Summary
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.
Definition
- Interstitial pneumonia caused by the yeast-like fungal organism Pneumocystis jirovecii [1]
Etiology
- 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]
- Immunosuppressive treatment (e.g., chronic glucocorticoid therapy)
- Malignancy (e.g., leukemia, non-Hodgkin lymphoma)
- Malnutrition
-
HIV infection [3]
Clinical features
Diagnostics
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
-
Specimen from
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
Treatment
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]
- Mild/moderate disease
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]
Complications
- ARDS
- Bullous formation with risk of rupture → secondary pneumothorax
- Pleural effusion
We list the most important complications. The selection is not exhaustive.
Prognosis
-
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).