History and physical exam are essential towards making an adequate diagnosis in cases of TVIE. Establishing diagnosis can be more difficult in these cases because presentation can often be subacute or present with absence of typical IE features. Peripheral phenomenon such as splinter hemorrhages is less common, as is a cardiac murmur. However, clinicians must always be aware of potential complications of this disease process that are manifested by the various embolic phenomenon. Characteristics, which should lead clinicians to consider TVIE, include:

• Fever
• Chills
• Anorexia
• Weight loss
• Fatigue
• Malaise
• Arthralgia
• Dyspnea on exertion
• A cough
• Pleuritic pain
• Abdominal Pain

Physical Exam Findings

• Tachypnea
• Hypotension
• Cardiac murmur
• Splenomegaly
• Splinter hemorrhages
• Petechiae
• Janeway lesions
• Osler nodes
• Roth spots
• Focal neurologic deficits
• Joint effusion
• Clubbing

Diagnosis of TVIE is based upon the modified Duke Criteria. This criterion is widely used to diagnose TVIE like all other forms of IE. This criterion allows one to stratify infective endocarditis into a category of definite, possible, or rejected. Based on clinical criteria definite endocarditis is defined as two primary criteria, one major with three minor criteria, or five minor criteria. Possible endocarditis is measured by the presence of one major with two minor criteria, or with three minor criteria alone.  [5] The criteria classes are as follows:

Major Criteria

Positive blood culture(any of the followings):

• Two separate blood cultures with organisms known to cause infective endocarditis or
• Organism consistent with endocarditis from blood cultures obtained 12 hours apart or
• Positive culture for organisms that are common skin contaminant in 3 or the majority of ≥4 separate blood cultures (first and last sample drawn at least 1 hour apart) or
• Single positive blood culture of Coxiella burnetti

Evidence of endocardial involvement (vegetation, abscess, new valvular regurgitation, dehiscence of a prosthetic valve)

Minor Criteria

• Fever > 38 degrees C (100.4 degrees F)
• Immunologic occurrence: Roth spots, Osler nodes, glomerulonephritis. 
• Predisposing heart defect or IVDU
• Vascular phenomena: septic emboli, arterial emboli, conjunctival hemorrhages, splinter hemorrhages, Janeway lesions, mycotic aneurysm
• A positive blood culture that does not meet essential criteria.

Routine laboratory values in IE are generally nonspecific. Basic workup should be done. Some abnormalities which may be found include leukocytosis, elevated ESR, elevated CRP, normocytic anemia, or urinalysis revealing hematuria, proteinuria, or pyuria. EKG may reveal conduction anomalies such as heart block. [6]

• Chest radiographs should be obtained to evaluate for septic emboli or infiltrate.
• CT scan of the abdomen is helpful to evaluate for metastatic emboli. Such emboli include splenic or renal infarcts. Clinicians should have a low threshold to locate these potential foci.
• Blood cultures should be obtained in all individuals with suspected TVIE. A minimum of three sets should be collected from different sites. [26341945]
• Echocardiography should be performed in all individuals with suspected TVIE. Transthoracic echocardiogram (TTE) is the first test that is done. TTE is very specific. Transesophageal echocardiography should be pursued if TTE is negative, but a high clinical suspicion for IE exists. TEE may also be used if significant valve regurgitation exists and needs to be further evaluated prior to surgery. [7]

Some individuals with TVIE may be candidates for shorter duration antibiotic regimens(no evidence of renal failure, the absence of extrapulmonary metastatic infections or simultaneous left sided infection). The 2-week regimens are not used in patients with IE of the aortic or mitral valve, in patients with MRSA, or patients with complicated IE. [8] Patients with TVIE should be started on an empiric antibiotic regimen once it is suspected.

Initial empiric antibiotics should include coverage against the most common pathogens. Thus staphylococcus and streptococcus coverage are recommended. Vancomycin is used as an initial choice of antibiotic. These medicines should be tailored based upon blood cultures results. Once an organism has been specified, antibiotics regimen should typically be continued for six weeks from the date of first negative blood culture. Very limited patients can be trialed with a short duration course. These candidates include those with isolated TVIE, those without any complications secondary to IE, and those with IE from HACEK organisms. [9] For patients with methicillin-sensitive Staph aureus (MSSA) IE, it is vital to change vancomycin to an antibiotic more specific against MSSA. Such antibiotics include nafcillin, oxacillin, or cefazolin. Patient with MRSA IE should be treated with vancomycin for six weeks.

Surgical treatment of IE is reserved for individuals with the following: [10]

• TV vegetation > 2cm with septic pulmonary emboli.
• Persistent bacteremia for one week despite adequate treatment.
• Severe tricuspid regurgitation with right-sided heart failure.

Infective endocarditis of any form can be difficult to identify. IE can have many nonspecific complaints which can overlap in various autoimmune, infectious, or neoplastic processes. It is important to think of IE as a syndrome. The Duke Modified Criteria serves as the principal diagnostic tool that takes into account all the potential manifestations of this disease process. Some of the differential diagnoses which may also be considered include:

• Systemic lupus erythematosus
• Polymyalgia rheumatic
• Lyme Disease
• Antiphospholipid syndrome
• Libman sacks endocarditis
• Atrial myxoma
• Rheumatic fever
• Marantic endocarditis

Patients with TVIE have good prognosis compared to those with other forms of IE. The fatality rate is lower in these patients. [11] In one study evaluating native valve endocarditis, overall mortality was 6%. [12] Vegetation size is an important prognostic factor. Those with vegetation greater than 1cm have significantly increased mortality. Individuals who have concurrent left-sided infective endocarditis have a worse prognosis. This diagnosis is due to the higher risk of abscess development in these cases. [1]

Complications of TVIE include [13]

• Peri-annular abscesses
• Septic pulmonary emboli
• Splenic abscess
• A mycotic aneurysm
• Heart failure

Infective Endocarditis requires management by a group of physicians. Some physicians who should be involved in the care of these patients include

• Internal medicine
• Infectious disease
• Cardiology
• Cardiothoracic surgery

Patients should be made aware of the potential risk factors for developing TVIE. When hospitalized, efforts should be made to educate these patients about the hazards of IV drug abuse. Furthermore, all available resources should be used to prevent these individuals from relapsing into IVDU again. These include information and access to local rehab centers, education, and pharmacologic options.

interprofessional management of the patient with IE is essential to ensure positive outcomes. Physicians are important clinicians in assessing these patients and helping establish the diagnosis of TVIE. Nurses involved in the patient's care can identify changes in clinical status or clinical deterioration. Pharmacists have an important role in assisting with antimicrobial management. Some aspects of this care include appropriate empiric regimens, narrowing antimicrobial coverage, and ensuring an adequate therapeutic range of medications and their dosages. Case managers and social workers also play an essential role in finding rehab facilities to help prevent future IVDU, as well as to help arrange for outpatient facilities to obtain longer term IV antibiotics if necessary. Treating TVIE requires a team approach to ensure successful outcomes. The outcomes for patients with TVIE depends on patient age, comorbidity, hemodynamic status, the presence of sepsis and time of treatment.