Primary prevention

Prophylaxis with granulocyte colony-stimulating factors (G-CSFs) reduces the incidence of febrile neutropenia in adults undergoing chemotherapy for solid tumours and lymphoma.[33][34][35][36]

Prophylactic use of G-CSF is recommended in patients:[23][37][38][39]

  • at high risk (>20%) for febrile neutropenia, or

  • at intermediate risk (10% to 20%) for febrile neutropenia who have ≥1 risk factor (i.e., age >65 years; prior chemotherapy; persistent neutropenia; prior radiotherapy; recent surgery; bone marrow involvement [by tumour]; liver dysfunction; renal dysfunction).

G-CSFs are not routinely recommended in patients at low risk (<10%) for febrile neutropenia, but may be considered (based on clinical judgment) in those who have two or more risk factors (i.e., age >65 years; prior chemotherapy; persistent neutropenia; prior radiotherapy; recent surgery; bone marrow involvement [by tumour] liver dysfunction; renal dysfunction).[23][37]​​​

If a patient developed febrile neutropenia during a prior cycle of chemotherapy and G-CSF prophylaxis was not used, then G-CSF prophylaxis should be considered for use with subsequent cycles of chemotherapy.[37][38][39]​ Risk assessment for febrile neutropenia should be carried out after each cycle of chemotherapy.

Biosimilar formulations of G-CSF, and long-acting formulations (such as lipegfilgrastim, eflapegrastim, and efbemalenograstim alfa) are approved in some countries for chemotherapy-induced febrile neutropenia prophylaxis. Long-acting formulations may offer clinical benefits compared with short-acting G-CSFs, such as filgrastim.[40][41][42][43]​​

One systematic review concluded that more clinical trials are necessary to assess the benefits and harms of CSFs compared with antibiotics for the prevention of infection in cancer patients of all ages receiving chemotherapy.[44]

Antibacterial prophylaxis

Joint ASCO and Infectious Diseases Society of America (IDSA) guidelines recommend antibiotic prophylaxis with a fluoroquinolone for patients at high risk for febrile neutropenia or profound, protracted (>7 days) neutropenia, such as patients with acute myeloid leukaemia, myelodysplastic syndromes, or haematopoietic stem-cell transplantation treated with myeloablative conditioning regimens.[45]

Fluoroquinolone prophylaxis in high-risk patients requires a careful risk-benefit assessment over time, accounting for local and regional rates of fluoroquinolone resistance and other consequences of prophylactic broad-spectrum antibiotic use.[46]

Patients receiving prophylaxis should be closely monitored for the emergence of resistant organisms.[1]

Antibiotic prophylaxis is not routinely recommended for patients with solid tumours.[45]

Antifungal prophylaxis

Prophylaxis using an oral azole or a parenteral echinocandin is recommended for patients at risk for profound and prolonged neutropenia; for example, those with acute myeloid leukaemia or myelodysplastic syndromes, or those undergoing haematopoietic stem-cell transplantation.[45]

A mould-active azole antifungal (e.g., voriconazole, posaconazole, isavuconazole) is recommended for prophylaxis where the risk of invasive aspergillosis is >6%, such as in patients with acute myeloid leukaemia or myelodysplastic syndromes during the neutropenic period associated with chemotherapy.[45] For standard-risk autologous and allogeneic haematopoietic stem-cell transplant recipients, use of fluconazole prophylaxis during neutropenia is the conventional approach, with use of mould-active azole prophylaxis typically reserved for those patients with increased risk for mould infection or prior history of mould infection (i.e., secondary prophylaxis).[1][45][47]​ Risk of invasive mould infection is increased in patients with corticosteroid-requiring graft-versus-host disease following allogeneic haematopoietic stem-cell transplantation, and a mould-active azole (e.g., posaconazole) should be strongly considered in this context.[45] Mould-active azoles are associated with adverse effects, toxicity, and drug-drug interactions that merit careful consideration.

Antifungal prophylaxis is not routinely recommended for patients with solid tumours.[45]

Secondary prevention

Patients with a history of febrile neutropenia are at risk for subsequent episodes of febrile neutropenia.

If a patient developed febrile neutropenia during a prior cycle of chemotherapy and granulocyte colony-stimulating factor (G-CSF) prophylaxis was not used, then G-CSF prophylaxis should be considered for use with subsequent cycles of chemotherapy.​​​[37][38][39]​​ Risk assessment for febrile neutropenia should be carried out after each cycle of chemotherapy.

There is no evidence to support the use of prophylactic antibiotics in these patients.

Use of this content is subject to our disclaimer