Infective endocarditis

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

IE is often a difficult diagnosis to make because bacteremia may not always lead to endocardial involvement, while endocardial involvement may occur in the absence of peripheral bacteremia following previous antibiotic use. A systematic approach to therapy is required. The management of IE is guided by identification of the causative organism and whether the infected valve is native or prosthetic.[6] All cases of IE should include multidisciplinary evaluation by infectious disease, cardiology, and cardiac surgery specialists.[6][7][20][91]

The role of the endocarditis team

The management of IE requires a collaborative, multidisciplinary approach with the involvement of cardiologists, cardiac surgeons, infectious diseases specialists, neurologists, neurosurgeons, and microbiologists.

The utilization of the multidisciplinary "endocarditis team" has proven vital in improving outcomes in IE with highly significant reductions in mortality rates, as well as reduced occurrence of culture-negative endocarditis, reduced rates of renal dysfunction, and improved surgical outcomes. This strategy has been effective with both native and prosthetic valve IE.[92][93] In France, where this concept has been adopted, the 1-year mortality has reduced from 18.5% to 8.2%.[93] Current guidance supports the management of patients with IE in reference centers by an endocarditis team.[7]

In patients with complicated IE, early referral should be made to the endocarditis team in a reference center with rapid access to cardiac surgery facilities. Approximately 50% of IE patients will require surgical intervention, therefore early discussion with the surgical team is paramount to optimal care and is essential in complicated IE.[6]

Noncomplicated IE may be managed in a nonreference center, in close consultation with the endocarditis team and the reference center.

Initial therapy

Initial management is aimed at controlling airway, breathing, and circulation.

Appropriate antimicrobial therapy should be started and continued after blood cultures are obtained, with guidance from antibiotic sensitivity data and the infectious disease experts on the multidisciplinary team.[6][20] It is vital to obtain blood cultures prior to the initiation of antimicrobial therapy, as one dose often masks an underlying bacteremia and delays appropriate therapy. However, empiric antibiotic therapy with broad-spectrum antimicrobial therapy should not be delayed while waiting to take three sets of blood cultures in patients with septic shock, or in those who show high-risk signs on presentation.[6][64] Subsequently, patients should undergo urgent echocardiography to determine the nature and extent of valvular lesions.[62]

Recommended antibiotic regimens may differ between countries and local guidance should be consulted.[94] Consideration of the following factors influences the choice of empiric treatment:[6][7]

Previous antibiotic therapy received; native or prosthetic valve involvement
Local epidemiology and knowledge of antibiotic-resistant and culture-negative pathogens
Community, nosocomial, or non-nosocomial healthcare-associated infection

Patients who are acutely ill or present with signs and symptoms of decompensated heart failure present the greatest challenge. Often, these patients are colonized with aggressive Staphylococcus aureus, and are at risk for decompensating quickly. Hemodynamic stability is the goal, and these patients often require urgent surgical intervention if the valvular lesion is beyond repair with medical treatment alone. Acutely ill patients presenting with decompensated heart failure will require surgery, with intravenous diuretics given to manage pulmonary edema prior to the surgery.

Native valves: streptococci and staphylococci

Oral streptococci (Streptococcus mitis, Streptococcus sanguinis, Streptococcus anginosus, Streptococcus salivarius, Streptococcus downei, and Streptococcus mutans), all part of the viridans group, remain the primary cause of native valve endocarditis. These are either penicillin-sensitive or relatively penicillin-resistant. Antibiotic regimens include a beta-lactam (with or without gentamicin) or vancomycin. Cure rates of >95% can be achieved in patients treated with parenteral penicillin or ceftriaxone for IE caused by penicillin-susceptible oral streptococci or Streptococcus gallolyticus.[6][7] Patients with native valves are generally treated for 4-6 weeks.[6][7]

Staphylococcal endocarditis is becoming an increasingly recognized entity, often resulting in acute and destructive disease. Treatment options for methicillin-susceptible S aureus (MSSA) include a beta-lactam or daptomycin. Patients with methicillin-resistant S aureus (MRSA) infection are treated with vancomycin or daptomycin.[6] Other regimens (e.g., trimethoprim/sulfamethoxazole plus clindamycin) may be recommended in some countries.[7]

S aureus is the most common cause of endocarditis on native valves of intravenous drug users.[3] In intravenous drug users with right-sided endocarditis, gentamicin has been shown to increase the rate of microbial killing when used in combination with a beta-lactam.[95] However, aminoglycosides are no longer recommended in this situation due to the increased risk of nephrotoxicity.[96][97] The American Heart Association recommends that intravenous drug users with IE should be offered 6 weeks of intravenous antibiotics. If this is not deemed achievable (e.g., patient decision or unplanned discharge), initial intravenous therapy should be followed up by appropriate oral treatment, with outpatient follow-up by addiction medicine and infectious disease specialists.[3]

Prosthetic valves: streptococci and staphylococci

Oral streptococci are a primary cause of endocarditis of prosthetic valves. Organisms are generally penicillin-sensitive though some have a relatively high minimum inhibitory concentration and are therefore relatively penicillin-resistant. Antibiotic regimens include a beta-lactam (with or without gentamicin) or vancomycin. Patients with prosthetic valves are generally treated for at least 6 weeks.[6][7]

S aureus endocarditis infections are often rapidly progressive and carry a mortality rate greater than 45%.[98][99] Treatment options for MSSA include a beta-lactam or vancomycin. Patients with MRSA infection are treated with vancomycin. However, in contrast to native valve infection with S aureus, an aminoglycoside and rifampin are added to the treatment regimens.[6][7]

Native and prosthetic valves: enterococci

The treatment of enterococcal endocarditis, similar to that of viridans group streptococci, is based on the sensitivities to penicillin. Enterococci, unlike the viridans group streptococci, are not usually killed by antimicrobials but merely inhibited. Hence prolonged administration of antimicrobials is required. Treatment options include a beta-lactam or vancomycin plus gentamicin (or streptomycin in some patients), or a double beta-lactam regimen. Vancomycin-resistant faecium species have emerged in recent years and require treatment with either linezolid or daptomycin.[6][7] Prolonged administration (6 weeks) of antibiotics is needed because enterococci are highly resistant to drug-induced killing by antibiotics.[7]

Native and prosthetic valves: gram-negative organisms

Increasingly, the gram-negative organisms Haemophilus, Aggregatibacter (formerly Actinobacillus), Cardiobacterium, Eikenella, and Kingella (HACEK) have become ampicillin-resistant, and ampicillin should never be used as first-line therapy for HACEK-organism endocarditis. These strains are susceptible to third- and fourth-generation cephalosporins, fluoroquinolones, and possibly ampicillin/sulbactam.[6] Ampicillin/sulbactam plus gentamicin may be recommended in some countries.[7] Fluoroquinolones have not been extensively studied in the treatment of IE, and therefore should be used only as an alternative for patients who cannot tolerate cephalosporins or ampicillin/sulbactam.[6]

Systemic fluoroquinolone antibiotics may cause serious, disabling, and potentially long-lasting or irreversible adverse events. This includes, but is not limited to: tendinopathy/tendon rupture; peripheral neuropathy; arthropathy/arthralgia; aortic aneurysm and dissection; heart valve regurgitation; dysglycemia; and central nervous system effects including seizures, depression, psychosis, and suicidal thoughts and behavior.[100]

Prescribing restrictions apply to the use of fluoroquinolones, and these restrictions may vary between countries. In general, fluoroquinolones should be restricted for use in serious, life-threatening bacterial infections only. Some regulatory agencies may also recommend that they must only be used in situations where other antibiotics, that are commonly recommended for the infection, are inappropriate (e.g., resistance, contraindications, treatment failure, unavailability).
Consult your local guidelines and drug information source for more information on suitability, contraindications, and precautions.

Other culture-negative organisms that may cause endocarditis include: Chlamydia spp; Coxiella spp; Bartonella spp; Brucella spp; and Legionella spp. Consultation with an infectious diseases specialist should be sought due to the various mechanisms of antibiotic resistance found in these non-HACEK organisms.[6]

Fungal infection

Fungal infections most frequently affect patients with prosthetic valves, or those who are immunocompromised. Intravenous drug users are also at increased risk of fungal IE.[101] The most common causative agents are Candida and Aspergillus, with mortality 40% to 50%.[101] Treatment includes valve replacement and antifungal therapy.[101][102]

Outpatient parenteral antibiotic therapy

Stable patients with uncomplicated IE can safely complete courses of intravenous antibiotics as an outpatient with appropriate care and follow up.[103]

Switching to oral antibiotic therapy

The 2020 American Heart Association/American College of Cardiology guideline states that stable patients with left-sided IE caused by streptococcus, Enterococcus faecalis, S aureus, or coagulase-negative staphylococci, and who have no evidence of paravalvular infection on transesophageal echocardiogram (TEE), can be considered for switching to oral antibiotic therapy after initial intravenous therapy.[20][104] Frequent follow-up from the multidisciplinary team is required, and a follow-up TEE is recommended 1-3 days prior to completion of the antibiotic course.[20]

Antibiotic allergies

Penicillin allergy is commonly self-reported, but often found to be spurious following formal allergy assessment.[105]

It is important to determine the timing, extent, and nature of any previous reaction.[6]

In general, patients with type I hypersensitivity anaphylactoid reactions or severe excoriating rashes should not receive penicillin or cephalosporins (10% to 15% cross-reactivity). In this subgroup of patients, vancomycin is an alternative drug.
In patients unable to recollect their reaction, or who developed mild rash, it is often necessary to obtain an allergy consultation for desensitization therapy or pretreat with an antihistamine (e.g., diphenhydramine) prior to administration.
In patients with methicillin-sensitive S aureus endocarditis, it becomes crucial to define the nature of the allergic reaction clearly, as nafcillin has been found to be superior in the treatment of these patients when compared with vancomycin.

Surgery

The aims of surgery are to remove infected tissue completely and to repair or replace the affected valves, thus restoring cardiac anatomy. Indications for surgery include the following:[6][7][91][106][107][108]

Heart failure, especially cardiogenic shock or pulmonary edema (requires emergency surgery), or poor hemodynamic tolerance (requires urgent surgery)
Uncontrolled infection with:
- Local complications (e.g., abscess, false aneurysm, fistula, and enlarging vegetation)
- Persistent positive blood cultures (despite appropriate antibiotic therapy for more than one week and control of septic embolic foci)
- Resistant bacteria or fungi
- Prosthetic valve endocarditis caused by S aureus or non-HACEK gram-negative bacilli
High risk of embolism or established embolism:
- Vegetation ≥10 mm and emboli despite appropriate antibiotic therapy
- Vegetation ≥10 mm and another reason for surgery (e.g., patients with significant valvular dysfunction, whether a direct result of endocarditis process or not)
- Vegetation ≥10 mm and no evidence of embolus

The 2023 European Society of Cardiology guideline and the 2020 American Heart Association/American College of Cardiology guideline recommend that the timing of surgical intervention should be decided by the multidisciplinary endocarditis team.[7][20][108] In addition to antibiotic therapy, early surgical intervention will be needed in around 50% of patients.[20] One meta-analysis suggested that early surgery, at ≤7 days or from diagnosis, affords mortality benefit in the long term.[109]

Temporary cardiac pacing is recommended in patients with atrioventricular block secondary to mycotic abscess of the aortic root.

Treatment failures often occur in patients with multiresistant organisms such as vancomycin-resistant enterococcus, and although these patients can present initially with a subacute course, persistent bacteremia often leads to severe valvular abnormalities. Under these circumstances, surgical intervention is often required to maintain stability and aid in bacteremic clearance.

Patients with perivalvular abscess, fistula, valve dehiscence, perforation, or rupture should also be closely followed by a cardiothoracic surgical team.

Patients who have large vegetations on echocardiogram or embolic phenomenon following 2 weeks of medical therapy are also candidates for valve surgery.

Generally, however, the decision to proceed with surgical intervention should be avoided as long as the patient remains stable. Prolonged antimicrobial therapy prior to surgery is recommended based on anecdotal expert opinion; however, there are currently no prospective data to support this recommendation.

Surgical intervention in older patients is associated with lower in-hospital mortality. Moreover, complications and mortality in older patients undergoing surgery are similar to those in younger groups.[110] Age, therefore, should not be a contraindication to surgery where other indications for surgery exist.

IE in pregnancy is very complex to manage; the endocarditis team should include obstetricians, gynecologists and neonatologists when managing a pregnant patient with IE.[7][24] The indications for surgery are the same in pregnant patients as nonpregnant patients; while there is significant risk to the fetus, urgent surgery should not be delayed when indicated.[7][24]

The 2020 American Heart Association/American College of Cardiology guideline recommends early surgical intervention (during initial hospitalization and before completion of the full course of antibiotics) for patients with any of the following:[20]

Heart failure symptoms
Left-sided IE caused by S aureus,fungal organism, or other highly-resistant pathogen
IE complicated by heart block, annular or aortic abscess or destructive penetrating lesions
Persistent bacteremia or fever for >5 days despite appropriate antimicrobial therapy

Early surgery should also be considered for patients with:[20]

Recurrent emboli and persistent vegetation
Native left-sided valve IE with a mobile vegetation >10 mm in length

IE in the intensive care unit

Surgical intervention for IE may result in subsequent admission to the intensive care unit (ICU). Additionally, patients with IE may be admitted for sepsis, heart failure, valvular dysfunction, or multiorgan failure. Nosocomial infection is also increasing in incidence and IE may develop during a hospital or ICU stay. The most common organisms to cause IE in the ICU are staphylococci, with streptococci being the second most common. Also specific to ICU is the increased incidence of fungal IE, which should therefore be considered in cases where there is a failure to respond to antibiotic therapy.

Anticoagulant and antiplatelet therapy

Although the majority of complications of IE occur as a result of embolization, there is no evidence that anticoagulation or antiplatelet therapy reduce this risk. In fact, data suggest that patients already on anticoagulants who develop prosthetic valve endocarditis are at higher risk of hemorrhagic transformation.[111] One double-blind, randomized controlled trial of high-dose aspirin in all patients with IE demonstrated no benefit of antiplatelet therapy, with an accompanying increase in bleeding risk.[112]

US guidelines recommend temporarily discontinuing anticoagulation in patients with IE who have evidence of cerebral embolism or stroke. In patients receiving warfarin or other vitamin K antagonists at the time of IE diagnosis, temporary discontinuation of the anticoagulation should be considered. These guidelines state that decisions about continued anticoagulation and antiplatelet therapy should ultimately be made by the cardiologist and cardiothoracic surgeon, in consultation with a neurology specialist if neurologic findings are present clinically or on imaging.[6] European guidelines indicate that antiplatelet therapy can be continued if there is no evidence of bleeding, that oral anticoagulants should be switched to unfractionated heparin if an ischemic stroke occurs, and that anticoagulation should be withheld entirely if an intracranial bleed occurs.[7]

Prophylaxis

Antibiotic prophylaxis is largely reserved for patients with the highest lifetime risk of developing IE and at high risk of experiencing adverse outcomes from it.[20][40] The American Heart Association, the American College of Cardiology, and the European Society of Cardiology list the following high-risk features:[6][7][20]

Prosthetic cardiac valves, including transcatheter-implanted prostheses and homografts
Prosthetic material used for valve repair, such as annuloplasty rings, chords, or clips
Previous IE
Unrepaired cyanotic congenital heart disease or repaired congenital heart disease with residual shunts or valvular regurgitation at the site of or adjacent to the site of a prosthetic patch or prosthetic device
Cardiac transplant with valve regurgitation due to a structurally abnormal valve

Antibiotic prophylaxis is recommended in high-risk patients undergoing dental procedures that involve manipulation of gingival tissues or the periapical region of the tooth, or perforation of the oral mucosa:[20][40]

The most common cause of IE following dental procedures is Streptococcus viridans (alpha-hemolytic streptococci). Antibiotics for prophylaxis are; therefore, directed toward this organism, and administered as a single dose 30 to 60 minutes before the procedure

Antibiotic prophylaxis is not recommended in high-risk patients for the following dental procedures:

Anesthetic injections through noninfected tissue
Taking dental radiographs
Placement of removable prosthodontic or orthodontic appliances
Adjustment of orthodontic appliances
Placement of orthodontic brackets
Shedding of primary teeth
Bleeding from trauma to the lips or oral mucosa[20]

Antibiotic prophylaxis is not recommended in high-risk patients undergoing nondental procedures (e.g., transthoracic echocardiogram, esophagogastroduodenoscopy, colonoscopy, or cystoscopy) in the absence of active infection.[20]

Antibiotic prophylaxis is not recommended in patients with moderate-risk lesions.[20][40]

Peripheral intravascular catheter: animated demonstration

How to insert a peripheral intravascular catheter into the dorsum of the hand.

Central venous catheter insertion: animated demonstration

Ultrasound-guided insertion of a non-tunnelled central venous catheter (CVC) into the right internal jugular vein using the Seldinger insertion technique.

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