Increasing US Rates of Endocarditis With Staphylococcus Aureus: 1999-2008

Study Questions:

What is the incidence of Staphylococcus aureus infective endocarditis (IE) in the United States, and is the incidence changing?


A retrospective cohort study was conducted using the 1999 through 2008 Nationwide Inpatient Sample (NIS; the largest all-payer inpatient database in the United States, containing approximately 8 million records per year), which is produced by the Agency for Healthcare Research and Quality. Admissions related to bacterial IE were identified by the presence of International Classification of Diseases, Ninth Revision (ICD-9) codes 421.0, 421.1, 421.9, or 996.61. The etiologic agent of IE was determined by the presence of organism-specific infection (e.g., 041.x) and bacteremia codes (038.x). Incidence was estimated using the rate of IE-related discharges per 100,000 US population-years. Rates were calculated quarterly based on discharge date; the denominator was adjusted annually based on the US population. The effect of organism on in-hospital mortality was measured using logistic regression, adjusting for age, sex, payer, and comorbidities.


Of 78.2 million records in the 1999–2008 NIS database, records for 83,700 discharges (409,665 weighted for US population) met inclusion criteria; for those with an identified organism, staphylococci were the most common (57.5%), followed by streptococci and/or enterococci (33.3%). Between the first quarter of 1999 and the first quarter of 2006, the rate of bacterial IE–related hospitalizations increased from 11.4 per 100,000 population-years to 16.6 per 100,000 population-years (p < 0.001), corresponding to an average percentage change of 1.1% per quarter (95% confidence interval [CI], 0.9%-1.3%). Admissions for staphylococcal IE grew at a rate of 1.1% per quarter (95% CI, 0.9%-1.3%), rising from 3.3 to 5.4 cases per 100,000 population-years from first quarter of 1999 to the fourth quarter of 2008 (p < 0.001), most of which was due to IE caused by Staphylococcus aureus. For the cohort of 33,956 admissions (165,563 weighted) that occurred in 2002 or later for which an etiologic organism was identified and that had complete covariate data, admissions for S aureus–related IE were associated with a higher probability of in-hospital mortality than streptococcal and/or enterococcal IE (17.5% vs. 8.9%, p < 0.001). After adjustment, S aureus IE was associated with a 57.1% greater risk of in-hospital mortality (risk difference 5.9%, p < 0.001) compared with streptococcal and/or enterococcal IE.


These data suggest that the rate of hospitalizations for IE grew at the beginning of the 21st century in the United States, that most of the increase was due to S aureus, and that IE related to S aureus is associated with a worse outcome than is IE associated with other organisms.


Research based on a large insurance-claims database offers the opportunity to study vast numbers of hospitalizations over broad demographic and geographic areas; limitations relate to reliance on discharge codes rather than prospectively or even retrospectively collected clinical data. The finding that S aureus is the predominant cause of IE in the 21st century is concordant with findings from the International Collaboration on Endocarditis; the finding of an increasing incidence of IE contrasts with a smaller single-center study performed at a single center. Unfortunately, limitations in the ability to accurately define the past incidence of IE affect the ability to monitor for change following the introduction of the 2007 Guideline revisions regarding the use of antibiotic prophylaxis against IE.

Clinical Topics: Diabetes and Cardiometabolic Disease

Keywords: Incidence, Enterococcus, Bacteremia, Staphylococcal Infections, United States Agency for Healthcare Research and Quality, International Classification of Diseases, Streptococcus, Staphylococcus aureus, Antibiotic Prophylaxis, Endocarditis, Bacterial, United States, Mitogen-Activated Protein Kinases

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