By Richard R. Watkins, MD, MS, FACP, FIDSA

Professor of Internal Medicine, Northeast Ohio Medical University; Division of Infectious Diseases, Cleveland Clinic Akron General, Akron, OH

Dr. Watkins reports no financial relationships relevant to this field of study.

SYNOPSIS: Data from a nationwide registry in Denmark from 2010 to 2017 showed that patients with Enterococcus faecalis bacteremia had the highest prevalence of infective endocarditis (16.7%), followed by Staphylococcus aureus (10.1%) and Streptococcus spp. (7.3%).

SOURCE: Østergaard L, Bruun NE, Voldstedlund M, et al. Prevalence of infective endocarditis in patients with positive blood cultures: A Danish nationwide study. Eur Heart J 2019; May 30. doi: 10.1093/eurheartj/ehz327. [Epub ahead of print].

Despite advances in the diagnosis and management of infective endocarditis (IE), it still causes considerable morbidity, mortality, and healthcare expense. Although there has been an increased awareness in recent years about the association between Staphylococcus aureus bacteremia and IE, the risk from other pathogens is less appreciated. Using a large patient cohort, Dutch investigators sought to characterize which bloodstream infections (BSIs) are associated with the highest risk of IE.

Researchers used three nationwide patient databases to identify cases of BSIs and IE between 2010 and 2017. The investigators chose to include BSIs from Enterococcus faecalis, Streptococcus spp., S. aureus, and coagulase-negative staphylococcus (CoNS) because these four pathogens cause approximately 70% of IE cases. For the study, a BSI was defined as at least one positive blood culture with one of the aforementioned pathogens. Patients were included who were hospital-ized at least 14 days, including those transferred between institutions, and the primary outcome was the diagnosis of IE. The underlying bacterial etiology was identified in a period of six months prior to admission in which IE was diagnosed. Furthermore, a sensitivity analysis was conducted for BSIs within 14 days prior to IE admission and up to IE discharge.

There were 3,408 cases of IE during the study period. The prevalence of IE was highest in patients with E. faecalis BSIs (16.7%), followed by S. aureus BSIs (10.1%), Streptococcus spp. BSIs (7.4%), and CoNS BSIs (1.6%). Investigators found a significant increase for the prevalence of E. faecalis IE (P = 0.0005; 14.4% in 2010 to 18.8% in 2017) and Streptococcus spp. IE (P = 0.03; 6.0% in 2010 to 8.0% in 2017) from the start until the end of the study. They observed a significantly higher prevalence of IE in males compared to females for E. faecalis (P < 0.0001), Streptococcus spp. (P < 0.0001), and CoNS (P < 0.0001), but not S. aureus (P = 0.06). Older age also was associated with a higher prevalence of IE caused by E. faecalis, Streptococcus spp., and CoNS. A sensitivity analysis that compared BSIs within 14 days to IE found the same described pattern. Another sensitivity analysis for CoNS required that two blood cultures be positive within one week of each other, with at least one day between cultures. This changed the prevalence of CoNS IE to 8.1%, compared to 1.6% when only one blood culture was positive.

COMMENTARY

An interesting finding from this study was the higher prevalence of IE in patients with BSIs due to E. faecalis compared to S. aureus. The current IE guidelines from the Infectious Diseases Society of America note that S. aureus is the most common cause of IE in much of the developed world and that the rate of S. aureus IE has increased significantly relative to other causes of IE.1 Enterococci reportedly are the third leading cause of IE, accounting for approximately 10% of cases, with E. faecalis constituting 97% of enterococcal IE; E. faecium, 2%; and other species, 1%. The high rate of enterococcal IE following BSI in the present study highlights the need for screening with echocardiography. This seems especially important for elderly patients and male patients. Why males have a higher rate of IE than females is unclear, but this also has been observed in previous studies. Perhaps males have more risk factors, such as prosthetic heart valves or intravenous drug abuse. Further epidemiologic studies will be beneficial, especially to ascertain if the prevalence of enterococcal IE is increasing compared to other common etiologies.

The study has some limitations worth mentioning. First, because of the retrospective and observational design, the findings could have been influenced by unmeasured confounding variables. Second, the data are from a small European country, so the findings might not be generalizable to other geographic areas and different patient populations. Third, the diagnosis of IE was derived from ICD-10 codes and not the modified Duke criteria, which may have led to reporting bias. Fourth, improvements in diagnostic modalities (e.g., better access to transesophageal echocardiography and nuclear imaging) may have increased the diagnostic accuracy during the last period of the study. Fifth, patients were included in the study who were hospitalized for 14 days or longer, which is quite long by current clinical practice standards. Finally, other (albeit rarer) causes of IE such as Candida spp. and gram-negative organisms were not included in the analysis.

The epidemiology of IE is dynamic, and studies like the one reported by Østergaard and colleagues are valuable for clinicians and public health practitioners alike. Whether BSIs due to enterococcus are leading to more cases of IE in other geographic areas, such as North America, warrants further investigation.

REFERENCE

  1. Baddour LM, Wilson WR, Bayer AS, et al. Infective endocarditis in adults: Diagnosis, antimicrobial therapy, and management of complications: A scientific statement for healthcare professionals from the American Heart Association. Circulation 2015;132:1435-1486.