Clinical trial NCT02115776: A New Antibiotic Prophylaxis Regimen to Prevent Bacteremia Following Dental Procedures
Official title: A New Antibiotic Prophylaxis Regimen to Prevent Bacteremia Following Dental Procedures
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Bacteremia
Keywords: bacteremia
prophylaxis
antibiotics
dentistry
Lead sponsor: University of Santiago de Compostela
Sponsor class: OTHER
Collaborators: name: Hospital Clinico Universitario de Santiago
First posted: 2014-04-16
Enrollment: 266
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: 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.

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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: Number of participants receiving a prophylactic dosage with amoxicillin-clavulanate i.v. with bacteremia following dental extractions
timeFrame: Changes from baseline in prevalence of bacteremia at 30 seconds, 15 minutes and 1 hour after the final dental extraction
Secondary outcomes:
measure: Number of participants receiving a prophylactic dosage with amoxicillin i.v. (following the American Heart Association´s guidelines) with bacteremia after dental extractions
timeFrame: Changes from baseline in prevalence of bacteremia at 30 seconds, 15 minutes and 1 hour after the final dental extraction
Other outcomes:
measure: Number of control participants with bacteremia following dental extractions under general anesthesia
timeFrame: Changes from baseline in prevalence of bacteremia at 30 seconds, 15 minutes and 1 hour after the final dental extraction
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: Universidad de Santiago (Grupo OMEQUI-2117); Hospital Clínico Universitario de Santiago
name: Pedro Diz, MD,DDS,PhD
role: STUDY_CHAIR
affiliation: Universidad de Santiago (Grupo OMEQUI-2117)
name: Jacobo Limeres, DDS,PhD
role: STUDY_DIRECTOR
affiliation: Universidad de Santiago (Grupo OMEQUI-2117)
name: Javier Alvarez, MD,DDS
role: PRINCIPAL_INVESTIGATOR
affiliation: Universidad de Santiago (Grupo OMEQUI-2117); Hospital Clínico Universitario de Santiago
name: Javier F Feijoo, MD,DDS,PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Universidad de Santiago (Grupo OMEQUI-2117)
name: Marcio Diniz, DDS,PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Universidad de Santiago (Grupo OMEQUI-2117)
name: Mercedes Outumuro, DDS,PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Clínico Universitario de Santiago
name: Juan Medina, MD,Anest,PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Universidad de Santiago (Grupo OMEQUI-2117)
name: Miguel Castro, MD,DDS, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Clínico Universitario de Vigo
name: Maximiliano Alvarez, MD,Micro,PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tomas I, Alvarez M, Limeres J, Potel C, Medina J, Diz P. Prevalence, duration and aetiology of bacteraemia following dental extractions. Oral Dis. 2007 Jan;13(1):56-62. doi: 10.1111/j.1601-0825.2006.01247.x.
citation: Tomas I, Pereira F, Llucian R, Poveda R, Diz P, Bagan JV. Prevalence of bacteraemia following third molar surgery. Oral Dis. 2008 Jan;14(1):89-94. doi: 10.1111/j.1601-0825.2006.01359.x.
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: Tomas I, Diz P, Tobias A, Scully C, Donos N. Periodontal health status and bacteraemia from daily oral activities: systematic review/meta-analysis. J Clin Periodontol. 2012 Mar;39(3):213-28. doi: 10.1111/j.1600-051X.2011.01784.x. Epub 2011 Sep 15.
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: Diz Dios P. Infective endocarditis prophylaxis. Oral Dis. 2014 May;20(4):325-8. doi: 10.1111/odi.12221. Epub 2014 Jan 13.
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.