Native Valve Endocarditis in Children - ( i.e. No Intra-Cardiac Prosthetic Material )

Publication: 01/12/2010  
Last review: 06/12/2018  
Next review: 01/12/2021  
Clinical Guideline
CURRENT 
ID: 2194 
Approved By: Improving Antimicrobial Prescribing Group 
Copyright© Leeds Teaching Hospitals NHS Trust 2018  

 

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 in Children (i.e. No Intra-Cardiac Prosthetic Material)

Summary
Native Valve Endocarditis in Children

This guideline applies to children with suspected or confirmed native valve endocarditis (NVE) [i.e. when no intra-cardiac prosthetic material is present.]

Guideline summary

Consider NVE in children with any of the following:

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

Additional points

  1. Native valve endocarditis in a previously well child is a very rare diagnosis-the cardiac unit in Leeds covering a population of 5.25 million and supporting 16 hospitals in the region treat less than 10 cases of per year.
  2. In children flow murmurs associated with fevers are extremely prevalent and therefore the majority of patients with pyrexia and a murmur will not have infective endocarditis. 
  3. Infective endocarditis is often considered only after blood cultures become positive hence the priority is to obtain multiple blood cultures prior to treating with antibiotics, in the clinical situations listed above.  A careful history should also be taken including consideration of animal contact and travel history.

Initial investigations

  1. 3 sets of blood cultures taken at different times, ideally 6 hours a part, 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 sets before starting empirical therapy as outlined below.
  2. Transthoracic echocardiography in suspected cases, after senior review and assessment [discuss with on call paediatric cardiology team].
  3. Full blood count, C-reactive protein, Urea and electrolytes, liver function tests, urinalysis, ECG.

Treatment
Ideally antimicrobial therapy should be withheld pending blood culture results. If the patient has severe sepsis, septic shock or requires urgent empirical treatment the following regimen is used:

Urgent empirical therapy: intravenous Flucloxacillin electronic Medicines Compendium information on Flucloxacillin 50mg/kg/dose (max. 2grams) 6-hourly and Gentamicin 2mg/kg/dose (max. 100mg) 12hourly* dose adjustments will be necessary according to creatinine clearance.

*Low-dose Gentamicin is for synergistic activity; pre-dose levels should be maintained <1mg/L and 1 hour post-dose levels 3-5mg/L

Note; If child is at high risk for MRSA: Vancomycin electronic Medicines Compendium information on Vancomycin 15mg/kg/dose 6 hourly (max dose 3grams in 24hours) and Gentamicin 2mg/kg/dose (max. 100mg) 12hourly should be started instead.

See full guideline for treatment of specific organisms

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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.  Streptococci, staphylococci 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.  In the modern era it is managed with either antimicrobial agents alone, or in combination with surgery, and in-hospital mortality is approximately 5-10%.1,2 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.3-6

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Clinical Diagnosis

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

  1. A febrile illness and a murmur of new valvular regurgitation;
  2. A febrile illness, a pre-existing at-risk cardiac lesion and no clinically obvious site of infection;
  3. A febrile illness associated with any of the following;
    (i) predisposition and recent intervention with associated bacteraemia,
    (ii) evidence of congestive heart failure,
    (iii) new conduction disturbance
  4. Vascular or immunological phenomena; embolic event, Roth spots,
    splinter haemorrhages, Janeway lesions, Osler’s nodes or a new stroke;
  5. Peripheral abscesses (renal, splenic, cerebral, vertebral) of unknown cause;
  6. A protracted history of sweats, weight loss, anorexia or malaise and an at-risk cardiac lesion;
  7. Any new unexplained embolic event (e.g. cerebral or limb ischaemia);
  8. Unexplained, persistently positive blood cultures;
    Intravascular catheter-related bloodstream infection with persistently positive blood cultures 72 h after catheter removal;
  9. Note; Not every patient with endocarditis has a murmur or known valvular heart disease.

History should include:

  • Onset and course of current illness (including professional assessment/investigations).
  • Oral intake. Stool/urine output.
  • Recent minor injuries/infections
  • Dental history and care
  • Recent surgery (and wound infections).
  • Past medical history.
  • Menstrual history and tampon use (as appropriate)
  • Birth history (<3 months).
  • Recent travel history (previous 1 year).
  • Animal contact/exposure.
  • Drug history including: recent antimicrobials; steroids/immunosuppressants.
  • Allergy history.
  • Immunisation history.

In the past, endocarditis has been a difficult condition to diagnose because of its protean clinical manifestations and frequent lack of localizing symptoms or signs. 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.

The Duke criteria7 [and recent modifications8] are diagnostic criteria that can be used to assist diagnosis but they lack sensitivity.3

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Severity Assessment

Consider severe sepsis in babies/children with any red features (table 1)

Table 1. Summary of “red” clinical features

 

Colour

  • Pale/mottled/ashen/blue

Activity

  • No response to social cues
  • Appears ill to a healthcare professional
  • Unable to rouse or if roused does not stay awake
  • Weak, high-pitched or continuous cry

Respiratory

  • Grunting
  • Tachypnoea: respiratory rate > 60 breaths/minute
  • Moderate or severe chest indrawing

Hydration

  • Reduced skin turgor

Other

  • Age 0–3 months, temperature ≥ 38°C
  • Age 3–6 months, temperature ≥ 39°C
    Bile-stained vomiting

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Investigation

Recommendation: Three sets of blood cultures should be taken at different times, ideally 6 hours a part during the first 24 hours in all patients with suspected native valve endocarditis and no features of severe sepsis, according to Standard operating procedure.3 (Evidence level C)

Recommendation: When antimicrobials have been given prior to admission, blood cultures should be taken as recommended above. 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. 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. (Evidence level C)

Recommendation: 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. (Evidence level C)

Recommendation: If blood cultures are negative send clotted blood for Bartonella and Coxiella serology. (Evidence level B)

Blood cultures are a fundamental component of the diagnosis of endocarditis and are positive in 95% of cases.9 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. Three sets of blood cultures will give a microbiological diagnosis 95% of the time.9

Echocardiography

Recommendation: Echocardiography should be performed in all cases where there is a clinical suspicion of endocarditis.3
(Evidence level C)

Recommendation: TTE is the initial method of assessment recommended for NVE.3
(Evidence level B)

TTE has been shown to have 86% sensitivity in detection of echocardiographic markers of endocarditis with a specificity of 93% in detection of vegetations.10 (Evidence level B)

Recommendation: TOE may be required in selected cases (e.g. young adults) where TTE is inadequate especially to visualise posterior structures, prosthetic valves and areas of heavy calcification.

Cardiac ultrasound (echocardiography) 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 valves 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.11 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, new valvular regurgitation and new dehiscence of a valvular prosthesis.8,11 Echocardiography can also indicate the degree of heart valve damage and its haemodynamic effect. Additionally, it provides an assessment of ventricular function. In children echocardiography is usually carried out using a probe on the chest wall (transthoracic or surface echocardiography, TTE).  Adolescents and young adults may require a transoesophageal echocardiogram (TOE) with a probe positioned in the oesophagus.

It should be noted that vegetations can persist after successful treatment of NVE, highlighting the fact that positive echocardiographic identification of vegetation does not have 100% specificity for a diagnosis of NVE.  Also, vegetations may not be detected on echocardiography even in the presence of clinically and microbiologically proven infective endocarditis.  Therefore an echocardiogram is not the definitive diagnostic tool in endocarditis.

Investigations

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

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.12 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: CRP should be measured at baseline and weekly during therapy.
(Evidence level D)

C-reactive protein (CRP) is a sensitive test, being raised in >95% of patients with endocarditis,12 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.12,13

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

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

Recommendation: A urine sample should be sent for microscopy and culture if the dipstick test is positive for leukocytes and 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.7

When a fungal infection is suspected, a clotted blood sample for Candida antibodies is no longer advised
(Evidence level C)

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Treatment
Non-Antimicrobial Treatment

All children being treated with antibiotics for confirmed infective endocarditis will need to be transferred to the tertiary cardiac centre (Children’s Yorkshire Heart Centre, Leeds General Infirmary) for ongoing care.  This is because infective endocarditis still carries a significant mortality and morbidity and requires close monitoring with specialist cardiac investigations during treatment.

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 or symptoms and signs of congestive heart failure.

Embolisation occurs in 20% of cases2,14 with majority involving and 65%the central nervous system, particularly to the middle cerebral artery. The risk of embolisation is highest in the first 14 days after diagnosis.

Recommendation: If intra-cranial lesions are detected the case should be discussed urgently with the Paediatric 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 in the first 48 hours unless there is a clear indication to use the latter route.  Ideally obtaining a PICC line or another non-cuffered CVC would be the preferred option in children, once the diagnosis and treatment course has been established.
(Evidence level B)

Recommendation: Full aseptic technique should be used when any venous access device is inserted and during subsequent handling for the administration of drugs.
(Evidence level B)

Recommendation: Peripherally inserted central venous cannulae (PICC) are preferred to subcutaneously-tunnelled central lines (e.g. Hickman lines) for delivery of long-term antibiotics. Specific attention should be paid to the site of line insertion particularly in children with complex congenital heart disease so as not to jeopardise veins that may need to be used for future diagnostic and interventional strategies.
(Evidence level D)

Recommendation: 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)

Recommendation: The Paediatric Cardiothoracic Surgical Consultant on-call should be made aware of patients with confirmed infective endocarditis who are likely to need surgical intervention so that the lines of communication and referral are clearly established.6
(Evidence level C)

The indications for surgical treatment are:

  1. uncontrolled infection
  2. worsening or intractable heart failure
  3. recurrent or high risk of a vegetation embolising
  4. periannular abscess formation

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

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Empirical Antimicrobial Treatment

Recommended urgent empirical therapy: intravenous Flucloxacillin electronic Medicines Compendium information on Flucloxacillin 50mg/kg/dose (max. 2grams) 6-hourly and Gentamicin 2mg/kg/dose (max. 100mg) 12-hourly * dose adjustments will be necessary if there is renal impairment

*Low-dose Gentamicin is for synergistic activity; pre-dose levels should be maintained <1mg/L and 1 hour post-dose levels 3-5mg/L.

Note: If child is at high risk for MRSA then Vancomycin electronic Medicines Compendium information on Vancomycin* 15mg/kg/dose 6-hourly (max dose 3gram in 24hours) and Gentamicin 2mg/kg/dose (max. 100mg) 12-hourly * should be started instead.

*dose adjustments will be necessary if there is renal impairment or renal failure. (Evidence level D)

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. Antimicrobials should not be started until after blood cultures have been taken (see blood culture section above). On occasion, alternatives to Vancomycin electronic Medicines Compendium information on Vancomycin might be needed because of allergy, intolerance or renal function, in this situation, daptomycin is the preferred alternative (and should be discussed with microbiology).

Recommendation: 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)

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Directed Antimicrobial Treatment (when microbiology results are known)

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

Staphylococcal endocarditis:3 For methicillin-susceptible staphylococci: intravenous Flucloxacillin electronic Medicines Compendium information on Flucloxacillin 50mg/kg/dose (max. 2grams) 6-hourly is recommended. 

Genuine Penicillin Allergy; use regimen for methicillin-resistant staphylococci.

For methicillin-resistant staphylococci: a combination of intravenous Vancomycin electronic Medicines Compendium information on Vancomycin* 15mg/kg/dose 6hourly (max. 3grams in 24 hours) with oral or intravenous Rifampicin electronic Medicines Compendium information on Rifampicin 10mg/kg/dose (max. 600mg) 12hourly is recommended.
(Evidence level C)

NB. For staphylococci that are resistant to Vancomycin electronic Medicines Compendium information on Vancomycin, or if an alternative is needed because of allergy, intolerance or renal function, Daptomycin electronic Medicines Compendium information on Daptomycin is the preferred alternative (and should be discussed with microbiology).

Alpha-haemolytic streptococcal endocarditis:3
For penicillin-susceptible streptococci (MIC≤0.125mg/L): intravenous Benzyl penicillin electronic Medicines Compendium information on Benzyl penicillin 50mg/kg/dose (max. 2.4gram) 4-hourly is recommended
.

For streptococci with reduced susceptibility to penicillin (MIC >0.125 -≤0.5mg/L): intravenous Benzyl penicillin electronic Medicines Compendium information on Benzyl penicillin 50mg/kg/dose (max. 2.4gram) 4-hourly is recommended together with intravenous Gentamicin# 2mg/kg/dose (max. 100mg) 12-hourly for the first 2 weeks.

For streptococci with reduced susceptibility to penicillin (MIC >0.5): intravenous Vancomycin electronic Medicines Compendium information on Vancomycin 15mg/kg/dose 6 hourly (max. 3grams in 24hours) with intravenous Gentamicin# 2mg/kg/dose (max. 100mg) 12-hourly for the first 2 weeks. (Evidence level C)

Enterococcal endocarditis3
For Amoxicillin-susceptible enterococci: intravenous Amoxicillin electronic Medicines Compendium information on Amoxicillin 100mg/kg/dose (max. 2grams) 4-hourly plus intravenous Gentamicin# 2mg/kg/dose (max. 100mg) 12-hourly.

Genuine Penicillin Allergy; use the regimen for Amoxicillin-resistant enterococci.

For Amoxicillin-resistant enterococci: a combination of intravenous Vancomycin electronic Medicines Compendium information on Vancomycin* 15mg/kg/dose 6-hourly (max. 3 grams in 24hours) with intravenous Gentamicin# 2mg/kg (max. 100mg) 12-hourly is recommended.

*dose adjustments will be necessary if there is renal impairment or renal failure.

#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.
(Evidence level C)

HACEK group bacteria (Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella): Cefotaxime electronic Medicines Compendium information on Cefotaxime 50mg/kg/dose (max. 3gram) 6 hourly OR Ceftriaxone electronic Medicines Compendium information on Ceftriaxone 100mg/kg/dose (max. 4 gram) 24 hourly OR IV Amoxicillin electronic Medicines Compendium information on Amoxicillin 100mg/kg/dose (max. 2grams) 4-hourly +/- intravenous Gentamicin# 2mg/kg/dose (max. 100mg) 12-hourly may be appropriate depending on susceptibility.

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.

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Duration of Treatment

Recommendation: In most instances, uncomplicated endocarditis affecting native cardiac structures i.e. no shunts, prostheses or conduits, should 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.

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

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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.

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Treatment Failure
Please contact Microbiology if the patient is not responding to the recommended antimicrobial regimens

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Provenance

Record: 2194
Objective:

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

Objectives

  • To provide evidence-based recommendations for appropriate diagnosis and investigation of infective endocarditis in children when no intra-cardiac prosthetic material is present
  • To provide evidence-based recommendations for appropriate non-antimicrobial management of infective endocarditis in children when no intra-cardiac prosthetic material is present
  • To provide evidence-based recommendations for appropriate empirical and directed antimicrobial therapy of infective endocarditis in children 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 to specialists.
Clinical condition:

Native valve endocarditis in children

Target patient group: Children (>1 month old to <16 years) with suspected or confirmed native valve endocarditis
Target professional group(s): Secondary Care Doctors
Pharmacists
Adapted from:

Evidence base

  1. Day MD, Gauvreau K, Shulman S, Newburger JW. Characteristics of children hospitalized with infective endocarditis. Circulation 2009; 119(6): 865-70.
  2. Yoshinaga M, Niwa K, Niwa A, et al. Risk factors for in-hospital mortality during infective endocarditis in patients with congenital heart disease. Am J Cardiol 2008; 101(1): 114-8.
  3. 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.
  4. Baddour LM, Wilson WR, Bayer AS, et al. Infective Endocarditis: Diagnosis, Antimicrobial Therapy, and Management of Complications: A Statement for Healthcare Professionals From the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: Endorsed by the Infectious Diseases Society of America. Circulation 2005; 111(23): e394-434.
  5. 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.
  6. Ramsdale DR, Turner-Stokes L. Prophylaxis and treatment of infective endocarditis in adults: a concise guide. Clinical medicine (London, England) 2004; 4(6): 545-50.
  7. 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.
  8. 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.
  9. Elliott TSJ, Foweraker J, Gould FK, Perry JD, Sandoe JAT. Guidelines for the antibiotic treatment of endocarditis in adults: report of the Working Party of the British Society for Antimicrobial Chemotherapy. Journal of Antimicrobial Agents and Chemotherapy 2004; 54: 971-81.
  10. Humpl T, McCrindle BW, Smallhorn JF. The relative roles of transthoracic compared with transesophageal echocardiography in children with suspected infective endocarditis. J Am Coll Cardiol 2003; 41(11): 2068-71.
  11. Bayer AS, Bolger AF, Taubert KA, et al. Diagnosis and management of infective endocarditis and its complications. Circulation 1998; 98(25): 2936-48.
  12. 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.
  13. 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.
  14. K. Thom, A Hanslik, J L Russell, et al. Incidence of infective endocarditis and its thromboembolic complications in a pediatric population over 30 years. Int J Cardiol 2018:252: 74-9.

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)

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Approved By

Improving Antimicrobial Prescribing Group

Document history

LHP version 1.0

Related information

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