Multisite external validation of a risk prediction model for the diagnosis of blood stream infections in febrile pediatric oncology patients without severe neutropenia

Abstract

Background Pediatric oncology patients are at increased risk for invasive bacterial infection due to immunosuppression. The risk of such infection in the absence of severe neutropenia (absolute neutrophil count (ANC) ≥500/μl) is not well established and a validated prediction model for blood stream infection (BSI) risk offers clinical utility. Methods A six-site retrospective external validation was conducted using a previously published risk prediction model for BSI in febrile pediatric oncology patients without severe neutropenia, the Esbenshade/Vanderbilt (EsVan) model. A reduced model (EsVan2) excluding two less clinically reliable variables was also created using the initial EsVan model derivative cohort, and validated using all five external validation cohorts. One dataset was only used in sensitivity analyses due to missing some variables. Results From the five primary data sets, there were a total of 1197 febrile episodes and 76 episodes of bacteremia. The overall C-statistic for predicting bacteremia was 0.695 with a 0.50 calibration slope for the original model and 1.0 calibration slope when recalibration was applied to the model. The model performed better in predicting high-risk bacteremia (Gram negative or Staphylococcus aureus infection) versus BSI alone with a C-statistic of 0.801 and a calibration slope of 0.65. The EsVan2 model outperformed the EsVan model across datasets with a C-statistic 0.733 for predicting BSI and 0.841 for high-risk BSI. Conclusions This external validation shows that the EsVan and EsVan2 models are able to predict BSI across multiple performance sites and could assist in decision making in clinical practice once validated and implemented prospectively.

Outcomes of observation without empiric intravenous antibiotics in febrile, nonneutropenic pediatric oncology patients

“…The majority of patients discharged home after initial evaluation without antibiotics with no adverse consequences. The overall incidence of positive blood culture was 3.4%, comparable to other similar‐sized cohorts of 3.1% to 3.6% . Other studies have found higher incidence ranging 6.1% to 10.9%, although these studies only included patients with CVCs.…”

“…If accounting for patients with CVCs alone, the incidence of positive blood culture in our study was 3.0% (6/203). Previous studies have proposed that characteristics such as height of fever, externalized CVCs, and absence of viral respiratory symptoms are associated with bacteremia. Our study demonstrated no significant differences in clinical variables between patients with and without positive blood cultures aside from rate of hospitalization.…”

“…The incidence of bacteremia in this population is reportedly 10% to 16.1% . In contrast, there are currently no consensus guidelines for the management of patients presenting with fever and nonneutropenia (FNN), in whom the incidence of bacteremia ranges 3.1% to 10.9% in recent studies . Historically, patients with FNN had been treated similarly to neutropenic patients with empiric antibiotics .…”

Nonneutropenic fever in children with cancer: A scoping review of management and outcome

“…A total of 646 titles and abstracts were reviewed, of which 83 full‐text articles were retrieved. From this, 16 relevant articles, describing 15 studies, were identified for inclusion in this review (Figure ) . No dedicated NNF treatment guidelines were identified in this search.…”

“…The inclusion criteria across the studies included in this review varied. Notably, nine (60%) studies only included patients with a central venous catheter (CVC) in situ . The type of CVC also varied across the studies with implanted ports more common in six, whereas tunneled external CVC were more common in two, albeit older, studies (type not reported in 7).…”