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We aimed to describe the effectiveness of our standardized protocol for febrile neutropenia (FN), which was targeted to minimize unintended outcomes and reduce antimicrobial consumption.The study was performed in a private hospital with 300 beds. We included all adult hematologic and oncologic cancer inpatients admitted between January 1, 2015-December 31, 2015, and January 1, 2016-May 31, 2017. The outcomes of the study were fatality, infections, and adherence to the antimicrobial stewardship program (ASP).We included 152 FN attacks of 95 adult inpatients from hematology and oncology wards; of these, 43% were women, and the median age was 57 years. The case fatality rate was 30% in the pre-ASP period and decreased to 11% in the post-ASP period (P = .024). The appropriate adding or changing (P = .006) and appropriate continuation or de-escalation or discontinuation of antimicrobials improved (P < .001). In the post-ASP period, Staphylococcus spp infections (from 22% to 8%, P = .02) and gram-negative infections decreased (from 43% to 20%, P = .003). In the multivariate analysis, appropriate continuation or de-escalation or discontinuation was increased in the post-ASP period (odds ratio [OR], 4.3; 95% confidence interval [CI], 1.82-10.41; P = .001), and gram-positive infections were decreased (OR, 0.32; 95% CI, 0.11-0.95, P = .041). Vancomycin and fluoroquinolone use decreased significantly.After implementation of the ASP, the case fatality rate among the patients with FN decreased. Appropriate antimicrobial use increased and overall antimicrobial consumption was reduced. Bacterial infections and Candida infections decreased.