Pneumocystis jirovecii Pneumonia in Critical Care: Evolving Host Populations, Diagnostic Uncertainty, and Management Controversies

Pneumocystis jirovecii pneumonia (PCP) remains a major cause of acute respiratory failure in immunocompromised patients and is increasingly encountered in critical care outside the traditional human immunodeficiency virus (HIV) population. This narrative review examines the evolving epidemiology, diagnosis, management, prophylaxis, and prognosis of PCP in critically ill adults. The epidemiological landscape has shifted toward patients with haematological and solid malignancies, solid organ or haematopoietic stem-cell transplantation, autoimmune and inflammatory diseases, and exposure to corticosteroids or other immunosuppressive therapies. Emerging data also implicate states of immune dysregulation such as cirrhosis. Diagnosis remains challenging because Pneumocystis cannot be routinely cultured and molecular detection alone cannot reliably distinguish colonisation from active infection. Accordingly, respiratory polymerase chain reaction (PCR) results require interpretation alongside host factors, imaging, serum β-D-glucan, microscopy, and, increasingly, metagenomic sequencing. Trimethoprim-sulfamethoxazole remains first-line therapy. Lower-dose regimens may reduce toxicity while maintaining efficacy, but current evidence is largely retrospective and prospective trials are needed. The benefit of adjunctive corticosteroids in non-HIV PCP remains uncertain, with conflicting observational data and no definitive mortality benefit demonstrated in the first randomised trial. Echinocandins remain investigational adjuncts, whereas venovenous extracorporeal membrane oxygenation may provide rescue support in selected patients with refractory acute respiratory distress syndrome. Prophylaxis is effective but remains inconsistently applied in several at-risk groups. Mortality among intensive care unit (ICU) patients remains high, particularly in non-HIV PCP, and varies substantially according to underlying disease, immune phenotype, co-infection, and severity of respiratory failure. Improved risk stratification and adequately powered prospective studies are priorities.