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pulm.atypical-pneumonia.v1PRODUCTION
pulm.atypical-pneumonia.v1

Atypical Pneumonia (Mycoplasma / Chlamydophila / Legionella / psittacosis / Q fever)

pulmonologysubacuteacuteadult
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12/12 authored

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

Current phase

Frame

Detailed

Frame as atypical-CAP pathogen-discrimination pathway (Mp / C. pneumoniae / Legionella / C. psittaci / C. burnetii) when subacute pattern + interstitial CXR + exposure/extrapulmonary clues, OR a positive atypical test, in an adult (2025 ATS CAP PMID 40679934)

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Atypical pattern or positive atypical test established; chronic/non-infective routed out

Patient inputs (22)

Mp peaks school-age/young adults; Legionella severe disproportionately elderly/smokers; doxycycline avoided <8 yr — drives pathogen prior + drug selection (2025 ATS CAP PMID 40679934)

Severity / sepsis screen — hypotension is a severe-CAP minor criterion and Legionella severe-disease risk (2025 ATS CAP)

CURB-65 element + tachypnea severity (Lim Thorax 2003 PMID 12728155)

Hypoxemia threshold for admission/ICU; disproportionate hypoxia favors atypical/viral (2025 ATS CAP)

High fever ≥39 °C with relative bradycardia (Faget sign) raises Legionella suspicion

Transplant/biologic/HIV/steroid → broader differential (PCP, Nocardia, Legionella longjbeachae), longer duration, lower threshold for BAL (2025 ATS CAP)

QTc-prolonging meds before macrolide/FQ; statin + macrolide rhabdo; warfarin + macrolide/FQ INR interaction (2025 ATS CAP)

eGFR for renal dosing of FQ/macrolide; renal failure is a Legionella severe-disease marker

Patchy/interstitial vs lobar; multilobar disease is a Legionella severity + severe-CAP minor criterion (2025 ATS CAP)

Cold-agglutinin hemolysis supports Mycoplasma (insensitive ~50%, low specificity — supportive only, not a rule-in)

Paired acute/convalescent serology for C. psittaci, Coxiella burnetii (phase II IgG/IgM), Mp where PCR unavailable — retrospective confirmation

Pulse-temperature dissociation (relative bradycardia) — Legionella, psittacosis, Q fever clue

CURB-65 element + Legionella encephalopathy (disproportionate to pneumonia severity)

Psittacine/poultry exposure → Chlamydia psittaci; parturient livestock / unpasteurized dairy → Coxiella burnetii (Q fever) — changes empiric duration/agent

Doxycycline and fluoroquinolone relatively contraindicated → macrolide pathway; psittacosis in pregnancy is severe (azithromycin)

Hyponatremia (SIADH) is a classic Legionella discriminator vs typical CAP

Transaminitis common in Legionella, Q fever, psittacosis; baseline before doxy/macrolide/FQ

Rhabdomyolysis association with Legionella (AKI risk)

Markedly elevated CRP/PCT favors typical bacterial or Legionella over Mp/C.pneumoniae/viral; low PCT supports holding/narrowing (2025 ATS CAP)

L. pneumophila serogroup-1: pooled sens 0.86 / spec ~1.00 → very high LR+ when positive but cannot exclude non-sg1 (Kawasaki PMID 34972680)

Positive supports typical pneumococcal disease and argues against pure-atypical pathway (2025 ATS CAP)

Multiplex RT-PCR detects Mp / C.pneumoniae / Legionella / viruses (LoD 5-10 copies; Wagner PMID 29397298); also identifies 23S rRNA macrolide-resistance mutation where assayed

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Severity triggers (10)

10 need judgement
  • informationallife_threateningsevere_legionella_organ_failure
    Suspected/confirmed Legionella with respiratory failure / septic shock / multilobar disease / encephalopathy / acute renal failure / rhabdomyolysis (CPK ≥5× ULN)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverelegionella_urinary_antigen_positive_high_LRplus
    Urinary Legionella antigen positive — L. pneumophila serogroup-1 pooled sensitivity 0.86 (95% CI 0.78-0.91), specificity ~1.00 (0.99-1.00) → very high LR+, rules IN serogroup-1; a NEGATIVE result does NOT exclude non-sg1/non-pneumophila Legionella
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseveremycoplasma_extrapulmonary_complication
    Mp + cold-agglutinin hemolytic anemia, MIRM (rash + mucositis), encephalitis/transverse myelitis, or myocarditis
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseveretreatment_failure_at_48_72h_revise_diagnosis
    No clinical/radiographic improvement at 48-72 h on an atypical-active regimen despite adequate coverage
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevereimmunocompromised_atypical_broaden_differential
    Atypical-pattern pneumonia in transplant / biologic / HIV / chronic-steroid host
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderatelegionella_clinical_pivot_pentad
    Hyponatremia (Na <130) + GI symptoms (diarrhea) + relative bradycardia (pulse-temp dissociation) + transaminitis + encephalopathy disproportionate to pneumonia — Legionella clinical pivot vs typical/other-atypical CAP
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderatemacrolide_resistant_mycoplasma_failure
    Mp confirmed/likely + persistent fever or non-improvement on a macrolide ≥48-72 h, OR detected 23S rRNA domain-V mutation (e.g., A2063G), OR high-prevalence region (East Asia)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderatezoonotic_exposure_pivot_psittacosis_qfever
    Psittacine/poultry exposure (psittacosis) OR parturient-livestock / unpasteurized-dairy exposure (Q fever) with atypical pneumonia ± hepatitis ± severe headache
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderatemacrolide_or_FQ_QTc_prolongation
    Baseline QTc ≥500 ms or ≥60 ms increase on macrolide/FQ therapy
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmildmycoplasma_clinical_pivot
    School-age/young adult, family/school cluster, dry cough, normal/mildly elevated WBC, cold-agglutinin hemolysis or extrapulmonary feature — Mycoplasma pivot vs Legionella/typical CAP
    Trigger could not be auto-evaluated — needs clinician judgement.

Workflow calculators

Run this disease's risk and dosing calculators inline.

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Recommended regimen

2025 ATS CAP — atypical-active empiric → pathogen-directed → resistance/failure ladder (severity × pregnancy × resistance-risk × comorbidity)
axis: atypical_pneumonia_empiric_to_directedstep outpatient_empiric - Outpatient empiric — Mp / C. pneumoniae suspected, no severe-Legionella features (2025 ATS CAP)
Selected step "Outpatient empiric — Mp / C. pneumoniae suspected, no severe-Legionella features (2025 ATS CAP)" — CURB-65 0-1, SpO2 ≥92%, not immunocompromised, no severe-Legionella features, tolerates PO
  • doxycycline
    first line
    tetracycline
    100 mg PO BID (200 mg load if severe atypical concern) • PO • q12h × 5 d (afebrile-stable; longer if Legionella/psittacosis/Q fever)
    triggers: no_pregnancy, age_>=8, macrolide_resistance_region_or_failure_risk
    2025 ATS CAP first-line atypical-active for low-resistance reliability — covers Mp incl. macrolide-resistant strains, C. pneumoniae, C. psittaci, Coxiella; preferred where MRMP prevalence high (Ding PMID 38634891). RxCUI 3640 RxNav-confirmed 2026-05-16.
    rxcui 3640
  • azithromycin
    first line
    macrolide
    500 mg PO ×1 then 250 mg PO daily ×4 d • PO • daily × 5 d total
    triggers: low_local_macrolide_resistance, doxycycline_contraindicated, pregnancy
    2025 ATS CAP atypical-active; preferred in pregnancy and where local Mp macrolide resistance is low. Verify QTc + statin interaction. RxCUI 18631 RxNav-confirmed 2026-05-16.
    rxcui 18631
  • clarithromycin
    second line
    macrolide
    500 mg PO BID • PO • q12h × 5 d
    triggers: azithromycin_unavailable
    Macrolide alternative; more drug interactions (CYP3A4) than azithromycin. RxCUI 21212 RxNav-confirmed 2026-05-16.
    rxcui 21212
  • levofloxacin
    second line
    respiratory_fluoroquinolone
    750 mg PO daily • PO • daily × 5 d
    triggers: macrolide_and_doxycycline_intolerance, outpatient_legionella_concern, comorbidity_requiring_broader_cover
    Reserve respiratory FQ for intolerance / Legionella concern / significant comorbidity — covers typical + all atypicals (2025 ATS CAP). RxCUI 82122 RxNav-confirmed 2026-05-16.
    rxcui 82122

outpatient playbook — drug actions (3)

  1. 1. doxycycline
    rxcui 3640
    100 mg PO BID • PO • q12h × 5 d (longer for Legionella/psittacosis/Q fever)
    trigger: Outpatient atypical CAP, age ≥8, not pregnant, esp. if macrolide-resistance risk
    2025 ATS CAP atypical-active; reliable vs MRMP (Ding PMID 38634891)
  2. 2. azithromycin
    rxcui 18631
    500 mg PO ×1 then 250 mg PO daily • PO • daily × 5 d total
    trigger: Low local macrolide resistance, pregnancy, or doxycycline contraindicated
    2025 ATS CAP atypical-active; pregnancy-safe
  3. 3. levofloxacin
    rxcui 82122
    750 mg PO daily • PO • daily × 5 d
    trigger: Macrolide + doxycycline intolerance OR outpatient Legionella concern OR significant comorbidity
    Reserve respiratory FQ — covers typical + all atypicals (2025 ATS CAP)

Auto-drafted A&P note

outpatient

Subjective

- Possible entry pathways: Subacute dry cough, low-grade fever, headache, myalgia, sore throat — gradual onset (2025 ATS CAP; Mp/C.pneumoniae pattern); Extrapulmonary features — rash/mucositis or hemolysis or neurologic (Mp ~25% extrapulmonary, Lofgren PMID 34532621); GI/encephalopathy/relative bradycardia (Legionella); Patchy / interstitial infiltrate disproportionate to exam (2025 ATS CAP; PMID 40679934).

Objective

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

Assessment

**Atypical Pneumonia (Mycoplasma / Chlamydophila / Legionella / psittacosis / Q fever)** (pulm.atypical-pneumonia.v1).
Phenotype framing: §5.5.2 pathogen discrimination AS DATA: Mp vs C. pneumoniae vs Legionella vs C. psittaci vs C. burnetii vs viral (influenza/SARS-CoV-2/RSV) vs typical bacterial CAP vs TB vs eosinophilic pneumonia / hypersensitivity pneumonitis — each pivot has discriminator + test characteristic (see sibling_differentiation + severity_triggers + workups.branches_to)
Scope: Frame as atypical-CAP pathogen-discrimination pathway (Mp / C. pneumoniae / Legionella / C. psittaci / C. burnetii) when subacute pattern + interstitial CXR + exposure/extrapulmonary clues, OR a positive atypical test, in an adult (2025 ATS CAP PMID 40679934)

No severity triggers fired against current inputs.

Plan

Regimen axis: **2025 ATS CAP — atypical-active empiric → pathogen-directed → resistance/failure ladder (severity × pregnancy × resistance-risk × comorbidity)** — step "Outpatient empiric — Mp / C. pneumoniae suspected, no severe-Legionella features (2025 ATS CAP)".
1. doxycycline 100 mg PO BID (200 mg load if severe atypical concern) PO q12h × 5 d (afebrile-stable; longer if Legionella/psittacosis/Q fever) (tetracycline, first line) — 2025 ATS CAP first-line atypical-active for low-resistance reliability — covers Mp incl. macrolide-resistant strains, C. pneumoniae, C. psittaci, Coxiella; preferred where MRMP prevalence high (Ding PMID 38634891). RxCUI 3640 RxNav-confirmed 2026-05-16.
2. azithromycin 500 mg PO ×1 then 250 mg PO daily ×4 d PO daily × 5 d total (macrolide, first line) — 2025 ATS CAP atypical-active; preferred in pregnancy and where local Mp macrolide resistance is low. Verify QTc + statin interaction. RxCUI 18631 RxNav-confirmed 2026-05-16.
3. clarithromycin 500 mg PO BID PO q12h × 5 d (macrolide, second line) — Macrolide alternative; more drug interactions (CYP3A4) than azithromycin. RxCUI 21212 RxNav-confirmed 2026-05-16.
4. levofloxacin 750 mg PO daily PO daily × 5 d (respiratory_fluoroquinolone, second line) — Reserve respiratory FQ for intolerance / Legionella concern / significant comorbidity — covers typical + all atypicals (2025 ATS CAP). RxCUI 82122 RxNav-confirmed 2026-05-16.

Setting playbook (outpatient) — Identify atypical CAP treatable at home with single-agent oral atypical-active therapy, weigh local macrolide-resistance, ensure 48-72 h follow-up and return precautions (2025 ATS CAP)
5. doxycycline 100 mg PO BID PO q12h × 5 d (longer for Legionella/psittacosis/Q fever) — Outpatient atypical CAP, age ≥8, not pregnant, esp. if macrolide-resistance risk (2025 ATS CAP atypical-active; reliable vs MRMP (Ding PMID 38634891))
6. azithromycin 500 mg PO ×1 then 250 mg PO daily PO daily × 5 d total — Low local macrolide resistance, pregnancy, or doxycycline contraindicated (2025 ATS CAP atypical-active; pregnancy-safe)
7. levofloxacin 750 mg PO daily PO daily × 5 d — Macrolide + doxycycline intolerance OR outpatient Legionella concern OR significant comorbidity (Reserve respiratory FQ — covers typical + all atypicals (2025 ATS CAP))

Non-pharmacologic actions:
- Hydration counselling
- Smoking cessation pharmacotherapy if applicable
- Influenza, pneumococcal (PCV20), COVID vaccination when recovered
- Return precautions: worsening dyspnea, confusion, fever ≥72 h, rash/mucositis, dark urine (hemolysis)
- Public-health reporting if Legionella / psittacosis / Q fever confirmed

AVOID / contraindication checks:
- Macrolide_QTc_baseline_and_on_therapy_check_before_azithro_clarithro (2025 ATS CAP)
- Fluoroquinolone_tendon_aortic_aneurysm_neuropathy_glucose_dysregulation_warning (FDA class warning; 2025 ATS CAP)
- Doxycycline_avoid_pregnancy_and_age_under_8 (tetracycline class)
- Fluoroquinolone_avoid_pregnancy_and_children_first_line (use macrolide pathway)
- Macrolide_or_FQ_statin_interaction_rhabdomyolysis_risk (2025 ATS CAP)
- Macrolide_or_FQ_warfarin_INR_potentiation_monitor (2025 ATS CAP)
- Corticosteroid_only_severe_inpatient_CAP_or_refractory_hyperinflammatory_Mp_not_routine (2025 ATS CAP PMID 40679934)
- Legionella_urinary_antigen_negative_does_not_exclude_non_serogroup1_or_non_pneumophila (Kawasaki PMID 34972680)

Monitoring

Regimen monitoring:
- clinical response reassessed at 48 72h (2025 ATS CAP)
- treatment failure triggers resistance or alternate dx workup MRMP TB fungal empyema PE (2025 ATS CAP)
- IV to PO when Halm stable (2025 ATS CAP)
- LFTs baseline and during therapy legionella qfever psittacosis (2025 ATS CAP)
- QTc baseline and on therapy if macrolide or FQ (2025 ATS CAP)
- sodium normalisation tracking in legionella
- duration 3 5d stable typical or Mp Cpneumoniae (2025 ATS CAP shorter-course)
- duration 7 14d legionella up to 21d immunocompromised severe abscess (2025 ATS CAP)
- duration 10 14d psittacosis acute qfever doxycycline to prevent relapse
- qfever serology surveillance for chronic endocarditis in valvulopathy or immunocompromise
- public health reporting legionella psittacosis qfever notifiable
- extrapulmonary complication screen Mp hemolysis MIRM encephalitis (Lofgren PMID 34532621)

Setting (outpatient) monitoring:
- Symptom check at 48-72 h — escalate if no improvement (consider MRMP, wrong pathogen, severity)
- CXR follow-up at 6 weeks if smoker / age ≥50

Follow-up plan: Public-health reporting for Legionella (notifiable; environmental source investigation if cluster) and psittacosis/Q fever (zoonotic notifiable); Q fever serology surveillance for chronic endocarditis in valvulopathy/immunocompromise; pneumococcal + influenza + COVID vaccination; smoking cessation; CXR follow-up at 6 wk if smoker / age ≥50
- Close-out criterion: Reporting + prevention + chronic-complication surveillance complete

Monitoring phase: Clinical response at 48-72 h (defervescence slower in Legionella/psittacosis); resistance/treatment-failure workup if no improvement (consider MRMP, wrong pathogen, TB/fungal, empyema, malignancy, PE); LFTs, QTc, sodium normalisation; IV→PO when Halm-stable; extrapulmonary complication screen (Mp hemolysis/MIRM/encephalitis — Lofgren PMID 34532621; Legionella endocarditis/abscess; Q fever endocarditis)

Disposition

Current setting: outpatient — Identify atypical CAP treatable at home with single-agent oral atypical-active therapy, weigh local macrolide-resistance, ensure 48-72 h follow-up and return precautions (2025 ATS CAP)

Disposition criteria:
- Discharge home: CURB-65 0-1, SpO2 ≥92% RA, PO-tolerant, not immunocompromised, no severe-Legionella features, follow-up arranged (2025 ATS CAP)

Escalation triggers (move to higher acuity):
- SpO2 <92% on room air → ED
- CURB-65 ≥2 → ED
- Failure of oral therapy at 48-72 h → ED + resistance/alternate-dx workup
- Hyponatremia + altered mentation + relative bradycardia suggesting severe Legionella → ED
- Hemolysis (dark urine, jaundice) or extensive mucositis (MIRM) → ED (Lofgren PMID 34532621)

Earlier-Return Triggers

Return-precaution thresholds (watch for):
- [LIFE_THREATENING] Suspected/confirmed Legionella with respiratory failure / septic shock / multilobar disease / encephalopathy / acute renal failure / rhabdomyolysis (CPK ≥5× ULN)
- [SEVERE] Urinary Legionella antigen positive — L. pneumophila serogroup-1 pooled sensitivity 0.86 (95% CI 0.78-0.91), specificity ~1.00 (0.99-1.00) → very high LR+, rules IN serogroup-1; a NEGATIVE result does NOT exclude non-sg1/non-pneumophila Legionella
- [SEVERE] Mp + cold-agglutinin hemolytic anemia, MIRM (rash + mucositis), encephalitis/transverse myelitis, or myocarditis

Citations

- 2025 ATS Diagnosis and Management of CAP — Official ATS Clinical Practice Guideline (Niederman, AJRCCM 2025;212(1):24; PMID 40679934; DOI 10.1164/rccm.202507-1692ST) + IDSA/CDC Legionellosis context; updates 2019 ATS/IDSA CAP (PMID 31573350) [PMID:40679934](https://pubmed.ncbi.nlm.nih.gov/40679934/)
- Cited evidence (PMID 31573350) [PMID:31573350](https://pubmed.ncbi.nlm.nih.gov/31573350/)
- Cited evidence (PMID 34972680) [PMID:34972680](https://pubmed.ncbi.nlm.nih.gov/34972680/)
- Cited evidence (PMID 28463665) [PMID:28463665](https://pubmed.ncbi.nlm.nih.gov/28463665/)
- Cited evidence (PMID 32296816) [PMID:32296816](https://pubmed.ncbi.nlm.nih.gov/32296816/)

Last reconciled with current guidelines: 2026-05-16.
References
  • 2025 ATS Diagnosis and Management of CAP — Official ATS Clinical Practice Guideline (Niederman, AJRCCM 2025;212(1):24; PMID 40679934; DOI 10.1164/rccm.202507-1692ST) + IDSA/CDC Legionellosis context; updates 2019 ATS/IDSA CAP (PMID 31573350) — PMID:40679934
  • Cited evidence (PMID 31573350) — PMID:31573350
  • Cited evidence (PMID 34972680) — PMID:34972680
  • Cited evidence (PMID 28463665) — PMID:28463665
  • Cited evidence (PMID 32296816) — PMID:32296816