Pneumocystosis (Pneumocystis jirovecii Pneumonia)

Essentials of Diagnosis

• Fever, dyspnea, dry cough, hypoxia

• Often only slight lung physical findings

• Chest radiograph: diffuse interstitial disease or normal

• P jirovecii in sputum, bronchoalveolar lavage fluid, or lung tissue, PCR in bronchoalveolar lavage; (1,3)-beta-D-glucan in blood

General Considerations

• P jirovecii affects humans worldwide

• Based on serology, asymptomatic infections occur at a young age in most persons

• Overt infection is an acute interstitial plasma cell pneumonia that occurs among older children and adults who have an abnormal or altered cellular immunity, either due to

  • An underlying disease process (eg, cancer, malnutrition, stem cell or organ transplantation or, most commonly, AIDS)

  • Treatment with immunosuppressive medications, such as corticosteroids or cytotoxic agents

• Accumulating evidence suggests airborne transmission

• Pneumocystis pneumonia occurs in up to 80% of AIDS patients not receiving prophylaxis, usually at CD4 cell counts < 200/mcL

• In non-AIDS patients taking immunosuppressives, symptoms often begin when corticosteroids are tapered or discontinued

Symptoms and Signs

• Fever; tachypnea; shortness of breath; and cough, usually nonproductive

• Normal lung examination or bibasilar crackles; findings may be slight compared with degree of illness and chest radiographic abnormality

• Spontaneous pneumothorax may occur if patient had previous episodes or received aerosolized pentamidine prophylaxis

• Onset may be subacute, characterized by dyspnea on exertion and nonproductive cough

Differential Diagnosis

• Bacterial pneumonia

• Tuberculosis

• Coccidioidomycosis

• Histoplasmosis

• Cytomegalovirus

• Kaposi sarcoma

• Lymphoma (including lymphocytic interstitial pneumonitis)

• Pulmonary embolism

Laboratory Tests

• Arterial blood gas shows hypoxemia and hypocapnia; peripheral oxygen saturation may be normal at rest but decreases rapidly with exercise

• Serologic tests not helpful

• Measurement of serum (1,3)-beta-D-glucan levels has good sensitivity and specificity

• Culture not possible

• Polymerase chain reaction (PCR) of bronchoalveolar lavage (BAL) is overly sensitive

  • Can be positive in colonized, noninfected persons

  • However, quantitative values may help with identifying infected patients

  • Negative PCR from BAL rules out disease

Imaging Studies

• Chest radiograph

  • Usually shows diffuse interstitial infiltrates, but early in infection, these may be heterogeneous, miliary, or patchy

  • May also show diffuse or focal consolidation, cystic changes, nodules, or cavitation within nodules

  • Pleural effusions not seen

• Chest radiograph is normal in 5–10%; high-resolution chest CT better able to demonstrate mild disease

• Upper lobe infiltrates common if patient received aerosolized pentamidine prophylaxis

Diagnostic Procedures

• Open lung biopsy and needle lung biopsy are infrequently required but may aid in diagnosing a granulomatous form of Pneumocystis pneumonia

• If induced sputum is negative and suspicion is high, diagnostic specimens may be obtained by bronchoalveolar lavage (sensitivity 86–97%) or, if necessary, by transbronchial lung biopsy (sensitivity 85–97%)

Medications

• If disease suspected clinically, initiate empiric therapy while work-up proceeds

• In patients with mild to moderately severe disease, continued treatment should be based on a proved diagnosis because of

  • Clinical overlap with other infections

  • Toxicity of therapy

  • Possible coexistence of other infectious organisms

• Symptoms often persist for 4–6 days after starting therapy and may worsen in first 3–5 days presumably due to immune response to dying organisms

• Trimethoprim-sulfamethoxazole (TMP-SMZ)

  • Strong data indicate that TMP-SMZ is the optimal first-line therapy

  • Oral formulation is preferred because of its low cost and excellent bioavailability

  • Intravenous formulation should be used in patients with nausea, vomiting, or intractable diarrhea until oral formulation can be tolerated

  • Dosage is 15–20 mg/kg/day (based on TMP component) given orally or intravenously daily in three or four divided doses for 14–21 days

  • Hypersensitivity reactions are especially common in AIDS patients

• Primaquine plus clindamycin

  • Best second-line therapy

  • Dosages: primaquine, 15–30 mg orally daily, plus clindamycin, 600 mg orally three times daily

• Pentamidine

  • Use has decreased as alternative agent

  • Can be administered intravenously (preferred) or intramuscularly as a single dose of 3–4 mg (salt)/kg/day for 14–21 days

  • Side effects occur in nearly 50% of patients

• Atovaquone

  • Used for patients with mild to moderate disease who cannot tolerate TMP-SMZ or pentamidine

  • However, failure is reported in 15–30% of cases

  • Mild side effects are common, but no serious reactions have been reported

  • Dosage is 750 mg orally twice daily for 21 days

  • Should be administered with a fatty meal

• TMP plus dapsone

  • An alternative oral regimen for mild to moderate disease or for continuation of therapy after intravenous is no longer needed

  • Dosage: TMP, 15 mg/kg/day in three divided doses daily, plus dapsone, 100 mg/day orally

• Prednisone

  • Given with antimicrobials for moderate to severe pneumonia (when PaO₂ on admission is < 70 mm Hg or oxygen saturation is < 90%)

  • The addition of corticosteroids in such patients is associated with significant reduction in morbidity and mortality; administration of adjunctive corticosteroids within 72 hours is preferred

  • Dosage is 40 mg orally twice daily for 5 days, then 40 mg daily for 5 days, and then 20 mg daily until therapy is completed (total course, 21 days)

Prognosis

• In the absence of early and adequate treatment, the fatality rate Pneumocystis pneumonia in immunodeficient persons is nearly 100%

• Early treatment reduces mortality rate to 10–20% in AIDS patients

• In immunodeficient patients,

  • Mortality rate is still 30–50%

  • Recurrences are common in those who do not receive prophylaxis (30% in AIDS patients)

Prevention

• Primary prophylaxis

  • Should be given to persons with CD4 counts < 200 cells/mcL, a CD4 percentage below 14%, or weight loss or oral candidiasis

  • Also beneficial in patients with hematologic malignancy and transplant recipients

• Secondary prophylaxis should be given to patients with history of Pneumocystis pneumonia until a durable virologic response to antiretroviral therapy has been achieved for at least 3–6 months and a CD4 count > 200 cells/mcL has been maintained