Pneumocystis jirovecii pneumonia in non-human immunodeficiency virus patients

Pneumocystis jirovecii pneumonia (PJP) is an important opportunistic fungal infection in immunocompromised hosts. Although its incidence has declined markedly in people with human immunodeficiency virus (HIV) following the widespread use of antiretroviral therapy and prophylaxis, PJP is increasingly encountered in HIV-negative patients receiving immunosuppressive or targeted immunomodulatory therapies. In this population, PJP often follows a more fulminant course, with rapid progression to severe hypoxemia and acute respiratory failure. Diagnosis remains challenging because clinical manifestations are nonspecific and pulmonary organism burden is often lower than in HIV-associated disease. Accordingly, diagnosis requires integration of host risk factors, radiologic findings, microbiologic testing, and adjunctive biomarkers. Chest computed tomography commonly shows bilateral ground-glass opacities, while bronchoalveolar lavage with microscopy and, increasingly, quantitative PCR remains central to microbiologic confirmation. Serum β-D-glucan may provide useful supportive information but should be interpreted as an adjunct rather than a stand-alone test. Trimethoprim-sulfamethoxazole (TMP-SMX) remains the first-line treatment for PJP, but the optimal dose in HIV-negative patients remains uncertain. Emerging evidence suggests that reduced-dose TMP-SMX may preserve efficacy while improving tolerability in selected patients, whereas standard-dose therapy remains the reference regimen in severe disease. The role of adjunctive corticosteroids in HIV-negative PJP also remains unsettled, supporting a selective rather than routine approach. Prevention remains essential, and current evidence supports risk-adapted primary prophylaxis and individualized secondary prophylaxis for as long as clinically meaningful immunosuppression persists, complemented by infection-control measures in units caring for highly immunocompromised patients.