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pulm.pcp-pneumonia.core.v1PRODUCTION
pulm.pcp-pneumonia.core.v1

Pneumocystis (jirovecii) Pneumonia

pulmonologyacutesubacuteadult
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12/12 authored

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

Current phase

Frame

Detailed

Establish the immunocompromised substrate and a PJP-compatible subacute illness pattern; assign the host CLASS (HIV CD4 band vs non-HIV iatrogenic) — this sets the Bayesian prior and selects the HIV-vs-non-HIV management branch (NIH/CDC OI 2025; Cilloniz 2019 PMID 31550942)

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Advance rule
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Immune substrate + host class (HIV vs non-HIV) confirmed

Patient inputs (20)

Adult dosing of TMP-SMX; pediatric PJP routes to pediatric OI guidance (out of scope here) (NIH/CDC OI 2025)

Resting room-air SpO2 <92% is a guideline adjunctive-steroid trigger and the bedside surrogate for the PaO2/A-a threshold (NIH/CDC OI 2025; Bozzette NEJM 1990 PMID 2233917)

Tachypnea + work of breathing — severity grading and respiratory-failure screen (NIH/CDC OI 2025)

Sets the Bayesian PRIOR — HIV CD4 band vs non-HIV iatrogenic substrate; the HIV-vs-non-HIV axis governs presentation tempo, β-D-glucan NPV, steroid-evidence strength, and mortality (Cilloniz 2019 PMID 31550942)

Drives alternative-agent selection and the desensitization-vs-alternative decision if sulfa-allergic (NIH/CDC OI 2025)

Renal dose-adjust TMP-SMX (CrCl <30 → reduce/avoid), pentamidine nephrotoxicity, dapsone; baseline before nephrotoxic alternatives (NIH/CDC OI 2025)

Weight-based TMP-SMX dosing 15-20 mg/kg/day of the TMP component ÷ q6-8h (NIH/CDC OI 2025)

CMV co-infection is a major non-HIV PJP mortality driver and a key differential — quantitative CMV PCR / BAL shell-vial (route → id.cmv-immunocompromised.core.v1) (Feng 2022 PMID 35313548)

Septic shock / concurrent bacterial sepsis screen (route → id.sepsis.core.v1) (SSC 2026)

HIV pretest band: CD4 <200 (esp. <100) → high PJP prior; CD4 >200 makes HIV-PJP unlikely and shifts the differential (NIH/CDC OI 2025)

Non-HIV substrate weighting: chronic steroid ≥20 mg pred ≥4 wk, rituximab/anti-CD20, anti-TNF, calcineurin inhibitor, alkylator/fludarabine, transplant — most non-HIV PJP occurs when NOT on prophylaxis (NIH/CDC OI 2025)

G6PD deficiency contraindicates dapsone and primaquine (hemolysis) — screen before either; do not delay treatment waiting for the assay if alternatives exist (NIH/CDC OI 2025)

TMP-SMX still first-line in pregnancy (folate supplementation; neonatal kernicterus risk near term — coordinate timing); avoid primaquine; weigh dapsone (NIH/CDC OI 2025)

Breakthrough PJP on adherent TMP-SMX prophylaxis is rare and lowers the prior — re-examine adherence, dose, alternative pathogens, resistant organism (NIH/CDC OI 2025)

Room-air PaO2 <70 mmHg OR A-a gradient >35 → adjunctive corticosteroids within 72 h of anti-PCP therapy (Bozzette NEJM 1990 PMID 2233917)

Elevated LDH supports PJP (sensitive, non-specific); tracks treatment response and prognosis (NIH/CDC OI 2025)

Serum (1→3)-β-D-glucan: pooled sens ~91% / spec ~79%; a NEGATIVE test rules out only at LOW-intermediate pretest (non-HIV ≤20%, HIV ≤50%) — post-test probability is CONDITIONAL on the host band, do not read in isolation (Del Corpo CMI 2020 PMID 32479781; Li 2015 PMID 26793343)

May be normal early; classically bilateral perihilar interstitial pattern — a normal CXR does NOT exclude PJP (HRCT more sensitive) (NIH/CDC OI 2025)

Diffuse/perihilar ground-glass opacities; a NORMAL HRCT has high negative predictive value and argues strongly against PJP (NIH/CDC OI 2025)

Definitive: immunofluorescence/silver/Giemsa stain (specific, organism = disease) vs quantitative PCR (more sensitive but a positive low-burden PCR may reflect COLONIZATION not invasive disease — interpret conditional on host + clinical-radiologic gestalt) on induced sputum or BAL (NIH/CDC OI 2025)

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

Severity triggers (11)

11 need judgement
  • informationalseveremoderate_severe_pao2_aa_spo2_steroid_threshold
    PaO2 <70 mmHg on RA OR A-a gradient >35 mmHg OR resting SpO2 <92% RA in confirmed/strongly-suspected PJP — moderate-severe disease (NIH/CDC OI 2025; Bozzette NEJM 1990 PMID 2233917)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverenon_hiv_pjp_fulminant_high_mortality
    PJP in a non-HIV iatrogenic host (rituximab/anti-TNF/chronic-steroid/transplant/chemo) — typically more abrupt, lower organism burden, lower β-D-glucan/BAL yield, and substantially higher mortality than HIV-PJP (Cilloniz 2019 PMID 31550942; Feng 2022 PMID 35313548)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverepneumothorax_in_PJP
    Spontaneous pneumothorax during PJP — classic complication (NIH/CDC OI 2025)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseveretrue_treatment_failure_day_7_to_10
    No improvement or deterioration at ~7-10 days of TMP-SMX, AFTER the expected days 3-5 phase (NIH/CDC OI 2025)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverehiv_pjp_ART_timing_and_IRIS
    HIV host with PJP — ART-naïve or off ART (NIH/CDC OI 2025; Zolopa ACTG A5164 PMID 19440326)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderatebeta_d_glucan_negative_conditional_on_host_band
    Negative serum β-D-glucan — rules OUT PJP only when host pretest probability is LOW-intermediate (non-HIV ≤20%, HIV ≤50%); at high pretest the post-test probability stays above the test threshold (Del Corpo CMI 2020 PMID 32479781)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderatebal_pcr_positive_low_burden_colonization_vs_disease
    A positive Pneumocystis PCR with LOW organism burden and no immunofluorescence-confirmed cysts/trophs — may reflect COLONIZATION rather than invasive PJP, especially in non-AIDS hosts (NIH/CDC OI 2025)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderatesevere_sulfa_allergy
    Documented SEVERE sulfonamide hypersensitivity (anaphylaxis, SJS/TEN, DRESS) (NIH/CDC OI 2025)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderateg6pd_deficiency
    Known/probable G6PD deficiency, or unable to verify before dapsone/primaquine (NIH/CDC OI 2025)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderateinitial_paradoxical_worsening_days_3_to_5
    Clinical worsening at days 3-5 of TMP-SMX — paradoxical inflammatory response (NIH/CDC OI 2025)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderatebreakthrough_pjp_on_adherent_prophylaxis
    PJP despite adherent TMP-SMX prophylaxis — rare; lowers the prior and broadens the differential (NIH/CDC OI 2025)
    Trigger could not be auto-evaluated — needs clinician judgement.

Workflow calculators

Run this disease's risk and dosing calculators inline.

RISK_STRATIFICATIONrequiredDrives severity classification
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Recommended regimen

PJP empirical regimen — severity tier × host class × sulfa-allergy / G6PD branching (NIH/CDC OI 2025)
axis: pcp_treatment_by_severity_and_allergystep mild_outpatient_HIV - Mild PJP — outpatient candidate (HIV host, oral options)
Selected step "Mild PJP — outpatient candidate (HIV host, oral options)" — Mild disease: PaO2 ≥70 mmHg, A-a <35, SpO2 ≥92% RA, can tolerate PO, social support + reliable follow-up; HIV host (mild non-HIV PJP usually admitted given fulminant potential)
  • sulfamethoxazole/trimethoprim
    first line
    antifolate_combination
    15-20 mg/kg/day TMP component PO ÷ q8h (≈ 2 DS tablets PO TID for a 70-kg adult) • PO • q8h × 21 days (HIV) (max: 20 mg/kg/day TMP)
    triggers: no_severe_sulfa_allergy, CrCl_>=30
    NIH/CDC OI 2025 — TMP-SMX is first-line for PJP at every severity; the combination MIN, not single-ingredient. RxCUI 10831 = sulfamethoxazole/trimethoprim RxNav-verified MIN 2026-05-16 (was 10180 sulfamethoxazole-alone — corrected).
    rxcui 10831
  • atovaquone
    second line
    naphthoquinone
    750 mg PO BID with a fatty meal • PO • q12h × 21 days
    triggers: mild_disease_only, sulfa_allergy, TMP_SMX_intolerance
    NIH/CDC OI 2025 — mild HIV-PJP only; less effective than TMP-SMX, requires fatty food for absorption. RxCUI 60212 RxNav-verified IN 2026-05-16.
    rxcui 60212
  • dapsone
    second line
    sulfone
    Dapsone 100 mg PO daily + trimethoprim 5 mg/kg PO q8h (combination) • PO • daily / q8h × 21 days
    triggers: mild_to_moderate_disease, sulfa_allergy_partial, G6PD_normal
    NIH/CDC OI 2025; Safrin ACTG 108 (PMID 8610948) — dapsone-TMP comparable to TMP-SMX in mild-moderate. SCREEN G6PD first (hemolysis); dapsone-class cross-reactivity caveat in severe sulfonamide hypersensitivity. RxCUI 3108 = dapsone RxNav-verified IN 2026-05-16 (prior notes referenced 3008 = cyclosporine — SAFETY-CRITICAL correction).
    rxcui 3108

outpatient playbook — drug actions (4)

  1. 1. sulfamethoxazole/trimethoprim DS
    ≈ 2 DS (160/800) PO TID (weight-based 15-20 mg/kg/day TMP) • PO • q8h × 21 d
    trigger: Mild HIV-PJP, no severe sulfa allergy
    NIH/CDC OI 2025 first-line
  2. 2. atovaquone
    750 mg PO BID with a fatty meal • PO • q12h × 21 d
    trigger: Mild only, sulfa allergy
    Less effective than TMP-SMX; mild only (NIH/CDC OI 2025)
  3. 3. dapsone-TMP
    Dapsone 100 mg PO daily + TMP 5 mg/kg PO q8h • PO • daily / q8h × 21 d
    trigger: Mild-moderate, sulfa allergy, G6PD normal
    Safrin ACTG 108 (PMID 8610948)
  4. 4. secondary prophylaxis
    TMP-SMX SS/DS PO daily • PO • daily
    trigger: After treatment course
    Until CD4 >200 ×3 mo on ART (NIH/CDC OI 2025)

Auto-drafted A&P note

outpatient

Subjective

- Possible entry pathways: Subacute progressive dyspnea + dry non-productive cough ± low-grade fever, often with marked exertional desaturation, in an immunocompromised host (NIH/CDC OI 2025); Bilateral perihilar / diffuse ground-glass opacities on HRCT (HRCT GGO LR+ high in the right host; near-perfect negative predictive value if HRCT normal) (NIH/CDC OI 2025); Elevated LDH (often >500 U/L) — sensitive but non-specific; tracks burden/response (NIH/CDC OI 2025).

Objective

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

Assessment

**Pneumocystis (jirovecii) Pneumonia** (pulm.pcp-pneumonia.core.v1).
Phenotype framing: PJP vs bacterial CAP vs viral pneumonia (CMV/influenza/COVID/RSV) vs TB vs invasive fungal vs lymphangitic carcinomatosis vs drug-induced pneumonitis vs IRIS — pivots on host band, β-D-glucan post-test, BAL IF-vs-PCR, LDH, HRCT pattern. HIV-vs-non-HIV is a key axis (tempo, burden, β-D-glucan NPV, mortality) (NIH/CDC OI 2025; Cilloniz 2019 PMID 31550942)
Scope: Establish the immunocompromised substrate and a PJP-compatible subacute illness pattern; assign the host CLASS (HIV CD4 band vs non-HIV iatrogenic) — this sets the Bayesian prior and selects the HIV-vs-non-HIV management branch (NIH/CDC OI 2025; Cilloniz 2019 PMID 31550942)

No severity triggers fired against current inputs.

Plan

Regimen axis: **PJP empirical regimen — severity tier × host class × sulfa-allergy / G6PD branching (NIH/CDC OI 2025)** — step "Mild PJP — outpatient candidate (HIV host, oral options)".
1. sulfamethoxazole/trimethoprim 15-20 mg/kg/day TMP component PO ÷ q8h (≈ 2 DS tablets PO TID for a 70-kg adult) PO q8h × 21 days (HIV) (antifolate_combination, first line) — NIH/CDC OI 2025 — TMP-SMX is first-line for PJP at every severity; the combination MIN, not single-ingredient. RxCUI 10831 = sulfamethoxazole/trimethoprim RxNav-verified MIN 2026-05-16 (was 10180 sulfamethoxazole-alone — corrected).
2. atovaquone 750 mg PO BID with a fatty meal PO q12h × 21 days (naphthoquinone, second line) — NIH/CDC OI 2025 — mild HIV-PJP only; less effective than TMP-SMX, requires fatty food for absorption. RxCUI 60212 RxNav-verified IN 2026-05-16.
3. dapsone Dapsone 100 mg PO daily + trimethoprim 5 mg/kg PO q8h (combination) PO daily / q8h × 21 days (sulfone, second line) — NIH/CDC OI 2025; Safrin ACTG 108 (PMID 8610948) — dapsone-TMP comparable to TMP-SMX in mild-moderate. SCREEN G6PD first (hemolysis); dapsone-class cross-reactivity caveat in severe sulfonamide hypersensitivity. RxCUI 3108 = dapsone RxNav-verified IN 2026-05-16 (prior notes referenced 3008 = cyclosporine — SAFETY-CRITICAL correction).

Setting playbook (outpatient) — Mild HIV-PJP managed with oral therapy + close follow-up, or post-discharge secondary prophylaxis + ART/immunosuppression management (NIH/CDC OI 2025)
4. sulfamethoxazole/trimethoprim DS ≈ 2 DS (160/800) PO TID (weight-based 15-20 mg/kg/day TMP) PO q8h × 21 d — Mild HIV-PJP, no severe sulfa allergy (NIH/CDC OI 2025 first-line)
5. atovaquone 750 mg PO BID with a fatty meal PO q12h × 21 d — Mild only, sulfa allergy (Less effective than TMP-SMX; mild only (NIH/CDC OI 2025))
6. dapsone-TMP Dapsone 100 mg PO daily + TMP 5 mg/kg PO q8h PO daily / q8h × 21 d — Mild-moderate, sulfa allergy, G6PD normal (Safrin ACTG 108 (PMID 8610948))
7. secondary prophylaxis TMP-SMX SS/DS PO daily PO daily — After treatment course (Until CD4 >200 ×3 mo on ART (NIH/CDC OI 2025))

Non-pharmacologic actions:
- Phone follow-up 48-72 h; office follow-up 1 wk then as needed (NIH/CDC OI 2025)
- ART initiation within 2 weeks in HIV (Zolopa ACTG A5164 PMID 19440326)
- PJP recognition + worsening education (NIH/CDC OI 2025)
- HIV linkage-to-care (route id.hiv-initial.chronic.v1) (NIH/CDC OI 2025)

AVOID / contraindication checks:
-  SCREEN G6PD before dapsone OR primaquine — deficiency causes severe hemolysis; absolute contraindication if deficient (NIH/CDC OI 2025)
-  severe sulfonamide hypersensitivity (anaphylaxis/SJS/TEN/DRESS) → avoid TMP SMX and dapsone class; use clindamycin primaquine or pentamidine; desensitization only after NON severe reactions (NIH/CDC OI 2025)
-  TMP SMX — monitor for hyperkalemia, AKI/elevated creatinine, cytopenias, hypersensitivity rash; renal dose adjust if CrCl <30 (NIH/CDC OI 2025)
-  pentamidine — nephrotoxicity, dysglycemia (hypo→hyperglycemia), pancreatitis, QT prolongation/torsades, infusion hypotension; monitor renal/glucose/QTc (NIH/CDC OI 2025)
-  methemoglobinemia + hemolysis with dapsone or primaquine — monitor methemoglobin and hemoglobin (NIH/CDC OI 2025)
-  corticosteroid adverse effects (hyperglycemia, GI bleed, neuropsychiatric, opportunistic superinfection, herpetic reactivation) — screen and counsel (Bozzette NEJM 1990 PMID 2233917)
-  atovaquone REQUIRES a fatty meal for absorption — under absorption risks treatment failure (NIH/CDC OI 2025)
-  do NOT add leucovorin/folinic acid to TMP SMX for PJP — associated with treatment failure and increased mortality (NIH/CDC OI 2025)
- Pregnancy: TMP SMX remains first line (add folate; weigh neonatal kernicterus/hyperbilirubinemia risk near term and coordinate delivery timing); AVOID primaquine; dapsone with caution (NIH/CDC OI 2025)
-  primaquine contraindicated in pregnancy and in G6PD deficiency (NIH/CDC OI 2025)
- Hepatic: caution with dapsone (hepatitis), pentamidine, and prolonged high dose steroid in hepatic impairment — monitor LFTs (NIH/CDC OI 2025)

Monitoring

Regimen monitoring:
- expect paradoxical clinical worsening days 3-5 of therapy — do NOT switch antibiotic empirically (NIH/CDC OI 2025)
- true treatment failure assessed at ~7-10 d (after the expected days 3-5 phase) → bronchoscopy/BAL + co-infection workup + agent switch (NIH/CDC OI 2025)
- LDH + oxygenation/SpO2 trend q24-48h as response surrogates (NIH/CDC OI 2025)
- CBC + BMP q48h on TMP-SMX (cytopenias, hyperkalemia, AKI) (NIH/CDC OI 2025)
- methemoglobin + hemoglobin if on dapsone or primaquine (NIH/CDC OI 2025)
- glucose q6h on pentamidine or systemic corticosteroid; QTc + renal on pentamidine (NIH/CDC OI 2025)
- transition to secondary prophylaxis immediately after the 21-d (HIV) / 14-21-d (non-HIV) treatment course (NIH/CDC OI 2025)
- STOP secondary prophylaxis — HIV: CD4 >200 ×3 mo on ART (consider stop at CD4 100-200 if HIV-RNA suppressed ≥3-6 mo); non-HIV: until immunosuppression resolved (NIH/CDC OI 2025)
- initiate/optimize ART within 2 weeks in HIV; monitor for IRIS (Zolopa ACTG A5164 PMID 19440326)

Setting (outpatient) monitoring:
- Symptom check + home pulse-oximetry (NIH/CDC OI 2025)
- CBC, BMP at 1 week on TMP-SMX (NIH/CDC OI 2025)
- CD4/VL after ART initiation; IRIS surveillance (Zolopa ACTG A5164 PMID 19440326)

Follow-up plan: Secondary prophylaxis (TMP-SMX SS daily) until immune reconstitution — HIV: CD4 >200 ×3 mo on ART (consider stop at CD4 100-200 if VL suppressed ≥3-6 mo); non-HIV: until immunosuppression resolved. Initiate/optimize ART within 2 weeks of PJP treatment in HIV (early ART reduces progression/death — Zolopa ACTG A5164 PMID 19440326); monitor IRIS; minimize/taper the iatrogenic immunosuppressant where feasible (NIH/CDC OI 2025)
- Close-out criterion: Prophylaxis + immune-recovery + ART/immunosuppression plan in place

Monitoring phase: Expect paradoxical clinical worsening days 3-5 (inflammatory; do NOT switch antibiotic empirically); LDH/oxygenation trend; CBC/BMP q48h on TMP-SMX (cytopenias, hyperkalemia, AKI); methemoglobin if dapsone/primaquine; glucose if pentamidine/steroid; true treatment failure assessed at ~7-10 d → bronchoscopy + co-infection workup + agent switch (NIH/CDC OI 2025)

Disposition

Current setting: outpatient — Mild HIV-PJP managed with oral therapy + close follow-up, or post-discharge secondary prophylaxis + ART/immunosuppression management (NIH/CDC OI 2025)

Disposition criteria:
- Continue outpatient if improving by 7 days; refer to ED if not improving or deteriorating (NIH/CDC OI 2025)

Escalation triggers (move to higher acuity):
- Worsening dyspnea or hypoxia → ED (NIH/CDC OI 2025)
- Rash, AKI, cytopenias on TMP-SMX → switch agent (NIH/CDC OI 2025)
- No improvement by 7 days → ED + bronchoscopy + co-infection workup (NIH/CDC OI 2025)

Earlier-Return Triggers

Return-precaution thresholds (watch for):
- [SEVERE] PaO2 <70 mmHg on RA OR A-a gradient >35 mmHg OR resting SpO2 <92% RA in confirmed/strongly-suspected PJP — moderate-severe disease (NIH/CDC OI 2025; Bozzette NEJM 1990 PMID 2233917)
- [SEVERE] PJP in a non-HIV iatrogenic host (rituximab/anti-TNF/chronic-steroid/transplant/chemo) — typically more abrupt, lower organism burden, lower β-D-glucan/BAL yield, and substantially higher mortality than HIV-PJP (Cilloniz 2019 PMID 31550942; Feng 2022 PMID 35313548)
- [SEVERE] Spontaneous pneumothorax during PJP — classic complication (NIH/CDC OI 2025)

Citations

- 2025 NIH/CDC/HIVMA-IDSA Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults & Adolescents with HIV — Pneumocystis section (clinicalinfo.hiv.gov, updated through Dec 2025; WebSearch-verified current 2026-05-16) + Bozzette/California Collaborative NEJM 1990 (adjunctive steroids) + non-HIV PJP literature (Cilloniz Expert Rev Anti Infect Ther 2019) [PMID:2233917](https://pubmed.ncbi.nlm.nih.gov/2233917/)
- Cited evidence (PMID 2233916) [PMID:2233916](https://pubmed.ncbi.nlm.nih.gov/2233916/)
- Cited evidence (PMID 32479781) [PMID:32479781](https://pubmed.ncbi.nlm.nih.gov/32479781/)
- Cited evidence (PMID 26793343) [PMID:26793343](https://pubmed.ncbi.nlm.nih.gov/26793343/)
- Cited evidence (PMID 31550942) [PMID:31550942](https://pubmed.ncbi.nlm.nih.gov/31550942/)

Last reconciled with current guidelines: 2026-05-16.
References
  • 2025 NIH/CDC/HIVMA-IDSA Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults & Adolescents with HIV — Pneumocystis section (clinicalinfo.hiv.gov, updated through Dec 2025; WebSearch-verified current 2026-05-16) + Bozzette/California Collaborative NEJM 1990 (adjunctive steroids) + non-HIV PJP literature (Cilloniz Expert Rev Anti Infect Ther 2019) — PMID:2233917
  • Cited evidence (PMID 2233916) — PMID:2233916
  • Cited evidence (PMID 32479781) — PMID:32479781
  • Cited evidence (PMID 26793343) — PMID:26793343
  • Cited evidence (PMID 31550942) — PMID:31550942