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id.pjp-pneumocystis.v1PRODUCTION
id.pjp-pneumocystis.v1

Pneumocystis jirovecii pneumonia (PJP/PCP)

infectious_diseaseacutesubacuteadult
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12/12 authored

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

Current phase

Frame

Detailed

Adult opportunistic Pneumocystis jirovecii pneumonia in HIV + non-HIV immunocompromised hosts; ABPA / bacterial CAP / viral pneumonitis covered by sibling engines

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scope confirmed (immunocompromised + compatible pneumonia)

Patient inputs (14)

Breakthrough on TMP-SMX prophylaxis changes empiric coverage + raises resistance concern (ECIL 2016)

HIV (esp. CD4 <200), transplant, ≥20 mg pred-eq ≥4 wk, biologics, lymphoma — defines pre-test probability (IDSA OI; ECIL)

Bilateral perihilar ground-glass classic; lobar consolidation / effusion argue against PJP (ATS 2019)

PaO2/SpO2 + exertional desaturation drive severity stratification + steroid indication (Bozzette 1990)

Tachypnea + work-of-breathing escalation marker

PaO2 <70 mmHg or A-a gradient ≥35 mmHg = adjunctive corticosteroid trigger in HIV (Bozzette NEJM 1990; NIH Consensus 1990)

TMP-SMX renal dosing + hyperkalemia + AKI monitoring (IDSA OI)

TMP-SMX hepatotoxicity baseline + monitoring (IDSA OI)

Sulfa allergy + interacting meds (warfarin, ACEI/ARB hyperkalemia, methotrexate) drive regimen choice (IDSA OI)

CD4 <200 defines HIV at-risk; <100 supports PJP > bacterial CAP in pre-test (IDSA OI)

Elevated LDH supports PJP (non-specific; trend correlates with severity)

High NPV when low; supports diagnosis when elevated (ATS 2019 microbiology CPG, Hage/Limper)

BAL with silver stain / IFA / PCR is gold standard; induced sputum lower sensitivity (IDSA OI; ATS 2019)

G6PD deficiency contraindicates primaquine + dapsone — confirm before salvage regimen (IDSA OI)

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

Severity triggers (8)

8 need judgement
  • informationallife_threateningpjp_respiratory_failure
    PaO2/FiO2 <200 OR mechanical-ventilation requirement OR refractory hypoxia despite NIV — life-threatening
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningpjp_pneumothorax
    New pneumothorax / pneumomediastinum during PJP — cystic disease predisposes to rupture especially on positive-pressure ventilation
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseveresevere_pjp_pao2_under_70_or_aa_35
    PaO2 <70 mmHg on room air OR A-a gradient ≥35 mmHg in suspected/confirmed PJP — Bozzette 1990 + NIH Consensus 1990 threshold for adjunctive corticosteroid in HIV
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseveretmp_smx_severe_toxicity
    TMP-SMX severe AKI / refractory hyperkalemia / severe BM suppression (ANC <500 or Plt <50k) / hepatotoxicity (AST/ALT >5× ULN) / severe rash or SJS/TEN
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverenon_hiv_severe_pjp_higher_mortality
    PJP in non-HIV immunocompromised host (transplant / malignancy / autoimmune-on-steroids / biologic) with PaO2 <70 OR ICU admission — mortality ~30-50% (Wang 2021 meta-analysis)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverebreakthrough_pjp_on_prophylaxis
    PJP developing despite documented TMP-SMX or alternative prophylaxis (adherence confirmed)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderateiris_after_art_initiation_in_hiv_pjp
    Worsening respiratory function / fever / new infiltrate in HIV PJP after ART initiation — immune-reconstitution inflammatory syndrome (IRIS)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderateg6pd_deficiency_excludes_primaquine_dapsone
    G6PD deficiency confirmed (qualitative or quantitative test) — contraindicates primaquine + dapsone due to hemolysis risk
    Trigger could not be auto-evaluated — needs clinician judgement.

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Recommended regimen

PJP first-line TMP-SMX + Bozzette adjunctive steroids (HIV severe)
axis: pjp_first_line_and_adjunct
Selected axis "PJP first-line TMP-SMX + Bozzette adjunctive steroids (HIV severe)" by default fallback (first axis)
  • sulfamethoxazole/trimethoprim
    first line
    sulfonamide_dhfr_inhibitor
    15-20 mg/kg/day TMP-component IV/PO divided q6-8h • IV→PO • q6-8h
    triggers: proven_or_high_suspicion_PJP
    IDSA OI first-line; 21 d HIV, 14-21 d non-HIV; AKI/hyperK/BM suppression/hepatotoxicity monitoring
    rxcui 10831
  • prednisone
    add on
    corticosteroid
    40 mg PO BID × 5 d → 40 mg daily × 5 d → 20 mg daily × 11 d (Bozzette taper) • PO • tapered
    triggers: HIV_PJP_PaO2_under_70, HIV_PJP_Aa_gradient_35_or_more, consider_in_severe_non_HIV
    Bozzette NEJM 1990 (PMID 2233917) + NIH Consensus 1990 (PMID 2136587) — mortality + respiratory-failure reduction when started within 72 h of TMP-SMX in HIV severe PJP; non-HIV evidence weaker (Wang 2021 meta-analysis)
    rxcui 8640
  • methylprednisolone
    contraindication substitute
    corticosteroid
    30 mg IV BID equivalent to prednisone 40 mg PO BID • IV • tapered per Bozzette
    triggers: NPO_patient_needs_IV_steroid
    IV equivalent of prednisone Bozzette taper for NPO patients
    rxcui 6902
  • primaquine
    second line
    8_aminoquinoline
    30 mg base PO daily (combined with clindamycin) • PO • daily
    triggers: TMP_SMX_intolerance, sulfa_allergy, salvage
    IDSA OI preferred salvage with clindamycin; G6PD screen mandatory before initiation
    rxcui 8687
  • clindamycin
    second line
    lincosamide
    600 mg IV q6h (or 300-450 mg PO q6h) • IV→PO • q6h
    triggers: TMP_SMX_intolerance, sulfa_allergy, salvage_combination_with_primaquine
    Pairs with primaquine; C. difficile + rash monitoring (IDSA OI)
    rxcui 2582
  • pentamidine
    rescue
    aromatic_diamidine
    4 mg/kg IV daily over ≥60 min • IV • daily
    triggers: multiple_intolerance, severe_disease_failing_first_line
    IDSA OI — severe nephrotoxicity, pancreatitis, dysglycemia, QTc; reserved when other options exhausted
    rxcui 7994
  • atovaquone
    second line
    hydroxynaphthoquinone
    750 mg PO BID with food • PO • BID
    triggers: mild_to_moderate_PJP_only, PaO2_over_70, sulfa_intolerance
    IDSA OI — mild-moderate disease only; requires high-fat meal for absorption; not for severe disease
    rxcui 60212
  • dapsone
    comorbidity specific
    sulfone
    100 mg PO daily (combined with trimethoprim 5 mg/kg q8h for treatment; or alone for prophylaxis 100 mg daily) • PO • daily
    triggers: TMP_SMX_prophylaxis_intolerance, G6PD_normal
    IDSA OI alternative for prophylaxis (alone) or treatment (with trimethoprim); G6PD screen required; methemoglobinemia + hemolysis monitoring
    rxcui 3108
  • caspofungin
    add on
    echinocandin
    70 mg IV load → 50 mg IV daily • IV • daily
    triggers: non_HIV_severe_refractory_salvage_combination
    Off-label combination data (e.g., Lazarte-Lalo 2025 and prior reports) — non-HIV severe refractory; not standard first-line; targets cyst-wall β-glucan
    rxcui 140108

outpatient playbook — drug actions (4)

  1. 1. PO TMP-SMX completion (mild outpatient cases)
    rxcui 10831
    DS 2 tablets PO TID (≈20 mg/kg/day TMP) to complete 14-21 d total • PO • TID
    trigger: Mild disease only + reliable adherence + close follow-up at d 3 / d 7 / EOT
    IDSA OI — mild outpatient management acceptable in highly selected cases
  2. 2. atovaquone PO alternative (mild only)
    rxcui 60212
    750 mg PO BID with high-fat food • PO • BID
    trigger: Sulfa intolerance + mild disease + PaO2 >70 on room air
    IDSA OI mild-moderate alternative — high-fat meal required for absorption
  3. 3. secondary prophylaxis post-PJP
    TMP-SMX 1 SS PO daily OR DS thrice weekly; alternatives: atovaquone 1500 mg daily, dapsone 100 mg daily (G6PD normal), aerosolized pentamidine 300 mg monthly • PO/inhaled • daily-weekly-monthly
    trigger: All PJP survivors until immune recovery (CD4 >200 ×6 mo on ART in HIV) OR ongoing transplant/biologic IS in non-HIV
    IDSA OI mandatory secondary prophylaxis to prevent relapse
  4. 4. primary prophylaxis re-initiation in at-risk hosts
    TMP-SMX 1 SS daily OR DS thrice weekly • PO • daily-thrice weekly
    trigger: CD4 <200 OR ≥20 mg pred-eq ≥4 wk OR biologic IS OR lymphoma OR transplant per protocol
    IDSA OI / ECIL primary prophylaxis triggers

Auto-drafted A&P note

outpatient

Subjective

- Possible entry pathways: Subacute progressive dyspnea + dry cough + fever in immunocompromised host (classic PJP triad); Profound exertional desaturation with widened A-a gradient; Bilateral perihilar ground-glass opacities on CXR/HRCT in immunocompromised host.

Objective

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

Assessment

**Pneumocystis jirovecii pneumonia (PJP/PCP)** (id.pjp-pneumocystis.v1).
Phenotype framing: CMV pneumonitis (especially transplant); bacterial CAP (atypical for PJP — lobar consolidation, lymphadenopathy, effusion); tuberculosis; invasive aspergillosis; mTOR-inhibitor pneumonitis (sirolimus/everolimus); pulmonary edema; COVID-19 pneumonia; lymphocytic interstitial pneumonia
Scope: Adult opportunistic Pneumocystis jirovecii pneumonia in HIV + non-HIV immunocompromised hosts; ABPA / bacterial CAP / viral pneumonitis covered by sibling engines

No severity triggers fired against current inputs.

Plan

Regimen axis: **PJP first-line TMP-SMX + Bozzette adjunctive steroids (HIV severe)**.
1. sulfamethoxazole/trimethoprim 15-20 mg/kg/day TMP-component IV/PO divided q6-8h IV→PO q6-8h (sulfonamide_dhfr_inhibitor, first line) — IDSA OI first-line; 21 d HIV, 14-21 d non-HIV; AKI/hyperK/BM suppression/hepatotoxicity monitoring
2. prednisone 40 mg PO BID × 5 d → 40 mg daily × 5 d → 20 mg daily × 11 d (Bozzette taper) PO tapered (corticosteroid, add on) — Bozzette NEJM 1990 (PMID 2233917) + NIH Consensus 1990 (PMID 2136587) — mortality + respiratory-failure reduction when started within 72 h of TMP-SMX in HIV severe PJP; non-HIV evidence weaker (Wang 2021 meta-analysis)
3. methylprednisolone 30 mg IV BID equivalent to prednisone 40 mg PO BID IV tapered per Bozzette (corticosteroid, contraindication substitute) — IV equivalent of prednisone Bozzette taper for NPO patients
4. primaquine 30 mg base PO daily (combined with clindamycin) PO daily (8_aminoquinoline, second line) — IDSA OI preferred salvage with clindamycin; G6PD screen mandatory before initiation
5. clindamycin 600 mg IV q6h (or 300-450 mg PO q6h) IV→PO q6h (lincosamide, second line) — Pairs with primaquine; C. difficile + rash monitoring (IDSA OI)
6. pentamidine 4 mg/kg IV daily over ≥60 min IV daily (aromatic_diamidine, rescue) — IDSA OI — severe nephrotoxicity, pancreatitis, dysglycemia, QTc; reserved when other options exhausted
7. atovaquone 750 mg PO BID with food PO BID (hydroxynaphthoquinone, second line) — IDSA OI — mild-moderate disease only; requires high-fat meal for absorption; not for severe disease
8. dapsone 100 mg PO daily (combined with trimethoprim 5 mg/kg q8h for treatment; or alone for prophylaxis 100 mg daily) PO daily (sulfone, comorbidity specific) — IDSA OI alternative for prophylaxis (alone) or treatment (with trimethoprim); G6PD screen required; methemoglobinemia + hemolysis monitoring
9. caspofungin 70 mg IV load → 50 mg IV daily IV daily (echinocandin, add on) — Off-label combination data (e.g., Lazarte-Lalo 2025 and prior reports) — non-HIV severe refractory; not standard first-line; targets cyst-wall β-glucan

Setting playbook (outpatient) — Complete PO TMP-SMX course at home with close follow-up (mild disease only), or post-discharge secondary prophylaxis maintenance until immune recovery (CD4 >200 ×6 mo in HIV) and primary prophylaxis re-initiation in at-risk hosts
10. PO TMP-SMX completion (mild outpatient cases) DS 2 tablets PO TID (≈20 mg/kg/day TMP) to complete 14-21 d total PO TID — Mild disease only + reliable adherence + close follow-up at d 3 / d 7 / EOT (IDSA OI — mild outpatient management acceptable in highly selected cases)
11. atovaquone PO alternative (mild only) 750 mg PO BID with high-fat food PO BID — Sulfa intolerance + mild disease + PaO2 >70 on room air (IDSA OI mild-moderate alternative — high-fat meal required for absorption)
12. secondary prophylaxis post-PJP TMP-SMX 1 SS PO daily OR DS thrice weekly; alternatives: atovaquone 1500 mg daily, dapsone 100 mg daily (G6PD normal), aerosolized pentamidine 300 mg monthly PO/inhaled daily-weekly-monthly — All PJP survivors until immune recovery (CD4 >200 ×6 mo on ART in HIV) OR ongoing transplant/biologic IS in non-HIV (IDSA OI mandatory secondary prophylaxis to prevent relapse)
13. primary prophylaxis re-initiation in at-risk hosts TMP-SMX 1 SS daily OR DS thrice weekly PO daily-thrice weekly — CD4 <200 OR ≥20 mg pred-eq ≥4 wk OR biologic IS OR lymphoma OR transplant per protocol (IDSA OI / ECIL primary prophylaxis triggers)

Non-pharmacologic actions:
- ART optimization in HIV (id.hiv-initial.chronic.v1 cross-engine)
- Transplant IS taper with primary team if feasible (ECIL)
- Vaccination catch-up per ACIP 2024
- Pulmonology referral if persistent functional impairment / pneumothorax sequelae
- Patient education: return for fever, worsening dyspnea, new-onset chest pain (pneumothorax), rash on TMP-SMX

AVOID / contraindication checks:
- G6PD deficiency contraindicates primaquine and dapsone (IDSA OI)
- TMP SMX hyperkalemia with ACEI ARB or K sparing diuretic (IDSA OI / DailyMed)
- TMP SMX warfarin INR elevation (DailyMed)
- Atovaquone only for mild moderate not severe (IDSA OI)
- Pentamidine nephrotoxicity pancreatitis QTc (IDSA OI)
- Bozzette steroid start within 72h of TMP SMX (Bozzette 1990; NIH Consensus 1990)
- Do not delay empiric TMP SMX awaiting BAL in high suspicion (IDSA OI)

Monitoring

Regimen monitoring:
- CBC with diff q3-7d during TMP SMX (IDSA OI — BM suppression)
- BMP q3-7d during TMP SMX (IDSA OI — AKI + hyperK)
- LFT baseline then weekly (IDSA OI — hepatotoxicity)
- oxygenation trend daily (Bozzette 1990 — paradoxical worsening day 3-4 expected on steroids)
- response assessment day 5-7 switch if failing (IDSA OI)
- secondary prophylaxis until CD4 over 200 x6mo in HIV (IDSA OI)

Setting (outpatient) monitoring:
- Visit at week 1 + week 2 + EOT during treatment (IDSA OI)
- BMP + CBC + LFT at week 1 + week 2 during TMP-SMX (IDSA OI)
- CD4 + HIV VL at month 1 + month 3 after ART start (DHHS)
- Prophylaxis adherence + tolerability at every visit (IDSA OI)
- Repeat CXR at 4-6 wk to document resolution (IDSA OI)

Follow-up plan: Secondary prophylaxis: HIV TMP-SMX 1 SS daily OR DS thrice weekly until CD4 >200 ×6 mo on ART; transplant per institutional protocol; reinforce primary prophylaxis triggers (CD4 <200, ≥20 mg pred-eq ≥4 wk, biologics, lymphoma); ART initiation if HIV-naive (2-wk delay OK); pulmonology if persistent lung impairment
- Close-out criterion: secondary prophylaxis prescribed + chronic immunosuppression plan reconciled

Monitoring phase: Daily K/Cr/CBC/LFT × first week then 2-3×/wk during TMP-SMX (BM suppression, AKI, hyperkalemia, hepatotoxicity); clinical response by day 4-8 — paradoxical worsening with steroids common day 3-4; reassess at 5-7 d for treatment failure → switch regimen; oxygenation trend

Disposition

Current setting: outpatient — Complete PO TMP-SMX course at home with close follow-up (mild disease only), or post-discharge secondary prophylaxis maintenance until immune recovery (CD4 >200 ×6 mo in HIV) and primary prophylaxis re-initiation in at-risk hosts

Disposition criteria:
- Completion: full course + secondary prophylaxis prescribed + CD4 recovery plan + vaccinations updated + chest imaging resolved → discharge from PJP-specific surveillance back to standard ID / primary care (IDSA OI)

Escalation triggers (move to higher acuity):
- New / worsening dyspnea or fever on outpatient regimen → return to ED for re-evaluation + possible BAL (IDSA OI)
- Rash / new cytopenias / new AKI on TMP-SMX → hold + clinic re-evaluation + switch (IDSA OI)
- Pneumothorax-like chest pain → ED (IDSA OI)
- IRIS features after ART start → ID + steroid adjustment (IDSA OI)

Earlier-Return Triggers

Return-precaution thresholds (watch for):
- [LIFE_THREATENING] PaO2/FiO2 <200 OR mechanical-ventilation requirement OR refractory hypoxia despite NIV — life-threatening
- [LIFE_THREATENING] New pneumothorax / pneumomediastinum during PJP — cystic disease predisposes to rupture especially on positive-pressure ventilation
- [SEVERE] PaO2 <70 mmHg on room air OR A-a gradient ≥35 mmHg in suspected/confirmed PJP — Bozzette 1990 + NIH Consensus 1990 threshold for adjunctive corticosteroid in HIV

Citations

- IDSA/CDC/HIVMA Adult/Adolescent Opportunistic Infections Guidelines (Pneumocystis section) + Bozzette NEJM 1990 RCT + NIH Consensus 1990 + ATS 2006 PCP workshop + ECIL 2016 prevention + ATS 2019 microbiologic testing CPG (Hage/Limper) + Wang 2021 non-HIV PCP meta-analysis [PMID:2233917](https://pubmed.ncbi.nlm.nih.gov/2233917/)
- Cited evidence (PMID 2136587) [PMID:2136587](https://pubmed.ncbi.nlm.nih.gov/2136587/)
- Cited evidence (PMID 17065370) [PMID:17065370](https://pubmed.ncbi.nlm.nih.gov/17065370/)
- Cited evidence (PMID 27550992) [PMID:27550992](https://pubmed.ncbi.nlm.nih.gov/27550992/)
- Cited evidence (PMID 34222179) [PMID:34222179](https://pubmed.ncbi.nlm.nih.gov/34222179/)

Last reconciled with current guidelines: 2026-05-26.
References
  • IDSA/CDC/HIVMA Adult/Adolescent Opportunistic Infections Guidelines (Pneumocystis section) + Bozzette NEJM 1990 RCT + NIH Consensus 1990 + ATS 2006 PCP workshop + ECIL 2016 prevention + ATS 2019 microbiologic testing CPG (Hage/Limper) + Wang 2021 non-HIV PCP meta-analysis — PMID:2233917
  • Cited evidence (PMID 2136587) — PMID:2136587
  • Cited evidence (PMID 17065370) — PMID:17065370
  • Cited evidence (PMID 27550992) — PMID:27550992
  • Cited evidence (PMID 34222179) — PMID:34222179