Pyothorax (Pleural Infection / Empyema) - BTS & ERS Key Points

Definitions

• Pleural infection (BTS 2023): Entry and replication of bacteria within the pleural cavity. Diagnosis requires a multimodality approach.
• Empyema: Accumulation of frank pus in the pleural cavity.
• Complicated parapneumonic effusion (CPPE): Pleural effusion in the context of pneumonia with biochemical signs of infection (pH <7.2, glucose <2.2 mmol/L, or positive culture) but without visible pus.
• These terms are often used interchangeably in clinical practice; empyema and CPPE are treated similarly once criteria are met.

Stages of Pleural Infection

Microbiology

• Community-acquired infections: Streptococcus milleri group, Streptococcus pneumoniae, anaerobes (Fusobacterium, Prevotella, Peptostreptococcus)
• Hospital-acquired infections: Staphylococci (including MRSA), gram-negative organisms (Klebsiella, Pseudomonas, Escherichia coli)
• Anaerobes found in ~35% alone and ~41% mixed aerobic-anaerobic infections in unselected patients (pre-antibiotic era data from Fishman's)
• Up to 40% of cultures may be negative despite clinical infection (increased by prior antibiotics)

Epidemiology & Prognosis

• ~60,000 patients/year in the US develop frank empyema from pneumonia
• Death or surgical intervention in >30% of patients
• Increased relative risk of mortality 3.4x higher with parapneumonic effusion vs. pneumonia alone
• Incidence has increased globally; morbidity/mortality static over the past decade despite advances

Diagnosis - BTS/ERS Key Points

Clinical

• Fever, pleuritic chest pain, breathlessness, and pleural effusion - always suspect pleural infection
• Subacute presentation is common (weeks), especially with anaerobic or community-acquired infection

Imaging

• Chest X-ray: D-shaped homogeneous peripheral opacity (loculated collection)
• Ultrasound (TUS): Preferred bedside tool - detects septations, loculations; guides safe aspiration/drain placement. Dense/complex adhesions may preclude thoracoscopy
• CT chest with contrast: Best for complex/loculated collections; shows contrast enhancement of thickened pleura ("split pleura sign"), identifies underlying parenchymal pathology, and guides surgical planning
• Serum biomarkers (including NT-proBNP) should not be used to diagnose pleural infection

Pleural Fluid Analysis - Diagnostic Criteria

• pH <7.2 is the primary marker mandating chest tube insertion (BTS/ERS)
• Intermediate risk (pH 7.2-7.4): consider drainage if LDH >900 IU/L, especially with ongoing fever, large volume, glucose ≤4.0 mmol/L, CT contrast enhancement, or TUS septations
• High pleural fluid CRP (>10 mg/dL) supports infection; no role for pleural procalcitonin
• Blood gas analyzer preferred over pH paper for accuracy

Microbiology

• Send pleural fluid in both blood culture bottles (aerobic and anaerobic) - increases yield
• Broad-range 16S ribosomal PCR/metagenomics can identify organisms in culture-negative cases (ERS)

RAPID Score (Risk Stratification)

• Low risk (<3): <5% mortality at 3 months
• High risk (≥5): >30% mortality at 3 months (OR 14.1)
• Guides intensity of intervention and monitoring

Treatment - BTS 2023 & ERS 2023 Recommendations

Antibiotics

• Start empirically and early - do not wait for cultures
• Community-acquired: cover streptococci and anaerobes - amoxicillin-clavulanate, or benzylpenicillin + metronidazole
• Hospital-acquired / post-surgical: cover MRSA and gram-negatives - piperacillin-tazobactam ± vancomycin; consider local resistance patterns
• Duration: typically 3-6 weeks; guided by clinical and radiological response
• Antibiotics alone are insufficient for established CPPE or empyema - drainage is required

Drainage (Initial)

• Intercostal drain (ICD) is the first-line intervention for CPPE and empyema
• Image-guided placement (ultrasound) is mandatory (BTS/ERS)
• Small-bore drains (10-14 Fr) are as effective as large-bore for non-purulent fluid
• For frank pus, larger bore drains are generally preferred
• Saline flushes (e.g., 30 mL three times daily) help maintain patency

Intrapleural Enzyme Therapy (IET) - BTS 2023 Recommendations

• Combination tPA + DNase is RECOMMENDED (Conditional, by consensus) - based on MIST2 trial evidence showing improved radiographic outcomes and reduced hospital stay
  • Regimen: tPA 10 mg + DNase 5 mg twice daily for 3 days
• Single-agent tPA or DNase alone should NOT be used (shown ineffective or potentially harmful vs. placebo)
• Streptokinase should NOT be used (Conditional - MIST1 trial showed no benefit)
• Saline irrigation can be considered when IET or surgery is not suitable (Conditional, by consensus)
• Patient consent required when using tPA + DNase

Surgical Management

• VATS should be considered over thoracotomy for adults (BTS 2023 - Conditional recommendation)
• Surgery indications:
  • Ongoing sepsis not responding to antibiotics + drainage
  • Persistent effusion despite maximal drainage + IET
  • Clinically unstable patients (direct surgical referral)
  • Late-stage (Stage III) empyema with established pleural peel
• Timing: Surgical consultation at 2-3 days after chest tube insertion if insufficient clinical (fever/CRP) or radiographic improvement (BTS and ERS consensus)
• VATS débridement is preferred in early disease; decortication (may require thoracotomy) for thick established peel
• VATS outcomes: shorter stay (6 days vs. 15 days for open decortication) but 42% report residual symptoms and 46% have some respiratory impairment on long-term follow-up
• Medical thoracoscopy is an intermediate option for early-stage empyema where surgery is not available - best before adhesions become fibrous

When NOT to Operate for Pleural Thickening

• Post-empyema pleural thickening generally resolves over 3-6 months spontaneously
• Surgery for residual pleural thickening should only be considered if symptomatic thickening persists or progresses beyond 6 months

Monitoring Response

• Reassess clinically at 48-72 hours - fever, CRP, drainage output
• Repeat TUS or CT if drainage is insufficient or clinical deterioration
• Escalate to IET or surgery if no adequate response by 2-3 days

Key Differences: BTS 2023 vs. ERS/ESTS 2023

• Both recommend combination tPA + DNase as first-line intrapleural therapy after drainage failure
• Both advise surgical consultation at 2-3 days of inadequate drainage response
• BTS explicitly recommends direct surgical referral for clinically unstable patients without trial of drainage
• ERS places additional emphasis on novel microbiological techniques (NGS/metagenomics) for culture-negative cases
• Both endorse VATS over open thoracotomy when surgery is needed