Have antibiotic changes upped heart infections?
"Rates of a deadly heart infection have increased after guidelines advised against giving antibiotics to prevent it in patients at risk," BBC News reports. But there is no evidence of a direct link between the two.
In 2008, the National Institute for Health and Care Excellence (NICE) produced guidelines regarding the use of antibiotics to prevent infective endocarditis – a potentially fatal infection of the lining of the heart that comes after bloodstream infection.
Prior to this guidance, common practice was to give antibiotics as a preventative measure to patients undergoing invasive procedures who were at increased risk of infective endocarditis (for example, patients with certain heart conditions).
In the 2008 guidance, NICE recommended that people undergoing dental or invasive surgical procedures were no longer given antibiotics as prevention for endocarditis, as the overall risks outweighed the benefits.
The current study examined trends before and after the guidance to see what effect the advice may have had on both antibiotic prescribing and rates of endocarditis.
This study demonstrates that the number of antibiotic prescriptions prior to invasive dental work or surgery significantly decreased after 2008. The rates of infective endocarditis have significantly increased since 2008, with an estimated 35 additional cases per month.
This is a valuable study, although this analysis of trends does not prove causation – that is, that reduced antibiotic prescribing in light of the NICE recommendations has directly caused the increase in cases.
NICE has announced a review of their guidelines, although current recommendations remain unchanged until the review takes place.
Where did the story come from?
The study was carried out by researchers from Taunton and Somerset NHS Trust, the University of Surrey, the University of Sheffield School of Clinical Dentistry, John Radcliffe Hospital in the UK, and the Mayo Clinic and Carolinas Medical Center in the US.
Funding was provided by Heart Research UK, Simplyhealth and the US National Institutes of Health.
It was published in the peer-reviewed medical journal The Lancet.
BBC News provides a good account of this study.
What kind of research was this?
This study aimed to examine the trends before and after the publication of NICE's 2008 guidance on the prevention of infective endocarditis in people undergoing invasive procedures.
The researchers aimed to look at:
- changes in the prescription of antibiotics for the prevention of infective endocarditis
- changes in the number of cases of infective endocarditis diagnosed
Infective endocarditis means infection and inflammation of the inner lining of the heart chambers (endocardium).
People with existing conditions affecting their heart valves or the structure of their heart are most at risk, as they are more at risk of having existing blood clots (thrombus) present in the heart, in which an infection can start.
The infection is caused by bacteria that have circulated in the bloodstream and reached the heart, so any invasive surgical or dental procedures could potentially carry a risk.
The most common bacterial cause of infective endocarditis is Streptococcus viridans – bacteria that are naturally present in the mouth and throat.
Invasive dental work can therefore potentially lead to these bacteria entering the bloodstream.
Symptoms of infective endocarditis are variable, but commonly include fever and general symptoms of being unwell, such as flu-like symptoms, aches and pains, loss of appetite and weight loss.
A person may also present symptoms after a blood clot has travelled from the heart and lodged in another part of the vascular system (for example, with a stroke).
People also usually have new heart murmurs. The condition carries a fairly high mortality risk, and treatment usually involves intravenous antibiotics, and sometimes surgery.
Prior to 2008, a single dose of amoxicillin (or clindamycin for patients allergic to penicillin) was recommended before invasive dental work for people who were at moderate to high risk of developing infective endocarditis.
In March 2008, NICE concluded that antibiotic prophylaxis (prevention) for infective endocarditis for people undergoing invasive surgical or dental procedures was no longer routinely recommended.
This was generally because the benefits of prophylaxis were outweighed by risks associated with antibiotics – both to the individual and in terms of population health in general in contributing to antibiotic resistance.
Equivalent guidance produced in the US and Europe is said to have also reduced the number of people for whom antibiotic prophylaxis is recommended.
But the US and Europe have not recommended antibiotic use is stopped altogether, as we have in this country.
The researchers aimed to see what effect the NICE recommendations have had on the number of infective endocarditis cases.
What did the research involve?
The researchers aimed to look at the change in prescriptions for antibiotic prophylaxis from January 2004 to March 2013, and to look at hospitalisation for a main diagnosis of infective endocarditis from January 2000 to March 2013 in England.
The prescriptions data came from the NHS Business Services Authority, from where they also got data on the number of individuals accessing dental care services.
Data for incidence of infective endocarditis and its associated mortality came from national hospital episode statistics (HES) and used standard diagnostic codes to identify infective endocarditis.
The researchers carried out statistical analyses looking at changes in incidence of infective endocarditis before and after the introduction of the guidelines in 2008, accounting for changes in population size.
For each case they identified, they also looked back to see if this person had been "high risk" in terms of having a susceptible heart condition or a previous episode of infective endocarditis.
What were the basic results?
Before 2008, the prescribing of antibiotics for the prevention of infective endocarditis was fairly constant.
After the introduction of the NICE guidance, it fell significantly from an average of 10,900 prescriptions per month from January 2004 to March 2008, to only 2,236 prescriptions per month from April 2008 to March 2013. Most prescriptions were for amoxicillin, and 90% were issued by dentists.
There were 19,804 cases of infective endocarditis between 2000 and 2013. Prior to 2008, there had been a steady upward trend in the number of cases, but from March 2008 onwards there was a steep increase in the number of cases above the projected historical trend. This amounted to an additional 0.11 cases per 10 million people each month.
By March 2013, there were an estimated 35 more cases per month 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 not considered to be at risk.
The researchers calculated 277 antibiotic prescriptions would need to be issued to prevent one case of infective endocarditis (number needed to treat, or NNT).
How did the researchers interpret the results?
The researchers say: "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 the introduction of the 2008 NICE guidelines."
Conclusion
This is valuable and timely research, which has looked at trends before and after NICE's 2008 guidance on the prevention of infective endocarditis in people undergoing invasive procedures. This examined:
- changes in the prescription of antibiotics for the prevention of infective endocarditis
- changes in the number of cases of infective endocarditis diagnosed
NICE's recommendation was based on an examination of the evidence of the effectiveness of antibiotics in preventing infective endocarditis, weighing the benefits and health outcomes (such as reduction in illness and deaths), risks and costs.
The data collected by this study comes from reliable data sources, and the researchers took various steps to make sure their data collection was as complete and accurate as possible.
The results demonstrate a clear decrease in antibiotic prescribing as the NICE guidance came in – as would be expected – but also a significant increase in the number of infective endocarditis cases diagnosed since then.
The increase in cases was seen both in those who would be considered to be at risk of the condition and those without risk factors.
As the researchers highlight, this analysis of trends cannot prove causation. It cannot prove that the decrease in the prescription of preventative antibiotics before invasive procedures was directly responsible for the increase in the number of cases of infective endocarditis that has been seen subsequently, even though this may seem the likely cause.
We only know the number of diagnosed cases – we do not know what the actual cause in the individual cases was, and whether the person had, or had recently had, any dental or surgical procedures.
As the researchers say, they did not have reliable data on specific bacterial causes, which would have been useful – for example, in indicating whether it was bacteria normally present in the mouth, and so may have followed dental procedures.
Other factors may be responsible for the change in trends, such as a change in the number of high-risk invasive procedures performed, or a change in the number of people at high risk of infective endocarditis.
However, the researchers did look into this and did not find a significant enough increase in the number of high-risk people with mechanical heart valves, or those having procedures for congenital heart disease, that could account for the trend.
It's also of note that there was an increase in infective endocarditis in people who weren't considered to be at risk of the condition – these people wouldn't routinely have been expected to have been offered antibiotic prophylaxis before the 2008 guidelines.
In light of this study, NICE has announced they will now review their guidelines. Until the review takes place, however, current recommendation are unchanged.
Even if there is a direct link between the 2008 guidelines and the rise in the number of cases of infective endocarditis, there are still other issues to consider.
Could it be justified to issue 277 antibiotic prescriptions to prevent one case of infective endocarditis, given the unnecessary exposure of many individuals to antibiotics, and given what we know about the growing threat of antibiotic resistance?
