01Approach to the Critical Patient/attcp51

Immediate priorities

›Airway and oxygenation threats

›Severe hypoxemia

›SpO2 <90% on room air

›PaO2 <70 mmHg on ABG

›A-a gradient >=35 mmHg

›Respiratory failure escalation

›Tachypnea >30 per minute with accessory muscle use

›Inability to speak in full sentences

›Rapid exertional desaturation

›Supplemental oxygen initiation

›Target SpO2 >90%

›Escalate to HFNC if standard O2 insufficient

›NIV as bridge in non-intubated deteriorating patient

›If refractory hypoxemia or rising PaCO2, early intubation planning

›Mortality rises to 50-58% with mechanical ventilation

›Goals of care discussion before intubation when appropriate

›Severity classification

›Mild PCP

›PaO2 >=70 mmHg on room air

›A-a gradient <35 mmHg

›Moderate PCP

›A-a gradient 35-45 mmHg

›Severe PCP

›PaO2 <70 mmHg or A-a gradient >=45 mmHg

›Adjunctive corticosteroids indicated

›ABG is mandatory for severity classification before treatment

02History/hx59

Presentation pattern

›Classic symptom triad in HIV

›Progressive exertional dyspnea

›Onset over days to weeks

›Initially exertional, progressing to rest dyspnea

›Dry nonproductive cough

›Productive cough suggests bacterial co-infection

›Low-grade fever

›Present in ~80-87% of cases

›Night sweats common

›HIV-negative host presentation

›More acute and fulminant onset

›Symptoms evolving over days rather than weeks

›Higher risk of rapid respiratory failure

›Higher mortality in this group

›30-50% compared to 10-20% in HIV-positive patients

Risk factors

›Immunosuppression context

›HIV/AIDS with CD4 <200 cells per mm3

›~90% of HIV-associated PCP occurs at this threshold

›Most cases occur in patients unaware of HIV status or not in care

›Solid organ transplant

›Highest risk within first 6 months post-transplant

›Calcineurin inhibitors and corticosteroids as drivers

›Hematologic malignancy

›Acute lymphoblastic leukemia

›Non-Hodgkin lymphoma

›Prolonged corticosteroid use

03Physical Exam/exam44

Vitals and general

›Vital sign priorities

›Temperature

›Fever present in ~80-87% of cases

›Absence of fever does not exclude diagnosis

›Respiratory rate

›Tachypnea as primary severity marker

›>=30 per minute indicates severe disease

›Oxygen saturation

›Room air SpO2 most informative

›Ambulatory desaturation with walking is sensitive finding

›Heart rate

›Tachycardia reflects hypoxemia and systemic inflammation

›General appearance

›Increased work of breathing

›Accessory muscle use

›Nasal flaring

›Signs of immunosuppression

›Cachexia and wasting

›Kaposi sarcoma skin or mucosal lesions

Lung and oropharyngeal exam

›Lung examination findings

›Often normal at rest in early or mild disease

›Classic diagnostic pearl

›Discordance between symptoms and exam findings

›Diffuse dry crackles when present

›Described as "cellophane" rales

›Bilateral, not focal

04Differential Diagnosis/ddx47

Life threats and close mimics

›Infectious mimics

›Community-acquired bacterial pneumonia

›ICD-10 J18.9

›More acute onset, productive cough, lobar consolidation, leukocytosis

›Mycobacterium tuberculosis

›ICD-10 A15.0

›Upper lobe cavitation, lymphadenopathy, subacute course

›Can co-exist with PCP

›CMV pneumonitis

›Especially in transplant recipients

›Often co-occurs with PCP, requiring dual treatment

›Invasive pulmonary aspergillosis

›ICD-10 B44.1

›Nodular or cavitary lesions, halo sign on CT

›Predominantly neutropenic patients

›Cryptococcal pneumonia

›ICD-10 B45.1

›Often with concurrent meningitis

›Cryptococcal antigen testing required

›Histoplasmosis or coccidioidomycosis

›ICD-10 B39 and B38 respectively

›Endemic area exposure history

›Non-infectious mimics

›Drug-induced pneumonitis

›ICD-10 J70.2

›Methotrexate, bleomycin, immunotherapy agents

›Temporal relationship with drug initiation

05Laboratory Tests/lt62

Core diagnostic markers

›Serum beta-D-glucan

›Sensitivity ~90% for PCP

›Positive threshold >80-100 pg/mL

›Low level <80 pg/mL has high negative predictive value

›Limitations

›False positives with bacteremia, other fungal infections, hemodialysis

›Not specific to PCP

›Serum LDH

›Often elevated >500 U/L in PCP

›LDH >495 U/L predicts death with ~70% sensitivity and specificity

›Correlates with disease severity

›Sensitive but nonspecific

›Elevated in hemolysis, hepatitis, and other pulmonary infections

Gas exchange and severity labs

›Arterial blood gas

›PaO2 on room air for severity classification

›Mild: PaO2 >=70 mmHg, A-a gradient <35 mmHg

›Moderate: A-a gradient 35-45 mmHg

›Severe: PaO2 <70 mmHg or A-a gradient >=45 mmHg

›Mandatory before initiating adjunctive corticosteroids

›A-a gradient >=35 mmHg triggers steroid use

›PaCO2 for ventilatory status

›Rising PaCO2 indicates impending respiratory failure

›Venous blood gas

›pH trend assessment when ABG not available

›Lactate for concurrent sepsis screening

06Diagnostic Tests/dt63

Scoring Systems

›Severity classification tools

›A-a gradient based severity

›Mild: A-a gradient <35 mmHg — outpatient treatment may be appropriate

›Moderate: A-a gradient 35-45 mmHg — admission and steroids indicated

›Severe: A-a gradient >=45 mmHg — ICU consideration, steroids mandatory

›Most clinically validated tool for PCP-specific severity staging

›LDH as prognostic marker

›LDH >495 U/L predicts mortality with 70% sensitivity and specificity

›Serial LDH trend correlates with treatment response

›APACHE II or SOFA

›Used in ICU-admitted PCP for general severity benchmarking

›Not PCP-specific but informative for overall prognosis

›Limitations

›No PCP-specific validated scoring tool equivalent to PSI or CURB-65

›Clinical trajectory and gas exchange remain primary decision drivers

MRI

›MRI chest role in PCP

›Not a first-line or routine modality for PCP

›Limited availability in acute setting

›Motion artifact limits quality in tachypneic patients

›Problem-solving indications

›Distinguishing malignancy from infection when CT inconclusive

›Complex pleural or mediastinal disease characterization

›Contraindications

›Unstable or intubated patient

›Ferromagnetic implants

›Practical note

07Disposition/dispo33

Admission and ICU criteria

›Hospital admission indications

›Moderate-to-severe disease

›PaO2 <70 mmHg or A-a gradient >=35 mmHg

›Requiring supplemental oxygen to maintain SpO2 >90%

›Inability to tolerate oral medications

›IV TMP-SMX required until clinical improvement

›New HIV diagnosis with workup needed

›CD4 count and baseline OI evaluation

›Significant comorbidities or hemodynamic instability

›ICU admission indications

›Respiratory failure

›Requirement for HFNC, NIV, or mechanical ventilation

›PaO2 <60 mmHg despite supplemental oxygen

›Hemodynamic compromise

›Vasopressor requirement

›Concurrent septic shock

›ARDS pattern

›Bilateral infiltrates with PaO2/FiO2 ratio <300 mmHg

›Mortality with ICU admission ~50-58%

Outpatient and discharge criteria

›Outpatient treatment eligibility

›Mild disease only

›PaO2 >=70 mmHg on room air

›A-a gradient <35 mmHg

›Reliable patient with close follow-up plan

›Within 3-5 days for oxygenation reassessment

›Able to take oral medications

08Treatment/t97

Oxygen and supportive care

›Respiratory support

›Supplemental oxygen

›Target SpO2 >90%

›Nasal cannula for mild supplemental needs

›High-flow nasal cannula

›For moderate-to-severe hypoxemia

›Flow titration to comfort and SpO2 target

›Non-invasive ventilation

›As bridge in deteriorating non-intubated patient

›Use with caution if secretion burden

›Mechanical ventilation when refractory

›Lung-protective strategy

›Tidal volume 6 mL per kg ideal body weight

›Plateau pressure target <30 cmH2O

First-line antimicrobial therapy

›TMP-SMX (trimethoprim-sulfamethoxazole)

›Preferred first-line agent for all severity levels

›TMP 15-20 mg per kg per day

›SMX 75-100 mg per kg per day

›Dosing route by severity

›IV for moderate-to-severe: divided every 6-8 hours

›Switch to PO after clinical improvement

›Treatment duration 21 days total

›Monitoring during therapy

›Potassium: TMP-SMX causes hyperkalemia

›Renal function for dose adjustment

›CBC for cytopenias

›LFTs for hepatotoxicity

›Common adverse effects

›Rash including risk of Stevens-Johnson syndrome

›Bone marrow suppression

›Hyperkalemia

›Nephrotoxicity

›Leucovorin is contraindicated during active PCP treatment

›Associated with higher treatment failure rates

›Class I recommendation against use

Adjunctive corticosteroids

›Indications for corticosteroids

›Moderate-to-severe PCP in HIV patients

›PaO2 <70 mmHg on room air

›A-a gradient >=35 mmHg

›Class I recommendation

›Start within 72 hours of anti-PCP therapy initiation

›Ideally concurrently with TMP-SMX

›Reduces mortality and respiratory failure risk

›Prednisone taper regimen

›Days 1-5

›Prednisone 40 mg PO twice daily

›Days 6-10

›Prednisone 40 mg PO once daily

›Days 11-21

›Prednisone 20 mg PO once daily

›If unable to take PO: methylprednisolone IV at 75-80% of prednisone dose

›Non-HIV patients and corticosteroids

›More controversial in HIV-negative immunocompromised hosts

›2025 PIC trial (Lancet Respir Med) showed potential benefit in severe hypoxic respiratory failure

›PaO2 <60 mmHg threshold in non-HIV population

›JAMA 2024 review supports individualized decision

›Risks include worsening underlying immunosuppression

›Discuss with ID and primary team

Alternative regimens for TMP-SMX intolerance

›Primaquine plus clindamycin

›Preferred alternative — more effective and less toxic than pentamidine

›Primaquine 30 mg base PO daily

›Clindamycin 600 mg IV every 6 hours or 900 mg IV every 8 hours

›PO option: clindamycin 450 mg every 6 hours

›G6PD testing required before primaquine

›Hemolytic anemia risk if G6PD deficient

›IV pentamidine

›Reserved for severe disease when other options unavailable

›4 mg per kg IV daily

›Infuse over 60 minutes

›Significant toxicity profile

›Hypoglycemia, nephrotoxicity, pancreatitis, QT prolongation

›Glucose monitoring during infusion

›Atovaquone

›Mild-to-moderate disease only

›750 mg PO twice daily with fatty meal

›Food required for adequate absorption

›Class IIb evidence for mild-moderate PCP

›Not appropriate for severe or non-oral-tolerant patients

Treatment monitoring and response

›Clinical response expectations

›Improvement typically begins within 4-8 days

›Do not consider treatment failure before 5-7 days

›Radiographic improvement lags clinical improvement

›LDH trend as response surrogate

›Declining LDH correlates with treatment response

›If no improvement by day 7

›Reassess diagnosis with bronchoscopy if not already done

›Consider co-infection evaluation

›ART initiation in HIV patients

›Initiate ART as soon as feasible after PCP treatment started

›Early ART associated with improved survival

›IRIS risk monitoring

›Acute worsening within weeks of ART initiation

›Continuation of ART generally recommended through IRIS

›Immunosuppression management in non-HIV patients

›Discuss reduction of immunosuppression with transplant or oncology team

›Balance PCP treatment efficacy with graft or disease control

›Individualized decision with specialist input

09Special Populations/sp65

Pregnancy

›PCP in pregnancy

›Rare but life-threatening in HIV-positive pregnant patients

›Immunosuppression of pregnancy increases vulnerability

›CD4 count may be misleadingly low in pregnancy

›TMP-SMX safety considerations

›Generally used despite theoretical risks given severity of PCP

›First trimester: theoretical neural tube risk with folate antagonism

›Near term: risk of neonatal hyperbilirubinemia and kernicterus

›Benefit generally outweighs risk in moderate-to-severe PCP

›Alternative agents

›Pentamidine used for severe cases when TMP-SMX contraindicated

›Primaquine and dapsone avoided due to hemolysis risk

›Atovaquone safety data in pregnancy limited

›Adjunctive corticosteroids

›Use for moderate-to-severe disease as in non-pregnant patients

›Fetal monitoring when viable gestation

›Maternal oxygenation target

›SpO2 >=95% to ensure adequate fetal oxygenation

›Delivery timing individualized

›Based on gestational age and maternal stability

›Multidisciplinary team: ID, maternal-fetal medicine, neonatology

Geriatric

›Older adult considerations

›Atypical presentation

›Fever may be absent or blunted

›Delirium or functional decline as presenting feature

›Lower respiratory rate thresholds for severity

10Background/b73

Epidemiology

›Disease burden and trends

›Most common AIDS-defining illness historically

›Incidence dramatically reduced with ART and prophylaxis

›Still significant in patients not in HIV care or with virologic failure

›Mortality rates

›HIV-positive patients: 10-20% in-hospital mortality

›HIV-negative immunocompromised: 30-50% mortality

›ICU-admitted patients: ~50-58% mortality

›Overall in-hospital mortality ~25%

›Shifting epidemiology

›Increasing proportion of cases in non-HIV patients

›Transplant, hematologic malignancy, and autoimmune diseases driving non-HIV burden

›~25-50% of PCP now occurs in HIV-negative patients at major centers

›Prophylaxis effectiveness

›~95% of PCP cases occur in patients not receiving prophylaxis

›TMP-SMX prophylaxis reduces incidence by >90%

›ICD-10 coding

›B59 — Pneumocystosis (Pneumocystis jirovecii pneumonia)

Pathophysiology

›Organism characteristics

›Pneumocystis jirovecii

›Fungal organism (previously misclassified as protozoan)

›Cannot be cultured on standard media

›Obligate extracellular pathogen

›Trophic and cyst life forms in alveoli

›Transmission

›Airborne transmission from colonized or infected individuals

›Asymptomatic carriage common in immunocompetent hosts

›Reactivation of latent infection in immunosuppressed hosts

›Disease mechanisms

›Alveolar filling

›Organisms fill alveolar spaces with foamy exudate

›Interstitial pneumonitis with mononuclear infiltrate

›Surfactant dysfunction from alveolar damage

›Gas exchange impairment

›Diffusion defect as primary mechanism of hypoxemia

›Ventilation-perfusion mismatch

›Diffusing capacity for carbon monoxide markedly reduced

›Progression to ARDS

›Cytokine storm in severe cases

›Neutrophil-mediated lung injury

›Bilateral alveolar infiltrates with refractory hypoxemia

Therapeutic Considerations

›Treatment strategy rationale

›TMP-SMX as preferred first-line agent

›Inhibits folate synthesis in Pneumocystis

›Broadest evidence base and lowest cost

›Oral bioavailability allows IV-to-PO transition

›Corticosteroid rationale

›Attenuates inflammatory response during organism kill

›Reduces alveolar damage from cytokine release

›Most survival benefit in first week of treatment

›Class I evidence for HIV patients with PaO2 <70 mmHg

›Leucovorin avoidance

›Pneumocystis lacks dihydrofolate reductase capable of using exogenous folate

›Leucovorin supplementation rescues Pneumocystis and reduces drug efficacy

›Prophylaxis strategy

›Primary prophylaxis indications

›HIV: CD4 <200 cells per mm3 or prior AIDS-defining illness

›Transplant: all solid organ recipients for 6-12 months post-transplant

›Hematologic malignancy on intensive therapy

›Prolonged corticosteroid use >=20 mg daily for >=4 weeks

›Secondary prophylaxis

›After completing PCP treatment: continue TMP-SMX until CD4 >200 for >=3 months on ART

›TMP-SMX 1 DS tablet daily or 3 times per week

›ART as prevention

›ART-mediated CD4 recovery eliminates PCP risk

›CD4 >200 sustained for 3 months allows prophylaxis discontinuation

›Diagnostic approach considerations

›Empiric treatment acceptable in high-probability cases

›BAL often performed after empiric initiation

›Treatment does not significantly reduce BAL sensitivity within first few days

›Clinical non-response by day 7 requires re-evaluation

›Bronchoscopy if not already performed

›Co-infection or alternative diagnosis

11Patient Discharge Instructions/pdi27

copy discharge instructions

›Pneumocystis pneumonia home care

›Take all medications exactly as prescribed for the full 21 days

›Do not stop antibiotics early even if feeling better

›Take trimethoprim-sulfamethoxazole with plenty of fluids

›If prescribed atovaquone, take with a fatty meal each time

›Rest and avoid strenuous activity during recovery

›Avoid contact with people who are sick

›Warning signs to return to emergency immediately

›Worsening shortness of breath or difficulty breathing at rest

›Chest pain (could indicate pneumothorax)

›Lips or fingertips turning blue

›Fever not improving after 5-7 days of treatment

›Widespread rash especially involving mouth, eyes, or genitals

›May indicate Stevens-Johnson syndrome from trimethoprim-sulfamethoxazole

›Inability to take medications due to vomiting

›Confusion, extreme sleepiness, or difficulty waking

›Fainting or near-fainting

›Follow-up instructions

›Mandatory follow-up within 3-5 days to reassess oxygen levels

›Complete the full 21-day antibiotic course

›After treatment, continue daily preventive antibiotic as prescribed

›Return for repeat blood work including CD4 count as directed

›HIV care follow-up if not already engaged

›Prevention after recovery

›Continue prophylactic antibiotics until immune system recovers

›Adhere to HIV medications (ART) every day

›Keep all specialist appointments

12References/r28

Guidelines and key sources

›Primary guidelines

›IDSA and DHHS Opportunistic Infections Guidelines 2025

›Benson et al. Guidelines for Prevention and Treatment of OIs in Adults with HIV

›DHHS/OARAC 2025 adult and adolescent OI guidelines

›AST Infectious Diseases Community of Practice 2019

›Fishman JA, Gans H — Pneumocystis jiroveci in solid organ transplantation

›Clinical Transplantation 2019

›DHHS 2025 pediatric OI guidelines

›Kapogiannis et al. — Guidelines for Prevention and Treatment of OIs in Children with HIV

›Key clinical studies

›Thomas CF, Limper AH — Pneumocystis Pneumonia

›New England Journal of Medicine 2004

›LDH >495 U/L mortality prediction 70% sensitivity and specificity

›Lemiale V et al. — PIC trial adjunctive corticosteroids in non-HIV PCP

›Lancet Respiratory Medicine 2025

›Double-blind RCT of corticosteroids in non-HIV severe PCP

›Schmidt JJ et al. — Clinical course of PCP over 17 years

›Critical Care 2018

›Gaborit BJ et al. — Outcome and prognostic factors of PCP

›Annals of Intensive Care 2019

›Sun R et al. — Diagnostic accuracy of beta-D-glucan and LDH for non-HIV PCP

›Scientific Reports 2021

›Giacobbe DR et al. — PCP in ICUs multicenter study ESGCIP and EFISG

›Critical Care 2023

›Pirracchio R et al. — Low-dose corticosteroids for severe pulmonary infections

›JAMA 2024

›Jaramillo Cartagena A et al. — Laboratory diagnosis of Pneumocystis jirovecii

Evidence & Review

Evidence & Review