In the present study, we found a high prevalence (22%) of IE in SAB patients when systematic screening with echocardiography was applied. This finding is of clinical importance, as S. aureus
IE is a potentially lethal infection that is often unsuspected on clinical grounds alone.7,18,21,29,30
Thus, it is vital that patients with S. aureus
IE are diagnosed early in the course of the disease in order to optimize clinical outcome.
One potential strategy for the early and accurate identification of S. aureus
IE is to perform screening echocardiography on all patients with SAB.22
One of the first studies supporting a general screening of SAB patients with echocardiography was a study by Fowler et al
, including 103 SAB patients who underwent both TTE and TEE. In this study, 25% of the patients were diagnosed with IE according to the Duke criteria, whereas clinical evidence of IE was present in only 7% of the patients. Based on these findings, the authors concluded that it was impossible, based on clinical findings and predisposing heart valve disease alone, to distinguish between SAB patients with and without IE and that TEE should be considered in all patients with SAB.7
Although well conducted, the study by Fowler et al
. was associated with several limitations, including (i) limited sample size, (ii) single-centre design; and (iii) potential for ascertainment bias associated with its observational methodology. Subsequent retrospective studies using echocardiography to evaluate the prevalence of IE in SAB patients have found similar estimates, but were similarly limited by study design.4,28,31
Thus, based on existing evidence it has not been possible to reach definite conclusions regarding the value of general screening with echocardiography in patients with SAB.
In the present study, we used a large, multicentre, prospective observational study of consecutive SAB patients to overcome these limitations and make an observation. First, our study validated the high rate of IE reported in the Fowler study, with reported prevalence rates virtually identical to those from the earlier investigation (25 vs. 22%). Taken together, our findings underscore that patients with SAB constitute a high-risk population and as such should be examined with echocardiography. The second key finding of this study was to identify a high-risk SAB population based on predisposing conditions and clinical findings. The likelihood of IE in SAB patients with a high initial risk of IE was six times higher compared with low-risk patients with no additional risk factors or stigmata of IE. This finding is in contrast with that encountered by Fowler et al., and may be due in part to time after onset of SAB to echocardiography, referral patterns, and difference in patient demographics (for example, the high rate of haemodialysis in the US vs. Danish patients). While the ability to define ‘high-risk’ patients with SAB is highly relevant, it is important to emphasize that all of the patients with SAB in our study were at risk for IE. In the present study, over half of our patients with confirmed S. aureus IE had no documented cardiac murmur, three-quarters of IE patients had no clinically detected embolic events, and almost 90% had no vascular or immunologic phenomena. As the initial risk of IE in SAB patients is high and the symptoms is unspecific TTE and TEE is recommended in the assessment of SAB patients in general. However, the present study indicate that high-quality TTE might be sufficient in SAB patients with no additional risk factors or clinical evidence of IE, but the threshold for additional TEE should be low. A third key finding was that the prevalence of IE in SAB patients admitted at Main Regional Hospitals and Tertiary Cardiac Hospitals was comparable indicating that this is a widespread problem, which is not isolated to Tertiary Cardiac Hospitals.
Collectively, our data provides compelling evidence that all patients with SAB should undergo echocardiographic screening in order to minimize the risk of missing this potentially lethal diagnosis.
The current investigation has several limitations. The study is susceptible to selection bias as not all of the eligible SAB patients were included. Therefore, it is possible that only high-risk patients were selected for echocardiography, especially as none of the eligible patients not referred for echocardiography were diagnosed with IE. However, it is likely that unrecognized IE patients in this population either were cured by antibiotic treatment due to a short duration of the disease, were readmitted with recurrent SAB infection, or died due to endocarditis, explaining the high mortality in this population. Accordingly, the prevalence reported in the present study has to be a conservative estimate of the ‘true’ IE prevalence. To minimize selection bias, the current study was designed as a multicentre study including patients from both Main Regional Hospitals and Tertiary Cardiac Hospitals and the inclusion rate (73%) is to our knowledge the highest yet to be reported. Furthermore, we were able to keep track on patients not included in our study allowing us to follow-up on all eligible patients. Another concern is the possibility that the prevalence reported in the current study is underestimated as 38% of the patients were examined with TTE without an additional TEE. However, as the quality and resolution of TTE continues to improve the ability of TTE to detect vegetations has become better especially in patients with native valve IE. For example, a recent study by Casella et al.20
reported that the sensitivity of TTE for diagnosing native valve IE was 82%, and almost 90% in patients with good image quality. Another concern is that as the quality of the images provided by echocardiography continues to improve smaller mobile structures are seen and the interpretation of significant vs. non-significant, i.e. degenerative echocardiographic findings becomes more difficult with the risk of false-positive results, which may result in inappropriate diagnosis of IE. To reduce the risk of false-positive cases in the present study only cases of definite IE, according to the modified Duke criteria, were included.