Our study investigated the factors influencing survival in patients with enterococcal bacteraemia, highlighting the critical role of early management strategies, including ID consultation, timely initiation of appropriate antimicrobial treatment, and source control interventions when warranted.

The overall 30-day mortality was 19%, which is slightly lower to that previously reported (21–28%) [3,4,5,6,7,8,9,10]. This discrepancy may be explained by several factors. In the present study, a higher proportion of episodes received appropriate antimicrobial treatment within 48 h compared to previous cohorts [4, 6, 9, 10]. Additionally, the percentage of bacteraemias caused by vancomycin-resistant enterococci (VRE) was lower in our study [5, 6, 10] and VRE cases were less likely to receive appropriate initial antimicrobial treatment in earlier studies [1, 10]. The low percentage of VRE in the present study was likely influenced by the recommendations of the Swiss Center for Infection Prevention (Swissnoso) aimed at preventing epidemic and endemic VRE spread [17]. Finally, the rate of ID consultations in our cohort was higher than what has been reported in the literature [3, 6, 10, 18].

Consistent with prior studies, our findings emphasize the importance of ID consultation in improving patient outcomes [3, 6, 10, 18]. ID consultations enhance overall management by facilitating earlier initiation of appropriate antimicrobial therapy and ensuring timely performance of source control interventions when needed. As shown in previous research, appropriate antimicrobial treatment was associated with improved survival [6, 8,9,10]. In earlier studies, inappropriate antimicrobial treatment was more common in cases of E. faecium bacteraemia or when the infecting isolate exhibited resistance to amoxicillin or vancomycin; [6, 9, 10] in our study, a higher proportion of episodes with E. faecalis bacteraemia received appropriate antimicrobial treatment within the 48-hour timeframe compared to those with E. faecium bacteraemia (88% versus 93%; P = 0.038). While the benefit of early source control interventions has been demonstrated in various infections, including abdominal infections, necrotizing fasciitis, sepsis, candidemia, and staphylococcal or streptococcal bacteraemia [11,12,13, 19,20,21,22,23,24], evidence specific to enterococcal bacteraemia is limited. Two prior small studies investigating only catheter-related enterococcal bacteraemia reported conflicting results regarding the impact of catheter removal on mortality [25, 26]. One study found an association between catheter removal and improved survival [25], while the other showed no impact [26]. However, both studies were affected by immortal-time bias, as no specific time cut-off was applied for catheter removal, and the influence of palliative care limitations on therapeutic interventions was not considered. To the best of our knowledge, the present study is the first to demonstrate improved outcomes associated with early source control across all types of enterococcal bacteraemia, and in the subgroups of E. faecalis and E. faecium. Moreover, the positive impact of timely source control procedures on outcomes remained significant even after excluding patients with limitations of care. These findings underscore the importance of a multifaceted approach to the management of enterococcal bacteraemia, which should include ID consultation, early initiation of appropriate antimicrobial therapy, and prompt implementation of source control measures.

As expected, age > 60 years was independently associated with mortality [3, 5, 6, 8]. Additionally, as previously shown, the presence of sepsis or septic shock also influenced outcome [5, 6, 9]. Factors such as age, comorbidities, and the presence of sepsis are not specific predictors of outcome in patients with enterococcal bacteraemia but are common predictors across bacteraemias caused by other species and even bacterial infections in general [11,12,13, 19,20,21,22, 27,28,29]. Furthermore, nosocomial bacteraemia was associated with higher mortality [3]. Some possible explanations are that nosocomial infections are usually caused by E. faecium which is more commonly amoxicillin-resistant and previously was found to be associated with higher mortality [6]. This may be due to a higher rate of early inappropriate treatment and a greater prevalence in complex abdominal infections, which, in the present study, had a low percentage of prompt source control procedures [6].

As previously shown, among bacteraemias caused by different Gram-positive pathogens, bacteraemia by enterococcal species was associated with high mortality, comparable to that of Staphylococcus aureus [1]. A possible explanation for this difference may lie in patient characteristics, such as age. In our institution, patients with enterococcal bacteraemia were older (median age of 70 years) compared to those with S. aureus (68 years) or streptococcal bacteraemia (66 years) [13, 30]. Furthermore, a higher percentage of enterococcal bacteraemias had a nosocomial onset (60%) compared to S. aureus (36%) and streptococci (32%). Moreover, enterococcal bacteraemias were associated with a higher proportion of sepsis or septic shock (46%) compared to S. aureus (42%) and streptococci (34%). Additionally, as previously shown [1], a lower proportion of patients with enterococcal bacteraemia received appropriate empiric antimicrobial treatment compared to those with bacteraemia caused by S. aureus or streptococci [13, 30]. Thus, bacteraemia caused by enterococcal species is more frequently associated with multiple factors linked to increased mortality, including older age, nosocomial infection, sepsis or septic shock, and inappropriate antimicrobial treatment [29].

Our study has several limitations. First, it is a retrospective single-center study conducted in a university institution with a low prevalence of VRE and thus not being representative of the epidemiology of non-university centers, or those with higher prevalence of vancomycin-resistant isolates. However, the study sample is large, and all data were reviewed by an ID physician. Second, the inclusion of episodes from the cohort of patients with suspected infective endocarditis may have led to an overrepresentation of cases at high risk for infective endocarditis. Third, source control interventions performance might be influenced by decisions to restrict treatment and the readiness of surgeons, or interventional radiologists to undertake such procedures, thus introducing a performance bias. However, we addressed this issue by dividing episodes that did not undergo source control procedures into two: those who were or were under discussion of transitioning to limitations of care within 48 h and those who remained on maximal care during the same period. Furthermore, we performed a separate analysis among episodes without limitations of care, which also found that performing the indicated source control procedure was associated with improved outcomes. Additionally, only 11 patients (1%) died within 48 h from bacteraemia onset, thus having a limited impact on our findings. Fourth, for cases of infective endocarditis, cardiac surgery was considered a source control intervention when performed for heart failure indications present at the onset of bacteraemia, as surgical indications related to infection control or embolism prevention are typically determined after the 48-hour threshold. Lastly, we did not stratify the analysis by different antimicrobial regimens. However, previous studies have shown that the use of vancomycin for enterococcal bacteraemia is associated with worse outcomes [31, 32]. At our institution, however, glycopeptides, linezolid, or daptomycin were used for targeted therapy only in cases of amoxicillin-resistant isolates or when beta-lactam use was contraindicated.

In conclusion, our study in patients with enterococcal bacteraemia emphasizes the importance of early ID consultation, appropriate antimicrobial treatment, and especially the prompt performance of source control interventions, when indicated. Future studies are needed to evaluate the impact of such a comprehensive approach to the enhancement of patient care and the reduction of mortality.