ACCEL | The technical term is ‘oops.’ Changes in infective endocarditis (IE) prevention guidelines in the U.S. and Europe have reduced the number of patients for whom antibiotic prophylaxis is recommended by more than 80 percent. It certainly has had the intended result saving money by avoiding “unnecessary” prophylactic treatment. For example, the 2008 National Institute for Health and Care Excellence (NICE) guidelines stated that antibiotic prophylaxis against IE was no longer recommended for people undergoing:

• Dental procedures
• Non-dental procedures at the following sites:
• upper and lower gastrointestinal tract
• genitourinary tract
• upper and lower respiratory tract

In the U.S, there was a similar evolution, as marked by the 2008 ACC/AHA guidelines¹, then subsequently echoed by updated Australian and European guidelines², along with others guidelines. In brief, expert opinion quickly evolved away from the dogma of “treating everyone with risk prophylactically” to targeting a truly high-risk population. It was a major departure from previous practice, and, despite unanimous interpretation and direction from relevant professional societies, the recommendations triggered considerable debate and pushback from some clinicians. Maybe the skeptics were right?

IE Antibiotic Prophylaxis

The problem with the change in guidelines relates to whether the precipitous drop in antibiotic prophylaxis was truly for “unnecessary” therapy. Dayer et al. conducted a retrospective study to investigate the effect of antibiotic prophylaxis versus no prophylaxis on the incidence of IE in England.³ They analyzed data for the prescription of antibiotic prophylaxis from January 1, 2004, to March 31, 2013, and hospital discharge episode statistics for patients with a primary diagnosis of IE from January 1, 2000, to March 31, 2013.

Prescriptions for antibiotic prophylaxis for the prevention of IE fell substantially after the introduction of the NICE guidance (mean 10,900 prescriptions per month prior vs. 2,236 prescriptions per month after; p<0.0001). Starting in March of 2008, the number of cases of IE increased significantly above the projected historical trend (p<0.0001). By March of 2013, 35 more cases per month were reported than would have been expected had the earlier trend (before the change in guidelines) continued. There was an increase, albeit not statistically significant, in mortality, too, with 1.5 more IE deaths per month.

According to Martin Thornhill, MBBS, PhD, at the University of Sheffield School of Clinical Dentistry, U.K., “Since the introduction of the NICE guidelines in March of 2008, there has been a large and significant fall in antibiotic prophylaxis prescribing and a significant increase in the incidence of infective endocarditis that has affected both lower-risk individuals as well as those at high risk of infective endocarditis.”

There is a temporal association, for sure – the change point for the uptick in IE was three months after the guidelines were published in the UK. However, Mark Dayer, MBBS, BSc, PhD, who presented the data, admitted “we cannot conclude there is a cause/effect relationship.” On the other hand, clinical practice does not change overnight, so a short delay in effect is not unreasonable. He added, “We have been unable to establish an alternative explanation.”

Valentin Fuster, MD, PhD, MACC, editor-in-chief of the Journal of the American College of Cardiology, noted that this news is “a real hit in the head” and we should think again about the recommendations for antibiotic prophylaxis for IE prevention.

What About in the U.S.?

In the May 19, 2015 issue of JACC, investigators reported the results of an analysis of more than a decade’s worth of data from the National Inpatient Sample (NIS) database.⁴ There were 457,052 IE-related hospitalizations in the U.S. from 2000 through 2011, with a steady increase in the incidence (p <0.001). In the U.S., guidelines changing the recommendations relating to IE prophylaxis were published online ahead of print in 2007, but the trend in IE hospitalization rates from 2000-2007 was not significantly different from 2008-2011 (p = 0.74). The increase in the number of Staphylococcus IE cases per 1,000,000 population during the study period 2000-2007 and 2008-2011 were similar (p = 0.13), but Streptococcus IE hospitalization rates were significantly higher after the release of the new guidelines (p = 0.002).

Valve replacement rates for IE steadily increased over the period 2000-2007 (p = 0.03), but showed a plateau from 2007-2011. Overall, there was no significant difference in the rates of valve replacement for IE before and after the release of the new guideline (p = 0.23).

In an accompanying editorial comment, Britain’s Dr. Dayer and Prof. Thornhill⁵ noted that the U.S. authors in their analysis included no estimation of the impact of the 2007 U.S. guidelines on the prescribing of antibiotic prophylaxis. Thus, it’s unclear how U.S. practice has changed, if at all, and who continues to get antibiotic prophylaxis, although there is a suggestion that there has been some shift, at least among dentists. Furthermore, correlation does not equal causation, and there is no proof the effect seen is the result of the guideline change.

As they—and the main JACC paper’s authors—note: the fundamental problem is that there has never been a randomized controlled clinical trial that looked into the efficacy of antibiotic prophylaxis, and so there is no reliable evidence to support its use. Dayer and Thornhill noted, “The time for this to change is long overdue.”

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References:

1. Nishimura RA, Carabello BA, Faxon DP, et al. J Am Coll Cardiol. 2008;52:676-85.
2. Habib G, Hoen B, Tornos P, et al. Eur Heart J. 2009;30:2369-413.
3. Dayer MJ, Jones S, Prendergast B, Baddour LM, Lockhart PB, Thornhill MH. Lancet. 2014 Nov 18. [Epub ahead of print].
4. Pant S, Patel NJ, Deshmukh A, et al. J Am Coll Cardiol. 2015;65:2070-6.
5. Dayer M, Thornhill M, J Am Coll Cardiol. 2015;65:2077-8.

Take-aways Changes in antibiotic prophylaxis guidelines in the U.S. and Europe have substantially reduced the number of patients with infective endocarditis (IE) for whom antibiotic prophylaxis is recommended. However, along with a large and significant fall in antibiotic prophylaxis, there has been a significant increase in the incidence of IE. The individuals affected include highest-risk and lower-risk individuals.

Keywords: CardioSource WorldNews, Antibiotic Prophylaxis, Endocarditis, Endocarditis, Bacterial, Guideline

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