Infective endocarditis resident survival guide

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Farman Khan, MD, MRCP [2]; Mohamed Moubarak, M.D. [3]; Rim Halaby, M.D. [4]

Infective endocarditis Resident Survival Guide Microchapters
Overview
Causes
FIRE
Diagnosis
Treatment
Prophylaxis
Do's
Don'ts

Overview

Infective endocarditis is the infection of the endothelium of the heart including but not limited to the valves. While acute bacterial endocarditis is caused by an infection with a virulent organism such as staphylococcus aureus, group A or other beta-hemolytic streptococci, subacute bacterial endocarditis is an indolent infection with less virulent organisms like streptococcus viridans. Patients with unexplained fever for more than 48 hours and who are at high risk for infective endocarditis and patients among whom valve regurgitation is newly diagnosed should undergo a diagnostic workup to rule out endocarditis. The diagnosis of endocarditis depends on a thorough history and physical exam as well as on the results of blood cultures and transthoracic echocardiogram. The modified Duke criteria is used to establish the diagnosis of endocarditis. Endocarditis is initially treated with empiric antibiotic therapy until the causative agent is identified.

Causes

Life Threatening Causes

Acute endocarditis is a life-threatening condition and must be treated as such irrespective of the underlying cause.

Common Causes

• Enterococcus infection
• Staphylococcus aureus infection
• Streptococcus viridans infection

FIRE:Focused Initial Rapid Evaluation

A Focused Initial Rapid Evaluation (FIRE) should be performed to identify patients in need of immediate intervention.

Boxes in salmon color signify that an urgent management is needed.

Abbreviations: TEE: Transesophageal echocardiography; TTE: Transthoracic echocardiography

Identify cardinal signs and symptoms that increase the pretest probability of endocarditis ❑ Persistent fever ❑ New valvular regurgitation murmur ❑ Bacteremia ❑ Janeway lesion ❑ Osler's node ❑ Roth's spots ❑ Glomerulonephritis ❑ New AV block ❑ High risk factors ❑ Pre-existing cardiac abnormality ❑ Prosthetic valve ❑ Recent surgical or medical procedures ❑ Intravenous drug use ❑ Recent bacterial infection ❑ History of previous endocarditis

❑ Order blood cultures (at least 2 sets) ❑ Order TTE, or ❑ Order a TEE if one or more of the following is present ❑ Non diagnostic TTE in a suspected infective endocarditis ❑ Clinical complications ❑ Intracardiac device leads ❑ Staphylococcus aureus bacteremia without a known cause ❑ Prosthetic valve with persistent fever without bacteremia ❑ Prosthetic valve with a new murmur ❑ Nosocomial Staphylococcus aureus bacteremia with known extra-cardiac port of entry ❑ Evaluate the modified Duke criteria

Identify findings suggestive of complications of endocarditis that require urgent intervention

Cardiac complications

Extra cardiac complications

No complications

❑ Dyspnea ❑ Edema ❑ Decreased ejection fraction

❑ Severe valvular insufficiency ❑ Valvular abscess ❑ Valvular dehiscence ❑ Valvular rupture ❑ Valvular fistula ❑ Periannular extension of the infection

Focal neurological deficits ❑ Facial droop ❑ Unilateral hemiparesis ❑ Aphasia ❑ Neglect ❑ Hemianopsia ❑ Headache ❑ Altered mental status

❑ Tender pulsatile mass ❑ Hematemesis, hemobilia, jaundice (suggestive of involvement of the hepatic artery) ❑ Hypertension Hematuria (suggestive of involvement of the renal artery) ❑ Massive bloody diarrhea (suggestive of involvement of a bowel artery)

❑ Order non contrast CT ❑ Order MRA or CTA

❑ Order CT scan or MRI

Decompensated heart failure

Severe valvular involvement

Embolism to the brain

Intracranial mycotic aneurysm

Extracranial mycotic aneurysm

Continue with the complete diagnostic approach below

❑ Consider valve replacement surgery ❑ Click here for heart failure resident survival guide

❑ Consider valve replacement surgery

❑ Click here for stroke resident survival guide

❑ Evaluate medical vs surgical intervention

❑ Consider surgical ligation of the involved artery

Complete Diagnostic Approach

A complete diagnostic approach should be carried out after a focused initial rapid evaluation is conducted and following initiation of any urgent intervention.

Abbreviations: TEE: Transesophageal echocardiography; TTE: Transthoracic echocardiography

Characterize the symptoms: ❑ Onset of the symptoms ❑ Acute ❑ Subacute ❑ Fever ❑ Chills ❑ Rigors ❑ Sweats ❑ Fatigue ❑ Pleuritic chest pain ❑ Back pain ❑ Weakness ❑ Myalgias ❑ Arthralgias ❑ Anorexia ❑ Shortness of breath ❑ Hemoptysis ❑ Productive cough ❑ Flank pain (suggestive of septic emboli or glomerulonephritis) ❑ Hematuria (suggestive of septic emboli or glomerulonephritis) ❑ Seizures (suggestive of septic emboli) ❑ Focal neurological deficits due to stroke (suggestive of septic emboli) or mycotic aneurysm ❑ Reversible focal neurological deficits due to transient ischemic attack (suggestive of septic emboli)

Identify existing risk factors for endocarditis: ❑ History of rheumatic heart disease ❑ Prosthetic valves ❑ Intravenous drug use ❑ Substances used in the mixture ❑ Sharing the equipment ❑ The process of cleaning the equipment ❑ Previous infective endocarditis ❑ Cardiac transplantation with valvular abnormality ❑ Congenital heart diseases with a shunt ❑ Acquired heart diseases ❑ Immunodeficiency ❑ Medical procedures ❑ Surgical procedures ❑ Indwelling prosthetic devices

Examine the patient: Vitals ❑ Temperature ❑ Fever ❑ Blood pressure ❑ Wide pulse pressure (suggestive of aortic insufficiency) ❑ Narrow pulse pressure (suggestive of left ventricular failure) Skin ❑ Petechiae ❑ Splinter hemorrhages ❑ Osler's nodes ❑ Janeway lesions Dental examination ❑ Teeth ❑ Gingiva Eyes ❑ Conjunctival hemorrhage ❑ Roth's spots in the retina Cardiovascular examination ❑ Heart murmur: New or change in the character of a previous murmur ❑ Aortic insufficiency (early diastolic, decrescendo, best heard in the left sternal border) ❑ Tricuspid regurgitation (holosystolic, best heard over the fourth intercostal area at left sternal border) ❑ Mitral regurgitation (holosystolic, best heard at the apex) Respiratory examination ❑ Rales (suggestive of heart failure) Abdominal examination ❑ Reduced bowel sounds (suggestive of mesenteric embolization or ileus) ❑ Abdominal pain ❑ Flank pain (suggestive of embolus to the kidney) ❑ Left upper quadrant pain (suggestive of splenic infarct) ❑ Splenomegaly Extremities ❑ Janeway lesions (painless hemorrhagic cutaneous lesions on the palms and soles) ❑ Gangrene of fingers ❑ Splinter hemorrhages ❑ Osler's nodes (painful subcutaneous lesions in the distal fingers) Neurological examination ❑ Full neurological exam ❑ Focal deficits (suggestive of stroke or brain abscess)

Order tests: ❑ Blood culture (at least two sets) ❑ Order a TTE ❑ Order a TEE if one or more of the following is present ❑ Non diagnostic TTE in a suspected infective endocarditis (Class I, level of evidence B) ❑ Clinical complications (Class I, level of evidence B) ❑ Intracardiac device leads (Class I, level of evidence B) ❑ Staphylococcus aureus bacteremia without a known cause (Class IIa, level of evidence B) ❑ Prosthetic valve with persistent fever without bacteremia (Class IIa, level of evidence B) ❑ Prosthetic valve with a new murmur (Class IIa, level of evidence B) ❑ Nosocomial Staphylococcus aureus bacteremia with known extra-cardiac port of entry (Class IIb, level of evidence B)

Evaluate the Modified Duke Criteria for infective endocarditis: Probability of infective endocaritis Characteristics Definite diagnosis by pathological criteria ❑ Microorganisms demonstrated by culture or histological examination of a vegetation, OR ❑ Pathological lesions; vegetation or intracardiac abscess confirmed by histological examination showing active endocarditis Definite diagnosis by clinical criteria ❑ 2 major criteria, OR ❑ 1 major criterion and 3 minor criteria, OR ❑ 5 minor criteria Possible diagnosis ❑ 1 major criterion and 1 minor criterion, OR ❑ 3 minor criteria Rejected diagnosis ❑ Firm alternative diagnosis explaining evidence of infective endocarditis, OR ❑ Resolution of infective endocarditis with antibiotic therapy for 4 days, OR ❑ No pathological evidence of infective endocarditis at surgery or autopsy, with antibiotic therapy for 4 days, OR ❑ Does not meet criteria for possible infective endocarditis as above

Consider alternative diagnoses: ❑ Culture negative endocarditis ❑ Previous treatment with antibiotics ❑ Fastidious bacterial infection ❑ Fungal infection ❑ Inappropriate blood culture technique ❑ Marantic endocarditis ❑ Valvular vegetations ❑ Negative blood culture ❑ Hypercoagulable state, lupus or antiphospholipid syndrome ❑ Cellulitis (skin inflammatory skin) ❑ Catheter related infection (presence of catheter associated with associated local erythema and tenderness) ❑ Cardiac device infection ❑ Prosthetic joint infection (localized inflammatory signs) ❑ Pneumonia ❑ Osteomyelitis

Treatment

Shown below is an algorithm depicting the management of infective endocarditis.

Abbreviations: TEE: Transesophageal echocardiography; TTE: Transthoracic echocardiography

Once the diagnosis of infective endocarditis is confirmed, initiate the treatment: ❑ Begin antibiotic treatment ❑ Order blood cultures every 24-48 hours until no bacteremia can be detected ❑ Temporarily discontinue anticoagulation if one of the following is present ❑ Signs and symptoms of CNS involvement consistent with embolism or stroke (Class IIa, level of evidence B) ❑ Vitamin K antagonist administration (Class IIb, level of evidence B) ❑ Remove the pacemaker of the defibrillator system if one of the following is present ❑ Documented infection of the device or leads (Class I, level of evidence B) ❑ Valvular infective endocarditis by Staphylococcus aureus or fungi in the absence of documented infection of the device or leads (Class IIa, level of evidence B) ❑ Patient scheduled for valve surgery (Class IIa, level of evidence C) ❑ Persistent vegetations and recurrent emboli despite the antibiotic regimen (Class IIa, level of evidence B) ❑ Manage the patient with a multidisciplinary team ❑ Consult an infectious disease specialist ❑ Consult a cardiologist ❑ Consult a cardiac surgeon

Does the patient have any of the following conditions that require an early valve replacement surgery during hospitalization? ❑ Heart failure due to the valve dysfunction (Class I, level of evidence B) ❑ Left sided infective endocarditis due to staphylococcus aureus, fungal or highly resistant organisms (Class I, level of evidence B) ❑ Heart block, annular or aortic abscess or destructive lesions (Class I, level of evidence B) ❑ Persistent bacteremia or fever 5 to 7 following the initiation of the antibiotics (Class I, level of evidence B)

Yes

No

❑ Schedule for early surgery

Follow up the patient: ❑ Repeat TTE before discharge ❑ Refer for cessation of drug abuse (if applicable) ❑ Educate the patient about the signs and symptoms of infective endocarditis ❑ Recommend a thorough dental examination ❑ Monitor for complications ❑ Relapse (fever, chills) ❑ New or worsening heart failure ❑ Antibiotic toxicity ❑ Vestibular toxicity ❑ Diarrhea or colitis

Reevaluate the patient with TTE and/or TEE if one of the following is present: ❑ Change in clinical signs and symptoms ❑ New murmur ❑ Embolism ❑ Persistent fever ❑ Heart failure ❑ Abscess ❑ Atrioventricular heart block ❑ High risk of complications ❑ Large vegetations on echocardiogram ❑ Staphylococcus, enterecoccal, or fungal infections

Antibiotic Regimens

A complete list of pathogen specific antibiotics regimens with appropriate dosages and duration of treatment is available here.

Modified Duke Criteria

Shown below is a table summarizing the major and minor Modified Duke Criteria.

Modified Duke Criteria Major criteria Minor criteria 1- Positive Blood Culture for Infective Endocarditis ❑ Typical microorganism consistent with infective endocarditis from 2 separate blood cultures, in the absence of a primary focus: ❑ Viridans streptococci, streptococcus bovis ❑ HACEK group ❑ Community-acquired staphylococcus aureus ❑ Enterococci OR ❑ Microorganisms consistent with infective endocarditis from persistently positive blood cultures defined as: ❑ At least 2 positive cultures of blood samples drawn >12 hours apart, or ❑ All of 3 or a majority of 4 separate cultures of blood (with first and last sample drawn 1 hour apart) OR ❑ Single positive blood culture for Coxiella burnetii or anti–phase 1 IgG antibody titer >1:800 2-Echocardiographic evidence of endocardial involvement ❑ Oscillating intracardiac mass on valve or supporting structures, in the path of regurgitant jets, or on implanted material in the absence of an alternative anatomic explanation, or ❑ Abscess, or ❑ New partial dehiscence of prosthetic valve, or ❑ New valvular regurgitation 1- Predisposition ❑ Predisposing heart condition or intravenous drug use 2- Fever ❑ Temperature > 38.0° C (100.4° F) 3- Vascular phenomena ❑ Major arterial emboli ❑ Septic pulmonary infarcts ❑ Mycotic aneurysm ❑ Intracranial hemorrhage ❑ Conjunctival hemorrhage ❑ Janeway lesions 4- Immunologic phenomena ❑ Glomerulonephritis ❑ Osler's nodes ❑ Roth spots ❑ Rheumatoid factor 5- Microbiological evidence ❑ Positive blood culture but does not meet a major criterion as noted above OR ❑ Serological evidence of active infection with organism consistent with infectious endocarditis

Prophylaxis

Shown below is an algorithm depicting the general prophylactic approaches of infective endocarditis.

Identify high risk patients: (Class IIa, Level of evidence B) ❑ Prosthetic valves patients ❑ Previous infective endocarditis ❑ Cardiac transplant recipients with valves regurgitation due to structurally abnormal valve ❑ Congenital heart diseases ❑ Unrepaired cyanotic congenital heart diseases ❑ Completely repaired defect with prosthetic material or device ❑ Repaired with residual defects
Identify high risk procedures: ❑ Dental procedures ❑ Manipulation of gingival tissue, or ❑ Manipulation of the periapical region of teeth, or ❑ Perforation of the oral mucosa ❑ Respiratory tract procedures involving incision of the respiratory tract mucosa ❑ Tonsillectomy ❑ Adenoidectomy ❑ Gastrointestinal (GI) and genitourinary (GU) procedures only if GI or GU tract infection is present
❑ Administer prophylaxis

Antibiotic Prophylaxis

Shown below is a table depicting the prophylaxis antibiotic regimes for infective endocarditis.

Infective Endocarditis Antibiotic Prophylaxis Oral treatment is tolerated Not allergic to penicillin Allergic to penicillin ▸ Amoxicillin 2 g ▸ Ampicillin 2 g IM or IV OR ▸ Cefazolin 1 g IM or IV OR ▸ Ceftriaxone 1 g IM or IV Oral treatment is not tolerated Not allergic to penicillin Allergic to penicillin ▸ Cefalexin 2 g OR ▸ Clindamycin 600 mg OR ▸ Azithromycin 500 mg OR ▸ Clarithromycin 500 mg ▸ Cefazolin 1 g IM or IV OR ▸ Ceftriaxone 1 g IM or IV OR ▸ Clindamycin 600 mg IM or IV

Do's

• Elicit a full medical history to identify the minor Duke criteria for the diagnosis.
• Consider alternative diagnoses for bacteremia and fever by searching for focus of infections.
• Initiate antibiotic therapy after withdrawing blood for culture (Class I, level of evidence B).

• If the blood cultures are negative in a patient suspected to have infective endocarditis, suspect HACEK infection and ask the laboratory to retain the blood cultures for more than two weeks.

• If HACEK bacteremia is detected without any focus of infection, suspect the presence of infective endocarditis even in the absence of the typical signs and symptoms.

• Do a transesophageal echocardiography intraoperatively among patients scheduled for valve surgery for infective endocarditis (Class I, level of evidence B).

• Consider ordering a cardiac CT scan when echocardiography does not provide clear details about the cardiac anatomy in the context of suspected paravalvular infections (Class IIa, level of evidence B).

• Suspect intraventricular septal abscess as a complication of endocarditis when the ECG is significant for a gradual increase in the PR interval or a new left bundle branch block.

Don'ts

• Don't administer prophylaxis for infective endocarditis in patients with valvular heart disease who are at risk infective endocarditis for procedures such as transesophageal echocardiography, cystoscopy, esophagogastroduodenoscopy or colonoscopy without any evidence of active infection (Class III; level of evidence B).

• Do not administer infective endocarditis prophylaxis for the following dental procedures:
  • Anesthetic injections in noninfected tissue
  • Dental radiographs
  • Shedding of deciduous teeth
  • Placement of orthodontic brackets
  • Placement or removal of prosthodontic or orthodontic appliances
  • Adjustment of orthodontic appliances
  • Bleeding following trauma to the oral mucosa or lips

• Do not administer prophylaxis for infective endocarditis for procedures involving the respiratory tract unless they involve incision of the respiratory tract mucosa.

• Do not administer cephalosporins in subjects with a previous history of anaphylaxis, angioedema, or urticaria following penicillin or ampicillin use.

References

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