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Focus on periodontal disease and development of endocarditis

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JOURNAL OF BIOLOGICAL REGULATORS & HOMEOSTATIC AGENTS Vol. 32, no. 2 (S1), 143-147 (2018)

FOCUS ON PERIODONTAL DISEASE AND DEVELOPMENT OF ENDOCARDITIS

F. CARINCI1*, M. MARTINELLI2*, M. CONTALDO3, R. SANTORO3, F. PEZZETTI2,

D. LAURITANO4, V. CANDOTTO5, D. MUCCHI6, A. PALMIERI2,
A. TAGLIABUE7** and L. TETTAMANTI7**

1
Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara,
Italy; 2Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna,

F
Bologna, Italy; 3Multidisciplinary Department of Medical-Surgical and Dental Specialties,
University of Campania Luigi Vanvitelli, Naples, Italy; 4Department of Medicine and Surgery,
University of Milano Bicocca, Monza, Italy; 5Department of Biomedical, Surgical and Dental

O
Sciences, University of Milan, Milan, Italy; 6LAB S.r.l., Codigoro, Ferrara, Italy; 7Department of
Medicine and Surgery, University of Insubria, Varese, Italy

*these authors contributed equally to this work and they are co-first authors
**these authors contributed equally to this work and they are co-last authors

O
Abstract Infective endocarditis is a devastating disease with high morbidity and mortality. The link to
oral bacteria has been known for many decades and has caused ongoing concern for dentists, patients and
cardiologists. The microbiota of the mouth is extremely diverse and more than 700 bacterial species have

R
been detected. Half of them are uncultivable so far. Oral microbiota is not uniform, specific sites exist in
the mouth such as tongue, palate, cheek, teeth and periodontal pockets that have their own microbiota.
Factors involved in the development of a bacterial endocarditis are difficult to define but a vulnerable

P
surface (i.e. a damaged endocardium) and a high bacterial load in the blood seems to be decisive. The
cause of microorganisms, in 90% of cases, are staphylococcus, streptococcus and enterococcus. Oral
streptococci belong to viridans group (streptococcus mutans and streptococcus sanguis). As they are
part of dental plaque, they could enter the bloodstream causing bacteraemia through daily habits like
chewing or tooth brushing. Effective treatment of periodontal infections is important to reduce local
inflammation and bacteraemia. In addition, poor periodontal health appears to increase the risk of
cardiovascular disease, pulmonary disease, and preterm and low birth weight. Conclusions: Long-
standing oral disease prevention protocols reduce the risk of developing periodontal disease. Data
suggest that methods used to prevent cases of IE that originate from oral bacteria should focus on
improving oral hygiene and reducing or eliminating gingivitis, which should reduce the incidence of
bacteraemia after tooth-brushing and the need to extract teeth owing to periodontal disease and caries.
Infective endocarditis is a devastating disease Infective endocarditis (IE) is a disease caused
with high morbidity and mortality. The link to oral by a bacteraemia that affects different organs or
bacteria has been known for many decades and has tissues, including the oral cavity. Although it has a
caused ongoing concern for dentists, patients and low incidence, it might imply a potential threat to the
cardiologists. life of the affected individual. Predominantly it tends

Key words: oral disease, periodontitis, bacteria, endocarditis

Mailing address:
Prof. Angelo Tagliabue, 0393-974X (2018)
Department of Medicine and Surgery, Copyright © by BIOLIFE, s.a.s.
University of Insubria, Via Piatti, 10, This publication and/or article is for individual use only and may not be further
reproduced without written permission from the copyright holder.
21100 Varese, Italy
Unauthorized reproduction may result in financial and other penalties
Tel.: +39.0332-825625 - Fax: +39.0332-825655
e-mail: angelo.tagliabue@uninsubria.it
143(S1) DISCLOSURE: ALL AUTHORS REPORT NO CONFLICTS OF
INTEREST RELEVANT TO THIS ARTICLE.
144 (S1) F. CARINCI ET AL.
to develop on cardiac valves previously damaged,
the mitral valve being its most frequent location,
followed by the aortic and in rare occasions the
pulmonary valve.
The incidence is estimated to be 1 to 5 cases per
100.000 inhabitants (1). It is rare amongst younger
population with the exception of intravenous drug
users. Heart valves, sometimes damaged by diseases
(i.e. a rheumatic heart disease), can frequently be
affected by bacterial endocarditis (BE), although this
disease might equally affect those people suffering
from a congenital heart disease or after undergoing a
valve surgery. Conversely, those people affected by a
non-complex myocardial infarction or having faced
non-complex angioplasties, coronary bypass or
cardiac pacemakers are not likely to risk an infected
endocarditis (IE) (2).
Microbiota of the mouth
The microbiota of the mouth is extremely diverse.
More than 700 bacterial species have been detected
here (3). Half of them are uncultivable so far. The
oral microbiota is not uniform. Specific sites exist in
the mouth such as tongue, palate, cheek, teeth and
periodontal pockets that have its own microbiota
(4). Most of it is located in biofilm on the teeth
and sub-gingivally. In periodontitis bacteria of the
periodontal pocket have easy access to the blood
circulation; this affects about 75% of the population
in the USA, with 20% to 30% having severe forms
(5, 6). It has been suggested that bacteraemia released
daily from periodontitis due to chewing and tooth
brushing can contribute to the cumulative deleterious
inflammatory effects on cardiovascular tissue
causing atherosclerosis and at the end endocarditis.
Oral bacteria and development of endocarditis
Factors involved in the development of a bacterial
endocarditis are difficult to define but a vulnerable
surface (i.e. a damaged endocardium) and a high
bacterial load in the blood seem to be decisive.
Causing microorganisms, in 90% of the cases, are
staphylococcus, streptococcus and enterococcus.
Oral streptococci belongs to viridans group
(streptococcus mutans and streptococcus sanguis)
(7). As they are part of the dental plaque, they can
enter the bloodstream causing bacteraemia through
daily habits like chewing or tooth brushing. Dental
extraction or other dental procedures might cause
bacteraemia as well. Because of dental treatment,
only a small amount of patients contract bacterial
endocarditis. Developing IE in valve disease patients
is statistically 1 every 3000 cases (8).
The role of dental hygiene is also confusing.
Tooth brushing or flossing may increase the risk of
oral streptococcal bacteraemia on a short-term basis,
but may also decrease this risk of IE on a long-term
basis. The development of IE because of everyday-
life bacteraemia may be determined by bacteraemia
characteristics, themselves related to oral hygiene
habits and/or orodental status (9).
Furthermore, a trend toward an increased
incidence of IE in the United Kingdom, after the 2008
National Institute for Health and Care Excellence
guidelines were implemented, was recently reported,
bringing back to the forefront the possible role of
dental procedures in the development of IE (10).
Diagnosis and prognosis
In the presence of infection, tooth-supporting
tissues become highly vascularized and enter an
intimate relationship with microbial bio-film,
increasing the risk of bacteraemia (7, 11, 12).
Surmounting evidence has indicated that dental
treatment in patients at risk of developing IE could
be beneficial because the elimination and/or control
of acute or chronic oral infections can reduce the
source of microorganisms and consequently the
likelihood of bacteraemia. However, the costs and
benefits of dental intervention prior to cardiac valve
surgery (CVS) have not been well-defined (13).
Additional risk factors include genetic
susceptibility, tobacco smoke, alcohol use and
systemic conditions such as diabetes, osteoporosis,
malnutrition and stress. Effective treatment of
periodontal infections is important to reduce local
inflammation and bacteraemia (14-21). In addition,
poor periodontal health appears to increase the risk
of cardiovascular disease, pulmonary disease, and
preterm and low birth weight.
The diagnosis of bacterial endocarditis is based
on four factors: changing murmurs, ECG diagnosing
 Journal of Biological Regulators & Homeostatic Agents
abnormal rhythms of the heart, echocardiography
identifying adenoids and evaluating valve and
heart functions and blood culture. It is essential to
perform blood culture before antibiotic treatment
begins, at half hourly intervals in order to increase
the prospects of positive blood cultures. Without
treatment, bacterial endocarditis is a fatal disease in
30% of the cases. Patient should be sent to a hospital
for intravenous antibiotic therapy (benzylpenicillin
and gentamicin are normally used) (22). Generally,
an extended treatment is needed. For this reason,
programs of home hospitalization service have been
progressively adopted administering antibiotics
intravenously. If staphylococcal endocarditis
is suspected, penicillin could be replaced for
vancomycin. In severe cases like prosthetic valve
endocarditis patients, it might be necessary to replace
the infected valve with a new valve (23).
DISCUSSION
In many countries, there are national guidelines
in order to use antimicrobial prophylaxis having
a bacterial endocarditis condition, in case dental
surgery is needed. The reduction of bacteraemia,
preventing the adherence of bacteria to the
endocardium (24), is the main benefit of the use
of prophylaxis. Nonetheless, the effectiveness of
these guidelines have been questioned by several
authors, publications and societies, such as; the
recommendations published in France in 2002, the
British Society for Antimicrobial Chemotherapy
(BSAC) in England (2006), the American Heart
Association (AHA) in 2007 and the National Institute
for Health and Clinical Excellence (NICE) in the
UK in 2008. Finally, these guidelines have been
questioned also by Australian recommendations in
2008 and the European Society of Cardiology (ESC)
in 2009 (25).
The literature indicates that most cases of infective
endocarditis are not related to procedures (26). Eykyn
(27) stated that it is becoming increasingly clear that
poor dental hygiene rather than dental procedures
are responsible for most, if not all, cases of viridans
streptococcal endocarditis.
In the study by Pogrel and Welsby (28), oral
(S1) 145
sepsis was associated with infective endocarditis
in 12% of cases. Guntheroth (29) pointed out that
bacteraemia was found in 11% of patients with oral
sepsis and no intervention.
Minimizing the occurrence of postoperative
bacteraemia has been considered the most important
factor in the prevention of IE, and the results of several
clinical studies using conventional blood culture
systems have demonstrated a marked reduction
in bacteraemia following dental extraction with
the use of antibiotic prophylaxis. In recent studies
using lysing and filtration of blood, prophylactic
administration of penicillin V, amoxicillin,
erythromycin, clindamycin, or cefaclor did not
reduce the incidence or the magnitude of bacteraemia
after dental extraction, as compared to placebo (30).
The antimicrobial mechanism of protection for IE is
apparently different from a mere killing in blood. The
implications of this for prophylaxis for IE in humans
is still not fully understood, but studies of animals
suggests that the protective effect may be exerted
by inhibiting bacterial growth on the vegetation,
thus allowing host defence mechanisms to gradually
eliminate the bacteria from the valves (31).
Long-standing oral disease prevention protocols
reduce the risk of developing periodontal disease (
32). Data suggest that methods used to prevent cases
of IE that originate from oral bacteria should focus on
improving oral hygiene and reducing or eliminating
gingivitis, which should reduce the incidence of
bacteraemia after tooth-brushing and the need
to extract teeth owing to periodontal disease and
caries. These findings also may provide measures by
which physicians and dentists can monitor the risk
of developing IE from oral pathogens by means of
both patient histories (assessment of bleeding with
tooth-brushing) and clinical examinations (general
assessment of plaque and calculus). Although a large
clinical study would be necessary to substantiate this
claim, our data suggest that maintenance of optimal
oral hygiene and the absence of gingival disease
should result in fewer cases of IE.
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