This study analyzed blood culture time-to-positivity (TTP) for gram-negative bacteremia in immunocompromised children, finding over 95% of cases tested positive within 24 hours, unrelated to underlying diseases or degree of neutropenia. The results support safe de-escalation of broad-spectrum antibiotics after 24 hours of negative blood cultures, reducing adverse effects and treatment costs.
Literature Overview
This article, 'Blood Cultures Time-to-Positivity as an Antibiotic Stewardship Tool in Immunocompromised Children with Gram-Negative Bacteraemia,' published in Antibiotics, reviews a single-center retrospective observational study analyzing blood culture time-to-positivity (TTP) data from 128 cases of gram-negative bloodstream infections (GNB-BSI) in immunocompromised children.
Background Knowledge
Immunocompromised children, particularly those with hematologic malignancies or other immunosuppressive conditions, face high infection risks and mortality. Rising multidrug-resistant (MDR) gram-negative bacterial infections have driven clinical reliance on broader-spectrum antibiotics like carbapenems or combination therapies, increasing drug-related toxicity and antibiotic selection pressure. Current guidelines recommend evaluating antibiotic de-escalation after 48-72 hours of blood culture incubation, but this study demonstrates that gram-negative bacteremia likelihood is minimal beyond 24 hours, supporting earlier de-escalation to reduce unnecessary broad-spectrum exposure. Blood culture TTP is a critical indicator for bacteremia assessment, with shorter TTP typically reflecting higher bacterial load and infection severity. While TTP-guided de-escalation strategies have been validated in adults, large-scale pediatric studies remain lacking. This research fills this gap, offering evidence for pediatric antibiotic management and providing significant value in early bloodstream infection identification and treatment optimization.
Research Methods and Experiments
This single-center retrospective cohort study included 128 gram-negative bacteremia cases among 100 immunocompromised children between 2020 and 2023. All blood cultures were detected using the BACT/ALERT 3D automated system. Primary endpoints included TTP distribution and its associations with clinical features (e.g., neutropenia severity, prior antibiotic exposure, infection source) and microbial characteristics (pathogen species, drug resistance). Secondary analyses evaluated risk factors for delayed positivity beyond 24 hours and their associations with clinical outcomes (e.g., PICU admission, 30-day mortality).
Key Conclusions and Perspectives
Research Significance and Prospects
This study provides a novel clinical decision-making tool for antibiotic management in immunocompromised children by optimizing de-escalation strategies through TTP analysis. Future multi-center prospective studies are required to validate the safety and efficacy of this approach, particularly in regions with high MDR prevalence. Additionally, further investigations should assess the impact of different blood culture systems and sample collection timing on TTP to enhance generalizability across clinical settings.
Conclusion
This study represents the first large-scale evaluation of TTP's clinical utility in gram-negative bacteremia among immunocompromised children. Findings demonstrate that over 95% of cases achieve positivity within 24 hours, with no severe outcomes observed in late-positive cases. These results support earlier antibiotic de-escalation at 24 hours post-culture, reducing unnecessary broad-spectrum therapy and its associated risks. The study further identifies delayed positivity beyond 24 hours as primarily associated with non-Escherichia coli pathogens (e.g., Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterobacter cloacae) and prior antibiotic exposure. These findings justify revising current guidelines to advance de-escalation timing from 72 hours to 24 hours, particularly in resource-limited or high-antibiotic-resistance environments, to minimize drug toxicity, healthcare costs, and resistance emergence. Future studies should validate these results across diverse blood culture systems and patient populations.
