Clinical trial NCT02783404: An Oral Amoxicillin-Clavulanate Regimen to Prevent Bacteremia Following Dental Procedures
Official title: An Oral Amoxicillin-Clavulanate Regimen to Prevent Bacteremia Following
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Bacteraemia
Endocarditis
Keywords: bacteraemia
endocarditis
antibiotic prophylaxis
dentistry
Lead sponsor: University of Santiago de Compostela
Sponsor class: OTHER
Collaborators: name: Hospital Clinico Universitario de Santiago
First posted: 2016-05-26
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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.

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

Primary outcomes:
measure: Bacteremia in participants receiving a prophylactic dosage with oral amoxicillin-clavulanate
timeFrame: Changes from baseline in prevalence of bacteremia at 30 seconds, 15 minutes and 1 hour after the final dent
Secondary outcomes:
measure: Bacteremia in participants receiving a prophylactic dosage with oral amoxicillin
timeFrame: Changes from baseline in prevalence of bacteremia at 30 seconds, 15 minutes and 1 hour after the final dental extraction
measure: Bacteremia in participants receiving no prophylaxis
timeFrame: Changes from baseline in prevalence of bacteremia at 30 seconds, 15 minutes and 1 hour after the final dental extraction
Other outcomes:
Locations:
city: Santiago de Compostela
country: Spain
facility: Hospital Clinico Universitario de Santiago
state: A Coruña
city: Santiago de Compostela
country: Spain
facility: Santiago de Compostela University Hospital
state: Coruña
Study officials:
affiliation: Santiago de Compostela University
name: Pedro Diz, MD, DDS, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Diz Dios P. Infective endocarditis prophylaxis. Oral Dis. 2014 May;20(4):325-8. doi: 10.1111/odi.12221. Epub 2014 Jan 13.
citation: 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.
citation: 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.
citation: 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.
citation: 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.