IE is a severe manifestation of SAB, and it has therefore been recommended to perform echocardiography, preferably TEE, in all patients with SAB [17
]. Although it is generally accepted standard to perform echocardiography in all patients with community-onset SAB and in those with nosocomial SAB associated with deep-seated infection, some clinicians are reluctant to perform TEE in patients who have uncomplicated SAB, show prompt clinical response to antimicrobial treatment, and have the focus of infection (eg, the intravascular catheter) promptly removed, as proposed previously [23, 24]. Even in a setting in which infectious diseases consultation is available, the compliance with the recommendation to perform echocardiography ranges between 34% and 73% [18
By use of independent cohorts from 2 different continents, we evaluated simple clinical prediction criteria that can be used to identify patients with nosocomial SAB who are at very low risk for the development of IE and in whom TEE might therefore be dispensable. The criteria set is geared to evaluate patients 6–8 days after the first positive blood culture result and is based on data that is usually available at this time point.
The rationale for selecting the prediction criteria was (1) prolonged bacteremia has been shown to be the strongest predictor for complicated SAB and S. aureus
]; (2) permanent intracardiac devices, such as a prosthetic heart valve, a pacemaker, or an implantable cardioverter-defibrillator in patients with SAB have been found associated with a higher risk for endocarditis [7
]; (3) patients with SAB who have end-stage renal disease and a history of hemodialysis are considered to be at risk to develop endocarditis [31
]; (4) spinal infections and nonvertebral osteomyelitis due to S. aureus
have been found to be associated with endocarditis [37
Although long-term intravascular access devices (eg, tunneled or totally implantable catheters) have been shown to be associated with an increased risk of IE [40
], the presence of these catheters was not included in the criteria set. Prolonged bacteremia or hemodialysis dependency may represent independent risk factors for IE rather than the presence of these devices per se, particularly if long-term catheters are promptly removed. In fact, only 1 of 29 patients in the INSTINCT cohort and 5 of 37 patients in the SABG cohort with a long-term intravascular access device present at onset developed IE.
The comparison between the European and North American cohorts showed strikingly similar results regarding patient characteristics and the source of SAB. Of note, MRSA was much more prevalent in the US cohort (65.7% vs 15.5%). Many studies, including a large meta-analysis, have shown that methicillin resistance is associated with a worse outcome in SAB [42
]. However, the 30-day and 90-day case-fatality rates did not differ significantly between the 2 study sites, despite the prominent difference in MRSA prevalence.
Prolonged bacteremia was more common among patients with IE in the US cohort (90% vs 69.2%). It might be argued that this was due to the increased prevalence of MRSA in SABG cohort members and because empirical antimicrobial therapy is often not appropriate and definitive therapy less effective in patients with BSI caused by MRSA. However, our data do not support this hypothesis because 20 (62.5%) of 32 SABG patients with IE caused by MRSA had documented prolonged bacteremia, compared with 6 (75%) of 8 patients with IE caused by MSSA (data not shown). It is tempting to speculate that the higher incidence of IE in the SABG cohort might be explained by the higher incidence of MRSA; however, our data do not prove this.
In both cohorts, the absence of any of the criteria had a high negative predictive value (100% and 99.2% in the INSTINCT and SABG cohorts, respectively) for the development of IE. Therefore, we propose that TEE to exclude IE may be dispensable in patients with nosocomial SAB who do not fulfill any of the clinical prediction criteria.
There are several limitations to the study. The reliable detection of IE is of critical importance. Neither of the 2 cohort studies was designed to measure the rate of IE at 3 months after the onset of SAB, and routine follow-up echocardiography data were not available. Also, a small number of patients were lost to follow-up or data were missing (INSTINCT, 1.6%; SABG, 5.9%). More importantly, only 39.5% (in INSTINCT) and 57.4% (in SABG) of patients underwent echocardiography ≤14 days after onset of SAB, despite considerable efforts of the investigators to include this diagnostic method into standard care. Thus, some cases of IE may have gone undetected. However, we reasoned that IE would become clinically apparent after discontinuation of antibiotic therapy; therefore, patients were observed closely for the development of clinical signs and symptoms suggestive of IE over a period of 3 months. One might argue that a considerable number of patients who did not fulfill any predictive criteria and in whom echocardiography was not performed died during follow-up, and in these patients undetected IE could have been present. However, a sudden death related to IE that goes undetected by the primary care physician and/or the hospital should occur only rarely. Furthermore, there was no case of IE observed among the surviving patients during the follow-up periods. One could also argue that prolonged antimicrobial therapy could have adequately treated undetected early stage IE, and indeed, 11 patients for whom echocardiography was not performed were given >3 weeks of antimicrobial treatment.
The comparatively low specificity of the criteria set is largely due to the conservative definition of prolonged bacteremia, ie the absence of negative blood cultures obtained at day 1–4 after the first positive blood culture. Using this definition, 145 patients in INSTINCT and 161 patients in the SABG cohort with “possible” prolonged bacteremia were included in the prolonged bacteremia group, although most likely a considerable number of these patients could have been excluded if follow-up blood cultures had been obtained. If “documented” prolonged bacteremia (ie, the presence of a follow-up blood culture positive for S. aureus 2–4 days after the first positive blood culture result) was used as a criterion, the specificity of the test would be markedly increased (data not shown). However, we decided not to use this approach, because some patients with ongoing bacteremia could be missed if no follow-up blood samples are obtained for culture, leading to a lower negative predictive value.
In summary, we propose that in patients with at least 1 clinical prediction criterion, echocardiography to exclude IE is highly recommended. In the subset of patients with a low probability of IE (ie, those without any of the criteria), TEE evaluation may not be necessary. However, physicians should not be discouraged from performing echocardiography in criteria-negative patients when IE is clinically suspected during the course of the infection.
Furthermore, clinicians should be encouraged by ID physicians and clinical microbiologists to perform follow-up cultures for all patients with SAB 2–4 days after the first positive blood culture result. This approach can be used to exclude prolonged bacteremia and thus helps to identify patients in whom TEE might be dispensable, and it could lead to a more economical use of echocardiographic evaluations. Nevertheless, it is of critical importance to confirm the validity of the proposed prediction criteria prospectively in a controlled study, in which all patients with SAB would undergo echocardiography and follow-up blood cultures.