Febrile Neutropaeina
Published by PIER Network Clinical Review Group • Ratified by Child Health Governance • Last updated: 2026-03
Introduction Febrile neutropenia (FN) remains one of the most critical oncological emergencies in paediatric practice. It is defined as a temperature of ≥38°...
Introduction
Febrile neutropenia (FN) remains one of the most critical oncological emergencies in paediatric practice. It is defined as a temperature of ≥38°C in a child with an absolute neutrophil count ≤0.5 ×10⁹/L, or any immunocompromised child with clinical signs of infection. Children undergoing chemotherapy are particularly vulnerable due to profound immunosuppression and mucosal barrier disruption, which predispose them to rapid-onset, life-threatening sepsis.
The clinical spectrum of FN ranges from a well-appearing child with no obvious focus of infection to severe septic shock. Importantly, infection can occur without fever, particularly in younger children or those receiving corticosteroids, and even in non-neutropenic patients with central venous access devices (CVADs).
Why is FN a medical emergency
Children with cancer can deteriorate rapidly due to impaired inflammatory responses and the high prevalence of Gram-negative bacteraemia. Mortality is strongly associated with delays in antibiotic administration. Current UK and NICE guidance mandate that intravenous broad-spectrum antibiotics be given within 60 minutes of hospital arrival for any child with suspected FN. This principle applies even before neutrophil count confirmation—clinical suspicion should trigger immediate treatment.
Risk stratification and evolving practice
Historically, all children with FN were admitted for prolonged intravenous antibiotics. However, recent evidence and CCLG guidance support risk-adapted strategies using validated tools such as the AUS score. This approach identifies low-risk patients who may be eligible for early discharge on oral antibiotics, provided strict eligibility criteria and safety nets are in place. Such strategies reduce hospital stay, improve quality of life, and optimise resource use without compromising safety.
Key principles for UK practice
Treat suspected FN as a medical emergency
Administer first-line intravenous antibiotics within 60 minutes of arrival
Perform prompt clinical assessment and targeted investigations (blood cultures, FBC, CRP, renal and liver function tests)
Consider additional investigations based on symptoms (e.g., chest X-ray, viral PCR, stool cultures)
Apply AUS-based risk stratification and discharge eligibility checklist for outpatient management
Maintain robust communication between Paediatric Oncology Principal Treatment Centres (PTCs) and Shared Care Units (POSCUs)
These guidelines aim to standardise care across the Wessex region and align with national recommendations, ensuring timely intervention and safe outpatient management where appropriate.
Management of Suspected Febrile Neutropaenia
Definition of febrile neutropaenia
Neutrophil count ≤0.5 x 109/L, and either
Temperature ≥ 38 °C, OR
Signs or symptoms consistent with clinically significant infection
Any patient with a low neutrophil count who appears unwell with or without a fever should be treated with intravenous antibiotics, even if they do not fit the definition of febrile neutropenia.
Treat suspected febrile neutropenia as a medical emergency and offer empirical antibiotics immediately after prompt assessment and appropriate investigations, i.e. start treatment if you suspect the patient is neutropenic and has a temperature ≥ 38°C or other signs/symptoms of infection. Do not wait for neutrophil count confirmation.
Intravenous antibiotics MUST be administered within 60 minutes of arrival to hospital
Neutropenia should be assumed in the following:
Any patients with a neutrophil count of ≤0.5 x 109/L in the last 48 hours
Patients with ALL in induction or delayed intensification – note that patients in ALL induction have a functional neutropenia so treat as febrile neutropenia regardless of neutrophil count
Patients receiving chemotherapy for AML
Patients receiving chemotherapy for solid tumours 7-10 days after the start of chemotherapy
Patients within 3 months of HSCT
Severe aplastic anaemia
History and examination
All patients should undergo an initial clinical assessment to determine whether they are well or unwell. A full and detailed history and examination should then be completed, alongside any immediate treatment required.
Pertinent points in the history and examination should include:
Symptoms of an URTI or LRTI
Vomiting and diarrhoea
Fluid intake and urine output
Mucositis, including examination of the peri-anal area
Line site – pain, tenderness, redness
Rigors, pyrexia or mottling shortly after flushing the CVAD (suggestive of a line infection)
Recent procedural sites, e.g. LP, bone marrow aspirate/trephine
Presence of other focal symptoms/signs of infection
Infection can occur without fever, particularly in younger children or those receiving corticosteroids
Unwell children may have tachycardia, tachypnoea or poor peripheral perfusion. Hypotension is a late sign as the child may compensate for some time.
Initial investigations
Assessments for all patients
Blood cultures (Bactec bottles optimised for 4ml) | From each lumen of central line take at least 1-2 mL (4mL if age > 36 months). |
Bloods | Urgent FBC, U&Es, LFTs, CRP, blood gas and lactate |
Assessments to consider
Chest Xray | If respiratory symptoms/signs |
Respiratory viral swab/NPA/bacterial throat swab/sputum | If respiratory symptoms/signs |
Stool | If history of diarrhoea. Send for MCS, virology and C. difficile toxin. |
Swabs | For all clinically infected lesions, e.g. line site, rashes, oral mucosa. NB: pus is not present when neutropenic. |
Urinanalysis | If <5yrs or urinary symptoms, ideally before starting antibiotics. Do not delay antibiotics in an unwell child. |
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Initial treatment of suspected febrile neutropaenia
All children should be given 1st line intravenous antibiotics. These MUST be administered within 60 minutes of arrival to hospital.
Intravenous antibiotics to be given within 60 minutes*
First line:
Piperacillin/Tazobactam 90mg/kg 6 hourly (max 4.5g per dose). For <1month of age, 90mg/kg 8 hourly
If mild/moderate reaction to penicillin (low risk) or receiving high dose IV methotrexate:
Ceftazidime 50mg/kg 8 hourly (max 2g per dose)
If severe or life-threatening anaphylaxis to penicillin (high risk):
Meropenem 20mg/kg 8 hourly (max 2g per dose)
Patient with signs of severe sepsis or septic shock (caution with renal impairment/recent cisplatin):
Add Gentamicin 7mg/kg OD as a second antibiotic and/or appropriate alternative antibiotic depending on microbiology/culture results.
*unless patient specific or local microbiological indications
Septic shock
Initial management should be as per the SORT guidelines for septic shock with early involvement of senior clinicians and critical care teams.
Patients on prophylactic antibiotics
Prophylactic antibiotics (other than co-trimoxazole which should continue) should be suspended when a patient is receiving intravenous antibiotics, and resumed once IV antibiotic treatment has been stopped.
Patients with suspected or confirmed penicillin allergy
For patients who have experienced a mild/moderate reaction to penicillin (low risk)
These patients are SAFE to have 3rd generation cephalosporins (e.g. ceftazidime), thus give IV ceftazidime as first-line antibiotic
They should avoid 1st or 2nd generation cephalosporins (e.g. cefalexin or cefaclor)
Please refer them to the local allergy team for further evaluation
For patients who have experienced severe or life-threatening anaphylaxis to penicillin (high risk)
Start IV meropenem as first-line antibiotic
Please refer them to the Paediatric Allergy Service at UHS for further evaluation
Subsequent Management
Assessment of suitability for outpatient management
Following the first dose of intravenous antibiotics, patients should be assessed for suitability for ongoing febrile neutropenia management as an outpatient. Patients with low-risk febrile neutropenia may be suitable for discharge, and can be managed safely as an outpatient on oral antibiotics with regular telephone reviews.
Calculate the AUS score (Table 1), and AFTER the minimum observation period is complete, assess the patient’s eligibility for home care (Table 3).
If unsure, please contact the Paediatric Oncology team at UHS.
AUS-rule variables and score
AUS-variable | Yes | No |
Preceding chemotherapy MORE intensive than ALL maintenance, LCH maintenance or weekly vinblastine | 1 | 0 |
Total white cell count <0.3 x109/L | 1 | 0 |
Platelets <50 x109/L | 1 | 0 |
Calculate the total AUS score (minimum 0, maximum 3).
AUS score interpretation
Score | . |
0 | Very low risk for bacterial infection. |
1 | Low risk for bacterial infection. |
2 | Moderate risk for bacterial infection. |
3 | Higher risk for bacterial infection. |
Eligibility for home care
Once the minimum observation period as suggested by the AUS score has been completed, assess the patient’s eligibility for home care (Table 3). Must be YES to all criteria to be eligible for home care.
Eligibility criteria for home care for low-risk febrile neutropaenia
Any responses in a shaded box mean the patient is NOT ELIGIBLE for outpatient febrile neutropenia management.
Criteria | Yes | No |
|---|---|---|
Disease status – within 6 weeks of first diagnosis or confirmation of relapse | ||
Higher risk disease – is the patient in any of the following groups:
| ||
Confirmed focus of infection requiring inpatient care* | ||
Medical complication requiring inpatient care** | ||
Severe sepsis at FN presentation*** | ||
Availability of a 24-hour caregiver | ||
Good education of patient and carer on reportable symptoms | ||
Availability of a telephone | ||
Within 1 hour of treating hospital | ||
Treating team prefer to manage as an inpatient | ||
History of non-compliance with medical care |
including, but not limited to, central venous access device (CVAD) site infection, cellulitis, perianal cellulitis or pain, significant pneumonia, infection with multi-drug resistant bacteria.
*including, but not limited to, pain requiring intravenous analgesia, poor oral intake or excessive loss requiring intravenous hydration; respiratory distress or oxygen requirement.
***severe sepsis includes any of (i) altered conscious state, (ii) inotrope requirement, (iii) fluid bolus requirement >40ml/kg or (iv) respiratory support requirement Variations may consider excluding ANY patient who has received a fluid bolus or had a past unplanned admission to ICU. If well, presence of infiltrates on CXR may not be a contraindication to oral antibiotic therapy.
Management of febrile neutropaenia as an outpatient
If a patient has been deemed eligible for outpatient management, ensure the following prior to discharge home:
The patient has been reviewed by a locally approved competent specialist for suitability for discharge
The family has received appropriate education and information leaflet
The patient has tolerated one dose of oral antibiotics in hospital
The family agrees to take the child’s temperature 4-6 hourly during waking hours
Choice and duration of oral antibiotics
Oral co-amoxiclav and oral ciprofloxacin (dosed as per the BNFc)
If penicillin allergy: oral clarithromycin and oral ciprofloxacin (dosed as per the BNFc)
Supply the patient with 5 days of antibiotics
Antibiotics can be stopped when:
Negative blood culture
Clinically well
Afebrile >24 hours
Absence of a focal infection requiring a treatment course of antibiotics
Daily telephone call and responsibilities
After the patient has been discharged home, a daily telephone call to parents/carer is required until the antibiotic is stopped.
The blood culture must be chased at least daily – antibiotics may need to be changed depending on these results.
Day | Appointment/interventions |
0 (day of discharge) | Bloods reviewed before discharge |
1 | Observations at home |
2-4 | Observations at home |
5 | If remains febrile, patient to attend hospital for medical review and decision made for readmission or to continue at home/parent-led care |
Reasons for medical review following discharge
Patients will need to be reviewed in hospital for the following:
Ongoing fever (>72 hours from presentation) or new fever after being afebrile for 24 hours
Feeling unwell/new symptoms and signs
Parental concern
Significant decrease in oral intake or significant increase in output (vomiting and diarrhoea)
Positive blood culture or new infection identified after transfer home
Severe or persistent pain
Chills/rigor/shaking
Not afebrile by day 5 of home-based care
Indications for re-admission
Patients should be re-admitted and restarted on intravenous antibiotics if:
Clinically unwell/unstable
Fever >38°C beyond 5 days from the start of the febrile neutropenic episode
Infection requiring inpatient care
All patients who are re-admitted to hospital should be restarted on intravenous antibiotics as per the standard febrile neutropenia protocol (above), unless sensitivities from a positive blood culture are available.
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Ongoing management for patients who remain as inpatients
Children who are deemed not eligible for home care should remain as inpatients on intravenous antibiotics.
In children who remain persistently febrile, repeat blood cultures daily.
If unsure, contact the Paediatric Oncology team at UHS.
If afebrile and well at 48 hours and all cultures negative | Stop antibiotics and discharge home |
If still febrile at 48 hours but cultures negative | Continue first-line intravenous antibiotics |
If still febrile at 96 hours | Consider systemic fungal infection and adding IV Ambisome |
If cultures positive | See section below on antibiotic plans for children with positive blood cultures |
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Specific microbiological considerations
Positive blood cultures
The following table gives an indication of the action required in case of blood culture growth. Discuss with local Microbiology, and if unsure, contact the Paediatric Oncology team at UHS.
Antibiotic plans for children with positive blood cultures
Type of Growth | . |
Pseudomonas | Often need to remove CVAD. |
E. coli | Usually due to translocation in the context of mucosal barrier injury. |
Enterococcus | Usually due to translocation in the context of mucosal barrier injury. |
S. aureus | Often need to remove CVAD. |
Coagulase negative staphylococcus (CONS) isolation from 1 bottle | Repeat blood cultures and decide clinically whether IV vancomycin/teicoplanin should be added. If so, stop if blood culture negative and low suspicion for CVAD infection. |
Coagulase negative staphylococcus (CONS) infection is genuine (in at least 2 bottles ± fever) | Treat with IV vancomycin/teicoplanin (confirm sensitivities) for 7-10 days. Line locks if line salvage attempted, if fails often need to remove CVAD. Consider ambulation |
Candida | Treat for 14 days after last positive culture. Usually remove CVAD. |
Stenotrophomonas | Almost always need to remove CVAD. |
Other organisms | Depends on count recovery and microbiology advice. |
Other microbiological considerations
MRSA colonisation | Add IV vancomycin/teicoplanin empirically. Stop if S. aureus not cultured on blood culture |
Previous growth of ESBL | IV meropenem is usually indicated empirically |
Systemic fungal infections | Consider if the patient is still febrile at 96 hours and add IV Ambisome |
Pneumocystis pneumonia (PCP) | Consider if fever, dry cough, shortness of breath, low SpO2 and if doses of PCP prophylaxis have been missed |
Typhlitis (neutropenic enterocolitis) | Consider if fever, abdominal pain, vomiting/diarrhoea and signs of peritonitis |
C. difficile diarrhoea | See UK PAS guidance |
References
National Institute for Health and Clinical Excellence. Neutropenic sepsis: prevention and management of neutropenic sepsis in cancer patients. CG151 London: National Institute for Health and Clinical Excellence, 2012 http://guidance.nice.org.uk/CG151.
The Children’s and Young People’s Cancer Association. Managing Febrile Neutropenia in the UK in 2020 - Proposed New Management Pathway. The Children’s and Young People’s Cancer Association, 2020.
Jackson TJ, Napper R, Haeusler GM et al. Can I go home now? The safety and efficacy of a new UK paediatric febrile neutropenia protocol for risk-stratified early discharge on oral antibiotics. Arch Dis Child. 2023 Mar;108(3):192-197
Haeusler GM, Gaynor L, Teh B, et al. Home-Based care of low-risk febrile neutropenia in children-an implementation study in a tertiary paediatric Hospital. Support Care Cancer 2021;29:1609–17.
Morgan J, Phillips B, on behalf of the CCLG Supportive Care Group. ‘Winter 2017’ CCLG Audit of NICE CG151 Neutropenic Sepsis in Children and Young Adults, 2017. Available: https://www.cclg.org.uk/write/MediaUploads/Member%20area/FN_Audit_report_2017.pdf
Lehrnbecher T, Robinson PD, Ammann RA et al. Guideline for the Management of Fever and Neutropenia in Pediatric Patients With Cancer and Hematopoietic Cell Transplantation Recipients: 2023 Update. J Clin Oncol 41:1774-1785.