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A child having cancer treatment who gets a fever, or seems unwell, needs to be seen in hospital straight away, using the team's number. There blood cultures are taken from every channel of the central line and one strong antibiotic is started through a drip. Children at low risk may finish at home or by mouth, and antibiotics can often stop after two days if cultures stay clear.
The International Pediatric Fever and Neutropenia Guideline Panel's 2023 update (79 randomised trials, GRADE) covers patients aged 0 to 18 receiving chemotherapy for cancer and recipients of haematopoietic cell transplant, and is endorsed by the Children's Oncology Group. Adopt a validated paediatric risk stratification rule (strong, low). Take blood cultures from all lumens of a central venous catheter at onset (strong, low); a peripheral culture alongside is conditional, because it adds 12% of bacteraemias but causes pain and contaminants. Urine where a clean-catch specimen is readily available (conditional); chest radiograph only with respiratory signs (strong, moderate).
High-risk episodes get monotherapy with an antipseudomonal beta-lactam, a fourth-generation cephalosporin or a carbapenem (strong, high); a second anti-Gram-negative agent or a glycopeptide is reserved for instability, suspected resistance or high-resistance centres. A new good practice statement asks for therapy as soon as possible in the clinically unstable child, ideally much sooner than an hour after presentation; the panel could not agree a time target for well, low-risk children. Low-risk episodes may be managed as outpatients or with oral antibiotics where the infrastructure allows (conditional). Antibiotics stop at 48 hours with negative cultures once the child has been well and afebrile for 24 hours, with marrow recovery (strong) or, new in 2023, without it in low-risk FN (conditional). For fever lasting 96 hours or more in children at high risk of invasive fungal disease: CT chest (strong), consider abdominal ultrasound, do not use beta-D-glucan or fungal PCR, and start caspofungin or liposomal amphotericin B (strong, high) unless a pre-emptive approach is chosen. NICE CG151, for any age, recommends piperacillin with tazobactam alone first and names the modified Alexander rule for children under 18.
Why: Most fevers start at home, so parents need to know what to look for and whom to call before it happens.
“Provide patients having anticancer treatment and their carers with written and oral information, both before starting and throughout their anticancer treatment, on:”
Why: A child with a serious infection and few white cells can get worse within hours, and early antibiotics are what improve survival.
“For febrile patients who are clinically unstable, initiate FN CPG-consistent empiric antibacterial therapy as soon as possible.”
International Pediatric Fever and Neutropenia Guideline Panel, Journal of Clinical Oncology 2023 · Good practice statement
Why: Risk decides who needs intravenous antibiotics in hospital and who can be treated more lightly, at home or by mouth.
“Adopt a validated risk stratification strategy and incorporate it into routine clinical management”
International Pediatric Fever and Neutropenia Guideline Panel, Journal of Clinical Oncology 2023 · strong recommendation, low-quality evidence
Why: Germs can sit in one channel of the line and not another; sampling all of them finds more infections.
“Obtain blood cultures at the onset of FN from all lumens of central venous catheters”
International Pediatric Fever and Neutropenia Guideline Panel, Journal of Clinical Oncology 2023 · strong recommendation, low-quality evidence
Why: In the panel's review, 12% of true bloodstream infections were found only in the peripheral culture; it is conditional because it hurts and it is not known whether finding them changes the outcome.
“Consider obtaining peripheral blood cultures concurrent with central venous catheter cultures”
International Pediatric Fever and Neutropenia Guideline Panel, Journal of Clinical Oncology 2023 · conditional recommendation, moderate-quality evidence
Why: Urine infections in these children often cause no symptoms; NICE asks for urinalysis in all children under 5.
“Consider urinalysis and urine culture in patients where a clean-catch, mid-stream specimen is readily available”
International Pediatric Fever and Neutropenia Guideline Panel, Journal of Clinical Oncology 2023 · conditional recommendation, low-quality evidence
Why: Pneumonia is very rare without chest symptoms, and leaving out the X-ray in those children did no harm.
“Obtain chest radiography only in patients with respiratory signs or symptoms”
International Pediatric Fever and Neutropenia Guideline Panel, Journal of Clinical Oncology 2023 · strong recommendation, moderate-quality evidence
Why: Twelve trials found adding an aminoglycoside did not reduce treatment failure or deaths, so one drug is enough for most children.
“Use monotherapy with an antipseudomonal β-lactam, a fourth-generation cephalosporin or a carbapenem as empiric antibacterial therapy in pediatric high-risk FN”
International Pediatric Fever and Neutropenia Guideline Panel, Journal of Clinical Oncology 2023 · strong recommendation, high-quality evidence
Why: Extra antibiotics add side effects and resistance without helping the stable child.
“Reserve addition of a second anti-Gram-negative agent or a glycopeptide for patients who are clinically unstable, when a resistant infection is suspected, or for centers with a high rate of resistant pathogens”
International Pediatric Fever and Neutropenia Guideline Panel, Journal of Clinical Oncology 2023 · strong recommendation, moderate-quality evidence
Why: Five trials found no difference in failure or death and almost four fewer days in hospital, provided the family can reach the team and come back quickly.
“Consider initial or step-down outpatient management if the infrastructure is in place to ensure careful monitoring and follow-up”
International Pediatric Fever and Neutropenia Guideline Panel, Journal of Clinical Oncology 2023 · conditional recommendation, moderate-quality evidence
Why: Oral treatment worked as well as intravenous in the trials, but readmission was more common, so it is offered rather than required.
“Consider oral antibacterial therapy administration if the patient is able to tolerate this route of administration reliably”
International Pediatric Fever and Neutropenia Guideline Panel, Journal of Clinical Oncology 2023 · conditional recommendation, moderate-quality evidence
Why: Fever on its own often settles; changing drugs adds harm. Instability is the signal to widen cover.
“Do not broaden the initial empiric antibacterial regimen based solely on persistent fever in patients who are clinically stable”
International Pediatric Fever and Neutropenia Guideline Panel, Journal of Clinical Oncology 2023 · strong recommendation, low-quality evidence
Why: The risk of the fever coming back is very low at this point, and every extra day of antibiotics has costs.
“In both high-risk and low-risk FN patients who have been clinically well and afebrile for at least 24 hours, discontinue empiric antibacterial therapy if blood cultures remain negative at 48 hours if there is evidence of marrow recovery”
International Pediatric Fever and Neutropenia Guideline Panel, Journal of Clinical Oncology 2023 · strong recommendation, low-quality evidence
Why: New in 2023: trials showed stopping was as safe as continuing in low-risk children, moving the point from 72 to 48 hours.
“In patients with low-risk FN who have been clinically well and afebrile for at least 24 hours, consider discontinuation of empiric antibacterial therapy if blood cultures remain negative at 48 hours despite no evidence of marrow recovery”
International Pediatric Fever and Neutropenia Guideline Panel, Journal of Clinical Oncology 2023 · conditional recommendation, moderate-quality evidence
Why: The lungs are the commonest site of fungal infection, and CT shows the typical signs.
“Perform computed tomography (CT) of lungs”
International Pediatric Fever and Neutropenia Guideline Panel, Journal of Clinical Oncology 2023 · strong recommendation, low-quality evidence
Why: These tests gave wrong positive results too often (positive predictive values of 49% and 17%) to be useful.
“Do not use fungal polymerase chain reaction testing in blood”
International Pediatric Fever and Neutropenia Guideline Panel, Journal of Clinical Oncology 2023 · strong recommendation, moderate-quality evidence
Why: These two worked equally well in trials, and liposomal amphotericin harms the kidneys less than the older form.
“In IFD high-risk patients with prolonged (≥ 96 hours) FN unresponsive to broad-spectrum antibacterial therapy, initiate caspofungin or liposomal amphotericin B for empiric antifungal therapy unless a pre-emptive antifungal therapy approach is chosen”
International Pediatric Fever and Neutropenia Guideline Panel, Journal of Clinical Oncology 2023 · strong recommendation, high-quality evidence
How care is usually carried out, read from the guidelines and standards cited. Your own team's protocol and their judgement come first; this page is for understanding it, not for doing it yourself.
The International Pediatric Fever and Neutropenia Guideline Panel's 2023 update, endorsed by the Children's Oncology Group in May 2023, is the only current guideline built on paediatric trials alone and is the standard to follow: validated risk stratification, cultures from every lumen, single-agent antipseudomonal therapy for high-risk episodes, outpatient or oral options for low-risk ones, and stopping at 48 hours once well and afebrile for 24 hours. On the first drug, NICE CG151 (written for any age) is narrower and names piperacillin with tazobactam alone, while the international panel allows any antipseudomonal beta-lactam, fourth-generation cephalosporin or carbapenem by local epidemiology; both advise against a routine aminoglycoside or glycopeptide. On timing, NICE says immediately with no clock, the international panel says as soon as possible for the unstable child (ideally well inside an hour) and could not agree a target for well, low-risk children, some preferring to wait for the neutrophil count. NICE asks for urinalysis in every child under 5; the panel makes urine conditional on an easy clean-catch sample.
International Pediatric Fever and Neutropenia Guideline Panel, Journal of Clinical Oncology 2023 · Children's Oncology Group 2023 · NICE 2012
Where it differs: Names one drug, piperacillin with tazobactam, as the first empiric antibiotic, asks for urinalysis in all children aged under 5, and names the modified Alexander rule as an example of a risk score for children under 18. NICE noted at publication that piperacillin with tazobactam had no UK marketing authorisation for children under 2.
Evidence: NICE does not grade recommendations; its evidence review for monotherapy is in the adult protocol. The international panel's broader choice rests on 12 paediatric trials of monotherapy against combination therapy.
NICE 2012 · International Pediatric Fever and Neutropenia Guideline Panel, Journal of Clinical Oncology 2023
Where it differs: Some centres give the first antibiotic only once the count confirms neutropenia, in children who look well and are at low risk; others give it before the count. The international panel was split and made no statement, asking institutions to speed up the count.
Evidence: No graded recommendation either way; the panel names it as needing more research.
International Pediatric Fever and Neutropenia Guideline Panel, Journal of Clinical Oncology 2023
Where it differs: In non-transplant children at high risk of fungal infection who are not on mould-active prophylaxis, antifungal treatment for prolonged fever is held until tests or imaging suggest fungal infection, instead of being started on fever alone.
Evidence: Conditional recommendation, moderate-quality evidence, from one trial in which pre-emptive therapy shortened antifungal use (median 6 against 11 days) with no difference in fungal infection; it excluded transplant recipients and children on voriconazole or posaconazole.
International Pediatric Fever and Neutropenia Guideline Panel, Journal of Clinical Oncology 2023
| Recommendation | Grade, as printed | Source |
|---|---|---|
| Validated risk stratification in routine care | strong recommendation, low-quality evidence | International Pediatric Fever and Neutropenia Guideline Panel, Journal of Clinical Oncology 2023 |
| Blood cultures from all lumens of a central venous catheter | strong recommendation, low-quality evidence | International Pediatric Fever and Neutropenia Guideline Panel, Journal of Clinical Oncology 2023 |
| Monotherapy for high-risk fever and neutropenia | strong recommendation, high-quality evidence | International Pediatric Fever and Neutropenia Guideline Panel, Journal of Clinical Oncology 2023 |
| Outpatient or step-down management in low-risk fever and neutropenia | conditional recommendation, moderate-quality evidence | International Pediatric Fever and Neutropenia Guideline Panel, Journal of Clinical Oncology 2023 |
| Stopping antibiotics at 48 hours in low-risk fever and neutropenia without marrow recovery | conditional recommendation, moderate-quality evidence | International Pediatric Fever and Neutropenia Guideline Panel, Journal of Clinical Oncology 2023 |
| Caspofungin or liposomal amphotericin B for prolonged fever in high-risk children | strong recommendation, high-quality evidence | International Pediatric Fever and Neutropenia Guideline Panel, Journal of Clinical Oncology 2023 |
| Do not use beta-D-glucan to guide empiric antifungal management “Do not use β-D-glucan (strong recommendation, low-quality evidence).” | strong recommendation, low-quality evidence | International Pediatric Fever and Neutropenia Guideline Panel, Journal of Clinical Oncology 2023 |
| Antibiotics as soon as possible in the clinically unstable child | Good practice statement | International Pediatric Fever and Neutropenia Guideline Panel, Journal of Clinical Oncology 2023 |
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