Infective Endocarditis Prophylaxis for Non-cardiac Procedure

Dyah W. Anggrahini
Department of Cardiology and Vascular Medicine
Faculty of Medicine Universitas Gadjah Mada
Dr. Sardjito General Hospital Yogyakarta, Indonesia

Abstract

The causes and epidemiology of Infective Endocarditis (IE) have evolved in

recent decades with a doubling of the average patient age and an increased prevalence
in patients especially when the medical technology has now allowed for placement of
cardiac devices. It is a rare, with a yearly incidence of about 3–10 per 10.000 people.
The development of IE is the net result of the complex interaction between the
bloodstream pathogen with matrix molecules and platelets at sites of endocardial cell
damage. Many of the clinical manifestations of IE depends on the host’s immune
response to the infecting microorganism. Although novel diagnostic and therapeutic
strategies have emerged, 1-year mortality has not improved and remains at 30%,
which is worse than for many cancers.
Several conditions associated with highest risk of infective endocarditis are
those with (1) previous IE; (2) prosthetic valve or prosthetic material used for cardiac
velve repair; (3) congenital heart disease; (4) cardiac transplantation recipients who
develop cardiac valvulopathy. Most of previous studies have focused on dental
procedures as a cause of IE and the use of prophylactic antibiotics to prevent IE in
patients at risk. Few data exist on the risk of or prevention of IE associated with a GI
or GU tract procedure.
In this review we will discuss what underlying cardiac conditions over a
lifetime have the highest predisposition of endocarditis; what underlying cardiac
conditions are associated with the highest risk of adverse outcome from endocarditis;
in which non-cardiac procedure should IE prophylaxis be administered and what kind
of regimens.
Keywords: Infective Endocarditis, prophylactic, non-cardiac procedure
Introduction

Within several decades after the intention of antibiotic penicillin for the
treatment of Infective Endocarditis (IE), the mortality caused by this disease remains
high. IE is considered rare disease, with an incidence of 3–10 per 100000 people
1,2
annually. The pattern of disease varies worldwide, with epidemiology in low-
income countries similar to that of high-income countries during the early antibiotic
era. In the low-income countries, rheumatic heart disease remains the major
underlying disease for infective endocarditis and accounts for 75% of the cases.3 In
the high-income countries, the prevalence of rheumatic heart disease has decreased
mainly due to improved living standards. However, in those areas, degenerative valve
disease, diabetes, cancer, intravenous drug use, and congenital heart disease have
replaced rheumatic heart disease as the major risk factors for infective endocarditis.
Moreover, patients with infective endocarditis are older.4
The epidemiology of infective endocarditis is complex to assess because
diagnosis is difficult and referral bias has a large impact on the clinical characteristics
of the population studied in different clinical settings. In 1955, The American Heart
Association (AHA) first introduced antibiotic prophylaxis for patients with congenital
or acquired cardiac conditions who were considered to be at risk of IE, and who
required dental treatment.5 However, since 2007 the AHA guidelines suggest
significantly different recommendations for IE prophylaxis.6 In addition, the recent
ESC guidelines significantly reduced the categories of cardiac conditions, which
required antibiotic prophylaxis only for dental or other mucosally invasive
procedures. In the new guidelines prophylaxis is no longer recommended on the basis
of lifetime risk of IE, but is now only required for cardiac conditions identified as
having the highest risk of an adverse outcome if IE occurs.7

Pathogenesis of Infective Endocarditis

The healthy cardiac endothelium is resistant to frequent bacteremia caused by

daily activities such as chewing and tooth brushing.8 However, when there is a
predisposition of cardiac condition, the endothelial layer of the heart injured, followed
release of inflammatory cytokines and tissue factors with associated fibronectin
expression leads to formation of a platelet-fibrin thrombus. The condition called non-
bacterial vegetation is not infectious and rarely results in symptoms to the patients.
Damage to the endothelium is caused by valve sclerosis, rheumatic valvulitis, or by
direct bacterial activity, usually particularly Staphylococcus aureus.9 Once, a person
is infected by bacteremia, that non-bacterial vegetation will ease bacterial adherence.
Bacterial colonisation triggers more endothelial injury and thrombus deposition,
eventually forming infected vegetation. Production of a multilayered bacterial
aggregate containing a polysaccharide and proteinaceous matrix assists bacterial
persistence and contributes to antibiotic tolerance.9
The Gram-positive cocci of the staphylococcus, streptococcus, and
enterococcus species account for 80–90% of infective endocarditis. S aureus is the
most frequently isolated microorganism associated with infective reported in up to
30% of cases. Staphylococcal infective endocarditis extends beyond traditional at-risk
groups such as patients on haemodialysis and intravenous drug users, and can affect
both native and prosthetic valves.10 Coagulase-negative staphylococci (eg,
Staphylococcus epidermidis, Staphylococcus lugdunensis, and Staphylococcus
capitis) are ubiquitous skin commensals.11 They colonise indwelling lines and devices
12
and are the most common isolate in early prosthetic valve endocarditis. Coagulase-
negative staphylococci also frequently cause hospital-acquired native valve
endocarditis.11
Streptococcal infective endocarditis caused by the oral viridans group remains
most common in low-income countries. These organisms are commensals of the oral,
gastrointestinal, and urogenital tract. Enterococci account for 10% of cases overall.
Most isolates are Enterococcus faecalis, causing both native valve endocarditis and
prosthetic valve endocarditis in elderly or chronically ill patients.
The remaining microbes that can cause infective endocarditis are a mixture of
fastidious bacteria, zoonotic bacteria, and fungi. The HACEK bacteria (haemophilus,
aggregatibacter, cardiobacterium, Eikenella corrodens, kingella), which cause about
3% of cases, are slow-growing organisms that colonise the oropharynx. Fungal
endocarditis, usually Candida or Aspergillus, is rare but often fatal, arising in patients
who are immunosuppressed or after cardiac surgery, mostly on prosthetic valves.13

Antibiotic Prophylaxis
 There are several reasons that antibiotic prophylaxis in high-risk patients are
necessary: (1) there is uncertainties regarding estimations of the risk of IE; (2) the
worse prognosis of IE in high-risk patients,in particular those with prosthetic IE; (3)
the fact that high-risk patients account for a much smaller number than patients at
intermediate risk, thereby reducing potential harm due to adverse events of antibiotic
prophylaxis. In the 2015 Guidelines, European Society of Cardiology mentioned
those who are at risk of having IE are: (1) Patients with a prosthetic valve or with
prosthetic material used for cardiac valve repair and also applies to transcatheter-
implanted prostheses and homografts. (2) Patients with previous IE; (3) Patients with
untreated cyanotic congenital heart disease (CHD) and those with CHD who have
postoperative palliative shunts, conduits or other prostheses who treated surgically or
percutaneously. Those with no residual shunts, then it recommends prophylaxis for
the first 6 months after the procedure. Antibiotic prophylaxis is not recommended for
patients at intermediate risk of IE, i.e. any other form of native valve disease
(including the most commonly identified conditions: bicuspid aortic valve, mitral
valve prolapse and calcific aortic stenosis). Nevertheless, both intermediate and high-
risk patients should be advised of the importance of dental and cutaneous hygiene.7
The current ESC guideline also recommends different procedures required for
IE prophylaxis than the old AHA, British or NICE guidelines. At-risk procedures
involve manipulation of the gingival or periapical region of the teeth or perforation of
the oral mucosa (including scaling and root canal procedures).14 The use of dental
implants raises concerns with regard to potential risk due to foreign material at the
interface between the buccal cavity and blood. There is no compelling evidence that
bacteraemia resulting from respiratory tract procedures, gastrointestinal or
genitourinary procedures, including vaginal and caesarean delivery, or dermatological
or musculoskeletal procedures causes IE. The complete recommendation is shown in
the following figure. 7
 Figure 1. Recommendation for IE prophylaxis in non-cardiac procedure ( ESC
Guidelines, 2015)

Based on the explanations above, we may conclude that antibiotic prophylaxis

should only be considered for patients at highest risk for endocarditis and is not
recommended in other situations. For dental procedure, the main targets for antibiotic
prophylaxis are oral streptococci. It is recommended to provide amoxycillin or
ampicillin 2 gr orally or iv before dental procedure, or clyndamycin for those who
allergic to penicillin. Fluoroquinolones and glycopeptides are not recommended due
to their unclear efficacy and the potential induction of resistance. Cephalosporins
should not be used in patients with anaphylaxis, angio-oedema or urticaria after intake
of penicillin or ampicillin due to cross-sensitivity.7
For non-dental procedure, even those who are at high risk are not
recommended for systemic antibiotic prophylaxis unless the procedure is performed
in the setting of infection. Patients at-risk who undergo an invasive respiratory tract
procedure to treat an established infection (i.e. drainage of an abscess) should receive
an antibiotic regimen that contains an anti- staphylococcal drug. In the case of an
established infection or if antibiotic therapy is indicated to prevent wound infection or
sepsis associated with a gastrointestinal or genitourinary tract procedure in at-risk
patients, it is reasonable that the antibiotic regimen includes an agent active against
enterococci (i.e. ampicillin, amoxicillin or vancomycin; only in patients unable to
tolerate beta-lactams). Use of an intrauterine device is now considered acceptable, in
particular when other contraceptive methods are not possible and in women at low
risk of genital infections. For those undergo surgical procedures involving infected
skin (including oral abscesses), skin structure or musculoskeletal tissue, it is
reasonable that the therapeutic regimen contains an agent active against staphylococci
and beta-haemolytic streptococci. 7
Conclusion

Infective Endocarditis is still cause high mortality despite the advancement of

medical technology and availability of high-end antibiotics. Antibiotics prophylaxis is
recommended only in selected patients at-risk and in selected procedure.

References

1. Murdoch DR, Corey GR, Hoen B, et al, and the International Collaboration on
Endocarditis-Prospective Cohort Study (ICE-PCS) Investigators. Clinical
presentation, etiology, and outcome of infective endocarditis in the 21st century:
the International Collaboration on Endocarditis-Prospective Cohort Study. Arch
Intern Med 2009; 169: 463–73.
2. Duval X, Delahaye F, Alla F, et al, and the AEPEI Study Group. Temporal trends
in infective endocarditis in the context of prophylaxis guideline modifications:
three successive population-based surveys. J Am Coll Cardiol 2012; 59: 1968–
76.
3. Allegranzi B, Bagheri Nejad S, Combescure C, et al. Burden of endemic health-
care-associated infection in developing countries: systematic review and meta-
analysis. Lancet 2011; 377: 228–41.
4. Hoen B, Alla F, Selton-Suty C, et al, and the Association pour l’Etude et la
Prévention de l’Endocardite Infectieuse (AEPEI) Study Group. Changing profile
of infective endocarditis: results of a 1-year survey in France. JAMA 2002; 288:
75–81.

5. American Heart Association Committee on Prevention of Rheumatic Fever and
Bacterial Endocarditis. (Jones TD, Baumgartner L, Bellows MT, et al.)
Prevention of rheumatic fever and bacterial endocarditis through control of
streptococcal infections. Circulation 1955;11:317–320.
6. Wilson W, Taubert K, Gewitz M, et al. Prevention of infective endocarditis:
guidelines from the American Heart Association: a guideline from the American
Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease in the
Young, and the Council on Clinical Cardiology, Council on Cardiovascular Sur-
 gery and Anesthesia, and the Quality of Care and Outcomes Research
Interdisciplinary Working Group. Circulation 2007;116:1736–1754.
7. The Task Force for the Management of Infective Endocarditis of the European
Society of Cardiology (ESC) (Habib G, Lancellotti P, Antunes MJ, et. al.). 2015
ESC Guidelines for the management of infective endocarditis. European Heart
Journal (2015) 36, 3075–3123
8. Lockhart PB, Brennan MT, Sasser HC, Fox PC, Paster BJ, Bahrani-Mougeot FK.
Bacteremia associated with toothbrushing and dental extraction. Circulation
2008; 117: 3118–25.

9. Widmer E, Que YA, Entenza JM, Moreillon P. New concepts in the
pathophysiology of infective endocarditis. Curr Infect Dis Rep 2006; 8: 271–79.
10. Durante-Mangoni E, Bradley S, Selton-Suty C, et al, and the International
Collaboration on Endocarditis Prospective Cohort Study Group. Current features
of infective endocarditis in elderly patients: results of the International
Collaboration on Endocarditis Prospective Cohort Study. Arch Intern Med 2008;
168: 2095–103.
11. Becker K, Heilmann C, Peters G. Coagulase-negative staphylococci. Clin
Microbiol Rev 2014; 27: 870–926.
12. López J, Revilla A, Vilacosta I, et al. Definition, clinical profile, microbiological
spectrum, and prognostic factors of early-onset prosthetic valve endocarditis. Eur
Heart J 2007; 28: 760–65.
13. Das M, Badley AD, Cockerill FR, Steckelberg JM, Wilson WR. Infective
endocarditis caused by HACEK microorganisms. Annu Rev Med 1997; 48: 25–
33.
14. Daly CG, Currie BJ, Jeyasingham MS, Moulds RFW, Smith JA, Strathmore NF,
Street AC, Gossaa AC. A change of heart: the new infective endocarditis
prophylaxis guidelines. Australian Dental Journal 2008; 53: 196–200