Strategies for Empiric Management of Pediatric Fever and Neutropenia in Patients With Cancer and Hematopoietic Stem-Cell Transplantation Recipients: A Systematic Review of Randomized Trials

Abstract

Purpose To describe treatment failure and mortality rates with different antibiotic regimens and different management strategies for empirical treatment of fever and neutropenia (FN) in pediatric patients with cancer and hematopoietic stem-cell transplantation (HSCT) recipients. Methods We conducted a systematic review and performed searches of MEDLINE, Embase, PubMed, and Cochrane Central Register of Controlled Trials. Studies were included if pediatric patients had cancer or were HSCT recipients and the intervention was related to the management of FN. Strategies synthesized were monotherapy versus aminoglycoside-containing combination therapy; antipseudomonal penicillin monotherapy versus fourth-generation cephalosporin monotherapy; inpatient versus outpatient management; oral versus intravenous antibiotics; and addition of colony-stimulating factors. Results Of 11,469 citations screened, 68 studies randomly assigning 7,265 episodes were included. When compared with monotherapy, aminoglycoside-containing combination therapy did not decrease treatment failures (risk ratio, 1.13; 95% CI, 0.92 to 1.38; P = 0.23), and no difference in mortality was observed. Antipseudomonal penicillin and fourth-generation cephalosporin monotherapy were associated with similar failure and mortality rates. Outpatient management and oral antibiotics were safe in low-risk FN with no infection-related mortality observed in any patient and no significant differences in outcomes compared with inpatient management and intravenous therapy. Therapeutic colony-stimulating factors were associated with a 1.42-day reduction in hospitalization (95% CI, 0.62 to 2.22 days; P < .001). Conclusion There were a moderate number of pediatric randomized trials of FN management. Monotherapy for high-risk FN and outpatient and oral management for low-risk FN are effective strategies. These findings will provide the basis for guideline recommendations in pediatric FN.