Native Valve Endocarditis - Guideline for the Management of

Publication: 18/01/2008  
Last review: 15/05/2017  
Next review: 01/05/2020  
Clinical Guideline
CURRENT 
ID: 1204 
Approved By: Improving Antimicrobial Prescribing Group 
Copyright© Leeds Teaching Hospitals NHS Trust 2017  

 

This Clinical Guideline is intended for use by healthcare professionals within Leeds unless otherwise stated.
For healthcare professionals in other trusts, please ensure that you consult relevant local and national guidance.

Guideline for the Management of Native Valve Endocarditis

Summary
Native Valve Endocarditis

This guideline applies to patients with suspected or confirmed native valve endocarditis (i.e. when no intracardiac prosthetic material is present.)

Consider NVE in patients:

  1. with a febrile illness and a murmur of new valvular regurgitation or,
  2. a febrile illness, a pre-existing heart murmur and no clinically obvious source of infection or,
  3. A febrile illness associated with any of:
    • Predisposition and recent intervention with associated bacteraemia,
    • Evidence of congestive heart failure,
    • New conduction disturbance,
    • Vascular or immunological phenomena: embolic event, Roth spots, splinter haemorrhages, Janeway lesions, Osler’s nodes,
    • A new stroke,
  4. Peripheral abscesses (renal, splenic, cerebral, vertebral) of unknown cause or,
  5. a protracted history of sweats, weight loss, anorexia or malaise and an at-risk cardiac lesion or,
  6. any new unexplained embolic event (e.g. cerebral or limb ischaemia) or,
  7. Unexplained, persistently positive blood cultures or,
  8. Intravascular catheter-related bloodstream infection with persistently positive blood cultures 72 h after catheter removal.

NB not every patient with NVE has a murmur or known valvular heart disease or a fever.

Initial investigations

  • 3 sets of Blood Cultures taken at different times (6 hours apart) during the first 24 hours.
  • If patient has severe sepsis or septic shock, take 2 sets of Blood Cultures at different times in the first hour, before starting empirical therapy.
  • When antimicrobials have been given prior to admission, Blood Cultures should be taken as recommended above.
  • Transthoracic echocardiography initially in all suspected cases (discuss with on call cardiology team).
  • Full blood count, C-reactive protein, Urea and electrolytes, liver function tests, urinalysis, ECG.
  • Cardiac CT/MRI and FDG-PET/CT may be needed as agreed by MDT.

Non antimicrobial treatment
Ideally, patients should be reviewed and examined dail, including heart sounds.

If intra-cranial lesions are detected the case should be discussed urgently with the Neurosurgical team on-call

In patients with a relapse of fever consider also the possibility of antimicrobial allergy; consider loss of control of the infection or the development of a new site of infection (e.g. intravascular catheter related infection, splenic abscess formation)

Peripheral cannulae should be used in preference to a central venous route unless there is a clear indication to use the latter route.

Peripherally inserted central venous cannulae (PICC) or “mid-lines” are appropriate alternatives if venous access becomes difficult.

If a central line is to be inserted then this should ideally be a single lumen device dedicated to administration of antimicrobials.

The Cardiothoracic Surgical Consultant on-call should be made aware of patients with confirmed infective endocarditis and any indications for surgery so that the lines of communication and referral are clear in the event of the need for surgical intervention.

The indications for surgical treatment are:
1) uncontrolled infection
a) Locally uncontrolled infection including abscess, false aneurysm, enlarging vegetation
b) Persisting fever and positive blood culture for ≥10 days after commencing appropriate antimicrobial therapy .
c) Infection caused by fungi or multiresistant micro organisms.
2) worsening or intractable heart failure
3) Prevention of embolism
a) Aortic or mitral IE with large vegetations (>10 mm) resulting in one or more embolic episodes despite appropriate antibiotic therapy.
b) Aortic or mitral IE with large vegetations (>10 mm) and other predictors of complicated course like heart failure, persistent infection or abscess.
c) Isolated very large vegetations >15 mm.

The timing of surgery will be determined on an individual basis.

Samples of valve or other infected tissue should be sent for microbiological and histopathological investigations.

Empirical antimicorbial treatment
Ideally antimicrobial therapy should be withheld pending blood culture results. If the patient has severe sepsis, septic shock or urgent empirical treatment is considered necessary:

intravenous Vancomycin electronic Medicines Compendium information on Vancomycin* see dosing guidelines plus intravenous Ciprofloxacin electronic Medicines Compendium information on Ciprofloxacin 400mg 12-hourly
*dose adjustments will be necessary according to creatinine clearance.

See full guideline for treatment of specific organisms, duration of therapy

Referral criteria
Refer suspected IE cases to the Leeds Endocarditis service by emailing Dr Sandoe and Dr Baig (jonathan.sandoe@nhs.net, wazir.baig@nhs.net). Please include all usual information required for microbiology consult which can be found at – link to contacting microbiology

Back to top

Background

Infective endocarditis can affect any part of the endocardium but most commonly involves heart valves. Native valve endocarditis (NVE) is a term used to describe infection of a native (or natural) heart valve in the absence of any prosthetic material. Congenital as well as acquired cardiac lesions can predispose to endocarditis. The pathological lesion of endocarditis is the vegetation a mixture of microorganisms and host-derived products such as platelets and fibrin, essentially an infected coagulum.

The most common cause of NVE is bacterial infection. Staphylococci, streptococci and enterococci remain the most common aetiological agents, but the list of potential pathogens is long.1

Clinical manifestations of endocarditis are varied and result from various infection-related pathological processes:

  1. Direct effects of pathogens either circulating in the blood or damaging cardiac structures (e.g. systemic inflammatory response, heart failure secondary to heart valve destruction, intra-cardiac abscess).
  2. Metastatic foci of infection as a result of infected emboli or sustained bacteraemia (e.g. brain abscesses, vertebral osteomyelitis, splenic abscess, septic pulmonary emboli).
  3. Ischaemic emboli as a result of vegetations or parts of vegetation breaking off into the systemic circulation (e.g. strokes, splenic infarcts, mycotic aneurysms).
  4. Immune mediated affects as a result of the constant intravascular challenge of organisms (e.g. renal failure).

Infective endocarditis was universally fatal in the pre-antibiotic era. Now it is managed with either antimicrobial agents alone, or in combination with surgery, and in-hospital mortality is approximately 20-30%. The necessity for prolonged antimicrobial therapy to achieve a cure was established early in the history of antimicrobial use when relapse was more common when short courses of treatment were employed. There are few randomized controlled trials on which to base recommendations, but there is plenty of observational evidence and expert opinion. Many of the recommendations summarized herein come from existing published guidelines.2-4

Back to top

Clinical Diagnosis

Infective endocarditis remains a difficult condition to diagnose because of its protean clinical manifestations and frequent lack of localizing symptoms or signs. Confirmation of the diagnosis has been improved by echocardiography and improved microbiological methods but diagnostic difficulties persist.

There are no clinical findings that are specific for a particular pathogen and the cornerstones of diagnosis are Blood Cultures and echocardiography.2-4

The Duke criteria5 (with modifications6) are diagnostic criteria that can help clinicains to objectively assess compex clinical cases but they lack sensitivity.2,4

There are a multitude of different clinical presentations of endocarditis and a high index of suspicion is required. It should be considered in patients:

1) with a febrile illness and a murmur of new valvular regurgitation or,
2) a febrile illness, a pre-existing heart murmur and no clinically obvious source of infection or,
3) A febrile illness associated with any of:
   a) Predisposition and recent intervention with associated bacteraemia,
   b) Evidence of congestive heart failure,
   c) New conduction disturbance,
   d) Vascular or immunological phenomena: embolic event, Roth spots, splinter haemorrhages, Janeway lesions, Osler’s nodes,
   e) A new stroke,
   f) Peripheral abscesses (renal, splenic, cerebral, vertebral) of unknown cause or,
4) a protracted history of sweats, weight loss, anorexia or malaise and an at-risk cardiac lesion or,
5) any new unexplained embolic event (e.g. cerebral or limb ischaemia) or,
6) Unexplained, persistently positive blood cultures or,
7) Intravascular catheter-related bloodstream infection with persistently positive blood cultures 72 h after catheter removal.

However, not every patient has a murmur or known valvular heart disease.

This guideline applies to patients without any intra-cardiac prosthetic material (e.g. pacing leads, intra-cardiac defibrillator devices, prosthetic heart valves, Dacron patches/conduits). For suspected infection in these settings see Guideline for treatment of infected cardiac devices, including prosthetic valve endocarditis

Back to top

Severity Assessment

Recommendation: In patients with severe sepsis or septic shock (link severe sepsis guideline) start empirical antimicrobial therapy as soon as possible, obtaining blood cultures first.
[Evidence level B]

In other situations urgent empirical antimicrobial therapy is not usually required, discuss with a senior colleague or infection specialist as required.

Back to top

Investigation

Blood cultures

Recommendation: Three sets of Blood Cultures should be taken at different times (at least 6 hours apart) during the first 24 hours in all patients with suspected native valve endocarditis [Evidence level C]

Recommendation: When antimicrobials have been given prior to admission, Blood Cultures should be taken as recommended above. [Evidence level C]

Recommendation: If initial Blood Cultures are negative, a set of three further blood cultures should be taken after one week off antimicrobial therapy, or sooner if there is recurrence of fever.4
[Evidence level C]

Recommednation: If the patient has severe sepsis or septic shock, two sets of blood cultures should be taken at different times in the first hour, during initial resuscitation before starting empirical therapy as outlined below.4
[Evidence level C]

Blood cultures are a fundamental component of the diagnosis of endocarditis and are positive in about 95% of cases.4 In order to demonstrate a sustained bacteraemia and because bacteria that are known to be common blood culture contaminants can also cause endocarditis (e.g. coagulase negative staphylococci and propionibacteria) multiple blood culture sets are required.4 Blood cultures are just as likely to impact on appropriate therapy and outcomes in patients with severe sepsis, hence the recommendation to send two sets prior to starting empirical therapy.

Echocardiography4
Recommendation: Echocardiography must be performed as soon as possible (ideally within 24 h) in all patients with suspected IE. [Evidence level C]

Recommendation: Transthoracic echocardiography (TTE) is the initial investigation of choice. [Evidence level C]

Recommendation: In cases with an initially negative TTE/transoesophageal echocardiography (TOE) examination, repeat TTE/TOE should be performed 7 – 10 days later if the clinical suspicion of IE remains high. [Evidence level C]

Recommendation: All patients with Staphylococcus aureus bacteraemia or candidaemia require echocardiography (ideally within the first week of treatment or within 24 h if there is other evidence to suggest IE). [Evidence level B]

Recommendation: TTE is recommended at completion of antibiotic therapy for evaluation of cardiac and valve morphology and function. [Evidence level C]

Recommendation: Follow-up echocardiography should be performed if there is evidence of cardiac complications or a suboptimal response to treatment—the timing and mode of assessment (TTE or TOE) is a clinical decision. [Evidence level B]

Recommendation: Routine repeat echocardiography while in therapy is not required. [Evidence level C]

Echocardiography (cardiac ultrasound) is a fundamental investigative tool in the diagnosis of endocarditis. The Duke criteria have been formulated around the demonstration of i} persistent bacteraemia and ii} demonstration of an area of infected endocardium, which is most commonly a heart valve. In adults, the aortic and mitral vaves are almost equally involved, followed by the tricuspid and very rarely the pulmonary valve. Echocardiography serves to confirm the presence of an at-risk heart valve lesion or other structural abnormality.7 It may demonstrate the pathological lesion of endocarditis, a vegetation or infected coagulum. A vegetation is defined as a mobile echodense mass attached to valve leaflets or the mural endocardium. Other echocardiographic features of endocarditis are periannular abscess formation (occurs in 10-40%), new valvular regurgitation and new dehiscence of a valvular prosthesis.6,7 Echocardiography can also indicate the degree of heart valve damage and its haemodynamic effect. Additionally, it provides an assessment of ventricular function. Echocardiography can be carried out using a probe on the chest wall (transthoracic or surface echocardiography, TTE) or use a probe positioned in the oesophagus (transthoracic echocardiography, TOE).

It should be noted that vegetations can persist after successful treatment of NVE, highlighting the fact that positive echocardiographic identification of a vegetationdoes not have 100% specificity for a diagnosis of NVE.

However, TTE has limitations and is dependent on several important variables. These include whether or not the subject has good acoustic windows to allow an adequate examination to be performed and the limited resolution of the images particularly in relation to heavily calcified and/or posteriorly sited structures such as the mitral valve. The specificity for the detection of a vegetation is up to 98% but the sensitivity is <60%. TOE has much higher powers of resolution and should be undertaken when the TTE is non-diagnostic and the clinical suspicion of infective endocarditis is high. The quoted sensitivity and specificity of TOE is 94% or more. It is also superior to TTE in allowing the assessment of valvular regurgitation and in the detection of periannular abscesses. Negative TTE and TOE scans have a combined negative predictive value for the diagnosis of infective endocarditis of 95%.

The specific indications for requesting a TOE are;

  1. TTE is non-diagnostic but clinical suspicion of infective endocarditis is high;
  2. failure of patient to improve despite appropriate antimicrobial therapy;
  3. suspected extension of infection beyond the annular margins to form an abscess or the development of another significant complication in relation to the infected valve;
  4. sudden change in the clinical picture;
  5. if the first TOE is negative but the diagnosis of infective endocarditis is still suspected, a repeat scan 7-10 days after the first may detect an abnormality compatible with the diagnosis

Cardiac CT/MRI or FDG-PET/CT
Recommendation: When a valve prosthesis is present and/or echocardiography suggests an abnormal aortic root, or there is diagnostic uncertaintly on echocardiography, cardiac CT/MRI or FDG-PET/CT should be undertaken following discussion with the multidisciplinary team. [Evidence level C]

Recent ECS guideline have recommended the addition of paravalvular lesions on cardiac CT or FDG-PET/CT as a major dagnostic criterion.2

ECG
Recommendation An electrocardiogram (ECG) should be performed at baseline, if conduction disturbances are suspected and at weekly intervals in patients with aortic valve involvement.1
[Evidence level C]

Other blood tests
Recommendation: FBC should be measured at baseline and repeated weekly during therapy unless there is a clinical indication for more frequent testing. [Evidence level D.]

The peripheral white blood cell count may be normal or elevated in patients with native valve endocarditis and is therefore not particularly useful in confirming a clinical diagnosis.8 A full blood count (FBC) is indicated however to determine if the patient is anaemic and to establish a baseline peripheral white blood cell count since several of the antimicrobials used in treatment can cause leukopenia.

Recommendation: C-reactive protein (CRP) should be measured at baseline and weekly during therapy. [Evidence level D.]

CRP is a sensitive test, being raised in >95% of patients with endocarditis,8 but it is non-specific. A raised CRP provides supportive evidence of infection, rather than confirming the diagnosis, and can be used to monitor response to treatment.8,9

Recommendation: Urea and electrolytes (U&E) and liver function tests (LFTs) should be measured at baseline and weekly during therapy (or more frequently if renal function is unstable). [Evidence level D.]

U&E and LFTs are necessary baseline tests. Results will influence choice and dose of antimicrobials as well as fluid balance, nutritional support etc.

Recommendation: Rheumatoid factor should be measured in cases of suspected endocarditis with negative blood cultures or equivocal echocardiographic findings.[Evidence level C.]

About 30-50% of patients with bacterial endocarditis develop rheumatoid factor10,11 and a positive result can be used to support a clinical diagnosis of endocarditis.

Urine
Recommendation: A urine sample should be sent for microscopy and culture if the dipstick test is positive for leukocytes, nitrites or red blood cells. [Evidence level D.]

Urinalysis is indicated at baseline because the presence of haematuria can help to confirm a diagnosis of endocarditis.5

Serology
Recommendation: A clotted blood sample for Bartonella,and Coxiella antibodies should be sent when blood cultures are negative.4 [Evidence level B]

Recommendation: Consider Brucella in patients with negative blood cultures and a risk of exposure (dietary, occupational or travel).4
[Evidence level C]

Back to top

Treatment
Non-Antimicrobial Treatment

Recommendation: Ideally, patients should be reviewed and examined daily.
[Evidence level D]

Particular attention during the examination should be given to any changes in the auscultatory findings, especially, new onset or worsening valve regurgitation. Similarly, the development of symptoms and signs of congestive heart failure indicates that the haemodynamic load on the heart from the valvular dysfunction is significant and is associated with a poor prognosis. Additionally, the peripheral pulses should be recorded regularly as mycotic aneurysms are relatively common. These can be divided into extra- and intra-cranial mycotic aneurysms; the former frequently require surgical treatment.

Embolisation occurs in 22-50% of cases and 65% of cases involve emboli to the central nervous system, particularly to the middle cerebral artery. The risk of embolisation is highest in the first 14 days after diagnosis. The fundi should be examined regularly to look for Roths spots. Vegetations greater than 15 mm in diameter and those on the mitral valve have the highest risk of embolising.

Recommendation: If intra-cranial lesions are detected the case should be discussed urgently with the Neurosurgical team on-call
[Evidence level D]

Recommendation: In patients with a relapse of fever consider loss of control of the infection with current antimicrobial therapy or the development of a new site of infection (e.g. intravascular catheter related infection, splenic abscess formation)
[Evidence level C]

Recommendation: In patients with a relapse of fever consider also the possibility of antimicrobial allergy.
[Evidence level C]

Recommendation: Peripheral cannulae should be used in preference to a central venous route unless there is a clear indication to use the latter route.12
[Evidence level B]

Peripherally inserted central venous cannulae (PICC) or “mid-lines” are appropriate alternatives if venous access becomes difficult.
[Evidence level D]

If a central line is to be inserted then this should ideally be a single lumen device dedicated to administration of antimicrobials.
[Evidence level D]

The Cardiothoracic Surgical Consultant on-call should be made aware of patients with confirmed infective endocarditis and any indications for surgery so that the lines of communication and referral are clear in the event of the need for surgical intervention.
[Evidence level C]

The indications for surgical treatment are:4

4) uncontrolled infection
a) Locally uncontrolled infection including abscess, false aneurysm, enlarging vegetation
b) Persisting fever and positive blood culture for ≥10 days after commencing appropriate antimicrobial therapy .
c) Infection caused by fungi or multiresistant micro organisms.
5) worsening or intractable heart failure
6) Prevention of embolism
a) Aortic or mitral IE with large vegetations (>10 mm) resulting in one or more embolic episodes despite appropriate antibiotic therapy .
b) Aortic or mitral IE with large vegetations (>10 mm) and other predictors of complicated course like heart failure, persistent infection or abscess.
c) Isolated very large vegetations >15 mm.

The timing of surgery will be determined on an individual basis.

Samples of valve or other infected tissue should be sent for microbiological and histopathological investigations.
[Evidence level B]

Back to top

Empirical Antimicrobial Treatment

Recommendation: If the patient is clinically stable without signs of severe sepsis or septic shock and is not in heart failure antimicrobials should be withheld pending blood culture results.4 [Evidence level C]

A microbiological diagnosis enables administration of directed antimicrobial therapy, avoiding the need for broad-spectrum, potentially toxic therapeutic combinations or erroneous empirical therapy. Outcomes are better if the pathogen is known. In patients who have been administered antimicrobials before blood cultures have been taken, the chance of obtaining a microbiological diagnosis is reduced, highlighting the need to withhold treatment until appropriate investigations have been carried out.4
Antimicrobials should not be started until after blood cultures have been taken (see blood culture section above).

Empirical antimicrobial therapy
A wide range of pathogens with varying antimicrobial susceptibilities can cause native valve endocarditis. Urgent empirical therapy may be needed for a patient with severe sepsis, septic shock or severe heart failure in whom it would be inappropriate to wait for blood culture results before starting antimicrobial therapy.

Recommended Urgent empirical therapy: intravenousVancomycin electronic Medicines Compendium information on Vancomycin * see dosing guidelines plus intravenous Ciprofloxacin electronic Medicines Compendium information on Ciprofloxacin 400mg 12-hourly
*dose adjustments will be necessary if there is renal impairment or renal failure.
[Evidence level C]

In a patient who is allergic to Vancomycin electronic Medicines Compendium information on Vancomycin or has existing renal impairment, daptomycin 6mg/kg/24 hours can be used instead. Daptomycin is a restricted antimicrobial and needs a microbiology approval code. Please see the daptomycin prescribing guideline for dosage adjustments in renal impairment and monitoring requirements.

Empirical antimicrobial therapy for a patient with clinical and echocardiographic findings suggestive of endocarditis but who is clinically stable and has negative blood cultures should be discussed with microbiology on a case-by-case basis.
Evidence level D

Back to top

Directed Antimicrobial Treatment (when microbiology results are known)

Specific recommendations can be made for a number of organisms causing NVE.

Staphylococcal endocarditis4.
1. meticillin-susceptible staphylococci:
intravenous flucloxacillin 2g 6-hourly.

Use regimen for meticillin-resistant staphylococci in patients with a genuine penicillin allergy. In patients with a penicillin allergy consider desensitization, to allow treatment with flucloxacillin where appropriate.

2. meticillin-resistant staphylococci (penicillin allergy):
a combination of intravenous Vancomycin electronic Medicines Compendium information on Vancomycin * see dosing guidelines with oral Rifampicin 600mg 12-hourly is recommended.
[Evidence level C]
*dose adjustments will be necessary if there is renal impairment or renal failure.

Alternative in patients with Vancomycin electronic Medicines Compendium information on Vancomycin allergy or deteriorating renal function:

Daptomycin* 6-8mg/kg IV once daily with oral Rifampicin 600mg 12-hourly.
A microbiology approval code is needed for daptomycin. Dosage adjustment may be needed if there is renal impairment.

Obtain baseline LFTs prior to starting rifampicin. May need dose adjustment if the patient has deranged LFTs.

Alpha-haemolytic streptococcal endocarditis4
For penicillin-susceptible streptococci (MIC≤0.125 mg/L): intravenous Benzyl penicillin 1.2g 4-hourly is recommended.

For streptococci with reduced susceptibility to penicillin (MIC >0.125-<0.5mg/L): intravenous Benzyl penicillin 2.4g 4-hourly is recommended together with intravenous Gentamicin# 1mg/kg 12-hourly for the first 2 weeks.

For streptococci with reduced susceptibility to penicillin (MIC >0.5mg/L): treat as for Amoxicillin-susceptible enterococci.
[Evidence level C]
#Use gentamicin with caution in patients with renal impairment. Gentamicin pre-dose levels should be maintained <1mg/l and 1 hour post-dose levels 3-5mg/l. Synergy may be lost in isolates with high-level resistance to Gentamicin.

Enterococcal endocarditis4
For Amoxicillin-susceptible enterococci (MIC ≤ 4mg/L): intravenous Amoxicillin 2g 4-hourly plus intravenous Gentamicin# 1mg/kg 12-hourly is recommended.

In a genuinely-penicillin-allergic patient, use the regimen for Amoxicillin-resistant enterococci.

For Amoxicillin-resistant enterococci: a combination of intravenous Vancomycin electronic Medicines Compendium information on Vancomycin (MIC≤4 mg/L)* see dosing guidelines with intravenous Gentamicin# 1mg/kg 12-hourly is recommended.

#Use Gentamicin with caution in patients with renal impairment. Gentamicin pre-dose levels should be maintained <1mg/l and 1 hour post-dose levels 3-5mg/l. Synergy may be lost in isolates with high-level resistance to Gentamicin.
*dose adjustments will be necessary if there is renal impairment or renal failure.
Evidence level C

Other organisms such as Enterobacteriaceae, Pseudomonas aeruginosa and fungi are uncommon and should be treated on a case-by case basis following discussion with Microbiology.

Antimicrobial allergy
contact Microbiology for advice if not stated above.

Back to top

Duration of Treatment

Recommendation: Uncomplicated NVE (without extracardiac foci of infection or the need for valve surgery) should usually be treated with four weeks of intravenous antimicrobials. If the patients symptoms of infection have resolved; they are afebrile; and CRP is returning to normal (<30mg /L) after four weeks treatment, antimicrobials can be stopped. [Evidence level C]

Recommendation: A two week course of penicillin plus gentamicin can be used for susceptible streptococci in patients <65 years, without renal impairment/indications for surgery/ or extracardiac foci of infection.2[Evidence level C]

Recommendation: The presence of a brain abscess, intracardiac abscesses or vertebral osteomyelitis usually requires treatment with six weeks antimicrobials. [Evidence level C]

Back to top

Switch to oral agent(s)

Adjunctive therapy with agents with good bioavailability such as rifampicin can be given orally otherwise standard therapy for endocarditis requires intravenous therapy for the duration.

Back to top

Provenance

Record: 1204
Objective:

Aims

  • To improve the diagnosis and treatment of infective endocarditis when no intra-cardiac prosthetic material is present.

Objectives

  • To provide evidence-based recommendations for appropriate investigation of suspected infective endocarditis on native cardiac structures.
  • To provide evidence-based recommendations for appropriate antimicrobial therapy of infective endocarditis when no intra-cardiac prosthetic material is present.
  • To recommend appropriate dose, route of administration and duration of antimicrobial agents.
  • To advise in the event of antimicrobial allergy.
  • To set out criteria for referral for cardiac surgery.
Clinical condition:

Infective endocarditis

Target patient group: Adult patients with suspected or confirmed infective endocarditis, where there is no intracardiac prosthetic material.
Target professional group(s): Secondary Care Doctors
Adapted from:

Evidence base

1. Habib G, Hoen B, Tornos P, et al. Guidelines on the prevention, diagnosis, and treatment of infective endocarditis (new version 2009): The Task Force on the Prevention, Diagnosis, and Treatment of Infective Endocarditis of the European Society of Cardiology (ESC). Eur Heart J 2009; 30(19): 2369-413.

2. Habib G, Lancellotti P, Antunes MJ, et al. 2015 ESC Guidelines for the management of infective endocarditis: The Task Force for the Management of Infective Endocarditis of the European Society of Cardiology (ESC)Endorsed by: European Association for Cardio-Thoracic Surgery (EACTS), the European Association of Nuclear Medicine (EANM). Eur Heart J 2015.s

3. Baddour LM, Wilson WR, Bayer AS, et al. Infective Endocarditis in Adults: Diagnosis, Antimicrobial Therapy, and Management of Complications: A Scientific Statement for Healthcare Professionals From the American Heart Association. Circulation 2015.

4. Gould FK, Denning DW, Elliott TS, et al. Guidelines for the diagnosis and antibiotic treatment of endocarditis in adults: a report of the Working Party of the British Society for Antimicrobial Chemotherapy. J Antimicrob Chemother 2012; 67(2): 269-89.

5. Durack DT, Lukes AS, Bright DK. New criteria for diagnosis of infective endocarditis: utilization of specific echocardiographic findings. Duke Endocarditis Service. Am J Med 1994; 96(3): 200-9.

6. Li JS, Sexton DJ, Mick N, et al. Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis. Clin Infect Dis 2000; 30(4): 633-8.

7. Bayer AS, Bolger AF, Taubert KA, et al. Diagnosis and management of infective endocarditis and its complications. Circulation 1998; 98(25): 2936-48.

8. Olaison L, Hogevik H, Alestig K. Fever, C-reactive protein, and other acute-phase reactants during treatment of infective endocarditis. Arch Int Med 1997; 157(8): 885-92.

9. McCartney AC, Orange GV, Pringle SD, Wills G, Reece IJ. Serum C reactive protein in infective endocarditis. Journal of Clinical Pathology 1988; 41(1): 44-8.

10. Cabane J, Godeau P, Herreman G, Acar J, Digeon M, Bach JF. Fate of circulating immune complexes in infective endocarditis. Am J Med 1979; 66(2): 277-82.

11. Williams RC, Jr., Kunkel HG. Rheumatoid factor, complement, and conglutinin aberrations in patients with subacute bacterial endocarditis. Journal of Clinical Investigation 1962; 41: 666-75.

12. Ahmed FZ, Baig WW, Munyombwe T, West R, Sandoe JA. Vascular access strategy for delivering long-term antimicrobials to patients with infective endocarditis: device type, risk of infection and mortality. J Hosp Infect 2013; 83(1): 46-50.

Evidence levels:

A. Meta-analyses, randomised controlled trials/systematic reviews of RCTs
B. Robust experimental or observational studies
C. Expert consensus.
D. Leeds consensus. (where no national guidance exists or there is wide disagreement with a level C recommendation or where national guidance documents contradict each other)

Back to top

Approved By

Improving Antimicrobial Prescribing Group

Document history

LHP version 1.0

Related information

Not supplied

Equity and Diversity

The Leeds Teaching Hospitals NHS Trust is committed to ensuring that the way that we provide services and the way we recruit and treat staff reflects individual needs, promotes equality and does not discriminate unfairly against any particular individual or group.