

immune-mediated arthritis. 3,4,6,9,35,36,39 Synovial tissue 

may contain IgG, IgM, and complement, indicating an 

immune basis for the arthropathy. 35,36 

Organ Failure 

Dogs with IE may present with signs consistent with 

CHF (usually left-sided), including coughing, dyspnea, 

pulmonary crackles (pulmonary edema), shortness of 

breath, weakness, and/or collapse. 3,6 CHF is most frequently 

associated with aortic valve IE. When the left 

heart appears radiographically normal in size, but pulmonary 

edema is present, IE should be considered 

because dramatic heart enlargement may not yet have 

occurred in the case of acute IE. The index of suspicion 

of IE rises in dogs that have no history of a heart murmur 

or are not prone to cardiomyopathy or myxomatous 

valvular degeneration. 6 

Renal failure is another complication that may 

detract from recognizing IE. Renal failure is usually 

due to chronic infarction or glomerulonephritis 

(Figure 2). 3,6,13,37,38 

Polysystemic Signs 

The constitutional signs of IE can mimic those of 

any polysystemic disease. 3,6 Many diagnostic differentials 

must be considered, including immune-mediated 

diseases, rickettsial infections, bacteremia alone, sequelae 

of neoplasia, causes of CHF, and causes of renal failure. 

2,6,12,13,33,35,36 Localized signs, such as lameness, 

edema, and pain, often arise from complications of 

Figure 2—Gross pathology kidney specimen from a dog with 

aortic valve IE. The kidney has been sectioned in the sagittal 

plane. Multiple triangular-shaped, pale infarctions of variable 

age are visible within the renal parenchyma. 


infection. 6,35,36,39 In order to avoid overlooking IE, the 

possibility should be investigated when one or more of 

the following signs are present: 

• An unexplained fever 

• A heart murmur of recent onset 

• A source of infection 

• Embolic phenomena 

Systemic Embolization 

IE always results in embolization. The kidneys consistently 

exhibit old and new infarcts that contribute to 

proteinuria and renal failure. The spleen, liver, and 

iliac or mesenteric arteries are sometimes involved. 

Splenic septic abscesses may contribute to persistent 

fever and leukocytosis. 

CLINICAL PATHOLOGY 

Hematologic findings of systemic inflammation are 

often absent in IE. This may be due to antibiotic or 

steroid administration or chronic, low-grade bacteremia. 

6,12 Although an inflammatory leukogram is not 

always present, monocytosis is present in 90% of 

cases. 6,12 In some instances, mature neutrophilia and 

monocytosis indicate low-grade, chronic inflammation. 

Thrombocytopenia is another common finding and 

can be attributed to systemic vasculitis and immune or 

coagulatory consumption. 6,12 

A variety of serum biochemical abnormalities may 

be observed. A septic triad may be present, characterized 

by low or decreasing albumin, increased serum 

alkaline phosphatase activity, and absolute or relative 

hypoglycemia. 6,13 Hypoalbuminemia may be explained 

by proteinuria, anorexia, or decreased liver function 

caused by toxins. 6,13 Increased serum alkaline phosphatase 

activity is usually due to toxin interference 

with bile metabolism or prior steroid use. 6,13,14 Hypoglycemia 

can be explained by bacterial toxin effects on 

intermediary metabolism. 13,14 Azotemia may be prerenal 

or caused by infarction and glomerulopathy. 3,9,10,37,38 

The urine often contains protein, blood, casts, and/or 

bacteria. 6,13 Urine culture is recommended not only 

because bacteria are filtered from the blood into the 

urine but also because the urinary tract may be a 

source of infection. 6,13 

SPECIAL DIAGNOSTICS 

The diagnosis of IE requires integration of clinical 

and laboratory findings. Arrhythmias (usually atrial or 

ventricular premature contractions) are present in at 

least 50% to 75% of documented cases; seldom life 

threatening; and best evaluated by long-term, continuous 

electrocardiographic monitoring (either cage-side


or Holter recorded). Other less-common electrocardiographic 

abnormalities include bundle branch and atrioventricular 

blocks. 

Radiographic interpretation may reveal chamber 

enlargements or no abnormalities. Chamber enlargement 

(most commonly left atrial) is usually present 

when IE is chronic. 2–4,6,41 If overt or impending leftsided 

CHF is present, pulmonary edema and/or distention 

of the pulmonary veins will be present. 2–4,6,9,10,41 

Echocardiography is the best diagnostic tool but is 

neither 100% sensitive nor 100% specific. 3,9–11 Modern, 

two-dimensional equipment can resolve 1-mm lesions 

in dogs. 10 Detection of an echogenic oscillating intracardiac 

mass on the aortic or mitral valve is a strong 

indication of the presence of IE. Both the M-mode and 

two-dimensional appearance of aortic valve vegetations 

are virtually pathognomonic (Figure 3). Echoes from 

vegetations on the mitral valve are usually on the cra- 

Figure 3—M-mode echocardiogram of a thickened aortic 

valve (AV). This echocardiographic image is typical of aortic 

valve vegetations. 

Figure 4—Two-dimensional echocardiogram in the right 

parasternal, long-axis plane demonstrating vegetative lesions 

on the cranial (anterior) mitral valve (arrowhead) and the aortic 

valve (arrow) leaflets during diastole. A = aorta; LA = left 

atrium; LV = left ventricle. 


nial (anterior) leaflet but are not pathognomonic; in 

some cases, however, the lesion is so large that IE 

should be suspected (Figure 4). Operator skill and 

experience, as well as image quality, influence interpretation. 

Furthermore, results must be considered in the 

context of other clinical and laboratory findings. Falsepositive 

test interpretation is most commonly attributable 

to mitral valve myxomatous degeneration. 9,10 A clinician 

should always consider the signalment and 

history of the dog in question. The signalment associated 

with IE is largely different from that of dogs with 

advanced myxomatous degeneration. The presence of a 

new heart murmur is of special importance if the breed 

or age of the patient is not characteristic of dogs 

affected by myxomatous valvular degeneration. 

Chamber enlargements and altered contractility may 

be evident. 3,6,9,10 Decreased contractility is typical of the 

high-pressure volume overload of advanced aortic valve 

IE but not of the low-pressure volume overload of 

mitral valve IE. Decreased contractility may also be 

related to chronicity of volume overload. Diastolic fluttering 

of the anterior (cranial) mitral valve leaflet is 

indicative of aortic insufficiency and, therefore, suggestive 

of endocarditis. This fluttering is the result of the 

jet of aortic regurgitation striking the anterior mitral 

valve leaflet when it is open in diastole. Color-flow 

imaging is used to identify hemodynamic consequences 

of endocarditis, such as valvular regurgitation or left 

ventricular outflow tract turbulence (Figure 5). 

Doppler interrogation of aortic regurgitation is used to 

confirm the severity. The spectral display of severe aortic 

regurgitation is characterized by a rapid deceleration 

of regurgitant velocity during diastole. Severe aortic 

regurgitation is incompatible with survival. 

DIAGNOSIS 

The diagnosis of IE requires integration of clinical 

and laboratory data. The advent of echocardiography 

has greatly facilitated the diagnosis. Because the aortic 

valve is usually involved in IE, 2,3,6 ultrasonographic 

recognition is seldom difficult. Diagnosis of mitral 

valve IE is more difficult because the lesions of myxomatous 

degeneration can resemble those of IE. 3 It 

should be recognized that dogs with the highest incidence 

of myxomatous degeneration of the mitral valve 

(older, small-breed dogs) are seldom affected by IE. Signalment, 

clinical findings, femoral pulse characteristics, 

confirmation of bacteremia, and a murmur of recent 

onset (especially a diastolic murmur) are important to 

the diagnosis of IE if echocardiography is not available. 

Identification of Bacteremia 

Although blood cultures lack sensitivity and speci-


Figure 5A Figure 5B 

Figure 5C Figure 5D 

Figure 5—(A) Two-dimensional echocardiogram in the left apical, long-axis, two-chamber imaging plane. During systole, an aortic 

valve leaflet thickened by vegetation (arrow) is opened into the aorta (A). There are also vegetations on the mitral valve leaflets 

(arrowhead). (B) In diastole, the vegetative aortic valve is closed, and a portion of the vegetation is protruding (arrowhead) into 

the left ventricle (LV). The open cranial (anterior) mitral valve leaflet is also thickened by vegetation (arrow). (C) Color-flow 

Doppler imaging in systole demonstrating the turbulent mitral regurgitation (arrowhead). (D) Color-flow Doppler imaging in 

diastole demonstrating the turbulent jet of aortic regurgitation (arrowhead). LA = left atrium. 

ficity, they should always be performed in an attempt 

to identify the offending organism. 10,12,14,42,43 Bacteremia 

may occur in other conditions, such as diskospondylitis, 

chronic wounds, prostate infections, and periodontal 

disease. 6,12–14 Performed properly, blood cultures often 

yield positive results (in our experience, approximately 

30% to 50% of patients have positive results). 6,9–11,13,14 

Decreased sensitivity may be explained by fastidious, 

slow-growing organisms; improper laboratory techniques; 

the failure to culture for anaerobes; low-blood 

bacterial concentrations; endogenous bactericidal 

factors (complement and phagocytes); intermittent 

shedding of the organism; chronic IE with encapsulated 

vegetative lesions; or infections with Bartonella. 

13,31–33,42–44 Other variables affecting the yield of 

microorganisms include the volume of the blood sample, 

number of cultures performed, and incubation 

atmosphere of the culture. 14,44 


Two or three sets of blood samples should be taken 

aseptically, preferably before antibiotic administration. 

6,13,14,43,44 Samples should be taken either from a 

freshly placed, meticulously maintained jugular 

catheter or from different veins. 14,42 Commercial vacuum 

bottles should be used. If the animal is receiving 

antibiotic therapy, collect the sample at the antibiotic 

trough level and use an antibiotic removal device. 14 

Duration of antimicrobial therapy is an important factor 

in detecting bacteria. 45 Therapy for only 2 to 3 days 

may not interfere; however, longer courses of therapy 

require the use of antibiotic removal devices or discontinuation 

of therapy. Suppression of bacteremia often 

persists longer than antibiotic blood levels. 

Sterile technique should be practiced when collecting 

blood samples. The area must be clipped and disinfected, 

and sterile gloves should be worn. Samples (7 to 10 

ml of whole blood) should be placed in two bottles:


Criteria for the Antemortem Diagnosis of Infective 

Endocarditis 

Without Echocardiographic Examination 

A murmur of recent onset 

plus 

Positive blood culture results (it is preferable to find 

more than one of the same microbe) 

plus 

Clinical findings and laboratory data consistent with 

bacteremia and IE 

With Echocardiographic Examination 

Aortic valve 

• Echocardiographic appearance is pathognomonic 

Mitral valve 

• Echocardiographic appearance is suggestive of IE 

• Supportive clinical data 

Signalment 

Murmur of recent onset 

Positive blood culture results 

Fever 

one unvented for anaerobic culture, and one vented for 

aerobic culture. 9–11,14 If acute sepsis is suspected, take 

three cultures 1 hour apart, and then institute antibiotic 

therapy. 10,42 

Many negative blood cultures in humans with IE are 

due to infection with Bartonella, a fastidious, gramnegative 

organism. 31 The incidence of Bartonella endocarditis 

is unknown but less than that of bacterial endocarditis 

and has been proven in a few dogs. Bartonella 

resides within or on the surface of RBCs, making it difficult 

to isolate from blood cultures; therefore, special 

techniques are recommended. 31–34 Special cultivation 

methods may be necessary to isolate fastidious 

pathogens. Tissue culture methods may be required for 

obligate, intracellular organisms, such as Coxiella, some 

Bartonella, and Chlamydia. Extraction of nucleic acid 

from blood and subsequent polymerase chain reaction 

amplification has been beneficial in the early diagnosis 

of bacteremia and confirmation of infection with fastidious 

or unculturable agents. 31,34 

TREATMENT 

Prolonged parenteral administration of one or more 

bactericidal antibiotics is recommended. The goal of 

treatment is to kill the organism as well as minimize 

and manage the consequences of infection. Therapy is 

ideally based on blood culture antibiogram results, but 

treatment is usually initiated before results. 46–49 Within 

the vegetation, organisms are protected, become meta- 


Principles of Antibiotic Treatment of Infective 

Endocarditis 

• Use bactericidal antibiotics. 

• Ensure high antibiotic serum concentrations by 

administering high doses intravenously. 

• Continue IV antibiotic administration for at least 1 

to 2 weeks. 

• Replace IV administration of antibiotics by SC 

administration when the former is no longer 

practical. 

• Continue antibiotic therapy for at least 2 to 3 

months. 

• Use oral antibiotics only after at least 1 month of IV 

and SC administration. 

bolically dormant, and are less vulnerable to the killing 

activities of antimicrobials. 8–11,14 

Because antibiotics reach the central areas of avascular 

vegetations by passive diffusion, antimicrobial therapy 

should be bactericidal and antibiotic serum concentrations 

should be high. 46 High serum 

concentrations are mandatory, and antibiotic serum 

concentrations should be maintained at the high end of 

the therapeutic range for at least 1 month. 4,6,9–13 We recommend 

at least 1 to 2 weeks of IV antibiotic therapy 

followed by subcutaneous (SC) administration 50 for 

several weeks, if possible; then oral bactericidal antibiotics 

should be continued for 1 to 2 months. 47 

For some drugs, SC administration produces higher 

serum concentrations than oral administration. For 

example, the sodium salt of ampicillin administered at 

10 mg/kg SC achieves a peak serum concentration of 

up to 80 µg/ml, whereas administration at 20 to 30 

mg/kg PO achieves a serum concentration of only 2 to 

4 µg/ml. Likewise, the salt of amoxicillin administered 

at 20 mg/kg PO achieves a peak serum concentration 

of only 8 µg/ml. Among the cephalosporins, cephapirin 

administered at 20 to 30 mg/kg SC produces peak 

serum concentrations of 20 to 30 µg/kg, and the same 

dosage of cefazolin produces peak serum concentrations 

of 40 to 60 µg/ml. Cephalexin at 30 mg/kg PO produces 

a peak concentration of 25 µg/ml. Clindamycin 

administered at 10 mg/kg SC produces a peak serum 

concentration of 8 µg/ml compared with 5 µg/kg when 

administered orally at the same dose. 50 

The most common infective bacteria are known, and 

their antimicrobial sensitivity patterns are somewhat 

predictable (Table 1). If blood cultures are negative or 

treatment is deemed necessary before culture results are 

obtained, ampicillin, a first-generation cephalosporin, 

or ticarcillin plus gentamicin or amikacin may be used. 

A fluoroquinolone may be substituted for an aminogly-


Table 1. Antimicrobial Recommendations for Bacteria Commonly Isolated in Dogs with Infective 

Endocarditis 9–11,13,14,42,48–50 

Antibiotic Staphylococci a Streptococci Gram-Negative Organisms Anaerobes 

Cephalosporins 

First generation S S V R 

Second generation S S V Gram negative 

Third generation 

Cefotaxime b V S S c S 

Ceftiofur d V V V V 

Penicillin G R S R S 

Ampicillin R S V V 

Amoxicillin–clavulanate V S V S 

Ticarcillin e S S V V 

Ticarcillin–clavulanate f S S S S 

Fluoroquinolones S V S R 

Aminoglycosides S V S R 

Clindamycin g V S R S 

a Coagulase-positive staphylococci. 

b Claforan ® , Hoechst Marion Roussel. 

c Pseudomonas resistant. 

d Naxcel ® , Pharmacia and Upjohn Co. 

e Ticar ® , GlaxoSmithKline. 

f Timentin ® , GlaxoSmithKline. 

g Cleocin ® , Pharmacia and Upjohn Co. 

R = usually resistant; S = usually sensitive; V = Variable sensitivity; use only if indicated by antibiogram. 

coside. 49 Clindamycin or metronidazole administration 

extends the anaerobic spectrum. A good combination is 

clindamycin plus enrofloxacin. Aminoglycoside therapy 

duration should be limited to 5 to 7 days because renal 

toxicity is possible and concurrent fluid support is necessary 

8–11 (Table 2). 

The choice for SC antibiotic administration should 

ideally be based on an antibiogram, but if blood cultures 

are negative or not performed, ceftiofur (2.2 

mg/kg SC q12h), azithromycin (5 mg/kg SC q12h), or 

ticarcillin (50 to 100 mg/kg SC q8h) may be used. 14 

We recommend that blood cultures be performed 4 

weeks after treatment to ensure eradication of the 

organism. Patients, including those with negative cultures, 

are monitored for improvement via constitutional 

signs, serial CBC and serum chemistry profiles, 

and echocardiography. The emergence of overt CHF is 

ominous. Although it may offer temporary amelioration 

of signs, glucocorticoid administration is associated 

with decreased survival. 6 

Supportive therapy is always a component of treatment. 

Acid–base, fluid, and electrolyte balance must 

be addressed. Nutritional support may be an important 

component of therapy and may be maintained by 

either parenteral or tube alimentation. The consequences 

of valvular destruction must be addressed. 


Although a positive influence on disease progression is 

unproven, 51 angiotensin-converting enzyme (ACE) 

inhibition is usually recommended if there is unequivocal 

left-atrial or left-ventricular enlargement. 

Enalapril (0.25 mg/kg PO q12h for 1 week followed 

by 0.5 mg/kg PO q12h) or benazepril (0.25 mg/kg PO 

q24h for 1 week followed by 0.5 mg/kg PO q24h) are 

common choices. Spironolactone (1 to 2 mg/kg PO 

q12h), an aldosterone antagonist, may be added to the 

regimen as cardiac enlargement progresses. A diuretic 

and digoxin (0.005 to 0.01 mg/kg PO q12h) should 

be used if CHF is overt. Again, the influence of 

digoxin on disease progression may be negligible. 52 

Furosemide (1 to 4 mg/kg PO q12h) is the diuretic of 

choice. A serum digoxin concentration should be 

obtained after 7 days of treatment from a sample 

drawn at 6 hours after the morning dose. For most 

laboratories, a desirable serum digoxin concentration is 

1 to 1.5 ng/ml. Renal function and serum electrolyte 

monitoring at 1 to 2 weeks and then monthly is recommended. 

Augmented afterload reduction may be a 

useful adjunct to ACE inhibition. Adjuvant afterload 

reduction (arteriolar dilation) may result in reduction 

of aortic or mitral regurgitant volume. When the total 

peripheral arteriolar resistance is decreased by increasing 

the total arteriolar cross-sectional area, the change


Table 2. Intravenous and Subcutaneous Antibiotic 

Dosages Recommended for Treating Bacterial 

Endocarditis 11,14 

Antibiotic Dose (mg/kg) Frequency 

Ampicillin 20–40 tid 

Amoxicillin–clavulanate 20 bid 

Cephalosporins 

First generation 22 tid 

Second generation 

Cefuroxime a 15 tid 

Cefaclor b 10–15 tid 

Cefoxitin c 20–30 tid 

Third generation 

Cefotaxime 50 bid 

Ceftiofur 2.2–4.4 bid 

Clindamycin 10 tid 

Azithromycin d 5–10 bid 

Enrofloxacin 10 Once daily 

5 bid 

Ticarcillin, ticarcillin– 50–100 tid 

clavulanate 

Gentamicin 6 Once daily 

Amikacin 10 Once daily 

a Ceftin ® , GlaxoSmithKline. 

b Ceclor ® , Eli Lilly Co. 

c Mefoxin ® , Merck and Co. 

d Zithromax ® , Pfizer Inc. 

in relative resistance to systolic and diastolic blood 

flow facilitates increased forward stroke volume and 

decreased aortic regurgitation. 

Systemic blood pressure should be monitored as adjuvant 

afterload reduction is initiated and up-titrated. 

Amlodipine and felodipine are effective afterload reducers 

when instituted at 0.1 mg/kg PO q12h and up-titrated 

every 4 to 7 days to a maximum of 0.3 to 0.4 mg/kg PO 

q12h. Indirect blood pressure monitoring is important, 

although it is subject to inaccuracies. Dogs that subsequently 

develop signs of hypotension have consistently 

had lower indirect blood pressures compared with pretreatment 

and during early dose titration. We discontinue 

up-titration if the systolic blood pressure is less than 

approximately 110 mm Hg. If clinical signs of hypotension 

(e.g., lethargy, trembling, weakness, anorexia) occur, 

withdraw amlodipine, ACE inhibitor, spironolactone, 

and diuretic therapy for 24 hours, and then reinstitute all 

drugs with amlodipine at the previous lower dose. Severe 

hypotension requires IV fluid administration. 

Anticoagulant Therapy 

Anticoagulant therapy has not been shown to prevent 

embolization and may increase the risk of hemor- 


rhage. 52 The role of aspirin in preventing embolization 

is under evaluation. 53 However, it may reduce vegetation 

bacterial density, bacterial dissemination, and 

embolic events. 53 

PROGNOSIS 

The prognosis for long-term survival of dogs with IE 

is poor. 1–4,6,8–14 Early diagnosis followed immediately by 

aggressive antibiotic therapy is critical for long-term 

survival, especially when the aortic valve is infected. 

Unfortunately, early diagnosis is difficult, and valvular 

damage is often advanced by the time of diagnosis. 

Aortic valve endocarditis is associated with a grave 

prognosis because animals with it develop left-sided 

CHF (often within 1 to 3 months, and almost always 

within 6 months of diagnosis). 

PREVENTION 

Chemoprophylaxis is controversial because the 

risk:benefit ratio and economic rationale can be questioned 

and clinical studies supporting efficacy are limited. 

9–11 Chemoprophylaxis, even if effective, does not 

apply to the majority of cases. However, the mortality 

associated with IE warrants chemoprophylaxis in 

patients at increased risk. 54,55 

It is recommended to use prophylactic antibiotics 

when performing dental scaling, dental extractions, or 

surgery in dogs with congenital heart diseases. 9–11 Such 

procedure-focused chemoprophylaxis should not be initiated 

several days before the procedure because of the 

potential to select for antibiotic-resistant organisms. 8 

Maintenance of oral hygiene is a more important preventive 

than procedure-focused chemoprophylaxis. 8 The 

male dog’s urinary tract is suspected to be a common 

source of chronic bacteremia; therefore, castration can be 

viewed as a prophylactic measure because it reduces the 

risk of bacterial prostatitis. For oral/dental procedures in 

patients that are at increased risk, it is prudent to administer 

ticarcillin or a first-generation cephalosporin intravenously 

1 hour before and 6 hours after the procedure. 

Because incision and drainage of infected skin are associated 

with coagulase-positive staphylococci, a first-generation 

cephalosporin, ticarcillin, or ticarcillin–clavulanate 

is a good choice for prophylaxis. 54,56 

REFERENCES 

1. Shouse CL, Meier H: Acute vegetative endocarditis in the dog 

and cat. JAVMA 129:278–289, 1956. 

2. Sisson D, Thomas WP: Endocarditis of the aortic valve in the 

dog. JAVMA 184:570–577, 1984. 

3. Lombard CW, Buergelt CD: Vegetative bacterial endocarditis in 

dogs: Echocardiographic diagnosis and clinical signs. J Small 

Anim Pract 24:325–329, 1993. 

4. Anderson CA, Dubielzig RR: Vegetative endocarditis in dogs.


JAAHA 20:149–152, 1984. 

5. Freedman LR: The pathogenesis of infective endocarditis. J 

Antimicrob Chemother 20:1–6, 1987. 

6. Calvert CA: Valvular bacterial endocarditis in the dog. JAVMA 

180:1080–1084, 1982. 

7. Weinstein L, Schlesinger JJ: Pathoanatomic, pathophysiologic 

and clinical correlations in endocarditis. N Engl J Med 

291:1122–1126, 1974. 

8. Karchmer AW: Infective endocarditis, in Braunwald E (ed): 

Heart Disease: A Textbook of Cardiovascular Medicine, ed 5. 

Philadelphia, WB Saunders Co, 1997, pp 1077–1099. 

9. Miller MW, Sisson D: Infectious endocarditis, in Fox PR, Sisson 

D, Moise NS (eds): Textbook of Canine and Feline Cardiology, ed 

2. Philadelphia, WB Saunders Co, 1999, pp 552, 567–580, 908. 

10. Kittleson MD: Infective endocarditis, in Kittleson MD, Kienle 

RD (eds): Small Animal Cardiovascular Medicine. St. Louis, 

Mosby, Inc, 1998, pp 402–412. 

11. DeFrancesco TC: CVT update: Infectious endocarditis, in 

Bonagura JD (ed): Kirk’s Current Veterinary Therapy VIII. 

Philadelphia, WB Saunders Co, 2000, pp 768–772, 

1241–1264. 

12. Calvert CA, Greene CE, Hardie EM: Cardiovascular infections 

in dogs: Epizootiology, clinical manifestations, and prognosis. 

JAVMA 187:612–616, 1985. 

13. Calvert CA, Greene CE: Bacteremia in dogs: Diagnosis, treatment, 

and prognosis. Compend Contin Educ Pract Vet 8: 

179–184, 1986. 

14. Calvert CA: Cardiovascular infections, in Greene CE (ed): Infectious 

Diseases of the Dog and Cat, ed 2. Philadelphia, WB Saunders 

Co, 1998, pp 567–582, 790–919. 

15. Thompson J, Meddens MJ, Thorig L, et al: The role of bacterial 

adherence in the pathogenesis of infective endocarditis. Infection 

10:196–198, 1982. 

16. Lepeschkin E: On the relation between the site of valvular 

involvement in endocarditis and the blood pressure resting on 

the valve. Am J Med Sci 224:318–322, 1952. 

17. Rodbard S: Blood velocity and endocarditis. Circulation 27: 

18–20, 1963. 

18. Buchbinder NA, Roberts WC: Left-sided valvular infective 

endocarditis: A study of forty-five necropsy patients. Am J Med 

53:20–35, 1972. 

19. Muna WF, Ferrans VJ, Pierce JE, et al: Discrete subaortic stenosis 

in Newfoundland dogs: Association of infective endocarditis. 

Am J Cardiol 41:746–754, 1978. 

20. Kienle RD, Thomas WP, Pion PD: The natural clinical history 

of canine congenital subaortic stenosis. J Vet Intern Med 

8:423–431, 1994. 

21. Wahl MJ: Myths of dental-induced endocarditis. Arch Intern 

Med 154:137–144, 1994. 

22. Bender IB, Barkan MJ, Einstein A: Dental bacteremia and its 

relationship to bacterial endocarditis: Preventive measures. Compend 

Contin Educ Pract Vet 10:472, 475–477, 1994. 

23. Black AP, Crichlow AM, Saunders JR: Bacteremia during ultrasonic 

teeth cleaning and extraction in the dog. JAAHA 

16:611–616, 1980. 

24. Ellison GW, King RR, Calderwood-Mays M: Medical and surgical 

management of multiple organ infarctions secondary to 

endocarditis in a dog. JAVMA 193:1289–1291, 1988. 

25. Ramirez-Ronda CH: Effects of molecular weight of dextran on 

the adherence of Streptococcus sanguis to damaged heart valves. 

Infect Immun 29:1–7, 1980. 


26. Hamill RJ: Role of fibronectin in infective endocarditis. Rev 

Infect Dis 9(Suppl 4):360–371, 1987. 

27. Rubinstein E, Lang R: Fungal endocarditis. Eur Heart J 16 

(Suppl B):84–89, 1995. 

28. Scheld WM, Mandell GL: Enigmatic enterococcal endocarditis. 

Ann Intern Med 100:904–905, 1984. 

29. Eriksen K, Fossum K, Gamlem H, et al: Endocarditis in two 

dogs caused by Erysipelothrix rhusiopathiae. J Small Anim Pract 

28:117–122, 1987. 

30. Takahashi T, Tamura Y, Yoshimura H, et al: Erysipelothrix tonsillarum 

isolated from dogs with endocarditis in Belgium. Res Vet 

Sci 54:264–265, 1993. 

31. Breitschwerdt EB, Kordick DL, Malarkey DE, et al: Endocarditis 

in a dog due to infection with a novel Bartonella subspecies. J 

Clin Microbiol 33:154–160, 1995. 

32. Raoult D, Fournier PE, Drancourt M, et al: Diagnosis of 22 

new cases of Bartonella endocarditis. Ann Intern Med 125: 

646–652, 1996. 

33. Breitschwerdt EB, Atkins CE, Brown TT, et al: Bartonella vinsonii 

subsp. berkhoffi and related members of the Alpha Subdivision 

of the Proteobacteria in dogs with cardiac arrhythmias, endocarditis, 

or myocarditis. J Clin Microbiol 37:3618–3626, 1999. 

34. Breitschwerdt EB, Kordick DL: Bartonellosis. JAVMA 206: 

1928–1931, 1995. 

35. Bennett D, Bilbertson EM, Grennan D: Bacterial endocarditis 

with polyarthritis in two dogs associated with circulating 

autoantibodies. J Small Anim Pract 19:185–196, 1993. 

36. Bennett D, Taylor DJ: Bacterial endocarditis and inflammatory 

joint disease in the dog. J Small Anim Pract 29:347–353, 1988. 

37. Neugarten J, Gallo GR, Baldwin DS: Glomerulonephritis in 

bacterial endocarditis. Am J Kidney Dis 3:371–379, 1984. 

38. Perez GO, Rothfield N, Williams RC: Immune-complex 

nephritis in bacterial endocarditis. Arch Intern Med 136: 

334–336, 1976. 

39. Caywood DD, Wilson JW, O’Leary TP: Septic polyarthritis 

associated with bacterial endocarditis in two dogs. JAVMA 

171:549–552, 1977. 

40. Gutman RA, Striker GE, Gilliland BC, et al: The immune complex 

glomerulonephritis of bacterial endocarditis. Medicine 

51:1–25, 1972. 

41. Root CR, Bahr RJ: The heart and great vessels, in Thrall DE 

(ed): Textbook of Veterinary Diagnostic Radiology, ed 3. Philadelphia, 

WB Saunders Co, 1994, pp 304–318. 

42. Dow SW, Curtis CR, Jones RL, et al: Bacterial culture of blood 

from critically ill dogs and cats: 100 cases (1985–1987). JAVMA 

195:113–117, 1989. 

43. Washington JA: The microbiologic diagnosis of infective endocarditis. 

J Antimicrob Chemother 20:29–39, 1987. 

44. Washington JA: The role of the microbiology laboratory in the 

diagnosis and antimicrobial treatment of endocarditis. Mayo 

Clin Proc 57:22–32, 1982. 

45. Hoen B, Selton-Suty C, Lacassin F, et al: Infective endocarditis 

in patients with negative blood cultures. Clin Infect Dis 

20:501–506, 1995. 

46. Cremieux AC, Maziere B, Vallois JM, et al: Evaluation of antibiotic 

diffusion into cardiac vegetations by quantitative autoradiography. 

J Infect Dis 159:938–944, 1989. 

47. Working Party of the British Society for Antimicrobial 

Chemotherapy. Antibiotic treatment of streptococcal, enterococcal, 

and staphylococcal endocarditis. Heart 1998 79:207–210, 1998.


48. Wilson WR, Karchmer AW, Dajani AS, et al: Antibiotic treatment 

of adults with infective endocarditis due to streptococci, 

enterococci, and staphylococci, and HACEK microorganisms. 

JAMA 274:1706–1713, 1995. 

49. Scheld WM: Evaluation of quinolones in experimental animal 

models of infection. Eur J Clin Microbiol Infect Dis 10:275–290, 

1991. 

50. Aronson AL, Aucoin DP: Antimicrobial drugs, in Ettinger SJ 

(ed): Textbook of Veterinary Internal Medicine, ed 3. Philadelphia, 

WB Saunders Co, 1989, pp 409–410. 

51. Kvart C, Haggstrom J, Pedersen HD, et al: Efficacy of enalapril 

for prevention of congestive heart failure in dogs with myxomatous 

valve disease and asymptomatic mitral regurgitation. J Vet 

Intern Med 16:80–88, 2002. 

52. Tormas P, Almirante B, Mirabet S, et al: Infective endocarditis 

due to Staphylococcus aureus: Deleterious effect of anticoagulant 

therapy. Arch Intern Med 159:473–475, 1999. 

53. Kupferwasser LI, Yeaman MR, Shapiro SM, et al: Acetylsalicylic 

acid reduces vegetation bacterial density, hematogenous bacterial 

dissemination, and frequency of embolic events in experimental 

Staphylococcus aureus endocarditis through antiplatelet and antibacterial 

effects. Circulation 99:2791–2797, 1999. 

54. Blatter M, Francioli P: Endocarditis prophylaxis: From experimental 

models to human recommendation. Eur Heart J 16 

(Suppl B):107–109, 1995. 

55. Durack DT: Prevention of infective endocarditis. N Engl J Med 

332:38–44, 1995. 

56. Rosin E, Dow SW, Daly WR, et al: Surgical wound infection and 

use of antibiotics, in Slatter D (ed): Textbook of Small Animal 

Surgery, ed 2. Philadelphia, WB Saunders Co, 1993, pp 89–91. 

ARTICLE 

CE 

#3 CE TEST 

The article you have read qualifies for 1.5 contact 

hours of Continuing Education Credit from 

the Auburn University College of Veterinary Med- 

icine. Choose the best answer to each of the follow- 

ing questions; then mark your answers on the 

postage-paid envelope inserted in Compendium. 

1. Which dog is least likely to develop IE? 

a. 6-year-old male German shepherd 

b. 11-year-old male miniature poodle 

c. 5-year-old male golden retriever 

d. 7-year-old female boxer 

e. 3-year-old female rottweiler with congenital 

subaortic stenosis 

2. Which heart valve is most often affected by IE? 

a. mitral 

b. pulmonic 

c. tricuspid 

d. aortic 

e. All valves are affected with equal frequency. 

3. Which sign by itself is most indicative of IE? 

a. diastolic heart murmur 

b. fever 


c. inflammatory leukogram 

d. systolic heart murmur 

e. shifting leg lameness 

4. Which microbe is least often a proven cause of IE in 

dogs? 

a. staphylococci 

b. gram-positive bacteria 

c. fungal agents 

d. streptococci 

e. Bartonella 

5. When the infecting microbe and its antibiogram 

results are not identified, which drug is the best first 

choice for treating IE in dogs? 

a. ampicillin 

b. first-generation cephalosporin 

c. gentamicin 

d. clindamycin plus enrofloxacin 

e. metronidazole 

6. Which clinical sign of CHF is least likely in a dog with IE? 

a. coughing 

b. dyspnea 

c. pulmonary edema 

d. ascites 

e. exercise intolerance 

7. Which sign is most suggestive of IE in a 4-year-old 

German shorthaired pointer? 

a. V/VI systolic heart murmur that was not present 6 

months previously 

b. inflammatory leukogram 

c. monocytosis 

d. fever 

e. lameness 

8. The most difficult aspect of antibiotic treatment of IE is 

a. choosing an antibiotic. 

b. the cost. 

c. safety. 

d. maintaining long-term parenteral administration. 

e. developing antibiotic resistance. 

9. Which drug is most likely to kill the two bacterial 

species most often involved in canine IE? 

a. gentamicin d. penicillin 

b. enrofloxacin e. ampicillin 

c. cephazolin 

10. Which factor is least likely to predispose dogs to IE? 

a. stomatitis/gingivitis 

b. chronic wounds 

c. bacterial prostatitis 

d. corticosteroid administration 

e. myxomatous mitral valve disease

Wall-July PV-Review - VetLearn.com

You also want an ePaper? Increase the reach of your titles

Delete template?

Save as template?