Clinical Commander

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id.invasive-aspergillosis.core.v1

Invasive aspergillosis

infectious_diseaseacutesubacuteadultacuteinpatientoutpatient
Start encounter →Print handoutPRODUCTION

Manifest is a Batch-23 scaffold — atoms / phenotypes not yet authored as a Tier-3 package (preserved at src/lib/tier3/problem-package/packages/aspergillosis/; out-of-scope for this shard). Voriconazole TDM and CYP-DDI surveillance is a PRODUCTION blocker — needs decision-rule wiring beyond the scaffold. Deepened 2026-05-15 (shard-5-obped-id depth-pass-1): added co-located _briefs/id.invasive-aspergillosis.core.v1.depth.md + _research-bundles/id.invasive-aspergillosis.core.v1.md and repointed design_brief from the tier3 package path to the in-scope _briefs/ convention. Added outpatient setting_playbook (OPAT extended-duration PO voriconazole / isavuconazole — preferred — or IV L-AmB OPAT for refractory; immunosuppression coordination; serial galactomannan + repeat HRCT for response; secondary prophylaxis through immunosuppression duration; photosensitivity / SCC surveillance on voriconazole; vaccination review per ACIP 2024; ID f/u at week 1 + week 2 + monthly thereafter). settings[] expanded to include outpatient. Added 4 severity triggers: capa_or_iapa_features (life-threatening — COVID/influenza + ICU steroids + new infiltrate + galactomannan + BAL Aspergillus → empiric voriconazole/isavuconazole per Verweij 2020 ECMM/ISHAM CAPA + Schauwvlieghe 2018 IAPA criteria); azole_resistance_suspected (severe — environmental TR34/L98H or TR46/Y121F/T289A exposure + treatment failure → switch to L-AmB or echinocandin combo + susceptibility testing); cns_aspergillosis (life-threatening — CNS imaging + biopsy/BAL → voriconazole CNS-penetrant with high-end TDM target 2-5 µg/mL + neurosurgery if resectable + duration ≥ 6 months); disseminated_aspergillosis_with_immunocompromise (life-threatening — multi-organ involvement → combination L-AmB + voriconazole/isavuconazole + immunosuppression reduction). Severity triggers: 6 → 10. The pre-existing cns_invasive_aspergillosis trigger is retained alongside the new cns_aspergillosis trigger — the new row makes the biopsy + CNS-penetration TDM + duration workflow explicit. Evidence array reconciled 2026-05-15, citation-remediated + live-verified 2026-05-22: removed 4 misattributed PMIDs (10471456 RALES spironolactone-HF, 25776532 ProMISe sepsis-EGDT, 29766750 POINT minor-stroke, 23900119 biomass-fuel-cooking Swaziland) — none are aspergillosis trials. The two CAPA/IAPA anchors added in May were ALSO mis-attributed and were corrected on live PubMed verify 2026-05-22: 33333020 (= "3D Cortico-Motor Assembloids" Cell paper) → 33333012 (Koehler/Verweij ECMM/ISHAM CAPA consensus, Lancet ID 2020); 29397376 (= SUSTAIN semaglutide diabetes trial) → 30076119 (Schauwvlieghe IAPA, Lancet Respir Med 2018). All 6 PMIDs verified live on PubMed 2026-05-22: 27365388 IDSA Patterson 2016, 12167683 Herbrecht NEJM 2002, 26684607 Maertens SECURE 2016, 33333012 Koehler/Verweij CAPA 2020, 30076119 Schauwvlieghe IAPA 2018, 25599346 Marr combination antifungal Ann Intern Med 2015. Phenotype matrix (site × host × species × treatment-response × severity) and Bayesian linkage (CT halo + air-crescent + GM + BDG + PCR LRs, T_treat threshold at host-risk + compatible CT + GM ≥ 1.0 BAL or ≥ 0.5 serum × 2 consecutive samples, cross-dossier routing edges) documented in the co-located brief + research bundle; first-class TS fields remain schema-blocked (deferred to shard schema proposal cache — see id.sepsis.core.v1 brief). Gaps still open: mucormycosis dedicated dossier not yet authored (critical for differential since voriconazole does NOT cover Mucorales); IDSA 2024 aspergillosis update not yet PMID-anchored (publication pending); prehospital not yet a DossierSetting value; tier-3 problem package preserved but not refactored; engine-specific protocol-runner test deferred.

Entry points (4)

  • imaging
    CT chest halo or air-crescent sign in immunocompromised host (EORTC/MSGERC 2020 imaging criterion)
    halo_or_air_crescent_sign
  • lab_abnormality
    Serum / BAL galactomannan elevated (EORTC/MSGERC 2020 mycology criterion)
    galactomannan_positive
  • symptom
    Persistent neutropenic fever despite broad antibacterials (IDSA 2016 / ECIL-6 2017)
    persistent_neutropenic_fever
  • problem_list
    SOT / HCT recipient with new pulmonary infiltrate (IDSA 2016 / ECIL-6 2017 host criterion)
    sot_or_hct_recipient_with_pulmonary_infiltrate

Required inputs (10)

  • immunocompromiserequired
    history • used at ENTRY
    Diagnosis is host-defined (EORTC/MSGERC 2020): prolonged neutropenia, HCT, SOT, high-dose steroids, biologics, advanced HIV
  • mold_active_prophylaxisrequired
    history • used at CONTEXT
    Posaconazole / isavuconazole prophylaxis affects empiric switch (IDSA 2016 / ECIL-6 2017)
  • spo2required
    vital • used at RED_FLAGS
    Hypoxia drives ICU triage (IDSA 2016)
  • serum_galactomannan
    lab • used at INITIAL_WORKUP
    EORTC/MSGERC 2020 mycology criterion; serial trend for treatment response (IDSA 2016)
  • bal_galactomannan
    lab • used at INITIAL_WORKUP
    Higher sensitivity than serum in non-neutropenic hosts (IDSA 2016 — BAL GM index ≥1.0)
  • beta_d_glucan
    lab • used at INITIAL_WORKUP
    Adjunct — positive in many invasive fungal infections; non-specific (IDSA 2016)
  • creatininerequired
    lab • used at TREATMENT
    Voriconazole IV cyclodextrin vehicle accumulates if eGFR <50 (IDSA 2016); lipid AmB nephrotoxicity monitoring
  • lftrequired
    lab • used at MONITORING
    Voriconazole / isavuconazole hepatotoxicity monitoring (IDSA 2016 / ESCMID 2018)
  • ct_chest_high_resolutionrequired
    imaging • used at INITIAL_WORKUP
    Halo / reverse-halo / air-crescent / nodules — EORTC/MSGERC 2020 imaging criteria; IDSA 2016 Class I
  • current_meds_voriconazole_ddirequired
    medication • used at TREATMENT
    Voriconazole has wide-ranging CYP2C19/3A4-mediated DDIs — cyclosporine, tacrolimus, sirolimus, warfarin (IDSA 2016 / ESCMID 2018)

12-phase flow (12)

  1. 1FRAME
    Adult invasive pulmonary / disseminated aspergillosis (IDSA 2016). ABPA / chronic pulmonary aspergillosis covered by sibling engines
    inputs: immunocompromise
    advance: scope confirmed
  2. 2ENTRY
    Recognize EORTC/MSGERC 2020 host + clinical / imaging + mycology criteria (IDSA 2016 / ECIL-6 2017)
    inputs: immunocompromise
    advance: host criterion + ≥1 clinical or mycological criterion
  3. 3CONTEXT
    Underlying disease, neutrophil count, prior mold-active prophylaxis (ECIL-6 2017), prior CYP-interacting drugs (IDSA 2016)
    inputs: mold_active_prophylaxis
    advance: risk + prophylaxis context captured
  4. 4RED_FLAGS
    Hypoxia, hemoptysis (angioinvasive — IDSA 2016), CNS involvement, disseminated disease → ICU + ID/heme escalation
    inputs: spo2
    advance: red flags acted on
  5. 5INITIAL_WORKUP
    Serial galactomannan — serum + BAL when feasible (EORTC/MSGERC 2020; IDSA 2016), HRCT chest, beta-D-glucan, BAL with culture + Aspergillus PCR; biopsy if accessible
    inputs: serum_galactomannan, ct_chest_high_resolution
    advance: mycology + imaging support diagnosis
  6. 6BRANCHING_WORKUP
    CT/MRI brain if CNS signs (IDSA 2016 — voriconazole preferred for CNS); sinus imaging if rhinosinusitis; echocardiogram if endocarditis suspected
    advance: extrapulmonary sites mapped
  7. 7DIFFERENTIAL
    Mucormycosis — reverse halo more typical, GM negative (ESCMID 2018); Pneumocystis; bacterial pneumonia; viral pneumonitis; tumor
    advance: mimics excluded or co-managed
  8. 8RISK_STRATIFICATION
    Probable vs proven disease (EORTC/MSGERC 2020), CNS involvement (IDSA 2016 — high mortality), persistent neutropenia, baseline organ function
    inputs: creatinine, lft
    advance: severity assigned
  9. 9TREATMENT
    Voriconazole 6 mg/kg q12h x 2 then 4 mg/kg q12h (Herbrecht NEJM 2002 — Class I) OR isavuconazole 200 mg q8h x 6 doses then 200 mg daily (SECURE Lancet 2016 — non-inferior); lipid AmB if azole-intolerant or mucormycosis-coverage needed (IDSA 2016); combination therapy controversial — voriconazole + echinocandin per case (Marr Ann Intern Med 2015); duration ≥6-12 wk and through neutrophil recovery (IDSA 2016 / ECIL-6 2017)
    inputs: creatinine, lft, current_meds_voriconazole_ddi
    advance: first-dose mold-active therapy started; voriconazole TDM ordered (target trough 1-5 ug/mL — IDSA 2016)
  10. 10DISPOSITION
    ICU if hypoxic / disseminated; otherwise inpatient with ID / heme (IDSA 2016)
    inputs: spo2
    advance: level of care set
  11. 11MONITORING
    Voriconazole TDM steady-state day 5-7 (IDSA 2016), weekly LFT x 4 then monthly (ESCMID 2018), twice-weekly galactomannan trend during induction (IDSA 2016); repeat HRCT q1-2 wk
    inputs: lft
    actions: panel.lft, panel.renal
    advance: GM trend + imaging show response by 2-4 weeks
  12. 12FOLLOWUP
    Step-down to oral voriconazole / isavuconazole (IDSA 2016); long-term secondary prophylaxis through immunosuppression duration (ECIL-6 2017); counsel photosensitivity / SCC risk on voriconazole (IDSA 2016)
    advance: long-term mold-active plan documented