New approaches to management of fever and neutropenia in high-risk patients

Patients receiving treatment for acute leukaemia and haematopoietic cell transplantation (HCT) have prolonged neutropenia and are at high risk of neutropenic fever, with bacterial and particularly invasive fungal infections as feared complications, possessing potentially serious consequences including intensive care admission and mortality. Concerns for these serious complications often lead to long durations of broad-spectrum antimicrobial therapy and escalation to even broader therapy if fever persists. Further, the default approach is to continue neutropenic fever therapy until count recovery, leaving many patients who have long defervesced on prolonged antibiotics.This article details recent progress in this field with particular emphasis on early discontinuation studies in resolved neutropenic fever and improved imaging techniques for the investigation of those with persistent neutropenic fever. Recent randomized controlled trials have shown that early cessation of empiric neutropenic fever therapy is well tolerated in acute leukaemia and autologous HCT patients who are clinically stable and afebrile for 72 h. Delineation of the best approach to cessation (timing and/or use of fluoroquinolone prophylaxis) and whether this approach is well tolerated in the higher risk allogeneic HCT setting is still required. Recent RCT data demonstrate utility of FDG-PET/CT to guide management and rationalize antimicrobial therapy in high-risk patient groups with persistent neutropenic fever.Acute leukaemic and autologous HCT patients with resolved neutropenic fever prior to count recovery can have empiric therapy safely discontinued or de-escalated. There is an emerging role of FDG-PET/CT to support decision-making about antibiotic and antifungal use in high-risk persistent/recurrent neutropenic fever patients.