Pneumocystis jirovecii Pneumonia

(See also Overview of Pneumonia Overview of Pneumonia Pneumonia is acute inflammation of the lungs caused by infection. Initial diagnosis is usually based on chest x-ray and clinical findings. Causes, symptoms, treatment, preventive measures, and... read more and Pneumonia in Immunocompromised Patients Pneumonia in Immunocompromised Patients Pneumonia in immunocompromised patients is often caused by unusual pathogens but may also be caused by the same pathogens that cause community-acquired pneumonia. Symptoms and signs depend on... read more .)

Pneumocystis jirovecii is a ubiquitous organism transmitted by aerosol route and causes no disease in immunocompetent patients. However, some patients are at risk of developing P. jirovecii pneumonia:

Patients with HIV infection Human Immunodeficiency Virus (HIV) Infection Human immunodeficiency virus (HIV) infection results from 1 of 2 similar retroviruses (HIV-1 and HIV-2) that destroy CD4+ lymphocytes and impair cell-mediated immunity, increasing risk of certain... read more and CD4+ T cell counts 200/microL

Organ transplant recipients

Patients with hematologic cancers

Patients taking corticosteroids or other immunosuppressive drugs

Most patients have fever, dyspnea, and a dry, nonproductive cough that evolves over several weeks (HIV infection) or over several days (other causes of compromised cell-mediated immunity). Dyspnea is common.

Chest x-ray

Pulse oximetry

Histopathologic confirmation

To diagnose Pneumocystis jirovecii pneumonia, patients should have chest x-ray and assessment of oxygenation by pulse oximetry.

Chest x-ray characteristically shows diffuse, bilateral perihilar infiltrates, but 20 to 30% of patients have normal x-rays.

Hypoxemia may be present even when chest x-ray shows no infiltrate; this finding can be an important clue to diagnosis. When pulse oximetry is abnormal, arterial blood gas (ABG) measurements are often obtained to show severity of hypoxemia (including an increase in the alveolar-arterial oxygen gradient).

In immunosuppressed patients who have a dry, nonproductive cough and abnormal chest x-ray or pulse oximetry, pursue further testing for P. jirovecii pneumonia.

If done, pulmonary function tests Overview of Tests of Pulmonary Function Pulmonary function tests provide measures of airflow, lung volumes, gas exchange, response to bronchodilators, and respiratory muscle function. Basic pulmonary function tests available in the... read more show altered diffusing capacity (although pulmonary function tests are rarely done as a diagnostic test for Pneumocystis jirovecii pneumonia).

Serum beta-D glucan assays are nonspecific but can support the diagnosis.

Histopathologic demonstration of Pneumocystis jirovecii is needed for confirmation of the diagnosis. Methenamine silver, Giemsa, Wright-Giemsa, modified Grocott, Weigert-Gram, or monoclonal antibody stain is used. Polymerase chain reaction (PCR)-based detection can add to the diagnostic yield. Sputum specimens are usually obtained by induced sputum or bronchoscopy. Sensitivity ranges from 30 to 80% for induced sputum and is > 95% for bronchoscopy with bronchoalveolar lavage.

Overall mortality for P. jirovecii pneumonia in hospitalized patients is high. Risk factors for death may include previous history of P. jirovecii pneumonia, older age, and, in HIV-infected patients, CD4+ T cell count 50/microL.

Trimethoprim/sulfamethoxazole

Corticosteroids if PaO2 70 mm Hg

Treatment is with trimethoprim/sulfamethoxazole (TMP/SMX) 15 to 20 mg/kg IV or orally 3 times a day for 14 to 21 days. Treatment can be started before diagnosis is confirmed because P. jirovecii cysts persist in the lungs for weeks. Adverse effects of treatment are more common among patients with acquired immunodeficiency syndrome (AIDS) and include rash, neutropenia, hepatitis, and fever.

Alternative regimens, which are also given for 21 days, are

Pentamidine 4 mg/kg IV once a day

Atovaquone 750 mg orally 2 times a day

Trimethoprim 5 mg/kg orally 3times a day with dapsone 100 mg orally once a day

Clindamycin 900 mg IV every 8 hours, 600 mg IV every 6 hours, 600 mg orally 3 times a day, or 450 mg orally 4 times a day, plus primaquine base 30 mg orally once a day

The major limitation of pentamidine is the high frequency of toxic adverse effects, including acute kidney injury, hypotension, and hypoglycemia.

Adjunctive therapy with corticosteroids is recommended for patients with a PaO2 70 mm Hg. The suggested regimen is prednisone 40 mg orally twice a day (or its equivalent) for the first 5 days, 40 mg orally once a day for the next 5 days (or 20 mg twice a day), and then 20 mg orally once a day for the duration of treatment.

HIV-infected patients who have had P. jirovecii pneumonia or who have a CD4+ T cell count 200/microL should receive prophylaxis with TMP/SMX 160/800 mg orally once a day or TMP/SMX 80/400 mg orally once a day; if this regimen is not tolerated, dapsone 100 mg orally once a day (or 50 mg orally twice a day) or aerosolized pentamidine 300 mg once a month can be used. These prophylactic regimens are also indicated for many non–HIV-infected patients at risk of P. jirovecii pneumonia.

Consider P. jirovecii pneumonia in patients who are immunosuppressed, even if they have mild respiratory symptoms and even if the chest x-ray is normal.

Do histopathologic examination on induced sputum or bronchoscopically obtained samples.

Treat patients with trimethoprim/sulfamethoxazole, adding a corticosteroid if PaO2 is 70 mm Hg.