Primary prevention

Comprises prophylaxis with granulocyte colony-stimulating factor (G-CSF), an antibacterial, or antifungal. Prophylactic use of a granulocyte-macrophage colony-stimulating factor (GM-CSF) is not recommended.[45]

G-CSF

Prophylaxis with G-CSF reduces the incidence of febrile neutropenia in adults undergoing chemotherapy for solid tumours and lymphoma.[53][54][55][56]

Prophylactic use of G-CSF is recommended in patients:[35][45][57][58]

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

  • at intermediate risk (10% to 20%) for febrile neutropenia who have ≥1 risk factor (i.e., aged >65 years receiving full-dose chemotherapy; prior chemotherapy; persistent neutropenia [≥7 days]; prior radiotherapy; recent surgery; bone marrow involvement [by tumour]; liver dysfunction; renal dysfunction).

G-CSF is not routinely recommended in patients at low risk (<10%) for febrile neutropenia, but may be considered (based on clinical judgment) for those who have two or more risk factors (i.e., aged >65 years receiving full-dose chemotherapy; prior chemotherapy; persistent neutropenia [≥7 days]; prior radiotherapy; recent surgery; bone marrow involvement [by tumour] liver dysfunction; renal dysfunction).[35][44][45]​​​​​​​

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.[45][57][58]​​​ Risk assessment for febrile neutropenia should be carried out after each cycle of chemotherapy.

Biosimilar formulations of G-CSF, and long-acting formulations (e.g., pegfilgrastim, eflapegrastim, efbemalenograstim alfa, and lipegfilgrastim) are approved in some countries for chemotherapy-induced febrile neutropenia prophylaxis. Long-acting formulations may offer clinical benefits compared with short-acting formulations (such as filgrastim).[59][60][61][62]​​​​

One systematic review concluded that more clinical trials are necessary to assess the benefits and harms of G-CSF compared with antibiotics for the prevention of infection in patients receiving myelotoxic chemotherapy.[63]

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.[44]

Fluoroquinolone prophylaxis is associated with risks, including antimicrobial resistance and toxicity.[64][65][66]​​​[67] Fluoroquinolone prophylaxis in high-risk patients requires a careful risk-benefit assessment over time, accounting for local and regional rates of fluoroquinolone resistance, individual contraindications to fluoroquinolones, and other consequences of prophylactic broad-spectrum antibiotic use.[66]

Systemic fluoroquinolone antibiotics may cause serious, disabling, and potentially long-lasting or irreversible adverse events. This includes, but is not limited to: tendinopathy/tendon rupture; peripheral neuropathy; arthropathy/arthralgia; aortic aneurysm and dissection; heart valve regurgitation; dysglycaemia; and central nervous system effects including seizures, depression, psychosis, and suicidal thoughts and behaviour.[68]

  • Prescribing restrictions apply to the use of fluoroquinolones, and these restrictions may vary between countries. In general, fluoroquinolones should be restricted for use in serious, life-threatening bacterial infections only. Some regulatory agencies may also recommend that they must only be used in situations where other antibiotics, that are commonly recommended for the infection, are inappropriate (e.g., resistance, contraindications, treatment failure, unavailability).

  • Consult your local guidelines and drug information source for more information on suitability, contraindications, and precautions.

​Patients receiving prophylaxis should be closely monitored for the emergence of resistant organisms.[3]

Antibiotic prophylaxis is not routinely recommended for patients with solid tumours.[44]

Antifungal prophylaxis

Prophylaxis using an oral azole or a parenteral echinocandin is recommended for patients anticipated to have profound and persistent neutropenia; for example, those with acute myeloid leukaemia or myelodysplastic syndromes, or those undergoing haematopoietic stem-cell transplantation.[44]

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.[44] 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).[3][44][69]​​​

Risk of invasive mould infection is increased in allogeneic haematopoietic stem-cell transplantation recipients receiving post-transplantation cyclophosphamide-based graft-versus-host disease prophylaxis, patients with corticosteroid-requiring graft-versus-host disease, and in recipients of haploidentical grafts.[44][70][71]​​ A mould-active azole (e.g., posaconazole) should be strongly considered as the prophylactic antifungal of choice in this context.[44] Mould-active azoles are associated with adverse effects, toxicity, drug-drug interactions, and costs that merit careful consideration.

Antifungal prophylaxis is not routinely recommended for patients with solid tumours.[44]

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.​​​[45][57][58]​​ Risk assessment for febrile neutropenia should be carried out after each cycle of chemotherapy.

Sargramostim, a granulocyte-macrophage colony-stimulating factor (GM-CSF), is primarily used for the treatment of febrile neutropenia and prophylactic use is not recommended.[45]

There is no evidence to support the use of prophylactic antibiotics in patients with a history of febrile neutropenia.

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