Elsevier

The Lancet

Volume 385, Issue 9974, 28 March–3 April 2015, Pages 1219-1228
The Lancet

Articles
Incidence of infective endocarditis in England, 2000–13: a secular trend, interrupted time-series analysis

https://doi.org/10.1016/S0140-6736(14)62007-9Get rights and content

Summary

Background

Antibiotic prophylaxis given before invasive dental procedures in patients at risk of developing infective endocarditis has historically been the focus of infective endocarditis prevention. Recent changes in antibiotic prophylaxis guidelines in the USA and Europe have substantially reduced the number of patients for whom antibiotic prophylaxis is recommended. In the UK, guidelines from the National Institute for Health and Clinical Excellence (NICE) recommended complete cessation of antibiotic prophylaxis for prevention of infective endocarditis in March, 2008. We aimed to investigate changes in the prescribing of antibiotic prophylaxis and the incidence of infective endocarditis since the introduction of these guidelines.

Methods

We did a retrospective secular trend study, analysed as an interrupted time series, to investigate the effect of antibiotic prophylaxis versus no prophylaxis on the incidence of infective endocarditis in England. We analysed data for the prescription of antibiotic prophylaxis from Jan 1, 2004, to March 31, 2013, and hospital discharge episode statistics for patients with a primary diagnosis of infective endocarditis from Jan 1, 2000, to March 31, 2013. We compared the incidence of infective endocarditis before and after the introduction of the NICE guidelines using segmented regression analysis of the interrupted time series.

Findings

Prescriptions of antibiotic prophylaxis for the prevention of infective endocarditis fell substantially after introduction of the NICE guidance (mean 10 900 prescriptions per month [Jan 1, 2004, to March 31, 2008] vs 2236 prescriptions per month [April 1, 2008, to March 31, 2013], p<0·0001). Starting in March, 2008, the number of cases of infective endocarditis increased significantly above the projected historical trend, by 0·11 cases per 10 million people per month (95% CI 0·05–0·16, p<0·0001). By March, 2013, 35 more cases per month were reported than would have been expected had the previous trend continued. This increase in the incidence of infective endocarditis was significant for both individuals at high risk of infective endocarditis and those at lower risk.

Interpretation

Although our data do not establish a causal association, prescriptions of antibiotic prophylaxis have fallen substantially and the incidence of infective endocarditis has increased significantly in England since introduction of the 2008 NICE guidelines.

Funding

Heart Research UK, Simplyhealth, and US National Institutes of Health.

Introduction

Infective endocarditis is uncommon, but has high morbidity and mortality.1 Oral viridans group streptococci are implicated as causal organisms in 35–45% of cases.2, 3, 4, 5 Antibiotic prophylaxis given before invasive dental procedures has been the focus for infective endocarditis prevention for more than 50 years and remains the standard of care for patients at high risk in most parts of the world.6, 7 The aim of antibiotic prophylaxis is to reduce or eliminate bacteraemia8, 9, 10, 11 that can cause infective endocarditis in susceptible individuals. No randomised clinical trials of antibiotic prophylaxis have been done12 and little evidence exists to support its effectiveness.2, 4, 9

Until recently, standard of care in most parts of the world was to provide antibiotic prophylaxis to patients at high risk of infective endocarditis (ie, those with previous infective endocarditis, prosthetic heart valves or valves repaired with prosthetic material, unrepaired cyanotic congenital heart disease, or some repaired congenital heart defects) and those at moderate risk (ie, with previous rheumatic fever, heart murmur, or evidence of native valve disease). In March, 2008, the UK National Institute for Health and Clinical Excellence (NICE; now the National Institute for Health and Care Excellence) produced new guidance recommending complete cessation of antibiotic prophylaxis.13, 14, 15 By contrast, the American Heart Association (AHA)7 and the European Society of Cardiology (ESC)6 produced new guidelines in 2007 and 2009, respectively, recommending cessation of antibiotic prophylaxis for patients at moderate risk only.

The NICE guidance13 provided an opportunity for a retrospective study to investigate the effect of antibiotic prophylaxis versus no prophylaxis on the incidence of infective endocarditis in England. In a preliminary study,16 2 years after the introduction of the NICE guidelines, no significant increase in incidence of infective endocarditis was identified, despite a 78% reduction in the prescription of antibiotic prophylaxis. However, some researchers and clinicians expressed concerns that 2 years was not long enough to detect a clinically significant change.17 Moreover, 2500 prescriptions for antibiotic prophylaxis per month were still being issued at this point, with evidence of targeting of individuals at high risk.18 Therefore, the aim of this study was to investigate changes in the prescribing of antibiotic prophylaxis and the incidence of infective endocarditis over a longer timeframe.

Section snippets

Study design and data sources

We did a retrospective secular trend study, analysed as an interrupted time series, to investigate the effect of antibiotic prophylaxis versus no prophylaxis on the incidence of infective endocarditis in England, using data for antibiotic prophylaxis prescribing from Jan 1, 2004, to March 31, 2013, and hospital discharge episode statistics for patients with a primary diagnosis of infective endocarditis from Jan 1, 2000, to March 31, 2013.

Before the introduction of the 2008 NICE guidelines,13 a

Results

Before 2008, the prescribing of antibiotic prophylaxis for prevention of infective endocarditis had remained fairly constant for many years. After the introduction of NICE guidelines recommending cessation of antibiotic prophylaxis,13 the mean number of antibiotic prophylaxis prescriptions per month fell significantly (from 10 900 [Jan 1, 2004, to March 31, 2008] to 2236 [April 1, 2008, to March 31, 2013]; p<0·0001). In the last 6 months studied (Oct 1, 2012, to March 31, 2013), the mean number

Discussion

Since the introduction of the NICE guidelines13 in March, 2008, which recommended cessation of antibiotic prophylaxis to prevent infective endocarditis, the number of prescriptions for antibiotic prophylaxis has fallen sharply and the incidence of infective endocarditis in England has increased significantly. This increase in incidence has affected both high-risk and lower-risk individuals. Infective endocarditis-associated in-hospital mortality also increased, although this increase was not

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