Pleural infection

Chest x-ray

Using routine chest x-ray, parapneumonic effusions of over 200 ml volume are usually detectable, associated with areas of consolidation. In addition, pleural infection often results in loculated effusions, occasionally with air-fluid levels.

Pleural ultrasound

Pleural ultrasound detects fluid in the pleural space with greater sensitivity than a chest x-ray and, in addition, enables real-time localisation, quantification and characterisation of the fluid (Table 1, Fig 1).^8,9 Selecting a site for pleural fluid drainage using bedside ultrasonography is safer than the traditional combination of chest x-ray and clinical examination which carries a 10% risk of organ puncture.¹⁰ Thoracentesis-associated complications were reduced from 8% to 1% in one study when a safety programme, including physician-led chest ultrasonography, was introduced.¹¹ Given such benefits, the recent British Thoracic Society pleural disease guidelines^12,13 and an NHS National Patient Safety Agency rapid response report¹⁴ now strongly recommend ultrasound prior to any procedure for pleural fluid. Furthermore, the Royal College of Radiologists has published ultrasound training guidelines for non-radiology clinicians.¹⁵

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Fig 1.

Ultrasound of a septated pleural effusion caused by gas-forming pleural infection.

Computed tomography

Cross-sectional imaging of the chest with pleural-phase contrast enhancement is used for ambiguous chest x-ray or ultrasound findings. Pleural thickening, enhancement and increased attenuation of extrapleural subcostal fat suggest pleural infection. Computed tomography is particularly useful in differentiating a peripheral pulmonary abscess and pleural infection: the ‘split pleura’ sign found in pleural infection describes enhancement of parietal and visceral pleura around pleural fluid which is not found with a pulmonary abscess.

Fluid sampling and analysis

Imaging features may suggest pleural infection, but fluid sampling and analysis are essential to confirm infection. Parapneumonic effusions deeper than 1–2 cm should be sampled (provided it is safe to do so), even in the absence of specific imaging features suggestive of infection. Shallower effusions are likely to resolve with antibiotics, but clinical progress should be monitored. Table 2 details investigations to be undertaken for parapneumonic effusions.

Pleural fluid analysis provides effusion categorisation into:

• simple non-infected effusions

• complicated infected effusions

• empyema.

Biochemical proxies (pH, glucose and lactate dehydrogenase [LDH]) are used to define pleural infection (Table 3)–necessary because microbiological cultures are slow and frequently negative. Fluid pH is an important clinical predictor of pleural infection,¹⁸ although malignancy and other causes of inflammation may also cause pH values below 7.2. Glucose and LDH levels do not improve diagnostic reliability and primarily have utility only when accurate pH values are unavailable.

Bacteriology

It is essential for clinicians to acknowledge that the microbiology pattern of pleural infection varies between community and hospital-acquired infection.¹ Gram-positive aerobic bacteria are the commonest cause of both community and healthcare-associated infection, Streptococcus pneumoniae (21%) and the Streptococcus ‘milleri’ (constellatus-intermedius-anginosus) group (24%) being the commonest in community-acquired infection and Staphylococcus aureus (35%) being the commonest in hospital-acquired infection. Gram-negative organisms occur in about 9–23% of infections with anaerobic organisms in about 12–34%. Polymicrobial infection is fairly common, particularly in the elderly and those with comorbidities. In healthcare-associated pleural infection, resistant pathogens such as methicillin-resistant Staphylococcus aureus and Gram-negative organisms such as Escherichia coli, Enterobacter spp and Pseudomonas spp are more common. Fungal pleural infection is rare, but important to consider in immunosuppressed patients. It has a mortality in excess of 70%, with Candida spp the most commonly isolated fungus.

Antibiotic therapy

Patients with pleural infection should be treated with empiric broad-spectrum antibiotic therapy until culture results are available. Antibiotic choice will be determined in accordance with local antibiotic policy and resistance patterns. However, as a guide, community-acquired pathogens are normally covered by a beta-lactam antibiotic in conjunction with a beta-lactamase inhibitor, such as amoxicillin and clavulanic acid or piperacillin-tazobactam. Metronidazole is frequently added to increase anaerobic coverage. Healthcare-associated pleural infection is often associated with resistant bacteria. A reasonable choice of antibiotic is a carbapenem combined with vancomycin.

Although not robustly tested in a randomised controlled trial (RCT) format, antibiotic treatment duration is usually given for 3–4 weeks. Initial therapy is with iv antibiotics for one week, guided by the clinical course.

Pleural fluid drainage

Pleural infection requires prompt tube drainage, but simple non-infected parapneumonic effusions do not usually require drainage. Recent evidence suggests that small-bore tubes (<15 F) have similar efficacy as large bore tubes in draining pus and are associated with less chest tube pain.²⁰ A chest tube flush regimen, such as 20 ml 0.9% sodium chloride solution every six hours, is often used for small-bore tubes together with suction using a dedicated thoracic suction unit.

Adjunctive intrapleural medication

The role of intrapleural fibrinolytics in improving the drainage of poorly resolving, heavily septated pleural infection has been investigated. Despite small studies suggesting that fibrinolytic streptokinase may improve fluid drainage when instilled into the pleural space, a large RCT (MIST-1) showed that intrapleural streptokinase did not improve clinical outcome.⁴ The MIST-2 RCT of intrapleural tissue plasminogen activator (tPA) and deoxyribonuclease (DNase), an enzyme which disrupts DNA, suggests that the combination of tPA and DNase increases the amount of pleural fluid drained.²¹ However, further studies are required to define the clinical treatment effect. A future trial should consider the combination of tPA and DNase in patients with ventilatory compromise and extensive comorbidities who are too high risk to undergo surgical intervention to evacuate the pleural space.

Consideration of surgery

The 30% of patients who fail to respond to medical management should be considered for an early surgical opinion. There are no published data on the timing or clinical criteria for surgical referral, but it is the authors' clinical practice to refer patients with ongoing signs of sepsis and incomplete pleural drainage on the fifth day of medical management. Conversely, patients who have residual pleural fluid, but are otherwise well with improving clinical and laboratory parameters, will normally have gradual resolution of the pleural fluid from the pleural space over time. Video-assisted thoracoscopic surgery (VATS) enables decortication of pleural thickening, septation division and fluid removal, allowing lung re-expansion. VATS is performed under general anaesthesia with single lung ventilation, but in expert centres this can be performed using regional anaesthesia. Several studies have investigated the role of primary VATS versus chest tube drainage on initial presentation with pleural infection, but the methodological limitations of these studies means that definitive evidence is lacking.

Nutritional support

Weight loss and low serum albumin concentration are commonplace in pleural infection and associated with poorer outcome.²² Specific nutritional therapy has not been subject to an RCT in this setting, but nutritional support is likely to be important in counteracting the catabolic state associated with infection. The patient should receive regular dietetic review with institution of continuous enteral feeding if regular oral supplements are not tolerated or ineffective to maintain weight.