An Oral Amoxicillin-Clavulanate Regimen to Prevent Bacteremia Following Dental Procedures

An Oral Amoxicillin-Clavulanate Regimen to Prevent Bacteremia Following

Although controversy exists regarding the efficacy of antibiotic prophylaxis for patients at risk of infective endocarditis, expert committees continue to publish recommendations for antibiotic prophylactic regimens. Recently, the investigators have evaluated the efficacy of the intravenous administration of 1000/200 mg of amoxicillin/clavulanate for the prevention of bacteraemia following dental extractions. The results of this study suggest that is highly effective, and that it might be considered a first-line choice for patients at high-risk for infective endocarditis who undergo dental procedures and for whom antimicrobial prophylaxis is recommended. This new project aims to evaluate the effectiveness of oral amoxicillin/clavulanate in preventing post-dental extraction bloodstream infection.

Study Overview

• Status: Terminated
• Conditions: Endocarditis; Bacteraemia
• Intervention / Treatment: Drug: Amoxicillin; Drug: Amoxicillin-Potassium Clavulanate

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 oral amoxicillin-clavulanate (AMX-CLV) 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 or CLV; any type of congenital or acquired immunodeficiency; or any known risk factor for bacterial endocarditis. By applying these criteria, 150 patients will be selected and will be randomly distributed into 3 study groups: control group (receiving no prophylaxis), AMX-CLV group (receiving 2 g/125 mg oral AMX-CLV), and AMX group (receiving 2 g oral AMX).

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.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • A Coruña
    • Santiago de Compostela, A Coruña, Spain, 15782
      • Hospital Clinico Universitario de Santiago
  • Coruña
    • Santiago de Compostela, Coruña, Spain, 15782
      • Santiago de Compostela University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control; Receiving no prophylaxis
Active Comparator: Amoxicillin; Receiving 2 gr oral Amoxicillin before any dental manipulation and following endotracheal intubation Intervention: Drug: Amoxicillin	Drug: Amoxicillin; Receiving 2 gr oral Amoxicillin before dental any manipulation and following endotracheal intubation; Other Names: Amoxicillin (generic drug)
Experimental: Amoxicillin-Potassium Clavulanate; Receiving 2gr/125 mg oral Amoxicillin-Potassium Clavulanate before any dental manipulation and following endotracheal intubation Intervention: Drug: Amoxicillin-Potassium Clavulanate	Drug: Amoxicillin-Potassium Clavulanate; Receiving 2 gr/125 mg oral Amoxicillin-Potassium Clavulanate before any dental manipulation and following endotracheal intubation Intervention: Drug: Amoxicillin-Potassium Clavulanate; Other Names: Amoxicillin-Potassium Clavulanate (generic drug)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bacteremia in participants receiving a prophylactic dosage with oral amoxicillin-clavulanate	Positive cultures	Changes from baseline in prevalence of bacteremia at 30 seconds, 15 minutes and 1 hour after the final dent

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bacteremia in participants receiving a prophylactic dosage with oral amoxicillin	Positive cultures	Changes from baseline in prevalence of bacteremia at 30 seconds, 15 minutes and 1 hour after the final dental extraction
Bacteremia in participants receiving no prophylaxis	Positive cultures	Changes from baseline in prevalence of bacteremia at 30 seconds, 15 minutes and 1 hour after the final dental extraction

Collaborators and Investigators

• Sponsor: University of Santiago de Compostela
• Collaborators: Hospital Clinico Universitario de Santiago
• Investigators: Principal Investigator: Pedro Diz, MD, DDS, PhD, Santiago de Compostela University

Publications and helpful links

General Publications

• Diz Dios P. Infective endocarditis prophylaxis. Oral Dis. 2014 May;20(4):325-8. doi: 10.1111/odi.12221. Epub 2014 Jan 13.
• Valdes C, Tomas I, Alvarez M, Limeres J, Medina J, Diz P. The incidence of bacteraemia associated with tracheal intubation. Anaesthesia. 2008 Jun;63(6):588-92. doi: 10.1111/j.1365-2044.2008.05449.x.
• Pineiro A, Tomas I, Blanco J, Alvarez M, Seoane J, Diz P. Bacteraemia following dental implants' placement. Clin Oral Implants Res. 2010 Sep;21(9):913-8. doi: 10.1111/j.1600-0501.2010.01928.x.
• Diz Dios P, Tomas Carmona I, Limeres Posse J, Medina Henriquez J, Fernandez Feijoo J, Alvarez Fernandez M. Comparative efficacies of amoxicillin, clindamycin, and moxifloxacin in prevention of bacteremia following dental extractions. Antimicrob Agents Chemother. 2006 Sep;50(9):2996-3002. doi: 10.1128/AAC.01550-05.
• Limeres Posse J, Alvarez Fernandez M, Fernandez Feijoo J, Medina Henriquez J, Lockhart PB, Chu VH, Diz Dios P. Intravenous amoxicillin/clavulanate for the prevention of bacteraemia following dental procedures: a randomized clinical trial. J Antimicrob Chemother. 2016 Jul;71(7):2022-30. doi: 10.1093/jac/dkw081. Epub 2016 Mar 29.

Study record dates

Study Major Dates

• Study Start (Actual): February 27, 2017
• Primary Completion (Actual): December 1, 2021
• Study Completion (Actual): May 17, 2022

Study Registration Dates

• First Submitted: May 22, 2016
• First Submitted That Met QC Criteria: May 25, 2016
• First Posted (Estimate): May 26, 2016

Study Record Updates

• Last Update Posted (Actual): May 24, 2022
• Last Update Submitted That Met QC Criteria: May 17, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: dentistry; antibiotic prophylaxis; endocarditis; bacteraemia
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Bacterial Infections; Bacterial Infections and Mycoses; Sepsis; Bacteremia; Endocarditis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Amoxicillin; Clavulanic Acid; Clavulanic Acids
• Other Study ID Numbers: Univ of Santiago de Compostela

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: IPD will be available on request
• IPD Sharing Time Frame: By the end of the study (for 1 year)
• IPD Sharing Access Criteria: On request
• IPD Sharing Supporting Information Type: Study Protocol; Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No