EMA Cited · Infectious disease · Oncology

Febrile neutropenia

Updated Nov 3, 2026Adults · ED management11 sources · 9 checked in PubMed2 figuresIDSA 2010 · ASCO/IDSA 2018

Bottom line

Fever is a single oral temperature ≥ 38.3 °C, or ≥ 38.0 °C for an hour; neutropenia is an ANC under 500, or expected to fall below 500 within 48 hours.¹
Give the first antibiotic dose within 1 hour of triage.² In one cohort, each hour of delay raised the risk of death within 28 days by 18%.³
High risk: admit for IV monotherapy with an antipseudomonal beta-lactam such as cefepime, piperacillin-tazobactam or a carbapenem.¹ Vancomycin is not routine.¹
Score the stable patient. A MASCC score ≥ 21 marks low risk.⁴ CISNE was more accurate in stable patients with solid tumors.⁵
Low risk can go home on an oral fluoroquinolone plus amoxicillin-clavulanate after at least 4 hours of observation, unless the patient took fluoroquinolone prophylaxis.² Most US EDs admit them anyway.^6,7

Definitions

Term	Definition
Fever	Single oral temperature ≥ 38.3 °C (101 °F), or ≥ 38.0 °C (100.4 °F) sustained over 1 hour
Neutropenia	ANC < 500/mm³, or expected to fall below 500 within 48 hours
Profound neutropenia	ANC < 100/mm³

IDSA 2010 definitions.¹ ANC = white count × (neutrophils % + bands %).⁸ Avoid rectal temperatures while neutropenic.¹

First hour

Resuscitate if unstable. These patients can progress quickly to septic shock.⁸
Draw at least 2 sets of blood cultures: one from each lumen of a central line plus one peripheral, or 2 separate venipunctures without a line.¹
Give the first antibiotic dose within 1 hour of triage.² Don't hold cultures or antibiotics for an isolation room.⁸
Labs: CBC with differential and platelets, creatinine, BUN, electrolytes, transaminases and bilirubin. Chest X-ray for respiratory symptoms.¹
Examine for a source, including the mouth, skin, line sites and perianal area, but skip the digital rectal exam.⁸
Sort high from low risk (below), then decide on IV admission or oral therapy at home.^1,2

FIG 1 · Decision flowCited

Fever after chemotherapy: one oral temperature ≥ 38.3 °C, or ≥ 38.0 °C for an hour, with an ANC under 500 or expected to fall there.¹
Cultures, then antibiotics within 1 hour of triage. At least 2 blood culture sets, including one from each line lumen.^1,2 No rectal temperatures or rectal exams.^1,8
Hypotension, pneumonia, new abdominal pain, new neurologic change, or profound neutropenia expected beyond 7 days?
Yes: high risk
Admit for IV monotherapy: cefepime 2 g every 8 hours, piperacillin-tazobactam or a carbapenem.^1,9 Penicillin anaphylaxis: ciprofloxacin plus clindamycin, or aztreonam plus vancomycin.⁸
Unstable: broaden, for example by switching to a carbapenem and adding an aminoglycoside, ciprofloxacin or aztreonam, with vancomycin.¹
Vancomycin only for a reason: instability, pneumonia, gram-positive blood culture, suspected line or skin infection, or MRSA colonization.¹
No
Score the stable patient with clinical judgment: MASCC ≥ 21 is low risk; CISNE 0 is low risk in solid tumors.^2,4,5
Low risk, with oncology follow-up and a safe home?
Yes
Oral fluoroquinolone plus amoxicillin-clavulanate (clindamycin if penicillin-allergic), unless on fluoroquinolone prophylaxis.²
Observe at least 4 hours before discharge. Agree the plan with the oncologist and arrange follow-up within 24 hours.^2,8
No
Not clearly low risk: admit for the IV regimen above.¹
Still febrile after 2–3 days of empiric therapy: re-evaluate and consider inpatient care.²

FIG 1Febrile neutropenia in the emergency department. Drawn for this page from the IDSA 2010 and ASCO/IDSA 2018 guidelines. Each box carries its own citations.^1,2

FIG 2The antibiotic clock. Drawn for this page. The 2018 guideline targets the first dose within 1 hour of triage; the 2010 guideline said within 2 hours.^2,1 Low-risk patients are observed at least 4 hours before discharge; the guideline sets only the minimum, so the bar's start is illustrative.²

Sources disagree

How fast is fast enough: within 2 hours per IDSA 2010,¹ within 1 hour of triage per ASCO/IDSA 2018.² A single-center cohort found 28-day mortality of 3.0% with antibiotics within 30 minutes versus 18.1% at 31–60 minutes, and its authors argue for a 30-minute target.³

Who is high risk

High risk (admit for IV therapy): profound neutropenia expected to last more than 7 days, or significant comorbidity such as hypotension, pneumonia, new abdominal pain or neurologic change.¹
Low risk: neutropenia expected to last 7 days or less, with few or no comorbidities.¹
Use clinical judgment with clinical criteria or a validated tool such as MASCC, and weigh psychosocial and logistic factors.²

MASCC risk index	Points
Burden of illness: no or mild symptoms	5
Burden of illness: moderate symptoms	3
No hypotension	5
No COPD	4
Solid tumor, or hematologic cancer without previous fungal infection	4
No dehydration	3
Outpatient when fever began	3
Age under 60	2

Burden-of-illness points are not added together. A score ≥ 21 identified low-risk patients with a positive predictive value of 91% in validation (sensitivity 71%, specificity 68%).⁴ IDSA 2010 adopts the same threshold.¹

CISNE (stable patients, solid tumors)	Points
ECOG performance status ≥ 2	2
Stress hyperglycemia	2
COPD	1
Chronic cardiovascular disease	1
Mucositis grade ≥ 2	1
Monocytes < 200/µL	1

Low risk 0, intermediate 1–2, high ≥ 3. In 1,133 patients with seemingly stable febrile neutropenia, serious complications occurred in 1.1%, about 6% and 32.5–36% of the three classes. CISNE discriminated better than MASCC (AUC 0.868 vs 0.721).⁵

Which score?

In a meta-analysis of 26 studies (6,617 patients), MASCC < 21 had a pooled sensitivity of 55.6% and specificity of 86.0% for serious complications. CISNE ≥ 3 had 78.9% and 64.9%. The authors favor CISNE in the acute setting.¹⁰ ASCO/IDSA 2018 names MASCC.² REBEL EM notes MASCC finds more low-risk patients but with more treatment failures.⁸

Antibiotics

Setting	Agent	Adult dose	Notes
High risk: IV monotherapy
First line	Cefepime	2 g IV every 8 hours	Labeled for empiric febrile neutropenia. Adjust for creatinine clearance ≤ 60 mL/min.^1,9
First line	Piperacillin-tazobactam, or meropenem or imipenem-cilastatin	Dose per institutional protocol and label	Antipseudomonal alternatives.¹
Hemodynamically unstable	Broaden: for example, switch to a carbapenem and add an aminoglycoside, ciprofloxacin or aztreonam, plus vancomycin	Dose per protocol	Consider anti-Candida coverage with systemic inflammatory response syndrome.¹
Avoid as monotherapy	Ceftazidime; aminoglycosides	—	Ceftazidime has weak streptococcal and declining gram-negative activity. Aminoglycoside monotherapy breeds resistance.¹
Add only for a reason
Vancomycin	Instability, pneumonia, gram-positive blood culture, suspected line or skin infection, MRSA or VRE colonization	Dose per protocol	Stop after 2 days if no gram-positive infection is found.¹
Penicillin allergy
Non-anaphylactic	Cefepime is not ruled out	As above	⁸
Anaphylaxis	Ciprofloxacin plus clindamycin, or aztreonam plus vancomycin	Dose per protocol	⁸
Low risk: oral, at home
Preferred	Fluoroquinolone plus amoxicillin-clavulanate (clindamycin if penicillin-allergic)	Dose per protocol and label	Not after fluoroquinolone prophylaxis.² Ciprofloxacin plus amoxicillin-clavulanate is graded A-I in IDSA 2010.¹

Unreviewed doses. Verify against the current label and your institution's protocol before giving anything.

Doses are given only where an FDA label confirmed them for febrile neutropenia; the guidelines' dose tables could not be read. Check earlier cultures, and follow your hospital's protocol if it has one.⁸

Disposition

High risk: admit for IV therapy.¹
Low risk: may go home on oral antibiotics after at least 4 hours of observation.² Discuss with the oncologist and arrange oncology follow-up within 24 hours.⁸
Home plan: decide how long to observe, whether home is suitable, how often to follow up, and when to come back.¹
No fever response in 2–3 days: re-evaluate and consider admission.² IDSA 2010 readmits outpatients whose fever and symptoms persist at 48 hours.¹

What EDs actually do

One academic ED, 173 visits: 25% were low risk, yet 98% of those were managed outside guidelines, mostly more aggressively.⁶
13 EDs in one system, 203 patients: every patient was admitted, including all 65 low-risk patients. None of the low-risk group died or had a positive blood culture.⁷
A protocol helps speed: in one ED, a triage-to-antibiotic protocol cut mean time to antibiotics from 197.6 to 97.7 minutes, partly by speeding room placement and the ANC result.¹¹

Pitfalls

Letting the room, isolation or the ANC result hold up the first dose.^8,11
Rectal temperatures or a digital rectal exam.^1,8
Adding vancomycin by reflex. It is not part of the standard first regimen.¹
Ceftazidime alone as the empiric drug.¹
Sending a patient on fluoroquinolone prophylaxis home on a fluoroquinolone.²
Admitting every low-risk patient by default.^6,7

How strong is the evidence?

The two anchor guidelines date from 2010 and 2018.^1,2 The 1-hour target and 4-hour observation are consensus recommendations carried over from the earlier ASCO version.² Time-to-antibiotic data are observational.³ Neither risk score is both sensitive and specific.¹⁰ The ASCO/IDSA 2018 full text was not openly accessible; its recommendations here come from the abstract.

On-shift teaching

Questions to ask a learner at the bedside. Tap a question to see the answer. Every answer uses facts cited above.

Q1Define fever and neutropenia for this diagnosis.

Fever: a single oral temperature ≥ 38.3 °C, or ≥ 38.0 °C sustained over an hour. Neutropenia: ANC < 500, or expected to fall below 500 within 48 hours.¹

Q2What are the MASCC items, and what score is low risk?

Burden of illness (5 or 3), no hypotension (5), no COPD (4), solid tumor or no previous fungal infection (4), no dehydration (3), outpatient at onset (3), age under 60 (2). ≥ 21 is low risk.⁴

Q3MASCC or CISNE: which misses fewer patients who go on to have complications?

CISNE. Pooled sensitivity for CISNE ≥ 3 was 78.9% versus 55.6% for MASCC < 21, at the cost of specificity (64.9% vs 86.0%).¹⁰

Q4When should vancomycin go in the first regimen?

Only for a reason: hemodynamic instability, pneumonia, a gram-positive blood culture, suspected line or skin infection, or MRSA or VRE colonization. Stop it after 2 days if no gram-positive infection is found.¹

Q5What oral regimen does ASCO/IDSA recommend for low-risk patients, and when not?

A fluoroquinolone plus amoxicillin-clavulanate, with clindamycin if penicillin-allergic, unless the patient was on fluoroquinolone prophylaxis. Observe for at least 4 hours first.²

Q6How much does an hour's delay in antibiotics matter?

In a prospective cohort of 307 episodes, each hour raised 28-day mortality risk by 18% (HR 1.18). Mortality was 3.0% with antibiotics within 30 minutes versus 18.1% at 31–60 minutes.³

References

Evidence base

What this page is built on

11 sources, cited 90 times. Dots are sources, filled by how far each was read; stronger color means a larger share of the citations. Tap a tier to see its sources.

Read in full · 3Abstract read · 8Record only · 0Link checked · 0

Checked by the writer, not a physician. The dots show how each source was read, not that anyone has confirmed the claims.

1
Freifeld AG, Bow EJ, Sepkowitz KA, et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis. 2011;52(4):e56–e93.GuidelinePMID 21258094 DOIFull text read
2
Taplitz RA, Kennedy EB, Bow EJ, et al. Outpatient management of fever and neutropenia in adults treated for malignancy: American Society of Clinical Oncology and Infectious Diseases Society of America clinical practice guideline update. J Clin Oncol. 2018;36(14):1443–1453.GuidelinePMID 29461916 DOIPubMed abstract read; full text not openly accessible
3
Rosa RG, Goldani LZ. Cohort study of the impact of time to antibiotic administration on mortality in patients with febrile neutropenia. Antimicrob Agents Chemother. 2014;58(7):3799–3803.CohortPMID 24752269 PMCPubMed
4
Klastersky J, Paesmans M, Rubenstein EB, et al. The Multinational Association for Supportive Care in Cancer risk index: a multinational scoring system for identifying low-risk febrile neutropenic cancer patients. J Clin Oncol. 2000;18(16):3038–3051.Diagnostic studyPMID 10944139PubMed
5
Carmona-Bayonas A, Jiménez-Fonseca P, Virizuela Echaburu J, et al. Prediction of serious complications in patients with seemingly stable febrile neutropenia: validation of the Clinical Index of Stable Febrile Neutropenia in a prospective cohort of patients from the FINITE study. J Clin Oncol. 2015;33(5):465–471.Diagnostic studyPMID 25559804PubMed
6
Baugh CW, Wang TJ, Caterino JM, et al. Emergency department management of patients with febrile neutropenia: guideline concordant or overly aggressive? Acad Emerg Med. 2017;24(1):83–91.CohortPMID 27611638PubMed
7
Pettit N, Boadu D, Bischof JJ. Emergency department management of chemotherapy related febrile neutropenia: an opportunity to improve care. Am J Emerg Med. 2021;50:5–9.CohortPMID 34265732PubMed
8
Swaminathan A. REBEL Core Cast 122.0: Neutropenic fever. REBEL EM; May 15, 2024.FOAMrebelem.comPage read
9
Cefepime for injection. FDA label, DailyMed.Drug labelDailyMedLabel text read
10
Zheng B, Toarta C, Cheng W, et al. Accuracy of the Multinational Association of Supportive Care in Cancer (MASCC) and Clinical Index of Stable Febrile Neutropenia (CISNE) scores for predicting serious complications in adult patients with febrile neutropenia: a systematic review and meta-analysis. Crit Rev Oncol Hematol. 2020;149:102922.Meta-analysisPMID 32244162PubMed
11
Seltzer JA, Frankfurt O, Kyriacou DN. Association of an emergency department febrile neutropenia intervention protocol with time to initial antibiotic treatment. Acad Emerg Med. 2022;29(1):73–82.CohortPMID 34245642PubMed

Not for clinical use

AI-generated draft. Not reviewed by a physician. This page is for education only and may contain errors, including in doses. Do not use it to diagnose, treat or make decisions about any patient. Rely on your own clinical judgment, your institution's protocols and current drug labeling. Reading this page does not create a physician-patient relationship. Full terms