A New Antibiotic Prophylaxis Regimen to Prevent Bacteremia Following Dental Procedures

Study Overview
=================
Brief Summary
-----------------
The aim of this study is to evaluate the efficacy of prophylactic dosage with amoxicillin (AMX), amoxicillin-clavulanate (AMX-CLV), and a combination of amoxicillin-clavulanate and a chlorhexidine mouthwash (AMX-CLV-CHX) in the prevention of bacteremia following dental extractions. The study hypothesis is that an antimicrobial regimen with amoxicillin-clavulanate will show higher effectiveness in reducing the prevalence and duration of bacteremia following dental extractions, than that achieved with the classical amoxicillin regimen.

Detailed Description
-----------------
PURPOSE: Despite the controversy about the risk of developing bacterial endocarditis of oral origin, numerous Expert Committees in different countries continue to publish prophylactic regimens. To date, the literature is unclear about the role of antimicrobial prophylaxis in the prevention of bacteremia following dental procedures. The aim of this study is to evaluate the efficacy of prophylactic dosage with amoxicillin (AMX), amoxicillin-clavulanate (AMX-CLV), and a combination of amoxicillin-clavulanate and a CHX mouthwash (AMX-CLV-CHX) in the prevention of bacteremia following dental extractions. SELECTION OF THE STUDY GROUP AND STUDY DESIGN: The study group will comprise patients who, for behavioral reasons (autism, learning disabilities, phobias, etc.), will undergo dental extractions under general anesthesia in the Santiago de Compostela University Hospital (Santiago de Compostela, Spain). The following exclusion criteria will be applied: age under 18 years; body weight under 40 kg; receipt of antibiotics in the previous 3 months; routine use of oral antiseptics; a history of allergy or intolerance to AMX, CHX or AMX-CLV; any type of congenital or acquired immunodeficiency; or any known risk factor for bacterial endocarditis. By applying these criteria, 200 patients will be selected and will be randomly distributed into 5 study groups: control group (receiving no prophylaxis), AMX group (receiving 2 g AMX i.v.), AMX-CLV group (receiving 1000/200mg AMX-CLV i.v.), CHX group (receiving a single 0.2% CHX mouthwash for 30 seconds), and AMX-CLV-CHX group (receiving 1000/200mg AMX-CLV i.v. and a single 0.2% CHX mouthwash for 30 seconds). COLLECTION OF SAMPLES FOR BLOOD CULTURE: To determine the prevalence of bacteremia, a peripheral venous blood sample (10 ml) will be drawn from each patient at the baseline (before any dental manipulation but after nasotracheal intubation) and 30 s, 15 min, and 1 h after the final dental extraction. Samples will be inoculated in BACTEC plus (Becton Dickinson and Company, Sparks, MD) aerobic and anaerobic blood culture bottles, and will be processed in the Bactec 9240 (Becton Dickinson). MICROBIOLOGICAL ANALYSIS OF BLOOD CULTURES: A Gram stain will be performed on each positive blood culture. The positive blood cultures in the aerobic media will be subcultured on blood agar and chocolate agar in an atmosphere of 5 to 10% carbon monoxide and on MacConkey agar under aerobic conditions. The same protocol will be used for the positive blood cultures in the anaerobic media, with subculture on Schaedler agar and incubation in an anaerobic atmosphere. The bacteria isolated will be identified by using the battery of biochemical tests provided with the Vitek system for Gram-positive bacteria, Neisseria spp., Haemophilus spp., and obligate anaerobic bacteria. The viridans group streptococci will be classified into five groups, the Streptococcus mitis, S. anginosus, S. salivarius, S. mutans, and S. bovis groups, by applying the Ruoff criteria. Facklam's criteria will be used to identify unusual Streptococcus spp. and other gram-positive cocci in chains. The subculture and further identification of the isolated bacteria will be performed by conventional microbiological techniques. The collection, handling, and transport of the blood samples for blood culture will be performed according to the recommendations of the Spanish Society of Infectious Diseases and Clinical Microbiology. .

Official Title
-----------------
A New Antibiotic Prophylaxis Regimen to Prevent Bacteremia Following Dental Procedures

Conditions
-----------------
Bacteremia

Intervention / Treatment
-----------------
* Drug: Amoxicillin-Potassium Clavulanate
* Drug: Amoxicillin
* Drug: Chlorhexidine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects must have at least 10 teeth Subjects must have the need for a dental extraction under general anesthesia (for behavioral reasons) Subjects will be recruited regardless of the extent and severity of their dental and/or periodontal disease Exclusion Criteria: Age under 18 years Body weight under 40 kg Receipt of antibiotics in the previous 3 months Routine use of oral antiseptics A history of allergy or intolerance to amoxicillin A history of allergy or intolerance to chlorhexidine A history of allergy or intolerance to amoxicillin-clavulanate Any type of congenital or acquired immunodeficiency Any known risk factor for bacterial endocarditis Any known risk factor for prolonged bleeding

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control<br>Receiving no prophylaxis | |
| Active Comparator: Amoxicillin<br>Receiving 2 g Amoxicillin intravenously before any dental manipulation and following endotracheal intubation | Drug: Amoxicillin<br>* Administer Amoxicillin following endotracheal intubation prior to single tooth-extraction<br>* Other names: AMOXICILINA SANDOZ EFG (code 694688);|
| Experimental: Amoxicillin-Potassium Clavulanate<br>Receiving 1000/200mg Amoxicillin-Potassium Clavulanate i.v. before any dental manipulation and following endotracheal intubation | Drug: Amoxicillin-Potassium Clavulanate<br>* Administer Amoxicillin-Potassium Clavulanate following endotracheal intubation prior to single tooth-extraction<br>* Other names: AMOXICILINA + ACIDO CLAVULANICO SANDOZ EFG (code 600144);|
| Active Comparator: Chlorhexidine (CHX)<br>Receiving a single 0.2% Chlorhexidine (CHX) mouthwash for 30 seconds before any dental manipulation and following endotracheal intubation | Drug: Chlorhexidine<br>* Administer Chlorhexidine Digluconate following endotracheal intubation prior to single tooth extraction<br>* Other names: Oraldine Perio (code 375725);|
| Experimental: Amoxicillin-Potassium Clavulanate-CHX<br>Receiving 1000/200mg Amoxicillin-Potassium Clavulanate i.v. and a single 0.2% Chlorhexidine (CHX) mouthwash for 30 seconds before any dental manipulation and following endotracheal intubation | Drug: Amoxicillin-Potassium Clavulanate<br>* Administer Amoxicillin-Potassium Clavulanate following endotracheal intubation prior to single tooth-extraction<br>* Other names: AMOXICILINA + ACIDO CLAVULANICO SANDOZ EFG (code 600144);Drug: Chlorhexidine<br>* Administer Chlorhexidine Digluconate following endotracheal intubation prior to single tooth extraction<br>* Other names: Oraldine Perio (code 375725);|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants receiving a prophylactic dosage with amoxicillin-clavulanate i.v. with bacteremia following dental extractions | Percentage of participants receiving a prophylactic dosage with amoxicillin-clavulanate i.v. with bacteremia confirmed by microbiological analysis at 30 seconds, 15 minutes and 1 hour after the final dental extraction | Changes from baseline in prevalence of bacteremia at 30 seconds, 15 minutes and 1 hour after the final dental extraction | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants receiving a prophylactic dosage with amoxicillin i.v. (following the American Heart Association´s guidelines) with bacteremia after dental extractions | Percentage of participants receiving a prophylactic dosage with amoxicillin i.v. with bacteremia confirmed by microbiological analysis at 30 seconds, 15 minutes and 1 hour after the final dental extraction | Changes from baseline in prevalence of bacteremia at 30 seconds, 15 minutes and 1 hour after the final dental extraction | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
bacteremia, prophylaxis, antibiotics, dentistry