12-phase flow (12)

1. 1FRAME
   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
   inputs: temperature, anc
   advance: Febrile neutropenia criteria confirmed
2. 2ENTRY
   Capture time of fever onset, current ANC, last chemo cycle date; activate neutropenic fever pathway — IDSA 2010 Freifeld; ASCO/IDSA 2018 Taplitz
   inputs: temperature, anc
   advance: FN diagnosis established
3. 3CONTEXT
   Cancer type (heme malignancy = higher risk), chemo regimen, prior FN episodes, CVAD presence, prior colonization with resistant organisms (VRE, ESBL, MRSA), HIV, organ transplant — IDSA 2010 Freifeld; NCCN 2024
   inputs: age, cancer_type_and_chemo_regimen, comorbidities
   advance: Risk context gathered
4. 4RED_FLAGS
   Hemodynamic instability (SBP <90, MAP <65), septic shock, respiratory failure, altered mental status, new organ dysfunction — requires ICU-level care and broad empiric coverage — IDSA 2010 Freifeld; SSC 2021; NCCN 2024
   inputs: blood_pressure, lactate
   advance: Critical features triaged
5. 5INITIAL_WORKUP
   2 sets blood cultures (peripheral + CVAD line); CBC with diff; CMP (Cr, LFTs); lactate; urinalysis; CXR; site-directed cultures (wound, stool if diarrhea, sputum if productive cough, LP if meningeal signs) — IDSA 2010 Freifeld; ASCO/IDSA 2018 Taplitz
   inputs: blood_cultures, cbc_with_diff, creatinine, chest_xray
   actions: panel.cbc, panel.renal
   advance: Cultures drawn + initial labs sent
6. 6BRANCHING_WORKUP
   CT chest if persistent fever >4 days without source (galactomannan, beta-D-glucan for IFI); CT sinuses if sinusitis suspected; stool C. diff if diarrhea; respiratory viral panel; MRSA nares — IDSA 2010 Freifeld; NCCN 2024
   advance: Second-line diagnostics sent if indicated
7. 7DIFFERENTIAL
   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
   advance: Infectious source stratified or unexplained FN confirmed
8. 8RISK_STRATIFICATION
   MASCC score (Klastersky, Support Care Cancer 2013 PMID 23443617): >=21 = low risk — ~91% positive predictive value for absence of serious medical complications (low-risk serious-complication rate ~6%, mortality <1%; sensitivity ~71%, specificity ~68%); <21 = high risk (inpatient IV abx). Components: burden of illness, no hypotension, no COPD, solid tumor or no prior fungal infection, no dehydration, outpatient at fever onset, age <60. CISNE is an adjunct for clinically-stable solid-tumor patients (depth-pass-2) — IDSA 2010 Freifeld; ASCO/IDSA 2018 Taplitz (PMID 29461916)
   inputs: comorbidities
   advance: Risk tier assigned (high vs low)
9. 9TREATMENT
   HIGH RISK: IV monotherapy — cefepime 2g IV q8h OR piperacillin-tazobactam 4.5g IV q6h OR meropenem 1g IV q8h; add vancomycin ONLY if hemodynamic instability, skin/soft tissue infection, MRSA colonization, CLABSI suspected, mucositis with fluoroquinolone prophylaxis; antifungal escalation at 4-7 days persistent fever — caspofungin non-inferior to liposomal amphotericin B for empiric antifungal (favourable response ~33.9% vs 33.7%) with significantly less nephrotoxicity/infusion toxicity (Walsh NEJM 2004 PMID 15459300). Empiric vancomycin added to all FN confers no survival benefit — reserve for specific indications (IDSA 2010 Freifeld). LOW RISK (MASCC >=21): oral ciprofloxacin 750mg q12h + amoxicillin-clavulanate 875mg q12h outpatient. Door-to-antibiotic <60 min is the IDSA standard (each hour of delay associated with increased mortality) — IDSA 2010 Freifeld (PMID 21258094); ASCO/IDSA 2018 Taplitz; NCCN 2024
   actions: protocol.sepsis_hour1_bundle.v1
   advance: Empiric antibiotics initiated within 60 min of presentation
10. 10DISPOSITION
    High risk (MASCC <21): admit; ICU if shock/organ failure. Low risk (MASCC >=21): outpatient with daily follow-up if reliable access, no fluoroquinolone prophylaxis, oral tolerance confirmed, observation 4-24h first — IDSA 2010 Freifeld; ASCO/IDSA 2018 Taplitz
    advance: Disposition set
11. 11MONITORING
    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
    inputs: cbc_with_diff
    actions: panel.cbc
    advance: Afebrile >=48h + ANC recovering
12. 12FOLLOWUP
    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
    advance: Recovery plan documented + oncology follow-up arranged