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Prophylaxis of dental infectious endocarditis

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					                                    PROPHYLAXIS OF DENTAL
                                   INFECTIOUS ENDOCARDITIS
                                                        Philippe CHOUSSAT*



                      INTRODUCTION                                   dures or surgery or dental treatments (scaling, endo-
                                                                     dontic treatment or dental extraction) or even brus-
Infectious endocarditis can be defined as fixation and               hing teeth and chewing.
multiplication of an offending microbial agent on the
endocardium resulting in fever and va l v u l a r                    A normal endocardium is resistant to bacteria bonding.
vegetations. This disease develops after bacteremia                  When the endothelium is damaged (trauma due to
originating from distant sites such gums or gastro-                  t u r bulence of flow caused by an underlying heart
intestinal or genitourinary systems. Even if mortality of            disease), a sterile fibrin-platelet growth will develop and
b a c t e rial endocarditis has decreased by 50%, the                allow germs to settle down. Then the cluster of growing
lethality stay at about 20% (4 ; 8).                                 bacteria constitute vegetations on the heart valves or
Despite recommendations of experts (3 ; 8), practi-                  on the lining of the heart and of the blood v essels.
cing dentists not always respect antibiotics choice,                 Bacterial colonies are then covered by more fibrin and
dosage and duration of antibioprophylaxis (12 ; 5).                  platelets which inhibit the reaction of the immune sytem
                                                                     by obstructing the passage the plexus of fibrin and take
                         ETIOLOGY                                    effect on the micro-organisms.

Numerous bacterial species as well as fungal                         The risk of endocarditis (probality of bacterial fixation)
organisms generate infectious endocarditis, b u t                    is related to :
S t a p hylococcus and Streptococcus species are                     - the intensity and frequenct of bacteremia
accountable for about 80% reported cases (4).                        - the ability of bacterial species to bind to the
• A p a rt from intravenous drug abu s e r s, the most                   endothelium
    common etiology is a common mouth micro                          - the expanse of the endothelial lesions.
    organism, Streptococcus Viridans, accounting for
    27% of cases (4). In oral flora we can found five                                  CLINICAL FORMS
    different Streptococcus Viridans species : S. mitis ;
    S. sanguis ; S. sanginosus ; S. mutans ; S. salivarius.          We can define three categories based upon the span
    The dental portal of entry account for nearly 25% of             of the disease, the symptoms and the complications :
    the occurrence (4).                                              - chronic (micro-organisms like LEGIONELLA and
• For the right sided vegetations (often intravenous                    BRUCELLA)
    drug abusers), Staphylococcus Aureus is the most                 - acute
    common germ (18,5% (4) of the total cases).                      - subacute
• Prosthetic Valve Endocarditis (PVE) has a different
    incidence rate from the other non-addict infectious              Acute infectious endocarditis are principally due to
    endocarditis population. Bacteria species found in :             Staphylococcus Aureus and Streptococcus Viridans
    - early prosthetic valve endocarditis : S. epidermi-             (14) :
       dis 33% (early : onset within 2 months of surgery)            • intravenous drug addict
    - late prosthetic valve endocarditis : S. Viridans               • patient in intensive care
       30% and S. epidermidis 29%.                                   • patient which undergo lately cardiac surgery.

                      PATHOGENESIS                                   Prosthetic va l ves endocarditis is associated with
                                                                     Staphylococcus Epidermidis and with Streptococcus
Transient massive bacteremia occur after upper                       V i ri d a n s. The prognosis for acute infectious endo-
respiratory, urologic or lower gastrointestinal proce-               carditis is severe (2, 3, 14).
* Assitant hospitalo-universitaire - Service d’Odontologie de Bor-   In the matter of subacute endocarditis, two cases may
deaux - Hôpital Xavier ARNOZAN - 33 PESSAC - FRANCE                  occur :
                                                                                                         Odonto-Stomatologie Tropicale
           Prophylaxis of dental…


• the portal of entry is extra-oral : investigations or                                       DIAGNOSIS
  i n t e rventions on genito-ur i n a ry system or on
  digestive tractus or on gynecologic system. The                    Diagnosis is made on the basis of three essential
  p rincipal germ discovered is group D strep-                       items :
  tococcus.                                                          • an interrogation (research of fever, weight loss,
• the oral portal of entry may be probable or highly                    dental or surgical procedure preceding the illness,
  p r o b a bl e. Streptococcus Vridans is the most                     underlying heart disease, ...)
                                                                     • blood cultures and identification of the responsible
  frequent germ. Group D streptococcus are found
                                                                        germ
  infrequently.
                                                                     • e c h o c a r d i o gram : tr a n s t h o racic or pref e ra bly
                                                                        transoesophageal echocardiography
                CLINICAL SIGNS (3 ; 14)
                                                                                             TREATMENT
Symptoms of acute and subacute infectious endo-
carditis are similar but the onset of disease is faster              Medical treatment
for the acute form. Anamnesis will show the following                An antibiotic intravenous ther a py is required to
constitutional symptoms :                                            eradicate the germ. The antibiotic is chosen on the
• low grade fever (<39°C)                                            basis of sensitivity of blood culture. The treatment
                                                                     should be fo l l owed by repeated blood cultures to
• feeling of weakness                                                ensure the antibiotics are taking effect and the
• anorexia and weight loss                                           bacteremia has been terminated.
                                                                     With some Streptococcus species that have become
• exhaustion                                                         penicillin resistant Penicillin must be given with
                                                                     Gentamycin for a longer period of time or Vancomycin
Then the valvular destruction induce valvular regur-                 alone.
gitation, heart failure and pericarditis. Later, systemic
emboli (left-sided lesions) or pulmonic emboli (r ight-              Surgical treatment
sided lesions) can occur with the liberation of a portion            For some specific conditions replacement of the
of the bacterial vegetation into the circulation (14).               damaged heart valves may be indicated.

                           GUIDE FOR THE IDENTIFICATION OF INFECTIOUS RISK RELATED
                                       TO THE CARDIOVASCULAR DISEASE

                              Table 1 : Cardiovascular disease and infectious risk (3 ; 8 ; 10)

Endocarditis Prophylaxis                     Endocarditis Prophylaxis                      Endocarditis Prophylaxis
Highly recommended                           Recommended                                   Not recommended
Significant or Important                     Moderate infectious risk                      Nil infectious risk
infectious risk

• mitral insufficiency                       • mitral stenosis                             • mitral valve prolapse without
 • mitral stenosis after surgical            • Tricuspid insufficiency                        valvular regurgitation
   repair (led to a mitral                   • Tricuspid stenosis                          • Coronary-aortic artery
   insufficiency)                            • pulmonary artery stenosis                   • previous coronary artery
• mitral valve prolapse with                 • aortic coarctation                             bypass graft surgery
   valvular regurgitation                    • FALLOT’S trilogy                            • angina pectoris
 • aortic valve insufficiency                • hypertrophied obstructive                   • myocardial infarction
• aortic valve stenosis                      cardiomyopathy                                • atrial fibrillation
 • bicuspid aortic valve                                                                   • isolated cardiac arrhythmia
• aortic stenosis                                                                          • cardiac pacemaker
 • ventricular sptal defect                                                                • implanted defibrillator



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Endocarditis Prophylaxis                  Endocarditis Prophylaxis                   Endocarditis Prophylaxis
Highly recommended                        Recommended                                Not recommended
Significant or Important                  Moderate infectious risk                   Nil infectious risk
infectious risk

• patent ductus arteriosus                                                           • bronchopulmonary disease at

• FALLOT’S tetralogy                                                                   origin of a cardiopathy

• prosthetic cardiac valves                                                          • diseases of the pericardium

   (including heterograft,                                                           • dilated cardiopathy

   homograft or synthetic valves)                                                    • arteritis

• recent cardiovascular surgery                                                      • phlebitis

   (less than 6 months)                                                              • isolated arterial hypertension

• acute rheumatic fever with                                                         • isolated secundum atrial septal

   valvular dysfunction                                                                defect

• previous infecious                                                                 • physiologic, functional, or

   endocarditis                                                                        innocent heart murmurs

• cardiac transplantation                                                            • previous KAWASAKI disease

   (insufficient data to sustain                                                       without valvular dysfunction

   recommendations)                                                                  • previous rheumatic fever

                                                                                       without valvular dysfunction
An important infectious risk remains after surgical              For ethic reason, no clinical controlled assay of the
repair of a ventricular septal defect when a residual            effect of antibiotics in preventing bacterial endocarditis
shunt persists. On the contrary, the infectious risk             has been done. The estimation of efficacy of antibiotic
became nil 6 months after surgical repair without                prophylaxis in relation with the infectious risk and of the
residua of ventricular septal defect or patent ductus            gesture accomplished and of the antibiotic regimen is
arteriosus.                                                      highly variable (3 to 91% of efficacy) (6). The recom-
                                                                 mended prophylactic regimen are based on in vitro
                  ANTIBIOPROPHYLAXIS                             assays, animal tests and clinical data.

For patients at risk for developing endocarditis, pro-           Tables 2 and 3 below described the guidelines for
p hylactic antibiotics must be prescribed before any             prophylactic regimen for oral and dental procedures in
procedure likely to induce bacteremia (3, 6, 8). To reach        patients who are at risk. These recommendations are
an antibiotics bactericidal concentration in the serum           adapted from the French Society of Infectious Patho-
d u ring bacteremia and to avoid the emergence of                logy (8) and from the American Heart Association (3)
microbial resistance, the antibiotic treatment should be         and approved by the American Dental Association.
started 1 to 2 hours before the act. Antibiotics should          The second half dose six hours after the first one is
not be continued for more than 6 to 8 hours (3, 8).              not recommended by the French Society of Infectious
Streptococcus viridans is the commonest responsible              Pathology for the antibioprophylactic oral regimen for
for dental bacterial subacute endocarditis. Tetracycli-          dental procedures (8).
nes and sulfonamides should not use for dental endo-
carditis prophylaxis. Amoxicillin, Penicillin V and Ampi-        Patients with previous rheumatism fever have
cillin are active against Streptococci. Better intestinal        c o n t i nuously an anti-streptococcus antibiotic cov e r.
a b s o r ption and high sustained serum level made              Among this population, antibiotic resistant species
Amoxicillin the most effective antibiotic for prophylaxis.       appears. So it is necessary to give a different antibiotic
Patients who are allergic to penicillins could be treated        from the usual bacteria killing drug. These patients
by Erythromycin (3), or by Clincamycin (3 ; 8).                  must be treated like penicillin allergic patients (9).


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                         Table 2 : Antibioprophylactic oral regimen for dental procedures (3 ; 8)
                          Antibiotic    Dosing regimen                                Pediatic doses
                                        Oral regimens
Standard oral             Amoxicillin   3 g orally 1 h before procedure               Orally 1 h before 50 mg/kg
Regimen                                 then 1,5 g 6 h after the first dose (3)       then 25 mg/kg 6 h after the first dose (3)
                                        3 g orally 1 h before procedure (8)           or
                                                                                      < 15 kg : 750 mg (then 375 mg)
                                                                                      15 to 30 kg : 1500 mg (then 750 mg)
                                                                                      > 30 kg : 3000 mg (adult dose) (then 1500 mg)
Oral regimen for         Erythromycin   Erythromycin ethylsuccinate                   20 mg/kg orally 2 h before then
amoxicillin /                           800 mg orally 2 h before the act              10 mg/kg 6 h after initial dose (3)
penicillin allergic                     then 400 mg 6 h after initial dose (3)
patients                                or
                                        Erythromycin stearate 1000 mg
                                        orally 2 h before the act then 500 mg
                                        6 h after initial dose (3)


Oral regimen for        Clindamycine    300 mg orally 2 h before the act then         10 mg/kg then 5 mg/kg 6 h after
amoxicillin and/or                      500 mg 6 h after initial dose (3)             initial dose (3)
penicillin allergic                     600 mg orally 1 h before (8)
patients

                      Table 3 : Antibioprophylactic parenteral regimen for dental procedures (3 ; 8)

                          Antibiotic    Dosing regimen                                                   Pediatric doses

                                        Parenteral regimens
                                        Intravenous (IV) or Intramuscular (IM)

Standard                  Ampicillin    2 g IV or IM administration 30 min before the act, then          50 mg/kg then 25 mg/kg (3)
Parenteral Regimen                      1 g IV or IM administration 6 h after initial dose (3)
                                        or
                                        2 g IV or IM administration 30 min before the act then,
                                        1,5 g orally 6 h after initial dose (3)

Standard                  Amoxicillin   2 g IV or IM administration 30 min before the
Parenteral Regimen                      act then 1 g orally 6 h after initial dose (8)

Amoxicillin /            Clindamycin    300 mg IV administration 30 min before the act, then             10 mg/kg then 5 mg/kg (3)
Penicillin allergic                     150 mg IV administration 6 h after initial dose (3)
patients                                or
                                        300 mg IV administration 30 min before the act, then
                                        150 mg 6 h orally after initial dose (3)

High risk patients        Ampicillin    2 g Ampicillin and 1,5 mg/kg of Gentamycin (not to               Ampicillin : 50mg/kg (3)
                         Gentamycin      exceed 80 mg) IV or IM administration 30 min.before             Gentamycin : 20 mg/kg (3)
                         Amoxicillin    the act, then 1,5 g Amoxicillinorally after initial dose (3)     Amoxicillin : 25 mg/kg (3)
                                        or
                                        2 g Ampicillin and 1,5 mg/kg of Gentamycin (not to
                                        exceed 80 mg) IV or IM administration 30 min. before
                                        the act, then 8 h after initial dose 2 g Ampicillin and
                                        1,5 mg/kg Gentamycin IV or IM administration (3)

High risk patients       Vancomycin     1 g IV during 1 h, starting 1 h before the act                   20 mg/kg (3)
and amoxicillin/                        no second dose necessary (3 ; 8)
penicillin allergic



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              Prophylaxis of dental…


 PRINCIPLES OF PROPHYLAXIS OF INFECTIOUS
                                                                       Important infectious risk
Endocarditis                                                           C o n s e rvation of vital tooth and tooth presenting
• Tooth decay, mortal tooth, insufficient canal filling,               superficial decay is desirable.
  periapical lesion (granuloma, dental cyst, abscess),                 • If no valvular surgery is planned, the endodontically
  periodontitis, antral cyst, gingival inflammation or                    teeth treated more than one year before, showing
  loss of teeth support lead to bacteremia, even                          no clinical sign and no radiologic sign (dense canal
  without a therapeutic action. These sources of                          filling up to the apex, absence of postendodontic
  infection should be eliminated (without starting an                     periapical radiolucencie) could be kept (2 ; 8 ; 11).
  infectious endocarditis) (11 ; 13).                                  • In case of a valvular surgery planned, only the vital
• Frequent dental check ups, fluoridation and oral                        teeth exhibiting no periodontal lesion should be
  hygiene allow to reduce necessity of urgent treat-                      kept. No endodontic treatment or renewal even
  ment (13)                                                               with apicectomy should be done (8 ; 11).
• F i ve minutes before eve ry dental care, a local
  disinfection with chlorhexidine would significantly                  Moderate infectious risk
  reduce bacteremia (1 ; 13).                                          Vital teeth or teeth with superficial tooth decay or endo-
• If a teeth should be devitalized, it must be done                    dontically well-treated teeth displaying no clinical and
  with a rubbler dam in a single session (7).                          no radiological sign should be kept (2 ; 8 ; 8 ; 11).
• Fixed dental prosthesis on vital tooth can be done.                  Difficulty appears with endodontically treated teeth
• Removable dental prosthese are recommended.                          without clinical and radiolgoical sign but e x h i b i t i n g
  They should fit correctly and if they result in lesion               insufficient root canal filling (periapical radiolucencie).
  of oral mucosa, the wearing should be delayed.                       Thes teeth represent potential dental infectious sour-
• Unerupted teeth totally impacted in bone could be                    ces. Avulsion may be discussed in function of dental
  kept (7 ; 11).                                                       a n a t o my, strategic position of tooth (bridge), dental
• Endosseous implants and periodontal surgery are                      hy g i e n e, possibility of a renewal of the endodontic
  not endorsed (1 ; 8).                                                treatment. For a single-rooted teeth : renewal of the
                                                                       endodontic treatment associate with apicectomy. Dental
Procedure to be followed for a check-up                                ex t raction are recommended (but renewal of the
An oral check-up had to be done after the diagnosis                    endodontic treatment is possible) for pluriradicular-
of a cardiovascular illness with an infectious risk.                   rooted teeth.
                                          Table 4 : Guidelines for a dental exam

                                                              CHECK-UP
                           Significant or important infectious risk         Moderate infectious risk
 Vital tooth               Conservation (if no periodontal infection)       Conservation
 Endodontically treated    Conservation of all endodontically well-         Endodontically well-treated teeth : conservation of all
 tooth and no valvular     treated teeth for more than one year,            teeth which show no clinical and radiographic sign
 surgery planned           with a root canal filling up to the apex,        insufficient root canal filling : renewal of endodontic
                           showing no clinical and radiographic sign        treatment and/or apicectomy (this should be discuss
                                                                            with the patient in function of each situation)
 Endodontically treated    Extraction of all non-vital and/or               Extraction of all non-vital and/or periodontal infected
 tooth and valvular        periodontal infected teeth                       teeth
 surgery planned
 Residual root or apex     Extraction                                       Extraction
 Gingivitis                If significant gingivitis : extraction of        Conservation
                           affected teeth possible
 Periodontitis             Extraction of affected teeth                     Conservation if unimportant periodontitis
                           affected teeth possible
Periodontosis              Extraction of affected teeth possible            Conservation
Unerupted teeth            Conservation (if not impacted)                   Conservation (if not impacted)



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     PROCEDURE TO BE FOLLOWED FOR ORAL                                  In the case, antibiotics should be replaced (Amoxicillin
           AND DENTALTREATMENTS                                         then Clindamycin for example).
                                                                        If there is no urgency, a delay will be respected after a
Communication between the dentist and the regular                       c a r d i ovascular accident and after a cardiov a s c u l a r
doctor and the cardiologist enables to consider a                       operation before carrying out dental care.
c a r d i ovascular illness, the f o l l owed treatments and            If prognosis or quality of a conservative treatment are
possibly a previous or future surgical operation.                       u n c e rtain an ex t raction should be conducted. Intra -
An epidemiological investigation showed that the risk of                ligamentary anesthesia should be avoid : the passage
d eveloping an infectious endocarditis raise with the                   through septic sulcus is a source of infectious risk. Five
number of act during the three last months prior to the                 minutes before an operation, a disinfection of oral cavit
endocarditis occurring. When sev e ral acts must be                     by the mean of a mouth washes (possibly completed by
done, they should be planned for a single appointment                   an irrigation to gingival sulcus with chlorhexidine) will
or spread out over a duration longer than one week (8).                 decrease bacteremia (1, 13).
                                Table 5 : Guidelines for dental treatment (2 , 7 , 8 , 11)

 Dental disorders and         Important infectious risk                        Moderate infectious risk
 treatment

 * Superficial tooth decay    Conservative treatment                           Conservative treatment

 * Deep tooth decay           Extraction if vitality is threaten               Conservative treatment

 * Pulpitis                   Extraction                                       for single-rooted tooth : root canal filling (in a single
 * Pulpless tooth                                                              session, with antibiotics)
 * Crown fracture with                                                         for multiple-rooted tooth : root canal appropriate
   pulpal lesion                                                                (or root canal filling conceivable)

 * Granuloma                  Extraction of the aching tooth                   for single-rooted tooth : root canal
 * Periodontitis                                                               filling associate with an apicectomy (in a single
 * Cellutitis                                                                  session, with antibiotics) for multiple-rooted tooth :
                                                                               extraction appropriate

 *   Dental cyst              Extraction of the liable tooth                   Extraction of the liable tooth
 *   Abscess
 *   Fistula
 *   Osteitis
 *   Antral cyst

 * Partial dental avulsion    Extraction                                       Splinting associate with antibiotics

 * Total dental avulsion      Extraction (no re-implantation)                  Extraction (no re-implantation)

 * Problems with the          Extraction of the liable tooth                   Extraction of the liable tooth
   eruption of wisdom teeth

 * Local anesthesia           avoid intra-ligamentary anesthesia               Avoid intra-ligamentary anesthesia

 * Crown on vital tooth       Contraindicated                                  Feasible
   root filled

 * Bonded bridge              Appropriate                                      Appropriate

 * Removable dental           Appropriate                                      Appropriate
   prostheses

 * Scaling                    Appropriate with antibiotics                     Appriate with antibiotics

 * Gingivectomy               Contraindicated                                  Feasible with antibiotics

 * Endo-osseous implant       Contraindicated                                  Contraindicated


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            Prophylaxis of dental…


                       CONCLUSION                                         endocarditis every year (2, 12).
                                                                          The infectious risks due to dental extractions seem to
With an efficacy assessed at 50%, antibioprophylaxis                      receive more systematic antibiotic cover than scalings
for cardiac patients who undergo some dental treat-                       and endodontic treatments (5).
ment, could probably avoid 5 to 10% of inf e c t i o u s

                                                               SUMMARY

 Infectious endocarditis develops after bacteremia originating from distant sites such gums or tooth. Despite
 recommendations of experts, dentists not always respect antibiotics choice, dosage and duration of
 antibioprophylaxis. This paper will emphasize on the identification of infectious risk in function of the
 cardiovascular disease and on antibiotics dosage for prophylaxis to be followed. In conclusion, we will
 review procedure to comply for oral and dental treatments.
 Key words : Infectious endocarditis ; antibioprophylaxis ; cardiac patients.

                                                                RESUME
                              Prophylaxie des endocardites infectieuses d’origine dentaire

 Les endocardites infectieuses se développent à la suite de bactériémie de source gingivale ou dentaire.
 Malgré les recommandations des experts, les dentistes ne respectent pas toujours le choix, la posologie et
 la durée de l’antibioprophylaxie. Cet article met l’accent sur l’identification du risque infectieux en fonction
 de la pathologie cardiaque et sur la posologie de l’antibiopr o p hylaxie à suivre. En conclusion nous
 soulignons les principes à observer lors des traitements dentaires.
 Mots clés : Endocardites infectieuses ; antibioprophylaxie ; patients cardiaques.

                                                           BIBLIOGRAPHY
1. M.L. BOY-LEFEBRE.                                                      8. JURY CONFERENCE DE CONSENSUS.
Manoeuvres et foyers bucco-dentaires à risque d’endocardite               Conférence de consensus en thérapeutique anti-infectieuse 5/Paris
infectieuse.                                                              FRA/1992-03-27.
Méd. Mal. Infect ; 22, Spécial : 1023 à 1030, 1192.                       Médecine et maladies infectieuses ; vol. 22 ; 12, pp. 1031-1040, 92.
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RAGOT, M.L. BOY LEFEVRE, L. MAMAN, M. SAPANET.                            Prévention du rhymatisme articulaire aigu.
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                                                                          10,5/07/95.
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S.T. SHULMAN, C. WATANAKUNAKORN, K.A. TAUBERT.                            Méd. Mal. Infect ; 22, Spécial : 993 à 1001, 1992.
Prevention of bacterial endocarditis - Recommendations by the             11. JP. RAGOT.
American heart Association.                                               Manoeuvres et foyers bucco-dentaires à risque d’endocardite
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http : / / www. http : // www. amhrt. org/pubs/scipub/endoasc.htm.        (Prophylaxis of infective endocarditis).
4. F. DELAHAYE, V. GOULET, F. LACASSIN, R. ECOCHARD, C.                   Société de pathologie infectieuse. (SPILF). Conférence de consensus
SUTY-SELTON, B. HOEN, J. ETIENNE, S. BRIANCON, C. LEPORT.                 en thérapeutique anti-infectieuse/5/Paris FRA/1992-03-27.
Epidémiologie de l’endocardite infectieuse en France en 1991 -            Médecine et maladies infectieuses ; vol. 22 ; 12, pp. 1031-1040.
Arch. Mal. Coeur, 86, 1801-1806, 1993.                                    12. D. SADOWSKY, C; KUNZEL.
5. Y. DOMART.                                                             Usual and customary’ practice versus recommendations of experts
Enquête sur la pratique actuelle de l’antibioprophylaxie de               : clinician noncompliance in the prevention of bacterial endocarditis.
l’endocardite infectieuse par des dentistes.
                                                                          J. Am. Dent. Assoc. 1989, 118, 175-180.
Méd. Mal. Infect ; Spécial : 1092 à 1098, 1992.
                                                                          13. A.A. TZUKERT, E. LEVINER, M. SELA.
6. T.F. DOMART.
Does prophylaxis prevent postdental infective endocarditis ? A            Prevention of infective endocarditis : not by antibiotics alone. A 7
controlled evaluation of protective efficacy.                             years follow-up of dental patients.
The American Journal of medecine, Volume 88, February 1990.               Oral Med. Oral Pathol. 1986, 62 385-687.
7. A. JEAN, O. LABOUX, D. MARION, H. HAMEL, L. LABOUX.                    14. M. VAVRIK.
Odontologie conservatrice et risque oslérien.                             Endocarditis.
Rev. Fr. d’Endo, vol. 7,4, p. 37-54, 1988.                                http : / / www. meddean.luc.edu/develop/mvavrik/endo/htm.


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