Pulmonary infections are a leading cause of morbidity and mortality in immunosuppressed patients including hematopoietic and solid organ transplant recipients, those with hematologic malignancies receiving chemotherapy or targeted therapies, HIV patients (especially with CD4 counts under 200), patients on corticosteroids, biologic therapy, or chronic immunosuppression for autoimmune disease. The pathogen spectrum varies by the type of immune defect: neutropenia predisposes to bacterial (Pseudomonas, gram-negative rods) and mold infections (Aspergillus, Mucorales, Fusarium); cellular immune defects favor mycobacteria, Pneumocystis jirovecii, viral (CMV, RSV, adenovirus), and fungal pathogens (cryptococcus, endemic mycoses); humoral defects predispose to encapsulated bacteria (pneumococcus, Haemophilus).
Clinical presentation may be subtle or fulminant, with cough, fever, dyspnea, hypoxemia, pleuritic chest pain, and nonspecific systemic symptoms. Imaging with high-resolution CT is essential, identifying patterns such as halo sign and reverse halo sign in invasive aspergillosis and mucormycosis, ground-glass opacities in PCP and viral pneumonias, tree-in-bud nodules in mycobacterial and bacterial infections, and cavitary lesions in nocardiosis and TB. Diagnosis combines galactomannan and beta-D-glucan serum biomarkers, blood and urine antigen testing, multiplex molecular assays, and bronchoscopy with bronchoalveolar lavage for direct sampling. Lung biopsy may be needed for definitive diagnosis when imaging and noninvasive tests are inconclusive.
Empirical therapy is initiated based on host immune status, local epidemiology, and imaging pattern, then narrowed to pathogen-directed regimens. Examples include voriconazole or isavuconazole for invasive aspergillosis, liposomal amphotericin B for mucormycosis, trimethoprim-sulfamethoxazole for PCP and nocardiosis, ganciclovir or letermovir for CMV pneumonitis, and antimycobacterial regimens for TB and NTM. Duration ranges from 14 days to several months. Adjunctive measures include immunosuppression reduction when feasible, neutropenic precautions, granulocyte colony-stimulating factor in severe neutropenia, prophylaxis with TMP-SMX for PCP, and aciclovir or ganciclovir for HSV and CMV. Vaccination, infection prevention, and antimicrobial stewardship are central to long-term management.