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Endocarditis - Infective

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Antibiotic Prophylaxis for the prevention of Endocarditis

There has never been a prospective clinical placebo-controlled trial of antibacterial prophylaxis in individuals with cardiac risk undergoing a potentially bacteraemia-producing procedure. A recent Cochrane review on penicillin prophylaxis could find only one publication on this topic worthy of analysis. The NHF Advisory Group considered carefully the option of abandoning all endocarditis prophylaxis, both before and after the NICE recommendations were published. Sensitive to the dictum proposed by Carl Sagan that 'Absence of evidence is not evidence of absence', we have not gone that far.

NZ National Heart Foundation Recommendations (2008)

Heart disease

The number of cardiac conditions for which prophylaxis is recommended has been reduced significantly (Table 1). These conditions have been selected because of a high lifetime risk of endocarditis and a high risk of mortality or major morbidity resulting from bacterial endocarditis, should it occur. In line with other recent recommendations we no longer recommend differentiation into high- and moderate-risk groups.

Significant numbers of disadvantaged New Zealanders, especially young Māori and Pacific people, have rheumatic valvular heart disease and important dental and periodontal disease. These individuals carry a life-long burden of illness and infective endocarditis can add greatly to this. For health practitioners and dentists in particular, 'Primum non nocere' remains a fundamental tenet of professional practice. To put this in perspective, a single dose of amoxycillin before the dental procedure is really a rather small issue for patient, dentist and global antimicrobial use when considered against the importance of providing the best preventive dental advice and care for these individuals.

Table 1: Cardiac conditions for which endocarditis prophylaxis is recommended
Previous endocarditis
Rheumatic valvular heart disease
Prosthetic heart valves (bio- or mechanical)
Unrepaired cyanotic congenital heart disease (includes palliative shunts and conduits)
Surgical or catheter repair of congenital heart disease within 6 months of repair procedure. 

Microbiology

Prophylaxis for dental procedures and tonsillectomy is directed against viridans streptococci. While they are not the only organisms that cause bacteraemia following these procedures they are the organisms most likely to cause endocarditis.

The principles of prophylaxis for prevention of endocarditis from viridans streptococci have been well established in animal models. Successful prophylaxis depends more on prolonged antibacterial activity than prevention of bacteraemia. Indeed, failure of a regimen to suppress post-procedure bacteraemia is not a surrogate marker for failure of prophylaxis

Because of this, both bactericidal (e.g. amoxicillin) and bacteriostatic or non-killing regimens (e.g. clindamycin or clarithromycin) are very effective so long as the antibacterial agent is present in the blood stream for long enough. This can be achieved with a single dose of these agents provided the correct dosage is given.

Dental Care

The NHF guidelines highlight the imperative that at-risk patients should remain free of dental disease. This requires emphasis on improved access to dental care and improved oral health in patients with underlying cardiac risk factors for infective endocarditis rather than a sole focus on dental procedures and antibiotic prophylaxis.

Optimal oral health is maintained through regular professional care and the use of appropriate products such as manual and powered toothbrushes, floss and other plaque-control devices such as antibacterial mouthwashes. Patients need to be strongly advised to comply with a continuing oral and dental care regimen.

Treatments to achieve this goal include:

  • Removal of impacted teeth and unerupted teeth.
  • Treatment of all teeth with periapical disease by endodontic debridement and root filling or apical surgery or extraction.
  • Removal of all carious teeth that cannot be restored.
  • Treatment of other abnormalities such as cysts or intra-bony lesions associated with the dentition and related structures.
  • Treatment of oral ulcers including those caused by ill-fitting or irritating dental appliances.
  • Treatment of inflammatory periodontal disease.
  • Oral hygiene instructions for the patient to ensure maintenance of ideal oral health.

Dental & oral surgery procedures (including tonsillectomy/adenoidectomy) for which antibiotic prophylaxis is recommended are listed in Table 2.

Table 2 Dental and ENT procedures for which prophylaxis is recommended
1. Dental procedures that involve manipulation of gingival tissue or the periapical region of teeth or perforation of the
   oral mucosa. 

2. Tonsillo-adenoidectomy
The following procedures and events do NOT need prophylaxis:
- Routine anaesthetic injections through non-infected tissue
- Taking dental radiographs
- Placement of removable prosthodontic or orthodontic appliances
- Adjustment of orthodontic appliances
- Placement of orthodontic brackets
- Shedding of deciduous teeth
- Bleeding from trauma to the lips or oral mucosa. 

Antibiotic Prophylaxis Regimens

Table 3 Antibiotic regimen for dental procedures (plus tonsillectomy &/or adenoidectomy) 
AMOXYCILLIN 50mg/kg up to max 2g, administered:  - Orally, 1 hour before the procedure, or
- IV, just before the procedure, or
- IM, 30 minutes before the procedure.

Administer parenterally (preferably IV) if unable to take medication orally. 
For penicillin allergy or if a penicillin- or cephalosporin-group antibiotic taken more than once in the previous month: This applies to Rheumatic fever population 
CLARITHROMYCIN 15mg/kg up to maximum 500mg orally, administered:  - Orally 1 hour before the procedure. 
CLINDAMYCIN 15mg/kg up to maximum 600mg, administered:  - Orally, 1 hour before the procedure, or
- IV, over at least 20 minutes, just before the procedure, or
- IM, 30 minutes before the procedure 
Notes  Clindamycin is not available in syrup form in New Zealand.
Beware potential interactions between clarithromycin and other medications.
If the antibiotic is inadvertently not administered before the procedure, it may be administered up to 2 hours after the procedure. 

Infective Endocarditis

Epidemiology:

Infective endocarditis accounts for 1 in 500 to 1000 paediatric admissions per year. The frequency of endocarditis cases have increased in recent years, partly due to improved survival among children who are at risk for endocarditis.

Risk Factors:

  • Rheumatic carditis - Incidence has decreased with declining rates of rheumatic fever, especially in developed countries.
    Five per cent of patients with rheumatic carditis develop endocarditis.
  • Congenital heart disease - Ventricular septal defect, patent ductus arteriosus, and Tetralogy of Fallot are the most commonly associated conditions.
  • Cardiac surgery - The presence of extracardiac shunts, valves, stents and patches for congenital heart disease repair are risk factors for endocarditis.
Time after surgery Types of pathogen 
<2 months  Hospital-acquired (i.e. coagulase- negative staphylococci or Candida sp). 
2-12 months  Hospital and community acquired. 
>12 months  Community-acquired (i.e. viridans strep). 
  • Hospital-acquired (nosocomial) - This occurs as a complication of bacteraemia or other sources like central venous line, genitourinary, gastrointestinal or wound infections. Morbidity and mortality is high due to other comorbid conditions. Bacteraemia may complicate established focal infection and its surgical management at any site, such as drainage of an abscess (dental, skin and soft tissues, lung etc) or of peritonitis. It may also complicate procedures (including urinary catheterisation) through infected fluids, such as urine, bile or peritoneal fluid. At all of these sites bacteria commonly associated with infective endocarditis may be present. Patients with established infections at these sites will necessarily receive antibacterial treatment and those at cardiac risk are advised to have appropriate antibacterial agents included in their overall antibacterial regimen before their procedure.
  • Prematurity - Risk factors in this group include extreme prematurity, major surgery after delivery and the use of central venous lines.
  • Mitral valve prolapse - MVP occurs in 2% of population. Risk factors for endocarditis = the presence of valve thickening and mitral regurgitation.

Microbiology

Pathogen Risk factors & Patient groups 
Viridans streptococci. (Streptococcus sanguis, Streptococ­cus bovis, Strep mutans, Strep mitis)  Rheumatic heart disease.
Late postoperative endocarditis 
Staph aureus  Acute endocarditis
IV drug abuse
Neonatal endocarditis
Long-term CVL site 
Coagulase-negative staphylococci Early postoperative endocarditis
Nosocomial infection esp. of prosthetic valve 
Enterococci Nosocomial infection
Secondary to GU tract infection 
Gram-negative pathogens  Very rarely from early postoperative endo­carditis or nosocomial infection 
HACEK organisms (Haemophilus parainfluenzae, Actino­bacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, Kingella kingae).
Coxiella burnettii (Q fever). 
Native valve
Late postoperative endocarditis 
 Fungi (Candida species) Neonatal endocarditis
Nosocomial infection
Infected homografts 
Moulds
(Aspergillus sp) 
Transplant recipients
Homografts 

Clinical Presentation of Infective Endocarditis

Subacute endocarditis
Indolent infection lasting weeks to months, involving fever, malaise, splenomegaly, regurgitant murmur, weight loss, night sweats and fatigue. It is most commonly immune mediated by continuous antigenic stimulation by micro-organisms within the vegetation.

Acute endocarditis
Fulminant process with presence of new murmur, congestive heart failure, sepsis and systemic emboli. Infection caused by invasive pyogenic bacteria, such as Staphylococcus aureus, and normally characterised by high fevers and a short toxic course (days to weeks).

Nosocomial endocarditis
Often complicated with comorbid conditions e.g. burns. Be aware when growing persistently positive blood cultures after removal of central venous catheter, presence of a new murmur, embolic phenomenon, or cardiac failure.

Diagnosis

The Modified Duke Criteria is the most preferred and has a high degree of predictive value. These criteria have been validated in children.

Definite endocarditis 2 major criteria or
1 major plus 3 minor criteria or
5 minor criteria 
Possible endocarditis:  1 major and 1 minor criteria or
3 minor criteria 
Major Criteria Comments   
Microbiologic  Typical microorganisms isolated from ≥2 blood cultures:
- Viridans strep.
- HACEK organisms (see above).
- Staphylococcus aureus.
- Community acquired enterococci or
- Coxiella burnetii detected in ≥1 blood culture. 
  Microorganisms consistent with IE from persistently positive blood cultures:
- ≥2 positive cultures of samples drawn >12 hours apart or
- All of 3 or majority of ≥4 separate cultures of blood (with first and last sample drawn 1 hour apart) 
Endocardial  New regurgitant murmur or
Findings on echocardiogram including:
- Echogenic, oscillating intracardiac mass.
- Periannular abscess.
- New dehiscence of prosthetic valve.
Minor criteria   
Predisposing risk factors  High risk:
Previous endocarditis, aortic valve disease, rheumatic heart disease, prosthetic valve, coarctation, complex cyanotic heart disease. 
Moderate risk:
Mitral valve prolapse (regurgitation/valve thickening), Mitral stenosis, tricuspid disease, pulmonary stenosis, Cardiomyopathy 
Low risk:
ASD, IHD, mitral valve prolapse without regurgitation 
Clinical  - Fever (Temperature ≥ 38ºC)
- Vascular phenomenon. (emboli, Janeway lesions). Immunologic phenomenon. ( RF+, nephritis) 
Microbiologic  Single positive blood culture (except coagulase negative staphylococci or gram negative bacilli) or serologic evidence of active infection with organism associated with endocarditis 

Blood cultures

  • Three BC should be obtained by separate venepuncture sites on the first day.
  • If there is no growth by the second day of incubation, two more may be taken.
  • Antibiotics maybe withheld for 48 hours or longer in clinically stable patients with negative blood cultures.
  • If patient is clinically unstable, three separate blood cultures should be taken over a short period. Empiric antibiotic therapy should be commenced.

Echocardiography

  • Details the site of infection, extent of valvular damage and cardiac function.
  • Transthoracic echocardiography ~ 90% sensitive in children compared with trans-oesophageal echo.
  • Consider trans-oesophageal echocardiography (TOE) when imaging is poor
  • Infants and children with staph aureus in a single positive blood culture don't require echocardiography unless there is underlying heart disease, suspicious clinical findings of endocarditis, persistent fever or prolonged bacteraemia >72 hours despite adequate doses of antibiotics.

Other Investigations

FBC, ESR, CRP, urinalysis, liver function tests, Rheumatoid factor, CXR and ECG.

NB: Rheumatoid factor has high specificity (94%) and CRP a high sensitivity (97%) for IE

Staph aureus bacteraemia complicating bone or soft tissue sepsis

A common clinical scenario is the isolation of staph aureus from a single blood culture in children admitted to surgical wards with bone, joint or soft tissue sepsis. The yield from echocardiography is low (<5%) in the absence of pre-existing heart disease or delayed or poor response to treatment.

Management

Empiric Antibiotic Use

  • Two or more blood cultures must be obtained prior to commencing antibiotics.
  • Initial treatment is with Penicillin + Flucloxacillin + Gentamicin.

Refer all proven or probable cases in Auckland to Paediatric Cardiology at Starship.

Complications of Infective Endocarditis

Consequence of Vegetation and Type of Complication Site  Description 
Fragmentation: 
Embolic
CNS
Extremities
Coronary arteries
Spleen
Kidneys
Lungs 
Stroke, hemiparesis, IVH.
Cool painful pulseless limb/ digit.
Congestive heart failure.
Shoulder pain, prolonged fever, pleuritic pain.
Haematuria, sterile pyuria.
SOB, chest pain, haemo­ptysis. 
Tissue destruction: 
Cardiac 
Valvular insufficiency
Myocardial abscess
Conduction abnormal 
Chordae tendinae rupture
Prolongation of PR
Arrhythmias 
Release of bacterial antigen:
Immunologic 
Skin, mucous membrane & digits

Ocular
Glomerulonephritis 
Petechiae, splinter
haemorr­hages, Janeway lesions,
Osler's nodes, clubbing
Roth's spots, conjunctival haemorrhages
Low complement, positive RF proteinuria, Haematuria. 

Prognosis

  • Mortality rates have improved. Current mortality rates are as low as 5-10%.
  • Factors associated with increased morbidity and mortality are:
    - Staph aureus, gram negative bacilli, fungal endocarditis.
    - Younger infants.
  • Relapse occurs most often with patients with complex congenital, cyanotic heart disease with prosthetic valves and shunts.
  • Recurrences with different pathogens or >6 months of treatment for the initial episode occurs in approximately 5-10% children.

Acknowledgements

This guideline was developed by Dr Ross Nicholson, Kidz First Hospital in collaboration with paediatric cardiology and infectious diseases services at Starship Children's Hospital.

It addresses: 
Current NZ Recommendations for Infective Endocarditis Prophylaxis (based on National Heart Foundation Guidelines 2008 - see National Heart Foundation Guideline for Prevention of Endocarditis with Dental and Medical Interventions )

References

Ellis-Pegler R.,Sharpe N.,Everts R.,Chambers s.,Hornung T.,Hay D.and Ting G. NHF advisory group

Guideline on the Prevention of Infective Endocarditis Associated with Dental and other Medical Interventions. New Zealand NHF Sept 2008

Ferrieri P, Gewitz M, Gerber M, Newburger J, Dajani A, Shulman S et al. Unique features of infective endocarditis in childhood. Pediatrics 109 (5): 2002.

Humpl T,McCrindle BW, SmallhornJF, The Relative Roles of Transthoracic Compared with Transesophageal Echocardiography in Children with Suspected Infective Endocarditis

J Am Coll Cardiol 2003;41:2068

Saiman L Endocarditis Krugman's Infectious diseases of Children. 11th Ed 2004 Mosby.

Oliver R; Roberts GJ; Hooper L. Penicillins for the prophylaxis of bacterial endocarditis in Dentistry.

The Cochrane Database of Systemic Reviews 2005.

Miles F, Voss L. Segedin E. Anderson BJ. Review of staphylococcal aureus infections requiring admission to a paediatric intensive care unit. Arch Dis Child 2005;

Koegelenberg CFN et al Infective Endocarditis: Improving the diagnostic yield

Cardio J of S Africa 2004 15;14-20

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Document Control

  • Date last published: 01 February 2010
  • Document type: Clinical Guideline
  • Services responsible: KidzFirst, Paediatric Cardiology
  • Author(s): Ross Nicholson
  • Editor: Greg Williams
  • Review frequency: 2 years

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