Repeat blood cultures in children with persistent fever and neutropenia: Diagnostic and clinical implications

Fever and neutropenia (FN) is one of the most common, life-threatening, and costly complications of treatment for childhood cancer [1–3]. Although initial blood cultures identify bloodstream infections (BSI) in 10–20% of children with FN, the majority of episodes do not have an identified infectious etiology, and fever persists despite antibiotic therapy in up to 40% of cases [4–7]. Although blood cultures are frequently repeated in children with persistent FN, it is unclear how often this strategy identifies additional BSI, and how management is altered based on subsequent blood cultures. Potential harms of excessive blood culture collection include iatrogenic blood loss, which may increase transfusion requirements, and false positive results, which lead to additional laboratory testing, unnecessary antibiotic therapy, and increased costs [8–10]. The optimal approach to repeating blood cultures during persistent FN was identified as an important research gap in recent pediatric FN guidelines [11]. Prior studies examining the yield of subsequent blood cultures in patients with FN have demonstrated varying rates of new BSI. In an adult hematopoietic stem cell transplant (HSCT) cohort, 1 (0.9%) of 109 patients who had blood cultures collected after day 1 of FN had a new pathogen identified by follow-up culture [12]. In a study of children with FN whose initial cultures were negative, new BSI were identified via subsequent cultures in 24 (10%) of 220 episodes [13]. Because secondary infections may occur during treatment for the initial infection, it is also important to evaluate the yield of subsequent blood cultures in children whose initial cultures are positive [6, 14]. Subsequent blood culture yield should also be evaluated in pediatric HSCT recipients, a group with high incidence of persistent FN and high risk for BSI [4, 15]. At our center, blood cultures are repeated every 24 hours in the setting of ongoing FN. We evaluated the diagnostic yield of subsequent cultures in order to better characterize the utility of this approach in children with persistent FN, including those with previous positive cultures and HSCT recipients.