Implementation and Evaluation of a Repeat Blood Culture Guideline in Hospitalized Children with Cancer and Febrile Neutropenia

Background

The overuse of repeat blood cultures beyond 48 hours in pediatric cancer patients with febrile neutropenia (FN) remains a challenge. Currently, no consensus guidelines exist for this practice, and the impact of institution-specific protocols has not been thoroughly studied. Addressing the timing and necessity of repeat blood cultures for persistent fever has been identified as a critical research gap in recent FN guidelines.

Methods

We conducted a single-center retrospective and prospective study at Riley Hospital for Children in Indianapolis, Indiana, evaluating pediatric hematology-oncology patients with FN episodes lasting ≥3 days. Episodes with positive blood cultures in the first 2 days or fever duration ≤2 days were excluded. Random effects were incorporated to account for patients with multiple admissions. Starting January 1, 2023, we implemented a new protocol limiting repeat blood cultures after 48 hours to cases of hemodynamic instability or recurrent fever (defined as a new fever occurring ≥72 hours after being afebrile). The study included an 8-year cohort (2016–2024), with a 7-year pre-implementation period and a 1-year post-implementation period.

Primary outcomes included reduction rates (pre- to post-implementation) in cultures collected per fever day after 48 hours, cultures per length of stay (LOS), and the yield of repeat blood cultures after 48 hours. Secondary outcomes included reductions in antibiotic use and cost savings.

Results

A total of 1,371 FN episodes (out of 2,648) met inclusion criteria, with 1,138 pre- and 233 post-guideline implementations. Among episodes with negative cultures in the first 48 hours, only four (0.29%) had new true pathogens detected on repeat cultures beyond 48 hours (three pre- and one post-implementation). Multivariate analysis demonstrated statistically significant reductions post-implementation in Antibiotic days (33%), total culture sets/ LOS (31%), post-Day 2 culture /LOS (30%), total culture sets/ fever day (27%), post-Day 2 culture sets/fever day (38%) (see Table 1 and Figure 1).

Conclusions

Repeat blood cultures are low yield in persistent FN without new clinical change. The implementation of repeat blood culture guidelines significantly reduced repeat cultures obtained after 48 hours and throughout FN admissions. This protocol proved to be safe, effective, and cost-efficient, particularly during the blood culture bottle shortage of 2024. These findings highlight the need for national consensus guidelines to standardize blood culture practices in pediatric cancer patients with FN and negative initial cultures.