• Author: Melissa A. Socarras, MD MS
  • Editor: Jonathan Kobles, MD

Definition and Background:

  • Pneumocystis is an atypical fungal microorganism that can cause potentially life-threatening pulmonary infection in immunocompromised individuals.
  • Highest risk patients: HIV positive with CD4 < 200 
    • PJP is the most common initial opportunistic infection that establishes the diagnosis of AIDS
    • PJP infection is the most common identifiable cause of death in patients with AIDS
  • Other at-risk patients:
    • Hematologic or solid organ transplant recipients
    • Malignancies (especially hematologic)
    • Chronic glucocorticoids, chemotherapeutics agents, and other immunosuppressive medications.



  • During WWI, PJP was first observed in humans through malnourished and premature infants.
  • In the 1980s, there was a steep rise in PJP infections correlating to the AIDS epidemic as pneumocystis became an AIDS-defining illness.



  • Transmission is via airborne route, and acquisition of new infections is likely person-to-person.
  • Pneumocystis attaches to Type 1 alveolar epithelial cells in the host, prompting the fungus to transition from the trophic state to the cystic state. This attachment initiates a cascade of cellular responses in both the pneumocystis organism and the host lung tissue, resulting in lung injury.
  • CD4+ T cells are essential for the control of pneumocystis infection.


Clinical Presentation: 

  • Symptoms and physical examination are typically non-specific. 
    • Symptoms: 
      • Nonproductive and dry cough (95% of patients) 
      • Low-grade fever (80% of patients)
      • Progressive dyspnea (95% of patients)
    • Exam: 
      • 50% of cases will have clear lung sounds; abnormal findings often include crackles and rhonchi. 
      • Hypoxemia, tachypnea, and tachycardia will be present in more severe cases. However, some of these can be elicited with exertion in mild cases. 
      • Ambulatory saturation can be a valuable tool in the ED to identify subtle hypoxia with exertion.
  • HIV-positive patients: More likely to present with indolent and subtle onset of symptoms over weeks
      • Mortality: 17-30%
  • Non-HIV immunocompromised patients: More likely to present with more abrupt onset of symptoms; will present with fulminant infection, especially if onset is shortly after receiving corticosteroids.
      • Mortality: 28 – 53%
  • Consider PJP and undiagnosed HIV in patients who present with:
    • Hypoxemia without any other explanation
    • History of high-risk sexual behavior or injection drug use
    • History of constitutional symptoms, including unexpected weight loss, night sweats, fatigue, and lymphadenopathy
    • Signs and symptoms of pneumonia with bilateral chest x-ray infiltrates (see below)


Evaluation and Differential Diagnosis: 

Most laboratory findings are non-specific.

  • Lymphocyte count: A value < 10% of normal has been associated with a poor prognosis.
  • Beta-d-glucan: Elevated value should raise suspicion if one is already concerned about possible PJP infection, but a positive test in isolation cannot be considered diagnostic. 
  • LDH: 
    • Extracellular LDH indicates lung tissue cellular damage and death. 
    • An elevated level is not specific to PJP infection; however, infection has been associated with levels > 500.
    • LDH values can help exclude PJP in  HIV-positive patients. 
      • HIV positive: sensitivity 100% / specificity 47%
        • A negative result can exclude Disease, but a positive result does not confirm the diagnosis.
      • HIV negative: sensitivity 63% / specificity 43%
  • ABG: Routine testing in hypoxic patients is important to calculate the alveolar-arterial (A-a) oxygen gradient. PJP increases the A-a gradient.


Radiographic findings are non-specific and cannot provide a definitive diagnosis. 

  • CXR: 
    • Classic findings are bilateral, diffuse interstitial infiltrates (bat-wing pattern); however, they may also present with focal consolidation, nodular lesions, cavitary lesions, and adenopathy.
    • 15 to 25% of CXR may appear negative, especially in the early stages of the Disease. 
  • Chest CT: 
    • Ground glass opacities with a patchy distribution, predominantly in the perihilar region of the lungs. 
    • CT chest is more sensitive than CXR and can show infection in early stages.
    • Early Stage PJP: 20% of CTs demonstrate GCOs.
    • Mid Stage PJP: 47% of CTs demonstrate GCOs and patchy consolidations.
    • Late Stage PJP: 80% of CTs demonstrate predominant consolidations.


Microbiological Testing: 

  • Confirmation of PJP infection involves inpatient diagnostics, including bronchoscopy with specimen analyses.
  • Pneumocystis cannot be cultured. 
  • PCR of BAL: sensitivity 100% / specificity 87%
  • PCR of induced sputum: sensitivity 97% / specificity 93%


Consider a broad differential diagnosis in HIV patients presenting with symptoms and findings suggestive of  respiratory infection, including:

  • Bacterial Pneumonia
    • Streptococcus pneumoniae is the most common cause of HIV-associated pneumonia in the US and Western Europe.
  • Tuberculosis
    • 10% of new cases in the US occur in HIV-infect4ed patients
    • TB should be considered in any HIV-infected patient presenting with pulmonary symptoms, and appropriate precautions should be taken to avoid transmission.
  • Mycobacterium avium-intracellulare complex (MAC)
  • Viral Pneumonia 
    • CMV, common respiratory viruses including influenza and COVID
  • Fungal infection 
    • Histoplasmosis, Coccidioidomycosis, Cryptococcus (abnormal pulmonary adenopathy)
  • Kaposi’s Sarcoma (nodular lesions)



  • Treatment for PJP should begin immediately when clinical suspicion is high. Treatment should not be delayed to obtain diagnostic confirmation. 
  • Treatment of PJP is determined by disease severity. 
    • Mild Disease: A-a O2 gradient < 35 mmHg or PaO ≥70 mmHg.
    • Moderate disease: A-a O2 gradient of 35-45 mmHg or PaO ≥60 and <70 mmHg
    • Severe Disease: A-a O2 gradient of ≥45 mmHg or PaO <60 mmHg or signs of respiratory failure.
  • Treat fulminant respiratory failure with ARDS principles:



  • Trimethoprim-sulfamethoxazole: mainstay of treatment 
    • Mild to Moderate Disease: TMP 15 to 20 mg/kg/day and SMX 75 to 100 mg/kg/day PO in 3-4 divided doses OR TMP-SMX DS two tablets three times a day.
    • Severe Disease: TMP 15 to 20 mg and SMX 75 to 100 mg/kg/day IV every 6 – 8 hours; switch to PO when the patient demonstrates clinical improvement. 
  • In cases of allergy or adverse reaction  to TMP-SMX: 
    • Adverse reactions to TMP-SMX are common in patients with AIDS and may present with rash, fever, or neutropenia.
        • Mild allergy: patients should undergo desensitization treatment.
        • Severe allergy: desensitization is not recommended. 
    • Alternative regimens for mild to moderate Disease: 
        • Atovaquone 750 mg, PO BID
        • Trimethoprim 15 mg/kg/day PO BID + dapsone 100 mg PO QD
        • Primaquine 30 mg QD + clindamycin 450 mg PO Q6 or 600 mg Q8
    • Alternative regimens for severe Disease: 
        • Pentamidine 4 mg/kg IV QD over 60 minutes
        • Primaquine 30 mg PO QD + clindamycin IV 600 mg Q6 or 900 mg Q8
  • Duration of Treatment: 
      • HIV Positive Patients: at least 21 days 
      • Non-HIV Patients: at least 14 days 
  • PJP Prophylaxis
      • Recommended for all patients with CD4+ T-cell counts of < 200 to mitigate PJP
      • The preferred regimen is TMP-SMX, one double-strength tablet daily.



  • Studies evaluating the benefits of steroids have almost exclusively been done in HIV-positive patients. Evidence in non-HIV-positive patients is sparse. 
  • HIV-positive patients with moderate to severe Disease (A-a > 35 or PaO2 < 70): 
    • 21-day prednisone taper: 
        • 40 mg PO BID x 5 days
        • 40 mg PO QD x 5 days
        • 20 mg PO QD x 11 days 
    • If IV dosing is necessary: 
        • Methylprednisolone at 75% of prednisone dose


Take Home Points:

  • Clinical presentation of PJP Pneumonia may vary, with notable differences in disease progression between HIV-positive and non-HIV-positive patients.
  • Symptoms are typically non-specific and include cough, fever, and dyspnea. Hypoxia presents in fulminant or late states of PJP infection; however, subtle hypoxia may be identified with ambulatory saturations in the ED.
  • Maintain a broad differential diagnosis in immunocompromised patients presenting with respiratory symptoms.
  • Treatment is dependent on the severity of the illness.
    • Mild Disease: oral Bactrim
    • Moderate Disease (A-a O2 gradient of 35-45 mmHg or PaO ≥60 and <70 mmHg): oral Bactrim with a 21-day steroid taper.
    • Severe Disease (A-a O2 gradient of ≥45 mmHg or PaO <60 mmHg or signs of respiratory failure): IV Bactrim with a 21-day steroid taper.



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