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heme.neutropenic-fever.core.v1PRODUCTION
heme.neutropenic-fever.core.v1

Neutropenic Fever (Febrile Neutropenia)

hematologyacuteadult
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Care setting:

Encounter flow

12/12 authored

Canonical 12-phase frame with authored status for this dossier.

Current phase

Frame

Detailed

Confirm febrile neutropenia: ANC <500 + temp >=38.3 C single or >=38.0 C sustained >=1h; identify chemotherapy timeline and expected nadir — IDSA 2010 Freifeld

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Advance rule
Set
Advance when

Febrile neutropenia criteria confirmed

Patient inputs (11)

MASCC score component; pediatric protocols differ — ASCO/IDSA 2018 Taplitz

Risk stratification: solid tumor vs heme malignancy; high-dose vs standard chemo — IDSA 2010 Freifeld; NCCN 2024

Single temp >=38.3 C or sustained >=38.0 C defines febrile episode — IDSA 2010 Freifeld

ANC <500 cells/mcL (or <1000 with predicted decline to <500) defines neutropenia — IDSA 2010 Freifeld

2 sets (peripheral + line if CVAD) before abx — IDSA 2010 Freifeld; ASCO/IDSA 2018 Taplitz

Confirm ANC, trend WBC nadir — IDSA 2010 Freifeld

Renal function for abx dosing; renal failure changes risk category — IDSA 2010 Freifeld

Hypotension is MASCC risk component and red flag — ASCO/IDSA 2018 Taplitz; Klastersky JCO 2000

MASCC burden of illness + COPD component; hepatic/renal impairment affects abx dosing — Klastersky JCO 2000; IDSA 2010 Freifeld

Baseline CXR for pneumonia; CT chest if persistent fever — IDSA 2010 Freifeld; NCCN 2024

Sepsis marker; elevated lactate escalates to ICU — SSC 2021; NCCN 2024

* = hard-required. Engine cannot meaningfully run until these are filled.

Severity triggers (5)

5 need judgement
  • informationallife_threateningneutropenic_septic_shock
    Septic shock in febrile neutropenia (SBP <90 or MAP <65 despite fluids, vasopressors needed) — SSC 2021; IDSA 2010 Freifeld
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseveremascc_low_high_risk
    MASCC score <21 — high-risk febrile neutropenia requiring inpatient IV antibiotics — Klastersky JCO 2000; IDSA 2010 Freifeld
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverepersistent_fever_day4_7
    Persistent fever >=4-7 days on broad-spectrum antibiotics without identified source — IDSA 2010 Freifeld; NCCN 2024
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverepneumonia_in_neutropenia
    Pulmonary infiltrate in neutropenic patient — IDSA 2010 Freifeld; NCCN 2024
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseveretyphlitis
    Neutropenic enterocolitis (typhlitis): fever + abdominal pain + neutropenia + bowel wall thickening on CT — NCCN 2024
    Trigger could not be auto-evaluated — needs clinician judgement.

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Recommended regimen

Febrile neutropenia empiric escalation ladder (IDSA 2010 Freifeld; ASCO/IDSA 2018 Taplitz; NCCN 2024)
axis: fn_empiric_escalationstep 1 - Empiric monotherapy — first-line IV anti-pseudomonal beta-lactam
Selected step "Empiric monotherapy — first-line IV anti-pseudomonal beta-lactam" — High-risk FN (MASCC <21) OR any FN requiring inpatient care — IDSA 2010 Freifeld; ASCO/IDSA 2018 Taplitz
  • cefepime
    first line
    cephalosporin_4th_gen
    2 g IV q8h • IV • q8h
    IDSA 2010 Freifeld — anti-pseudomonal monotherapy; ASCO/IDSA 2018 Taplitz first-line
    rxcui 20481
  • piperacillin-tazobactam
    first line
    beta_lactam_BLI
    4.5 g IV q6h • IV • q6h
    IDSA 2010 Freifeld — equivalent efficacy to cefepime; extended infusion preferred — ASCO/IDSA 2018 Taplitz
    rxcui 74169
  • meropenem
    first line
    carbapenem
    1 g IV q8h • IV • q8h
    IDSA 2010 Freifeld — reserve for ESBL colonization or critically ill; broader spectrum — NCCN 2024
    rxcui 29561

ed playbook — drug actions (3)

  1. 1. cefepime
    2 g IV • IV • q8h
    trigger: FN confirmed — IDSA 2010 Freifeld; ASCO/IDSA 2018 Taplitz
    IDSA 2010 Freifeld — empiric monotherapy within 60 min of presentation
  2. 2. vancomycin
    15-20 mg/kg IV • IV • q8-12h
    trigger: Hemodynamic instability, suspected CLABSI, MRSA colonization, skin infection — IDSA 2010 Freifeld
    IDSA 2010 Freifeld — NOT routine; specific indications; reassess at 48h
  3. 3. IV fluids
    30 mL/kg crystalloid • IV • bolus if hypotensive
    trigger: Sepsis/hypotension — SSC 2021
    SSC 2021 — standard sepsis resuscitation

Auto-drafted A&P note

ed

Subjective

- Possible entry pathways: Temp >=38.3 C (single) or >=38.0 C sustained >=1h + ANC <500 cells/mcL — IDSA 2010 Freifeld; ASCO/IDSA 2018 Taplitz; ANC <500 cells/mcL or expected to decline <500 within 48h — IDSA 2010 Freifeld; Oncology patient on cytotoxic chemotherapy presenting with fever — NCCN 2024.

Objective

- No vitals, labs, or imaging entered for this encounter.

Assessment

**Neutropenic Fever (Febrile Neutropenia)** (heme.neutropenic-fever.core.v1).
Phenotype framing: Bacteremia (gram-negative carries higher attributable mortality — empiric coverage must always include anti-pseudomonal gram-negative), gram-positive (CLABSI, mucositis streptococci), pneumonia, skin/soft tissue, typhlitis (neutropenic enterocolitis), perianal abscess, sinusitis, invasive fungal infection. Named Bayesian pivots: IFI favoured by persistent fever >4-7 days on broad-spectrum abx + galactomannan/beta-D-glucan positivity; typhlitis pivot = neutropenia + RLQ pain + diarrhea + diffuse cecal/ascending bowel-wall thickening on CT (vs focal appendicitis); CLABSI pivot = differential time-to-positivity (line vs peripheral >=2h) — IDSA 2010 Freifeld (PMID 21258094); Walsh NEJM 2004 (PMID 15459300); NCCN 2024
Scope: Confirm febrile neutropenia: ANC <500 + temp >=38.3 C single or >=38.0 C sustained >=1h; identify chemotherapy timeline and expected nadir — IDSA 2010 Freifeld

No severity triggers fired against current inputs.

Plan

Regimen axis: **Febrile neutropenia empiric escalation ladder (IDSA 2010 Freifeld; ASCO/IDSA 2018 Taplitz; NCCN 2024)** — step "Empiric monotherapy — first-line IV anti-pseudomonal beta-lactam".
1. cefepime 2 g IV q8h IV q8h (cephalosporin_4th_gen, first line) — IDSA 2010 Freifeld — anti-pseudomonal monotherapy; ASCO/IDSA 2018 Taplitz first-line
2. piperacillin-tazobactam 4.5 g IV q6h IV q6h (beta_lactam_BLI, first line) — IDSA 2010 Freifeld — equivalent efficacy to cefepime; extended infusion preferred — ASCO/IDSA 2018 Taplitz
3. meropenem 1 g IV q8h IV q8h (carbapenem, first line) — IDSA 2010 Freifeld — reserve for ESBL colonization or critically ill; broader spectrum — NCCN 2024

Setting playbook (ed) — Recognize febrile neutropenia, calculate MASCC, initiate empiric IV abx within 60 min, determine inpatient vs outpatient management — IDSA 2010 Freifeld; ASCO/IDSA 2018 Taplitz
4. cefepime 2 g IV IV q8h — FN confirmed — IDSA 2010 Freifeld; ASCO/IDSA 2018 Taplitz (IDSA 2010 Freifeld — empiric monotherapy within 60 min of presentation)
5. vancomycin 15-20 mg/kg IV IV q8-12h — Hemodynamic instability, suspected CLABSI, MRSA colonization, skin infection — IDSA 2010 Freifeld (IDSA 2010 Freifeld — NOT routine; specific indications; reassess at 48h)
6. IV fluids 30 mL/kg crystalloid IV bolus if hypotensive — Sepsis/hypotension — SSC 2021 (SSC 2021 — standard sepsis resuscitation)

Non-pharmacologic actions:
- Blood cultures x2 BEFORE antibiotics (IDSA 2010 Freifeld)
- Abx within 60 min of triage (IDSA 2010 Freifeld; ASCO/IDSA 2018 Taplitz)
- Contact oncology for chemo history and expected nadir (NCCN 2024)
- Rectal exam contraindicated in neutropenia (IDSA 2010 Freifeld)

AVOID / contraindication checks:
- No routine vancomycin (IDSA 2010 Freifeld — vancomycin NOT routine; specific indications only; discontinue at 48h if cultures negative)
- No fluoroquinolone outpatient if on fq prophylaxis (IDSA 2010 Freifeld; ASCO/IDSA 2018 Taplitz — resistance risk)
- Voriconazole hepatic monitor (NCCN 2024 — hepatotoxicity + visual disturbances; trough monitoring 1 5.5 mcg/mL)
- Aminoglycoside avoid monotherapy (IDSA 2010 Freifeld — insufficient gram pos coverage; renal toxicity in neutropenic patients)
- Cefepime neurotoxicity renal dose (IDSA 2010 Freifeld — dose adjust for CrCl <60; seizure risk at supratherapeutic levels)

Monitoring

Regimen monitoring:
- CBC with diff daily (ANC trend to recovery) — IDSA 2010 Freifeld
- Blood cultures q48h if persistent fever — IDSA 2010 Freifeld; ASCO/IDSA 2018 Taplitz
- CRP/procalcitonin trend (adjunctive, not definitive) — NCCN 2024
- Renal function (Cr, BUN) q24-48h if on nephrotoxic agents — IDSA 2010 Freifeld
- Vancomycin AUC/MIC if started (target 400-600) — IDSA 2020 vancomycin consensus
- Galactomannan + beta-D-glucan if persistent fever >4 days — IDSA 2010 Freifeld; NCCN 2024
- CT chest at day 4-7 for IFI evaluation if persistent fever — IDSA 2010 Freifeld

Setting (ed) monitoring:
- Vitals q1-4h depending on stability — IDSA 2010 Freifeld
- Repeat CBC in 4-6h if borderline ANC — IDSA 2010 Freifeld
- Lactate repeat if initially elevated — SSC 2021

Follow-up plan: Continue abx until afebrile AND ANC >=500 rising; G-CSF consideration for high-risk patients or prolonged neutropenia; oncology follow-up for chemo dose adjustment; secondary prophylaxis assessment (fluoroquinolone or antifungal ppx next cycle) — IDSA 2010 Freifeld; ASCO/IDSA 2018 Taplitz; NCCN 2024
- Close-out criterion: Recovery plan documented + oncology follow-up arranged

Monitoring phase: Daily CBC with diff (ANC recovery); blood cultures q48h if persistent fever; vitals q4-8h; reassess abx at 48-72h (de-escalate if culture-directed, escalate if worsening); CT chest at day 4-7 for IFI if persistent fever — IDSA 2010 Freifeld; NCCN 2024

Disposition

Current setting: ed — Recognize febrile neutropenia, calculate MASCC, initiate empiric IV abx within 60 min, determine inpatient vs outpatient management — IDSA 2010 Freifeld; ASCO/IDSA 2018 Taplitz

Disposition criteria:
- MASCC >=21 + meets all low-risk criteria → outpatient with 24h follow-up — IDSA 2010 Freifeld; ASCO/IDSA 2018 Taplitz
- MASCC <21 or high-risk features → admit — IDSA 2010 Freifeld
- Sepsis/shock → ICU — SSC 2021

Escalation triggers (move to higher acuity):
- Septic shock (hypotension despite fluids + vasopressors needed) → ICU — SSC 2021; NCCN 2024
- Respiratory failure → ICU — NCCN 2024
- Altered mental status → ICU — NCCN 2024

Earlier-Return Triggers

Return-precaution thresholds (watch for):
- [LIFE_THREATENING] Septic shock in febrile neutropenia (SBP <90 or MAP <65 despite fluids, vasopressors needed) — SSC 2021; IDSA 2010 Freifeld
- [SEVERE] MASCC score <21 — high-risk febrile neutropenia requiring inpatient IV antibiotics — Klastersky JCO 2000; IDSA 2010 Freifeld
- [SEVERE] Persistent fever >=4-7 days on broad-spectrum antibiotics without identified source — IDSA 2010 Freifeld; NCCN 2024

Citations

- IDSA 2010 Clinical Practice Guideline for the Use of Antimicrobial Agents in Neutropenic Patients with Cancer (Freifeld CID 2011); ASCO/IDSA 2018 Update on Outpatient Management (Taplitz JCO 2018); NCCN 2024 Prevention and Treatment of Cancer-Related Infections [PMID:21258094](https://pubmed.ncbi.nlm.nih.gov/21258094/)
- Cited evidence (PMID 29461916) [PMID:29461916](https://pubmed.ncbi.nlm.nih.gov/29461916/)
- Cited evidence (PMID 23443617) [PMID:23443617](https://pubmed.ncbi.nlm.nih.gov/23443617/)
- Cited evidence (PMID 15459300) [PMID:15459300](https://pubmed.ncbi.nlm.nih.gov/15459300/)

Last reconciled with current guidelines: 2026-05-22.
References
  • IDSA 2010 Clinical Practice Guideline for the Use of Antimicrobial Agents in Neutropenic Patients with Cancer (Freifeld CID 2011); ASCO/IDSA 2018 Update on Outpatient Management (Taplitz JCO 2018); NCCN 2024 Prevention and Treatment of Cancer-Related Infections — PMID:21258094
  • Cited evidence (PMID 29461916) — PMID:29461916
  • Cited evidence (PMID 23443617) — PMID:23443617
  • Cited evidence (PMID 15459300) — PMID:15459300