Evaluation of the Changes in Oral and Gut Bacterial Resistance Caused by Short Term Antibiotic Treatment Following a Surgical Dental Procedure - A Prospective Clinical Study.
试验速览
- 阶段
- 不适用
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Quantification of antibiotic resistance genes by Resistance genes output at each timepoint from HUmanN 1.0 .Validation by QPCR values for Blatem and erm genes at each timepoint.
研究概览
简要总结
The aim of this study is to evaluate the nature of the change in oral and gut bacterial resistance profiles after antibiotic therapy for a surgical procedure in two groups. The intervention group will receive a course of amoxicillin and analgesics after surgical extraction and have bacterial samples taken from saliva, tongue coatings and stool samples at four appointments over a period of six months. This will be compared to the control group which receive only analgesics after the surgical extraction.
An examination of the development and sustainability of antibiotic resistance in the oral and gut microbiome of healthy cohorts will be followed up for 6 months, after surgical extraction of impacted teeth.
Change in proportion of antibiotic resistant bacterial components will be studied using Metagenomic DNA sequencing and quantification of resistant genes .
详细描述
Trial Design This is a prospective, longitudinal, observational, cohort study investigating young adults undergoing surgical extraction of a wisdom tooth with and without antibiotics post-operatively. The prescription of antibiotics will be based on clinical judgment based on case complexity, trauma and length of procedure. No randomization will be performed. Four observational time points will be undertaken for collecting 3 bacterial samples (tongue coating, saliva and stool sample at: baseline, 1 week, 1 month and 6 months.
To survey the extent and persistence of a range of bacterial resistance genes within the oral and gut microbiota of a cohort of systemically healthy young adults before and after the surgical extraction of third molars who receive and do not receive amoxicillin.
Hypothesis It is anticipated that a single course of amoxicillin (250 mg three times daily for five days) prescribed after a surgical tooth extraction, such as an impacted third molar, alters the short-term and long-term antibiotic resistance profile and causes a significant shift in the composition of the oral and gut resistome in a healthy cohort.
From analysis of the bacterial resistance, comparison from the baseline data over time will give insight on the impact of increased antibacterial resistance. Understanding of this should help pave the way for determining guidelines for the rational prescription of antibiotics for dental surgical clinical procedures and so form a basis for antibiotic stewardship as well as determine a potential risk to benefit awareness when prescribing antibiotics.
This baseline data can be followed-up in a longer timeframe to examine the persistence of resistance genes over time in a later study. It is expected a significant number of patients will be from student cohorts at HKU which will make later recall straightforward. Patients will be asked to keep a record log of antibiotic consumption after the initial study that may inform later research.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Men and women aged between 18 and 45 years
- •Subjects who are scheduled to have a surgical tooth extraction.
- •Subjects who have signed an informed consent after being informed of the study design, objectives and, risks/benefits
- •No history of use of antibiotics up to three months prior to participation in the study.
- •No medical condition that prevents the surgical procedure or antibiotic therapy.
- •No history of hypersensitivity to beta lactams.
- •No contraindication to amoxicillin therapy.
- •Subjects are not pregnant or currently breast feeding.
- •No known or suspected immunodeficiency.
排除标准
- •History of antibiotic use within 3 months from baseline evaluation.
- •Any medical condition that prevents the surgical procedure or antibiotic therapy.
- •History of hypersensitivity to beta lactams
- •Contraindication for amoxicillin therapy
- •Pregnant or breast feeding women.
- •Subjects with known or suspected immunodeficiency.
- •Caries active subjects defined as subjects with active caries involving more than 3 teeth.
- •Subjects diagnosed with chronic periodontitis.
- •Subjects regularly using an antibacterial mouth rinse or planning to use one after the extraction.
研究组 & 干预措施
Amoxicillin
No randomization is performed. Patients who are prescribed antibiotics by the clinician performing the tooth extraction ( based on case complexity and intra operative judgement) are recruited into this group.The principal investigator is not involved in the decision to prescribe antibiotics or not.
干预措施: Amoxicillin (Drug)
Amoxicillin
No randomization is performed. Patients who are prescribed antibiotics by the clinician performing the tooth extraction ( based on case complexity and intra operative judgement) are recruited into this group.The principal investigator is not involved in the decision to prescribe antibiotics or not.
干预措施: Extraction (Procedure)
No Amoxicillin
Patients who do not receive antibiotics after extractions are recruited into this group.
干预措施: Extraction (Procedure)
结局指标
主要结局
Quantification of antibiotic resistance genes by Resistance genes output at each timepoint from HUmanN 1.0 .Validation by QPCR values for Blatem and erm genes at each timepoint.
时间窗: Baseline,One week,One month,Six months
Resistome analysis Changes in the (relative) concentration of total resistance genes (the resistome) in the metagenomic DNA sequences will be analyzed as follows: Antibiotic resistance genes will be downloaded from the Antibiotic Resistance Genes Database (20). The downloaded dataset (ardbAnno1.0), containing 7828 entries, will be made non-redundant first and UBLAST from USEARCH v7.0.1090 (20) will be used to map the reads to the (ARDB) proteins (E-value threshold 10, post-filtered to include hits with a maximum E-value of 1E-10 inclusive). The results will be processed with HUMAN (21) to assign weights to the proteins. These weights were then normalized by dividing by the total number of filtered (non-human) reads, and summarized per antibiotic resistance type in the resistome. Next, fold changes will calculated for all resistance types with a baseline weight larger than 1E-8.
次要结局
未报告次要终点
研究者
Dr Michael G. Botelho
Clinical Associate Professor
The University of Hong Kong