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Pulmonary infiltrates in immunocompromised patients (patients with HIV disease, absolute neutrophil counts less than 1000/mcL [less than 1.0 × 109/L], current or recent exposure to myelosuppressive or immunosuppressive medications, or those currently taking more than 20 mg/day of prednisone) may arise from infectious or noninfectious causes. Infection may be due to bacterial, mycobacterial, fungal, protozoal, helminthic, or viral pathogens. Noninfectious processes, such as pulmonary edema, alveolar hemorrhage, medication reactions, pulmonary thromboembolic disease, malignancy, and radiation pneumonitis, may mimic infection.

Although almost any pathogen can cause pneumonia in an immunocompromised patient, two clinical tools help the clinician narrow the differential diagnosis. The first is knowledge of the underlying immunologic defect. Specific immunologic defects are associated with particular infections. Defects in humoral immunity predispose to bacterial infections; defects in cellular immunity lead to infections with viruses, fungi, mycobacteria, and protozoa. Neutropenia and impaired granulocyte function predispose to infections from S aureus, Aspergillus, gram-negative bacilli, and Candida. Second, the time course of infection also provides clues to the etiology of pneumonia in immunocompromised patients. A fulminant pneumonia is often caused by bacterial infection, whereas an insidious pneumonia is more apt to be caused by viral, fungal, protozoal, or mycobacterial infection. Pneumonia occurring within 2–4 weeks after organ transplantation is usually bacterial, whereas several months or more after transplantation P jirovecii, viruses (eg, cytomegalovirus) and fungi (eg, Aspergillus) are encountered more often.


Chest radiography is rarely helpful in narrowing the differential diagnosis. Examination of expectorated sputum for bacteria, fungi, mycobacteria, Legionella, and P jirovecii is important and may preclude the need for expensive, invasive diagnostic procedures. Sputum induction is often necessary for diagnosis. The sensitivity of induced sputum for detection of P jirovecii depends on institutional expertise, number of specimens analyzed, and detection methods.

Routine evaluation frequently fails to identify a causative organism. The clinician may begin empiric antimicrobial therapy before proceeding to invasive procedures, such as bronchoscopy, transthoracic needle aspiration, or open lung biopsy. The approach to management must be based on the severity of the pulmonary infection, the underlying disease, the risks of empiric therapy, and local expertise and experience with diagnostic procedures. BAL using flexible bronchoscopy is a safe and effective method for obtaining representative pulmonary secretions for microbiologic studies. It involves less risk of bleeding and other complications than transbronchial biopsy. BAL is especially suitable for the diagnosis of P jirovecii pneumonia in patients with HIV/AIDS when induced sputum analysis is negative. Surgical lung biopsy, now often performed by video-assisted thoracoscopy, provides the definitive option for diagnosis of pulmonary infiltrates in immunocompromised patients; however, a specific diagnosis is obtained in only about two-thirds of cases, and the information obtained may not affect the outcome.

Cillóniz  C  et al. Pneumocystis pneumonia in the twenty-first century: HIV-infected versus HIV-uninfected patients. Expert Rev Anti Infect Ther. 2019;17:787.
[PubMed: 31550942]  

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