Pneumocystis jirovecii pneumonia (PJP) 

— formerly known as Pneumocystis carinii pneumonia (PCP) — is a life-threatening opportunistic fungal infection that primarily affects immunocompromised hosts, especially those with HIV/AIDS, malignancy, organ transplantation, or on long-term immunosuppressive therapy.

Although Pneumocystis jirovecii is classified as a fungus, it behaves more like an atypical protozoan, being unresponsive to antifungal drugs such as amphotericin B or azoles.

 MICROBIOLOGY

• Organism: Pneumocystis jirovecii (human-specific; formerly P. carinii)
• Classification: Fungal (based on rRNA sequencing)
• Reservoir: Humans (no animal or environmental reservoir)
• Transmission: Airborne person-to-person spread (likely via inhalation)

 EPIDEMIOLOGY

• Ubiquitous organism: >80% of humans develop antibodies by age 3–4 years.
• Reactivation or reinfection occurs in immunocompromised states.

Common at-risk groups:

 PATHOGENESIS

• P. jirovecii attaches to type I alveolar epithelial cells → damages alveolar-capillary membrane.
• Foamy eosinophilic exudate fills alveoli → impairs gas exchange.
• Diffuse interstitial pneumonitis develops.
• CD4+ T-cell–mediated immunity is crucial for clearance; deficiency leads to uncontrolled proliferation.

 CLINICAL FEATURES

1. Symptom Onset

• Subacute (1–4 weeks) in HIV patients.
• Acute fulminant course in non-HIV immunocompromised (e.g., transplant).

2. Symptoms

• Progressive dyspnea (especially on exertion)
• Nonproductive cough
• Fever, malaise, fatigue
• Pleuritic chest pain (occasionally)
• Hypoxemia disproportionate to clinical findings.

3. Signs

• Tachypnea, tachycardia
• Fine end-inspiratory crackles
• Cyanosis (advanced disease)
• May be minimal auscultatory findings despite severe hypoxia.

 LABORATORY FINDINGS

🩻 RADIOLOGICAL FEATURES

1. Chest X-ray

• Bilateral diffuse interstitial infiltrates (ground-glass pattern)
• May progress to alveolar consolidation
• Cystic lesions / pneumatoceles in some patients (predispose to pneumothorax)

2. HRCT Chest

• Ground-glass opacities (predominantly perihilar)
• Crazy-paving pattern (GGO + septal thickening)
• Cysts / pneumatoceles common in AIDS-related PJP
• May show mosaic attenuation in early disease

 DIAGNOSIS

Diagnosis requires microscopic identification of the organism or molecular confirmation.

1. Specimen collection

• Induced sputum (sensitivity ~50–90%)
• BAL fluid (gold standard; sensitivity >95%)
• Transbronchial / open lung biopsy if diagnosis uncertain

2. Stains

3. PCR-based assays

• High sensitivity; useful in low fungal burden
• Quantitative PCR differentiates colonization from active infection

 TREATMENT

1. First-line therapy

Trimethoprim–sulfamethoxazole (TMP–SMX)

• Dosage: TMP 15–20 mg/kg/day + SMX 75–100 mg/kg/day IV or PO in 3–4 divided doses
• Duration:
• 21 days (HIV-related)
• 14 days (non-HIV immunocompromised)

Switch to oral therapy when clinically improved.

2. Adjunctive corticosteroids (for HIV-related PJP)

Indicated when:

• PaO₂ <70 mmHg on room air, or
• A–a gradient >35 mmHg

Prednisone regimen:

• Day 1–5: 40 mg BID
• Day 6–10: 40 mg OD
• Day 11–21: 20 mg OD
  (Alternatively, IV methylprednisolone 75% equivalent if unable to take orally)

Rationale: Reduces risk of respiratory failure and mortality.

3. Alternative regimens

 PROPHYLAXIS

Indications:

• HIV: CD4 <200 cells/µL or oropharyngeal candidiasis
• Transplant / malignancy / immunosuppression: Prednisone ≥20 mg/day >4 weeks or equivalent
• Prior PJP episode

Regimens:

Prophylaxis discontinued when CD4 >200 cells/µL for >3 months on ART.

 COMPLICATIONS

• Pneumothorax (from rupture of cysts)
• ARDS
• Respiratory failure requiring mechanical ventilation
• Relapse if prophylaxis not maintained
• Drug toxicity (sulfa rash, hepatitis, cytopenias, nephrotoxicity)

 DIFFERENTIAL DIAGNOSIS

• CMV pneumonitis
• Bacterial pneumonia (esp. Legionella)
• Viral pneumonitis (influenza, RSV)
• Fungal pneumonia (Aspergillus, Histoplasma)
• Noninfectious interstitial pneumonitis (drug-induced, radiation)

 PROGNOSIS