12-phase flow (12)

1. 1FRAME
   Partition neonatal sepsis by hour-of-life: early-onset < 72 h (vertical-maternal pathogens — GBS / E. coli / Listeria) vs late-onset 72 h - 28 d (nosocomial — CoNS / MRSA / Klebsiella / Pseudomonas / Candida). Phoenix criteria 2024 explicitly exclude < 18 d; use AAP Puopolo 2018 framework.
   inputs: chronologic_age_in_hours, gestational_age_weeks
   advance: Onset partition assigned + gestational-age cohort tagged
2. 2ENTRY
   Recognise via clinical features (temperature instability, poor feeding, lethargy, apnoea, hypoglycaemia, jaundice progression, respiratory distress) OR maternal intrapartum risk factor (GBS without IAP, chorio, PROM > 18 h, preterm, intrapartum fever) OR positive blood culture in neonate. HSV features (vesicles / seizures / hypothermia / hepatitis / maternal HSV) drive empiric acyclovir.
   inputs: temperature, hr_neonate, rr_neonate, maternal_gbs_status_with_iap_quality, maternal_chorioamnionitis, rom_duration_hours
   advance: Sepsis suspected by clinical + risk-factor combination
3. 3CONTEXT
   Gestational age, birth weight, maternal history (GBS / chorio / PROM / HSV / antepartum infections), prior antibiotic exposure, central line / device, TPN duration, household exposures (siblings with viral illness)
   inputs: gestational_age_weeks, birth_weight_grams, maternal_hsv_status, central_line_or_device, tpn_or_prolonged_abx_exposure
   advance: Risk-factor profile + setting context captured
4. 4RED_FLAGS
   Hemodynamic instability (SBP < gestational age in wk for first 24 h, lactate ≥ 4, capillary refill > 3 s, mottling), respiratory failure (intubation), AMS / encephalopathy / seizures, hypothermia in preterm, bulging fontanelle / petechiae / purpura fulminans, bell-stage II-III NEC features, HSV features → immediate empiric antibiotics within 1 h + NICU + neonatologist + escalation
   inputs: temperature, sbp_neonate, spo2_neonate
   actions: protocol.septic_shock
   advance: Red flags actioned; empirics within 1 h of recognition
5. 5INITIAL_WORKUP
   Hour-1 bundle (neonatal adaptation): blood culture (≥ 1 mL per bottle), CBC with diff (age-adjusted), CRP at presentation, glucose, BMP, LFT, coag, lactate, platelets; LP if culture-positive OR clinical concern OR persistent deterioration (some centres always at ≤ 21 d); CXR if respiratory features; surface HSV swabs + HSV PCR if ≤ 28 d + features; KUB if NEC features; empiric antibiotics within 1 h: < 72 h → ampicillin + gentamicin (or + cefotaxime if meningitis); ≥ 72 h → vancomycin + cefepime (or meropenem); + acyclovir if HSV features; + micafungin / L-AmB if Candida risk
   inputs: cbc_with_diff_neonate, blood_culture, csf_studies, crp, glucose_neonate, platelets_neonate
   actions: workup.pediatric_fever, panel.cbc, panel.renal, panel.lft, panel.coag, panel.csf, panel.inflammation, panel.glucose_a1c
   advance: Cultures sent; empiric antibiotics in; baseline labs drawn
6. 6BRANCHING_WORKUP
   Source-directed: KUB + bowel-wall thickening + pneumatosis intestinalis on KUB → bell-stage II/III NEC; CXR → congenital pneumonia / RDS / TTN; UA + urine culture (catheterised) → UTI rare but possible; CRBSI workup if central line — differential time-to-positivity (Mermel IDSA 2009); echo if endocarditis suspected (rare in neonate); HSV PCR (CSF + blood + surface) + hepatic panel if ≤ 28 d + features; fungal cultures + 1,3-β-D-glucan if Candida risk
   inputs: urine_culture_neonate, kub_xray_neonate, cxr_neonate, hepatic_panel_neonate
   actions: workup.crbsi, workup.bacterial_meningitis, panel.ua
   advance: Source identified or empirically covered
7. 7DIFFERENTIAL
   Non-infectious mimics: transient tachypnea of newborn (TTN), respiratory distress syndrome (RDS), congenital cardiac disease (PPHN, ductal-dependent lesions, total anomalous pulmonary venous return), inborn errors of metabolism (hyperammonaemia, organic acidaemias), neonatal hypoglycaemia, hypothyroidism, polycythaemia, NEC primary (without sepsis), congenital adrenal hyperplasia. HSV without bacterial coinfection. Viral (enterovirus, parechovirus). Coexistence pairs: sepsis + AKI, sepsis + DIC, sepsis + NEC, sepsis + intraventricular hemorrhage (IVH).
   advance: Mimics excluded or co-managed
8. 8RISK_STRATIFICATION
   Kaiser EOS calculator (Escobar 2014 PMID 24379228) for asymptomatic ≥ 34 wk with maternal risk factor — risk per 1000 live births drives action (no culture / blood culture + observe / blood culture + empiric antibiotics). For symptomatic + < 34 wk: clinical-illness-based mandatory full sepsis workup + empirics. Phoenix-conceptual organ-dysfunction scoring (severe hypotension, vasoactive, severe respiratory failure, AMS, oligo-anuria, lactate ≥ 5) drives NICU + escalation.
   inputs: sbp_neonate, spo2_neonate
   advance: Severity + NICU need set; Kaiser EOS output documented for asymptomatic-with-risk-factor cohort
9. 9TREATMENT
   Empiric within 1 h (early-onset: ampicillin 200 mg/kg/d divided q8h DOL 0-7 or q6h DOL > 7 + gentamicin 4 mg/kg/d extended-interval per gestational age, or + cefotaxime 50 mg/kg q8h if meningitis instead of gentamicin); (late-onset: vancomycin 45 mg/kg/d divided q8h DOL > 7 + cefepime 50 mg/kg q12h DOL < 7 or q8h DOL ≥ 7 OR meropenem 40 mg/kg q12h-q8h if severe/CNS/Pseudomonas); + acyclovir 60 mg/kg/d divided q8h IV if HSV features; + micafungin 4 mg/kg/d OR L-AmB 5 mg/kg/d if Candida risk (TPN + broad-abx + preterm); IV crystalloid 10-20 mL/kg over 30-60 min reassess (slower than older child); vasoactive — epinephrine 0.05-0.3 µg/kg/min OR dopamine 5-15 µg/kg/min (neonatal-specific first-line per institutional preference) OR norepinephrine 0.05-0.5 µg/kg/min; hydrocortisone 1 mg/kg q8h if catecholamine-resistant. NPO + NG decompression + add metronidazole / pip-tazo / meropenem if bell-stage II-III NEC. Surgical consult if bell-stage III (pneumoperitoneum or clinical deterioration).
   inputs: birth_weight_grams, gestational_age_weeks, sbp_neonate
   advance: Antibiotics + fluids + vasopressors + source-control plan in place
10. 10DISPOSITION
    NICU for ill / preterm / shock / mechanical-ventilation / NEC / suspected HSV / refractory anyway; newborn nursery with q4h monitoring for well-appearing term with maternal risk factor + Kaiser EOS calculator-stratified low-risk; PICU rare (most centres NICU manages all neonates). Discharge home with reliable follow-up only after culture-negative + clinically improved + tolerating feeds.
    inputs: sbp_neonate, spo2_neonate
    advance: Level of care set
11. 11MONITORING
    Vitals q4h (q1h initially in ill neonate), feeds + UOP + weight daily, lactate trend q2-4h until normalised, CBC + CRP at 24 + 48 h, blood culture follow-up at 24 + 48 h, vancomycin / gentamicin levels per pharmacy (trough or AUC), echocardiogram if line-positive S. aureus or persistent positive cultures, repeat LP at end of treatment for meningitis, daily reassessment of antibiotic + duration with goal de-escalation by 48-72 h if cultures negative (Cantey 2018 stewardship); developmental + feeding follow-up.
    inputs: cbc_with_diff_neonate, crp, blood_culture
    actions: panel.cbc, panel.renal, panel.inflammation
    advance: Response confirmed; antibiotics narrowed by culture or discontinued at 48-72 h rule-out
12. 12FOLLOWUP
    Outpatient peds visit within 24-48 h of discharge for high-risk; 1-week visit for all; growth + feeding tracking + developmental milestones; immunization catch-up per cause (PCV / Hib not yet age-eligible at < 28 d but tracked for first dose); hearing screen if meningitis (AABR + audiology referral); developmental peds referral at 6-12 mo if functional decline / neurological sequelae; family education on return precautions; vaccination of family contacts (Tdap, influenza, COVID-19 per ACIP); breastfeeding support; PT/OT if neurological sequelae; PICS-p / PICU-Family syndrome screening at 1-3 months for caregivers + child.
    advance: Outpatient plan documented; follow-up scheduled; family education delivered