What is the impact of anti-enterococcal empirical therapy on survival of patients with enterococcal bloodstream infections?

Objective: the impact of early administration of active anti-enterococcal empirical therapy (EET) on outcomes of patients with enterococcal bloodstream infections (EBSI) is unclear. We aimed to compare the outcome of patients with EBSI receiving or not empirical therapy targeting Enterococcus spp. Methods: this is a retrospective multicenter study enrolling all hospitalized patients with monomicrobial EBSI during 2011-2019. Exposure variable was considered receiving EET defined as administration of antibiotic(s) in-vitro active against Enterococcus spp isolated from index blood cultures (BC) within 48 hours from collection. The primary outcome was 14- and 30-day all-cause mortality from index BC. The impact of EET on mortality was assessed by Kaplan-Meier curves and multivariable Cox-regression model after adjustment with inverse probability treatment weighting (IPTW). A post-hoc analysis explored the effect of EET given within 24 hours from EBSI onset. Results: Overall, 758 patients (male 62%; median age 71) had EBSI and 342 received EET. 14-and 30-day mortality were 24% and 42%, respectively. After IPTW-adjustment, higher number of comorbidities and EBSI without identified source but not EET were independent predictors of 14- and 30-day mortality. No significant mortality risk reduction was associated with EET either in the real or in the IPTW-adjusted. In the subgroup analysis, EET reduced 14-day mortality only in patients with vancomycin-resistant EBSI. Among 237 (31%) patients receiving EET <24h from EBSI onset, EET did not affect survival in multivariable Cox model. Conclusion: early administration of EET may not have prognostic impact in patients with EBSI. Delivering EET might affect short-term survival only in patients with vancomycin-resistant EBSI.