Background and objectiveInappropriate initial antimicrobial therapy has been associated with high mortality in patients with gram-negative bacilli bloodstream infections during febrile neutropenia following chemotherapy for hematological malignancies. The aim of this study is to determine this association in our hospital. MethodsA single center, retrospective, cohort study of bloodstream infection due to gram-negative bacilli and febrile neutropenia was conducted. Clinical characteristics, microbiological etiology, antimicrobial resistance profile, empirical and targeted antibiotic therapy, intensive care unit admission, persistent bacteremia and mortality were analyzed. ResultsOf the 171 episodes of bloodstream infection due to gram-negative bacilli, empirical antimicrobial therapy was inappropriate in 43 episodes (25.1 %). There was a significant difference in mortality at 7 and 30 days between patients who received appropriate versus inappropriate empirical treatment (4.6 % versus 13.9 %, p = 0.04; 15.6 % versus 32.5 %, p = 0.016). Inappropriate empirical treatment (RR, 2.97 [95 % CI, 1.01–8.74]), shock at the time of febrile neutropenia diagnosis (RR, 6.5 [95 % CI, 1.83–23.05]) carbapenem-resistant microorganism (RR, 3.73 [95 % CI, 1.14–12.24]) and persistent bacteremia (RR, 84.6 [95 % CI, 11.3–629.4]) were associated with an increased mortality at 7 and 30 days. In the multivariate analysis, shock (RR, 4.85 [95 % CI, 2.10–11.65]) and persistent bacteremia was independently associated with increased 30-day mortality, but inappropriate empirical antimicrobial therapy was not an independent prognostic determinant (RR, 1.66 [0.53–4.82]). ConclusionShock at the time of febrile neutropenia diagnosis contributes to mortality in patients with gram-negative bacilli bloodstream infection, in this scenario, appropriate empirical antimicrobial therapy should be encouraged.