Antibiotic use and outcome in patients with negative blood cultures, a new target population for antimicrobial stewardship interventions: A prospective multicentre cohort (NO-BACT)

[Objectives] To evaluate the appropriateness of antimicrobial treatment and the risk factors for mortality in patients with negative blood cultures (BC), in order to evaluate whether this population would be a suitable target for antimicrobial stewardship (AMS) interventions.[Methods] A multicentre prospective cohort study of patients with negative BC in three Spanish hospitals between October 2018 and July 2019 was performed. The main endpoints were the appropriateness of antimicrobial treatment (evaluated by two investigators according to local guidelines) and 30-day mortality. Cox-regression was performed to estimate the association between variables and 30-day mortality.[Results] Of 1011 patients in whom BC was obtained, these were negative in 803 (79%) and were included; 30-day mortality was 9% (70 patients); antibiotic treatment was considered inappropriate in 299 (40%) of 747 patients evaluated at day 2, and in 266 (46%) of 573 at day 5–7. The variables independently associated with increased risk of 30-day mortality were higher age (HR 1.05; 95% CI 1.03–1.07), neoplasia (HR 2.73; 95% CI 1.64–4.56), antibiotic treatment in the 48 h prior to BC extraction (HR 2.06; 95% CI 1.23–3.43) and insufficient antibiotic coverage at day 2 after BC obtainment (HR 2.35; 95% CI 1.39–4.00). Urinary, catheter and biliary sources of infection were associated with lower risk (HR 0.40; 95% CI 0.20–0.81).[Conclusions] Antimicrobial treatment is frequently inappropriate among patients with negative BC; insufficient antibiotic coverage at day 2 was associated with mortality. These results suggest that patients with negative BC are a suitable population for AS interventions.[Summary] Antimicrobial treatment in patients with negative blood culture was frequently inappropriate, and inappropriate coverage at day 2 was associated with increased risk of death. These data support the consideration of this population as a potential target for antimicrobial stewardship interventions.This study was funded by Acción Estratégica en Salud, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (PI17/01809), the Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0001 and RD16CIII/0004/0002), the Spanish Clinical Research and Clinical Trials Platform (SCReN, PT17/0017/0012), and CIBERINFEC (CB21/13/00012, CB21/13/00087), all from Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades, and co-funded by European Development Regional Fund “A way to achieve Europe,” Operative Program Intelligence Growth 2014–2020 and ERDF/ESF, “Investing in your future.”Peer reviewe

CAR immunotherapy for the treatment of infectious diseases: a systematic review

Immunotherapy treatments aim to modulate the host’s immune response to either mitigate it in inflammatory/autoimmune disease or enhance it against infection or cancer. Among different immunotherapies reaching clinical application during the last years, chimeric antigen receptor (CAR) immunotherapy has emerged as an effective treatment for cancer where different CAR T cells have already been approved. Yet their use against infectious diseases is an area still relatively poorly explored, albeit with tremendous potential for research and clinical application. Infectious diseases represent a global health challenge, with the escalating threat of antimicrobial resistance underscoring the need for alternative therapeutic approaches. This review aims to systematically evaluate the current applications of CAR immunotherapy in infectious diseases and discuss its potential for future applications. Notably, CAR cell therapies, initially developed for cancer treatment, are gaining recognition as potential remedies for infectious diseases. The review sheds light on significant progress in CAR T cell therapy directed at viral and opportunistic fungal infections