Pleural infection encompasses a continuum from uncomplicated parapneumonic effusion (sterile reactive effusion accompanying bacterial pneumonia) through complicated parapneumonic effusion (bacterial invasion of pleural space without frank pus) to empyema (frank pus in pleural space). The American Thoracic Society and modern guidelines (BTS 2010, ATS 2017) classify pleural infection into three sequential stages reflecting pathophysiologic progression and guiding management.
Stage 1 — Exudative (uncomplicated parapneumonic effusion) — occurs early during pneumonia (first 24-72 hours). Pleural inflammation increases capillary permeability, causing free-flowing exudate without bacterial invasion. Pleural fluid is sterile with pH greater than 7.20, glucose greater than 60 mg/dL, LDH less than 1000 U/L, and negative Gram stain/culture. Most resolve with appropriate antibiotic therapy alone. Stage 2 — Fibrinopurulent (complicated parapneumonic effusion progressing to empyema) — occurs days 5-10. Bacterial invasion of pleural space triggers neutrophil influx, fibrin deposition, and loculation formation. Fluid becomes turbid or frankly purulent with low pH (less than 7.20), low glucose (less than 40-60 mg/dL), high LDH (greater than 1000 U/L), positive Gram stain or culture, and visible loculations on imaging. Treatment requires chest tube drainage (often image-guided 12-14 Fr) plus systemic antibiotics; intrapleural fibrinolytics (tPA + DNase combination based on MIST2 trial) increase drainage efficacy and reduce surgical referral.
Stage 3 — Organizing (chronic empyema) — occurs after 2-3 weeks if inadequately treated. Fibroblasts proliferate creating a thick fibrous pleural peel encasing the lung, restricting expansion (trapped lung). Pleural fluid may be minimal but lung function is severely compromised. Surgical decortication (video-assisted thoracoscopic surgery — VATS, or open thoracotomy for established peel) is required. Diagnostic workup of suspected pleural infection includes contrast-enhanced CT showing pleural enhancement, loculations, and air-fluid levels; ultrasound for guidance and septation assessment; diagnostic thoracentesis as soon as effusion identified with pH testing on heparinized syringe (most critical parameter), gross appearance, Gram stain, culture (aerobic, anaerobic, fungal, mycobacterial), cytology, and biochemistry. Empiric antibiotics should cover community-acquired (Streptococcus species, Staphylococcus aureus, anaerobes) or hospital-acquired pathogens; common regimens include ampicillin-sulbactam or piperacillin-tazobactam plus vancomycin if MRSA risk. Treatment duration is 2-6 weeks depending on response and stage. MIST2 (2011) demonstrated combination intrapleural alteplase 10 mg + DNase 5 mg twice daily for 3 days reduced surgical referral and length of stay versus placebo. Mortality in pleural infection reaches 10-20%, with higher rates in elderly, comorbid, hospital-acquired, and stage 3 disease.