Neutropenic Sepsis: Prevention and Management in People with Cancer in Secondary Care

Overview

This specialist Guidelines summary covers preventing, identifying, and managing neutropenic sepsis in children, young people, and adults receiving treatment for cancer in secondary care. It aims to reduce the risk of infection in people with neutropenia (low number of white blood cells) who are receiving anticancer treatment, and improve management of neutropenic sepsis. This summary is intended for use in a secondary care setting by oncologists.

A table of NHS England interim treatment regimens gives possible alternative treatment options for use during the COVID-19 pandemic to reduce infection risk. This may affect decisions for patients with cancer. See the COVID-19 rapid guideline: delivery of systemic anticancer treatments for more details.

Information, Support, and Training

Information and Support for Patients and Carers

• Provide patients having anticancer treatment and their carers with written and oral information, both before starting and throughout their anticancer treatment, on:
  • neutropenic sepsis
  • how and when to contact 24-hour specialist oncology advice
  • how and when to seek emergency care.

Training for Healthcare Professionals

• Healthcare professionals and staff who come into contact with patients having anticancer treatment should be provided with training on neutropenic sepsis. The training should be tailored according to the type of contact.

Reducing the Risk of Septic Complications of Anticancer Treatment

• For adult patients (aged 18 years and older) with acute leukaemias, stem cell transplants or solid tumours in whom significant neutropenia (neutrophil count 0.5×10⁹ per litre or lower) is an anticipated consequence of chemotherapy, offer prophylaxis with a fluoroquinolone^[A] during the expected period of neutropenia only. Follow the MHRA safety advice on fluoroquinolone antibiotics.
• Rates of antibiotic resistance and infection patterns should be monitored in treatment facilities where patients are having fluoroquinolones for the prophylaxis of neutropenic sepsis.^[B]
• Do not routinely offer granulocyte-colony stimulating factor (G-CSF) for the prevention of neutropenic sepsis in adults receiving chemotherapy unless they are receiving G-CSF as an integral part of the chemotherapy regimen or in order to maintain dose intensity.

Managing Suspected Neutropenic Sepsis in Secondary and Tertiary Care

Emergency Treatment and Assessment

• Treat suspected neutropenic sepsis as an acute medical emergency and offer empiric antibiotic therapy immediately.
• Include in the initial clinical assessment of patients with suspected neutropenic sepsis:
  • history and examination
  • full blood count, kidney, and liver function tests (including albumin), C-reactive protein, lactate, and blood culture.

Further Assessment

• After completing the initial clinical assessment (see above) try to identify the underlying cause of the sepsis by carrying out:
  • additional peripheral blood culture in patients with a central venous access device if clinically feasible
  • urinalysis in all children aged under 5 years.
• Do not perform a chest X-ray unless clinically indicated.

Starting Antibiotic Therapy

All patients

• Offer beta lactam monotherapy with piperacillin with tazobactam^[C] as initial empiric antibiotic therapy to patients with suspected neutropenic sepsis who need intravenous treatment unless there are patient-specific or local microbiological contraindications.
• Do not offer an aminoglycoside, either as monotherapy or in dual therapy, for the initial empiric treatment of suspected neutropenic sepsis unless there are patient-specific or local microbiological indications.

Empiric Glycopeptide Antibiotics in Patients with Central Venous Access Devices

• Do not offer empiric glycopeptide antibiotics to patients with suspected neutropenic sepsis who have central venous access devices unless there are patient-specific or local microbiological indications.
• Do not remove central venous access devices as part of the initial empiric management of suspected neutropenic sepsis.

Confirming a Diagnosis of Neutropenic Sepsis

• Diagnose neutropenic sepsis in patients having anticancer treatment whose neutrophil count is 0.5×10⁹ per litre or lower and who have either:
  • a temperature higher than 38^oC, or
  • other signs or symptoms consistent with clinically significant sepsis.

Managing Confirmed Neutropenic Sepsis

Assessing the Patient's Risk of Septic Complications

• A healthcare professional with competence in managing complications of anticancer treatment should assess the patient's risk of septic complications within 24 hours of presentation to secondary or tertiary care, basing the risk assessment on presentation features and using a validated risk scoring system.^[D]

Patients at Low Risk of Septic Complications

• Consider outpatient antibiotic therapy for patients with confirmed neutropenic sepsis and a low risk of developing septic complications, taking into account the patient's social and clinical circumstances and discussing with them the need to return to hospital promptly if a problem develops.

Patients at High Risk of Septic Complications

• For patients with confirmed neutropenic sepsis and a high risk of developing septic complications, a healthcare professional with competence in managing complications of anticancer treatment should daily:
  • review the patient's clinical status
  • reassess the patient's risk of septic complications, using a validated risk scoring system.^[D]
• Do not switch initial empiric antibiotics in patients with unresponsive fever unless there is clinical deterioration or a microbiological indication.
• Switch from intravenous to oral antibiotic therapy after 48 hours of treatment in patients whose risk of developing septic complications has been reassessed as low by a healthcare professional with competence in managing complications of anticancer treatment using a validated risk scoring system.^[D]
• Offer discharge to patients having empiric antibiotic therapy for neutropenic sepsis only after:
  • the patient's risk of developing septic complications has been reassessed as low by a healthcare professional with competence in managing complications of anticancer treatment using a validated risk scoring system,^[D] and
  • taking into account the patient's social and clinical circumstances and discussing with them the need to return to hospital promptly if a problem develops.

Duration of Empiric Antibiotic Treatment

• Continue inpatient empiric antibiotic therapy in all patients who have unresponsive fever unless an alternative cause of fever is likely.
• Discontinue empiric antibiotic therapy in patients whose neutropenic sepsis has responded to treatment, irrespective of neutrophil count.

Footnotes

[A] At the time of review (November 2019), fluoroquinolone antibiotics did not have a UK marketing authorisation for this indication. The prescriber should follow relevant professional guidance, taking full responsibility for the decision. Informed consent should be obtained and documented. See the General Medical Council's Prescribing guidance: prescribing unlicensed medicines for further information.

[B] For more information, see the Department of Health's Updated guidance on the diagnosis and reporting of Clostridium difficile and guidance from the Health Protection Agency and the Department of Health on Clostridium difficile infection: how to deal with the problem.

[C] At the time of publication (September 2012), piperacillin with tazobactam did not have a UK marketing authorisation for use in children aged under 2 years. The prescriber should follow relevant professional guidance, taking full responsibility for the decision. The child's parent or carer should provide informed consent, which should be documented. See the General Medical Council's Good practice in prescribing medicines – guidance for doctors and the prescribing advice provided by the Joint Standing Committee on Medicines (a joint committee of the Royal College of Paediatrics and Child Health and the Neonatal and Paediatric Pharmacists Group) for further information.

[D] Examples of risk scoring systems include the Multinational Association for Supportive Care in Cancer risk index: a multinational scoring system for identifying low-risk febrile neutropenic cancer patients (Journal of Clinical Oncology 2000; 18: 3038–3051) and the modified Alexander rule for children (aged under 18) (European Journal of Cancer 2009; 45: 2843–2849).