Infective endocarditis

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Infection of the endocardium, the innermost layer of the heart. Reviewed in BMJ in 2006.[1]. The lack of good clinical trial evidence for prophylactic antibiotics in high risk dental patients lead to a change of practice in England and Wales which has been associated in time with an increased incidence of SBE[2]which as not been seen in other countries[3].

Contents

Aetiology

Transient bacteraemia may allow deposition of organisms into an area where blood flow is such that normal immune mechanisms are unable to work well. Adherence is enhanced by pre-existing tissue damage or prosthetic material. Surgery may introduce contamination directly.

Viridans streptococci (as found in the mouth) are still the most common organisms, but the spectrum of organisms responsible for the disease is becoming more diverse and staphlycoccus in particular is becoming more common. This change is probably due to increasing numbers of critically ill patients getting central lines, in addition to the expanding group of pediatric patients surviving cardiac surgery.

Clinical

Fever with a new or variable murmur should cause the doctor to consider this diagnosis. Symptoms are manifestations of:

  • systemic inflammation
  • damage to heart valves
  • septic emboli

Duke Criteria

Several different diagnostic criteria systems, but Modified Duke criteria in common use: [4]

Major

  • positive blood cultures with typical organism, on multiple occasions
  • evidence of endocardial damage:
    • echocardiographic evidence
    • new murmur

Minor

  • fever
  • predisposing factors eg rheumatic valve disease
  • vascular manifestations
    • pulmonary emboli (wedge-like consolidation)
    • Janeway lesions (round skin lesions on palms)
    • Osler's nodes (subcutaneous nodules in pulp of fingers)
    • Retinal haemorrhages
    • Emboli to brain eg stroke, nerve palsies
  • immunological manifestations
    • splenomegaly
    • glomerulonephritis
    • systemic vasculitis eg skin purpura, hypergammaglobulinaemia, cryoglobulinaemia, low C3
  • positive blood culture once, or positive serology
  • echocardiographic suspicion eg new AR

Those with central lines will tend to get right-sided endocarditis, with no peripheral embolic phenomena. Symptoms tend to be mild but there is persistent bacteremia despite ongoing appropriate antibiotic treatment.

Investigations

Echocardiography is clearly useful, but its predictive value is highly dependent on other features consistent with the diagnosis.

Blood tests

Multiple blood cultures with good volumes of blood are required.

Treatment

Medical

Treatment is difficult because the fibrin meshwork of the vegetation protects bugs not only from antimicrobial agents but also the host's immune defences. Secondly, susceptibility to antibiotics may be less because the dense concentration of bugs in the vegetation can force them into a slowed state of cell division, which reduces the window of opportunity for drugs that work at just one stage of the life cycle. This also means that organisms highly susceptible in the lab may not be quite so sensitive in vivo. The key to successful treatment is to use high concentration of bactericidal (not bacteriostatic) therapy over an extended period of time.

MIC is vaguely useful - but remember too that efficacy for time-dependent drugs (eg penicillins) is dependent on the duration of contact between the drug and the bug. So use high doses at short intervals ie 4-6hrly. Concentration-dependent drugs (eg aminoglycosides) work best at higher concentrations - still debate about optimal frequency viz once daily vs conventional administration).

Most strains of viridans streptococci are highly penicillin susceptible (MIC <0.1 mcg/ml) and monotherapy with penicillin or ceftriaxone for 4 weeks is effective. Adding gentamicin for the first 2 weeks of treatment has been associated with more rapid sterilisation of the vegetation.

For viridans streptococci with intermediate penicillin susceptibility (MIC >0.1 mcg/ml but <0.5 mcg/ml) give penicillin for 4 weeks plus gent for 2 weeks.

If penicillin resistant (MIC >0.5mcg/ml) use 4-6 weeks ampicillin or vanc plus gentamicin. 4 weeks treatment sufficient if symptoms have been going on for <3 months, otherwise treat for 6. Enterococcus is rare in kids but common in the elderly. Difficult to treat as it is resistant to cephalosporins, only slightly susceptible to penicillins and usually inhibited rather than killed by vanc and aminoglycosides. So use combination amp or vanc plus gent as above, and look closely at sensitivities. Staphlycoccus without prosthetic valve - give fluclox 4-6 weeks plus gent for 3-5 days. Else vanc (monotherapy), but fluclox works faster. If prosthetic, needs at least 6 weeks fluclox and rifamp (oral), plus 2 weeks gent (which covers MRSA too). Not a huge amount of evidence to support this, however.

HACEK organisms are slow-growing Gram negative bacteria that form a normal part of the human flora esp in the mouth:

  • Haemophilus aphrophilus/ parainfluenzae /paraphrophilus
  • Actinobacillus actinomycetemcomitans
  • Cardiobacterium hominis
  • Eikenella corrodens
  • Kingella kingae

Most common cause of Gram-negative endocarditis, and probably responsible for a lot of culture negative cases (which make up 10-30% of total). They have a propensity to form friable vegetations (especially H. parainfluenzae) that break off and cause symptomatic emboli. May well involve previously normal hearts. Mostly resistant to penicillin so use cephalosporin monotherapy 4/52.

Streptococcus pneumoniae more common in kids but still rare. High mortality even where nominally susceptible. Resistance in other countries is a big problem but not yet in UK. 4 weeks ceftriaxone or vanc.

Although oral therapy has been shown to be effective in certain situations, most would use parenteral to ensure good levels and compliance. Changing to oral therapy later on is certainly a viable option in uncomplicated, responsive cases.

Surgical

Surgery is required in patients with intracardiac abscess, severe valvular regurgitation and infected prosthetic material. Timing is difficult, since fresh prosthetic material may be introduced.

Prophylaxis of Bacterial Endocarditis

LogoWarningBox4.pngControversial
The 2008 NICE guidelines recommended restrictions in antibiotic prophylaxis compared to American and other European guidelines. Unhappily this has been associated in time with increased hospitalisation due to SBE[2]which as not seen in the USE[3]

See BNF article and other guidelines.[5][6][7] Note: NICE guidelines were published in March 2008.[8][9][10] There are no trials of prophylaxis and, according to the NICE press release:[11]

"...there is no consistent association between having an interventional procedure, dental or non-dental, and the development of IE and that the clinical effectiveness of antibiotic prophylaxis is not proven. The evidence also suggests that antibiotic prophylaxis against IE for dental procedures is not cost effective and may lead to a greater number of deaths through fatal anaphylactic reactions than not using preventive antibiotics. The guideline makes a number of key recommendations, including:

  • Patients should not be offered antibiotics to prevent IE for any of the following procedures:
  • a dental procedure
  • an obstetric or gynaecological procedure, or childbirth
  • a procedure on the bladder or urine system
  • a procedure on the gullet, stomach or intestines
  • a procedure on the airways, including ear, nose and throat and bronchoscopy.
  • Healthcare professionals should regard people with the following cardiac conditions as being at risk of developing IE:
  • acquired valvular heart disease with stenosis or regurgitation
  • valve replacement
  • structural congenital heart disease, including surgically corrected or palliated structural conditions, but excluding isolated atrial septal defect, fully repaired ventricular septal defect or fully repaired patent ductus arteriosus, and closure devices that are judged to be endothelialised
  • previous IE
  • hypertrophic cardiomyopathy.
  • Healthcare professionals should offer people at risk of IE clear and consistent information about prevention, including:
  • the benefits and risks of antibiotic prophylaxis, and an explanation of why antibiotic prophylaxis is no longer routinely recommended
  • the importance of maintaining good oral health
  • symptoms that may indicate IE and when to seek expert advice
  • the risks of undergoing invasive procedures, including non-medical procedures such as body piercing or tattooing.
  • People at risk of IE who are receiving antimicrobial therapy because they are undergoing a gastrointestinal or genitourinary procedure at a site where there is a suspected infection should be offered an antibiotic that covers organisms that cause IE.
  • Investigate and treat promptly any episodes of infection in people at risk of IE to reduce the risk of endocarditis developing."


Despite the lack of evidence of benefits, some authors (principally cardiologists, who see the consequences, rather than public health experts who look at the whole systems) recommend that some patients should be offered antibiotic chemoprophylaxis.[12] If antibiotics are used, Amoxicillin is good against oral streps, and azithromycin is better than erythromycin - better tissue penetration, tolerance, longer action. Clindamycin is an alternative.

Previous rheumatic fever or Kawasaki's without valvular dysfunction considered not to be at risk. High risk include:

  • Previous IBE episode
  • Oral procedures likely to result in bleeding
  • tonsillectomy
  • rigid bronchoscopy or surgery involving mucosa (not intubation or flexible bronchoscopy)
  • GI instrumentation beyond endoscopy + biopsy
  • GU instrumentation beyond catheterization

But most cases have no such history of course, and toothbrushing is likely to be a much more important cause. Regular antibiotics rapidly induce resistance in viridans strep so not much you can do.

References

  1. Beynon RP, Bahl VK, Prendergast BD. Infective endocarditis. BMJ (Clinical research ed.) 2006;333:334-9. (Direct link – subscription may be required.)
  2. a b Dayer MJ, Jones S, Prendergast B, Baddour LM, Lockhart PB, Thornhill MH. Incidence of infective endocarditis in England, 2000-13: a secular trend, interrupted time-series analysis. Lancet (London, England). 2015 Mar 28; 385(9974):1219-28.(Link to article – subscription may be required.)
  3. a b Bikdeli B, Wang Y, Krumholz HM. Infective endocarditis and antibiotic prophylaxis. Lancet (London, England). 2015 Aug 8; 386(9993):528-9.(Link to article – subscription may be required.)
  4. 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 Mar;96(3):200-9.
  5. Gould FK, Elliott TS, Foweraker J, Fulford M, Perry JD, Roberts GJ, Sandoe JA, Watkin RW. Guidelines for the prevention of endocarditis: report of the Working Party of the British Society for Antimicrobial Chemotherapy. J Antimicrob Chemother. 2006 Jun;57(6):1035-42. Direct link: http://jac.oxfordjournals.org/cgi/content/full/57/6/1035
  6. Task Force Members on Infective Endocarditis of the European Society of Cardiology; ESC Committee for Practice Guidelines (CPG). Guidelines on prevention, diagnosis and treatment of infective endocarditis executive summary. Eur Heart J. 2004 Feb;25(3):267-76. Direct link: http://eurheartj.oxfordjournals.org/cgi/content/full/25/3/267]]
  7. FK, Elliott TSJ, Foweraker J, Fulford M, Perry JD, Roberts GJ, et al. Guidelines for the prevention of endocarditis: report of the Working Party of the British Society for Antimicrobial Chemotherapy. J Antimicrob Chemother 2006;57(6):1035-42
  8. National Institute for Health and Clinical Excellence (NICE). Press release: NICE guideline on prophylaxis for infective endocarditis set to change current clinical practice. 2008 (March 17).
  9. National Institute for Health and Clinical Excellence (NICE). NICE clinical guideline 64. Prophylaxis against infective endocarditis: Antimicrobial prophylaxis against infective endocarditis in adults and children undergoing interventional procedures. NICE clinical guidelines. London: National Institute for Health and Clinical Excellence, 2008
  10. National Institute for Health and Clinical Excellence (NICE). Prophylaxis against infective endocarditis: Antimicrobial prophylaxis against infective endocarditis. 2008 Accessed: 2008(March 18):Clinical guideline
  11. National Institute for Health and Clinical Excellence (NICE). Press release: NICE guideline on prophylaxis for infective endocarditis set to change current clinical practice. 2008 (March 17).
  12. Cahill TJ, Dayer M, Prendergast B, Thornhill M. Do patients at risk of infective endocarditis need antibiotics before dental procedures? BMJ 2017;358, DOI: 10.1136/bmj.j3942
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