What is the treatment approach for pleuritis?

Treatment Approach for Pleurisy

The treatment of pleurisy depends critically on the underlying etiology, with infectious pleurisy requiring immediate antibiotics plus drainage for complicated cases, while non-infectious causes (such as lupus pleuritis) respond to corticosteroids and immunosuppressive therapy. 1

Initial Diagnostic Evaluation

• Perform diagnostic thoracentesis within 24 hours when pleural infection is suspected, with pleural fluid sent for pH, glucose, LDH, protein, cell count with differential, Gram stain, and culture 1
• Ultrasound is the preferred initial imaging modality for suspected pleural effusion and should guide thoracentesis or drain placement 1, 2
• Obtain blood cultures in all patients with suspected parapneumonic effusion 1

Risk Stratification Based on Pleural Fluid Analysis

The pleural fluid pH is the most critical parameter for determining need for drainage:

• pH <7.2: High risk of complicated parapneumonic effusion (CPPE) or empyema—insert chest tube immediately 2
• pH 7.2-7.4: Intermediate risk—measure LDH; if >900 IU/L, consider chest tube drainage, especially with fever, large volume, glucose ≤4.0 mmol/L (72 mg/dL), pleural enhancement on CT, or septations on ultrasound 2
• pH ≥7.4: Low risk—no immediate drainage indicated 2

Important caveat: In the absence of immediate pH measurement, pleural fluid glucose <3.3 mmol/L can indicate high probability of CPPE/pleural infection and guide the decision to insert a chest tube 2

Treatment of Infectious Pleurisy/Pleural Infection

Antibiotic Therapy

All patients must receive antibiotics immediately upon identification of pleural infection 2, 1

Community-Acquired Pleural Infection (Culture-Negative)

Choose one of the following regimens 2, 3:

• Cefuroxime 1.5 g IV three times daily + metronidazole 400 mg oral three times daily (or 500 mg IV three times daily) 2
• Amoxicillin-clavulanate (amoxicillin 1 g + clavulanic acid 125 mg three times daily) 2
• Benzyl penicillin 1.2 g IV four times daily + ciprofloxacin 400 mg IV twice daily 2
• Clindamycin 300 mg four times daily (particularly useful for penicillin-allergic patients, provides single-agent coverage of aerobes and anaerobes) 2, 3

Hospital-Acquired Pleural Infection

Requires broader spectrum coverage 2, 3:

• Piperacillin-tazobactam 4.5 g IV every 6 hours (preferred first-line choice) 2, 3
• Ceftazidime 2 g IV three times daily 2
• Meropenem 1 g IV three times daily ± metronidazole 2

Key Antibiotic Principles

• Adjust antibiotics based on culture results when available 2, 1
• Avoid aminoglycosides—they have poor pleural space penetration and are inactivated by pleural fluid acidosis 2, 3
• Beta-lactams (penicillins and cephalosporins) show excellent pleural space penetration; there is no need for intrapleural antibiotic administration 2, 3
• Anaerobic coverage is essential as anaerobes are frequently present and associated with treatment failure if not covered 3

Duration of Antibiotic Therapy

• Initial IV therapy until clinical improvement (fever resolution, improved respiratory status, decreased inflammatory markers) 1, 3
• Transition to oral antibiotics at discharge for 1-4 weeks, longer if residual disease persists 1, 3
• Total duration typically 2-4 weeks depending on clinical response 3

Drainage Strategy for Pleural Infection

Initial drainage should be undertaken using a small bore chest tube (14F or smaller) 2

Indications for Chest Tube Drainage

• Purulent pleural fluid (frank pus) 2
• Pleural fluid pH <7.2 2
• Loculated pleural collections (associated with poorer outcomes, warrant earlier drainage) 2
• Large non-purulent effusions causing symptoms 2

Drainage Technique

• Use ultrasound or CT guidance for chest tube placement 1, 3
• Small bore catheters (≤14F) are preferred—they cause less post-treatment pain with equivalent efficacy compared to large bore tubes 2
• Early surgical drainage (VATS or thoracotomy) should NOT be considered over initial chest tube drainage due to lack of supporting evidence 2

Management When Drainage Ceases with Residual Collection

When chest tube drainage stops but imaging shows persistent pleural collection:

Consider combination tissue plasminogen activator (TPA) and DNase 2:

• Dosing: TPA 10 mg twice daily + DNase 5 mg twice daily for 3 days 2
• Alternative reduced-dose regimen: TPA 5 mg twice daily + DNase 5 mg twice daily for 3 days (based on retrospective data, may be as effective) 2
• Obtain patient consent due to potential bleeding risk; consider reduced TPA doses in high bleeding risk patients 2
• Evidence: Reduces length of hospital stay, reduces persistent fevers, and improves chest x-ray opacification, though may increase complications 2

Alternative option: Saline irrigation (250 mL three times daily) can be considered when TPA/DNase or surgery is not suitable, may reduce need for surgery 2

Do NOT use:

• Single agent TPA or DNase alone—ineffective 2
• Streptokinase—increases complications without improving outcomes 2

Specialist Involvement

A respiratory physician or thoracic surgeon should be involved in the care of all patients requiring chest tube drainage for pleural infection 2, 1, 3

Consider surgical consultation if:

• No clinical improvement within 7 days of drainage and antibiotics 2, 1
• Inadequate drainage despite appropriate chest tube placement 3

When surgery is required, video-assisted thoracoscopic surgery (VATS) is preferred over thoracotomy 2, 1:

• 2.3 days shorter hospital stay (95% CI: 1.2-3.4 days) 2
• Less postoperative pain 2
• Fewer complications (152/1000 vs 197/1000 patients) 2
• Slightly lower mortality (35/1000 vs 47/1000 patients) 2

Treatment of Non-Infectious Pleurisy

Lupus Pleuritis

• Corticosteroids (oral prednisone) combined with immunosuppressive agents (such as methotrexate or cyclophosphamide) are the mainstay of treatment 4, 5
• Most cases respond to medical therapy within 1 month 5
• In medically refractory cases with severe restrictive lung disease, pleural decortication may be considered as a viable alternative, with significant improvement in dyspnea and pulmonary function 4

Nonspecific Pleuritis

• Tuberculosis is the most common cause of nonspecific pleuritis (48% in one series), particularly in endemic areas 6
• When initial pleural biopsy shows nonspecific pleuritis with high WBC count (>2,000/mm³) and lymphocyte percentage (>60%), therapeutic trial with antituberculous medication should be considered 6
• Follow-up is critical: Up to 15% of patients with nonspecific pleuritis are eventually diagnosed with pleural malignancy 1
• Repeat pleural biopsy, thoracoscopy, or therapeutic trials may be needed to establish diagnosis 6

Common Pitfalls and Caveats

• Delayed chest tube drainage increases morbidity, hospital stay, and possibly mortality 1, 3
• Inappropriate antibiotic selection (particularly using aminoglycosides or omitting anaerobic coverage) leads to poor outcomes 1, 3
• Pleural fluid samples for pH must not be contaminated with local anesthetic or heparin, as this lowers pH; delays in measurement increase pH 2
• Alternative diagnoses can mimic pleural infection with low pH and loculations (rheumatoid effusion, malignancy/mesothelioma)—maintain clinical suspicion 2
• Explosive pleuritis (rapid development of massive effusion >90% hemithorax within 24 hours) is a medical emergency requiring urgent intervention 7
• Regular clinical reviews are essential when initial decision is made not to drain, with repeat thoracentesis considered to ensure CPPE is not missed 2