The 2007 American Heart Association (AHA) recommendations for restriction of antibiotic prophylaxis to only individuals at high risk for infective endocarditis (IE) may have resulted in a significant increase in infective endocarditis in patients at moderate and high risk, according to study results published in the Journal of the American College of Cardiology.
Although uncommon, infective endocarditis is a life-threatening infection with an approximate 30% first-year mortality. Individuals with predisposing cardiac conditions are at increased risk for infective endocarditis. International guidelines have focused on preventing infective endocarditis in patients at risk since the AHA advocated antibiotic prophylaxis for all patients scheduled for invasive medical and dental procedures in 1955.
However, in 2007 the AHA amended their recommendation for antibiotic prophylaxis, advising that it be restricted to only patients at high risk for infective endocarditis and its complications undergoing invasive dental procedures. This change was a result of the lack of clinical trials demonstrating the efficacy of antibiotic prophylaxis and concerns about the risk for adverse reactions and the development of antibiotic resistance.
The European Society of Cardiology also recommended similar guidance in 2009 and the United Kingdom National Institute for Health and Care Excellence (NICE) recommended complete cessation of antibiotic prophylaxis in 2008. Following the NICE recommendation, a previous study showed an 89% fall in prophylactic antibiotic prescribing in England but a significant increase in cases of infective endocarditis. Therefore, this investigation aimed to quantify changes in prophylactic antibiotic prescribing and the incidence of infective endocarditis following the 2007 AHA recommendations.
Study investigators used information gathered from Truven Health MarketScan databases between May 2003 and August 2015. They identified and included individuals who were high-risk, moderate-risk, and unknown/low-risk with linked prescription and either Medicare or commercial health insurance (198,522,655 enrollee-years of data). Prophylactic antibiotic prescriptions were defined, according to the AHA recommendations, as a single oral dose of amoxicillin 2 g, clindamycin 600 mg, azithromycin 500 mg, or clarithromycin 500 mg. Infective endocarditis hospital admissions were identified using International Classification of Disease (ICD) diagnosis codes: ICD-9 code 421.0, 421.1, or 421.9, as primary or secondary discharge diagnoses. Poisson model analysis was used to evaluate prophylactic antibiotic prescribing and infective endocarditis incidence.
By 2015, the recommendation change was associated with a significant fall in prescribing prophylactic antibiotics in both moderate-risk (64% decrease; 95% CI, 59%-68%) and high-risk individuals (20% decrease; 95% CI, 4%-32%). During the same time period, there was a less significant increase in incidence of infective endocarditis in moderate-risk individuals (75% increase; 95% CI, 3%-200%) but a significant increase in infective endocarditis incidence in high-risk individuals (177% increase; 95% CI, 66%-361%). In unknown/low-risk individuals, there was a significant decrease in antibiotic prophylaxis prescriptions (52% decrease; 95% CI, 46%-58%), but no significant increase in the incidence of infective endocarditis.
Overall, the study authors concluded that, “[a]lthough these data do not establish a cause-effect relationship between [antibiotic prophylaxis] reduction and [infective endocarditis] increase, the fall in [antibiotic prophylaxis] prescribing in those at high risk is of concern and, coupled with the borderline increase in [infective endocarditis] incidence among those at moderate risk, warrants further investigation.”
Thornhill MH, Gibson TB, Cutler E, et al. Antibiotic prophylaxis and incidence of endocarditis before and after the 2007 AHA recommendations. J AM Coll Cardiol. 2018;72:2543-2554.