Efficacy and safety of withholding antimicrobial therapy in children with cancer, fever, and neutropenia, with a demonstrated viral respiratory infection: a randomized clinical trial.

OBJECTIVES: To validate the efficacy and safety of withholding antimicrobial therapy in a new cohort of children with cancer and febrile neutropenia (FN) having a demonstrated viral respiratory tract infection. METHODS: Prospective, multicenter, noninferiority, randomized study, approved by the ethical committee, in children presenting with FN at seven hospitals in Chile, evaluated at admission for diagnosis of bacterial and viral pathogens. Children who were positive for a respiratory virus, negative for a bacterial pathogen, and had a favourable evolution after 48-72 hours of antimicrobial therapy were randomized to either maintain or withhold antimicrobial therapy. The primary endpoint was the percentage of episodes with an uneventful resolution, whereas the secondary endpoints were days of fever, days of hospitalization, requirement of antimicrobial treatment readministration, sepsis, paediatric intensive care unit admission, and death. RESULTS: A total of 301 of 939 children with FN episodes recruited between March 2021 and December 2023 had a respiratory virus as a unique identified microorganism, of which 139 had a favourable evolution at 48-72 hours and were randomized, 70 to maintain and 69 to withdraw antimicrobial therapy. The median days of antimicrobial therapy was 5 (IQR 3-6) versus 3 (IQR 3-6) days (p < 0.001), with similar frequency of uneventful resolution 66/70 (94%) and 66/69 (96%); relative risk, 1.01; (95% CI, 0.93 to 1.09), absolute risk difference 0.01; (95% CI, -0.05 to 0.08) and similar number of days of fever and days of hospitalization. No cases of sepsis, paediatric intensive care unit admission, or death were reported. DISCUSSION: We validated the strategy of withdrawal antimicrobial therapy in children with FN and viral respiratory tract infection based on clinical and microbiological/molecular diagnostic criteria. This will enable advances in antimicrobial stewardship strategies with a possible future impact on antimicrobial resistance.

Clinical Outcome in Children With Cancer With Two or More Microorganisms Isolated From Blood Cultures During Episodes of Fever and Neutropenia.

BACKGROUND: Bacterial bloodstream infections are a major cause of morbidity and mortality in children with cancer and episodes of fever and neutropenia (FN). The aim of this study was to evaluate the clinical outcome in children with cancer with 2 or more microorganisms isolated from blood cultures during their episodes of FN. METHODS: Between 2016 and 2021, children presenting with high-risk FN, admitted to any of the 6 participating hospitals in Santiago, Chile, were included in this study if they have positive blood cultures. We compared the clinical outcome of children with 2 or more microorganisms versus those with single agent isolation. RESULTS: A total of 1074 episodes of high-risk FN were enrolled in the study period, of which 27% (298) had positive blood cultures and 3% (32) had 2 or more microorganisms isolated from blood cultures. The most frequent identified agents were Viridans group streptococci and Escherichia coli in 20%, followed by Coagulase negative staphylococci in 14%. Children with 2 or more microorganisms presented more days of fever (7 vs. 4 days, P = 0.02), needed longer courses of antimicrobial therapy (16 vs. 14 days, P = 0.04) and had higher mortality at day 30 (13% vs. 1%, P = 0.003). CONCLUSIONS: Children with cancer and FN with 2 or more microorganisms isolated from blood cultures had a worse clinical outcome than children with single agent isolation.