Pleural infection: from bench to bedside

Pleural infection remains a significant clinical challenge, associated with rising incidence, substantial healthcare burden, and considerable mortality. Frequently arising as a pneumonia complication, it develops in a subset of patients with parapneumonic effusions following bacterial invasion of the pleural space. Despite advances in management, outcomes remain suboptimal, with notable variability in diagnostic and therapeutic approaches worldwide. Recent progress in translational research has enhanced understanding of the complex pathophysiology underlying pleural infection, including dysregulated immune responses, impaired fibrinolysis, and polymicrobial ecosystems within the pleural cavity. Advances in microbiological techniques, particularly metagenomic sequencing, have revealed a predominance of polymicrobial infections and highlighted the limitations of conventional culture methods. Imaging modalities, especially thoracic ultrasound, now play a central role in diagnosis, prognostication, and treatment guidance. Current management relies on prompt antimicrobial therapy and effective pleural drainage, often supported by intrapleural enzyme therapy (tPA and DNase), which can reduce the need for surgery and length of hospital stay. Surgery remains a critical component of management in patients with ongoing sepsis, established organised empyema, or failure of IET, although less invasive approaches such as medical thoracoscopy may represent a promising alternative to surgery in selected patients. Emerging evidence supports a shift toward personalised care. Biomarkers such as PAI-1 and suPAR, microbiome and proteomic profiling, and validated risk stratification tools such as the RAPID score are associated with adverse outcome, but none has yet been shown to identify patients who preferentially benefit from a particular treatment, and the distinction between prognostic association and predictive treatment utility is maintained throughout this review. In conclusion, pleural infection is increasingly recognised as a biologically heterogeneous condition. Integrating translational insights into clinical practice may in future enable precision-based management, but the steps required to move from biological association to treatment allocation have not yet been taken, and management today continues to rest on prompt antimicrobial therapy, effective drainage and timely escalation.