Pneumocystis pneumonia

Pneumocystis jirovecii pneumonia (PCP), previously known as Pneumocystis carinii pneumonia, is an opportunistic fungal lung infection occurring almost exclusively in immunocompromised individuals. In 50% of cases, PCP is the first manifestation of AIDS (acquired immune deficiency syndrome), but it may be caused by other immunodeficiency disorders. PCP should be suspected in patients with a history of progressive dyspnea and a dry cough with resistance to standard antibiotic treatment. Signs that support this diagnosis include a CD4 count < 200/μL, an increased beta-D-glucan level, and diffuse bilateral infiltrates on chest x-ray. Management of PCP includes high-dose trimethoprim/sulfamethoxazole (TMP/SMX), treatment of the underlying immunodeficiency disorder, and steroids in the case of severe respiratory insufficiency.

• Interstitial pneumonia caused by the yeast-like fungal organism Pneumocystis jirovecii ^[1]

• Pathogen: P. jirovecii (former P. carinii): ubiquitous, yeast-like fungus previously classified as a protozoan
• Route of transmission: airborne ^[2]
• Risk factors
  • HIV infection ^[3]
    • CD4 count: usually < 200/μL
    • Poor compliance with PCP prophylaxis or HAART
    • History of PCP infection
  • Primary immunodeficiency disorders ^[4]
    • Severe combined immunodeficiency disorder
    • Hyper IgM syndrome
  • Immunosuppressive treatment (e.g., chronic glucocorticoid therapy)
  • Malignancy (e.g., leukemia, non-Hodgkin lymphoma)
  • Malnutrition

• Usually asymptomatic
• Symptoms typically have a gradual onset (days to weeks) and include:
  • Low-grade fever and malaise
  • Dyspnea, tachypnea, and nonproductive cough
  • Fatigue, weight loss, chills
• May progress to fulminant respiratory failure

A definitive diagnosis of PCP is not always possible. The following criteria should lead to a presumptive diagnosis of PCP:

• History and clinical examination
• Oxygen saturation
• CD4 count
• Beta-D-glucan level
• Chest x-ray (if CXR is inconclusive, a CT scan should be performed)

The diagnosis should generally be confirmed via microscopic identification of P. jirovecii from respiratory secretions.

Clinical examination

• Chest auscultation
  • Bilateral crackles and rhonchi
  • Unremarkable auscultatory findings are possible in the early stages of disease.
• Pulse oximetry: oxygen saturation < 90 % at rest (worsens with exertion)

PCP is often misdiagnosed as atypical pneumonia or bronchitis because of the persistent cough and similar auscultatory findings.

Laboratory tests

• CD4 count: typically < 200/μL
• Laboratory measures
  • ↑ Beta‑D‑glucan levels ^[5]
  • ↑ LDH (typically)
• Polymerase chain reaction (PCR) ^[6]
• Confirmatory test: microscopic identification of P. jirovecii
  • Specimen from
    • Bronchoalveolar lavage
    • Induced sputum ^[7]
    • Lung tissue biopsy
  • Staining: enables visualization of disc-shaped P. jirovecii cysts with central spores ^[8]
    • Methenamine silver staining, Wright stain, or Diff-Quik stain
    • Immunofluorescence

Imaging

• Chest x‑ray
  • Typically symmetrical, diffuse interstitial infiltrates extending from the perihilar region
  • May sometimes be normal
• High-resolution CT
  • Indicated if PCP is still suspected in a patient with a normal CXR
  • High sensitivity for PCP (a negative scan thus suggests the diagnosis of PCP is unlikely)
  • Typical features
    • Ground-glass attenuation: symmetrical diffuse, interstitial infiltrates
    • Pneumatoceles: cystic air-filled spaces within the lung tissue

Acute infection ^[9]

• Treatment of choice: high‑dose TMP/SMX for up to 3 weeks
• Glucocorticoids: add in the case of severe respiratory insufficiency (either PaO₂ < 70 mmHg or arterial‑alveolar oxygen gradient ≥ 35 mmHg)
• Alternatives if allergic to TMP/SMX or treatment of choice is ineffective
  • Mild/moderate disease
    • Oral trimethoprim PLUS dapsone
    • Oral atovaquone
    • Oral primaquine PLUS clindamycin
  • Moderate/severe disease
    • Oral primaquine PLUS IV clindamycin
    • Intravenous pentamidine (monotherapy) ^[10]

If a patient with suspected PCP is acutely ill then empiric treatment should be started without delay.

PCP prophylaxis ^[9][11]

• Indication
  • Primary prophylaxis: CD4‑cell count < 200/μl (e.g., AIDS, bone marrow suppression due to cytotoxic therapy, or primary immunosuppressive disorders)
  • Secondary prophylaxis: to prevent recurrence in patients with AIDS or other immunocompromising conditions
• Implementation
  • Low‑dose TMP/SMX
  • Alternative (e.g., if allergic to TMP/SMX): oral dapsone OR oral atovaquone ^[12][13]

• ARDS
• Bullous formation with risk of rupture → secondary pneumothorax
• Pleural effusion

We list the most important complications. The selection is not exhaustive.

• PCP was formerly the most common cause of death in HIV‑positive patients during the early years of the HIV epidemic. ^[2]
  • The introduction of HAART (highly active antiretroviral therapy) and TMP/SMX prophylaxis in patients with a CD4 count < 200/μl has significantly improved the long-term outcome of the disease.
  • Despite adequate prophylaxis, PCP infection may lead to death in patients presenting with severe symptoms (e.g., respiratory failure).

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10. Pentamidine. https://www.drugs.com/mtm/pentamidine.html. . Accessed: February 23, 2018.
11. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents. https://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf. Updated: October 18, 2017. Accessed: February 23, 2018.
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