Infective endocarditis (IE) is an infection of the heart valves, most often caused by circulating bacteria (bacteremia). There are ~27,000 cases a year in the USA and it is associated with high mortality (~30% within the first year) and serious long-term complications. Oral bacteria are implicated in 35-45% of IE cases. It is well documented that bacteremia occur during eating, tooth-brushing and invasive dental procedures. Because of this, the American Heart Association (AHA) guideline committee recommends that patients at highest risk from developing IE should be given antibiotic prophylaxis (AP) before invasive dental procedures, with the aim of killing bacteria that enter the circulation. Most cardiovascular guidelines committees around the world recommend AP for these people. However, there has never been a clinical trial of AP and there is a lack of scientific evidence to support the practic of giving AP. In the UK, AP was the 'standard of care'until March 2008 when the National Institute for Health and Clinical Excellence (NICE) introduced new guidelines recommending the complete cessation of AP prescribing in the UK. Since then the 'standard of care'has been NOT to prescribe AP prior to dental procedures. Objectives: To determine the efficacy of AP in preventing IE by performing a before and after study comparing the incidence of IE when AP was the 'standard of care'in the UK (before March 2008) with the incidence of IE when the 'standard of care'was NOT to give AP (after March 2008).
Specific Aims : To perform a before and after study of the impact of the recommendation in the UK to stop giving AP, prior to invasive dental procedures, on the incidence of IE. Methods: We will: (1) Analyze National Prescribing data to determine the level of AP prescribing prior to and in the 4 years after the introduction of the NICE guidelines. (2) Analyze national Hospital Episode Statistics (HES) data to determine the incidence of IE prior to and in the 4 years after the introduction of the NICE guidelines. (3) Analyze links between HES data and Office of National Statistics data to determine the incidence of IE related mortality, during the hospital stay to treat IE and within 90 days of hospital admission, before and after the introduction of the NICE guidelines. (5) In addition, we will do the following sub-analysis of the IE incidence and mortality data: (a) In orde to more directly assess the benefit of AP in preventing IE caused by oral bacteria, we will determine the incidence of IE and IE related mortality for those patients where the causal organism was recorded as being of oral origin. (b) To more directly evaluate the potential benefit of the current AHA guidelines, we will also determine the incidence of IE and IE related mortality in those patients with a pre-existing prosthetic heart valve or previous history of IE, and who therefore fall into the AHA 'High-Risk'category indicated to receive AP under the current AHA guidelines.

Public Health Relevance

Infective endocarditis (IE) is a serious disease with a high death rate (~30% within the first year) and serious long-term complications. Some cases of IE are caused by bacteria from the mouth and so in an attempt to prevent cases, national guidelines produced by the American Heart Association (AHA) recommend that patients at high risk from IE are given antibiotics before having dental treatment. This is called antibiotic prophylaxis (AP). However, there is a lack of evidence to support this practice and there has never been a clinical trial to show that AP is of any benefit in preventing IE. Since, hundreds of thousands of patients require AP each year, the practice is expensive, carries a risk of patients developing serious adverse reactions to the antibiotics and the wide spread use of antibiotics for preventative rather than treatment purposes may encourage the development of antibiotic resistant bacteria. It is therefore of extreme public health importance that we know if AP is effective and safe in preventing IE. The practice of giving AP to prevent IE, as currently happens in the USA, was stopped in the UK in 2008 after the introduction of new guidelines. In the UK, it is therefore possible to study if giving AP (before 2008) resulted in fewer cases of IE than not giving AP (after 2008). The proposed study will examine what happened to the prescribing of AP and to the incidence of IE before and after the change in clinical practice in the UK in 2008. This will provide much needed evidence about the efficacy (or not) of using AP to prevent IE. The results are of direct relevance to the AHA guidance to give AP to patients at highest risk from IE and will either provide reassurance about the validity of the AHA guidelines or prompt a major reconsideration of the guidance.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Small Research Grants (R03)
Project #
1R03DE023092-01
Application #
8423913
Study Section
Special Emphasis Panel (ZDE1-VH (21))
Program Officer
Fischer, Dena
Project Start
2013-09-18
Project End
2014-08-31
Budget Start
2013-09-18
Budget End
2014-08-31
Support Year
1
Fiscal Year
2013
Total Cost
$108,000
Indirect Cost
$8,000
Name
University of Sheffield
Department
Type
DUNS #
228147328
City
Sheffield
State
Country
United Kingdom
Zip Code
S10 2-GW