• Summary
  Click here to print a Quick Reference Guide
• Background
• Clinical Diagnosis
• Investigation
• Treatment
• Non-Antimicrobial Treatment
• Empirical Antimicrobial Treatment
• Directed Antimicrobial Treatment (when microbiology results are known)
• Duration of Treatment
• Switch to oral agent(s)
• Treatment Failure
• Referral Criteria

History
A parapneumonic effusion or empyema should be suspected in patients with pneumonia failing to respond to appropriate antibiotic therapy (persistently elevated CRP and/or temperature) or with examination findings suggestive of a pleural effusion.

Examination
Reduced breath sounds and tactile vocal fremitus may indicate a pleural effusion.

Initial Investigations

• CRP, WCC, Chest X-ray
• Patients with a pleural effusion and sepsis require a diagnostic pleural aspiration under ultrasound guidance.
• Fluid pH should be analysed immediately by taking the sample in a blood gas syringe to Clinical Chemistry (not if fluid is very thick or presence of pus). Prior notification is required.
• Samples should be sent for microscopy/culture and sensitivity, LDH, Glucose, and Protein. AAFB and cytology should be requested if TB or malignancy is suspected. is conducted urgently and phoned back to the sender. Consider placing some of the pleural sample in blood culture bottles in addition to a sample in a sterile universal.

Non-antimicrobial treatment - see full guideline re chest drain insertion
Antimicrobial treatment

Empirical therapy (microbiology negative or awaited)

Community-acquired infection
First line:  Co-amoxiclav IV 1.2g 8-hourly
Penicillin allergy: Levofloxacin 500mg IV 12-hourly and Metronidazole IV 500mg 8-hourly

Prior to commencing Levofloxacin the possibility of tuberculosis should be considered and , if appropriate, sputum sent for AAFBs

Patients identified as ‘High Risk’ for MRSA: Patients identified as ‘High Risk’ for MRSA: 1st line Linezolid * 600mg 12-hourly PO/IV and Ciprofloxacin IV 400mg 12-hourly (or ORAL: 500mg 12-hourly if absorbing) and Metronidazole IV 500mg 8-hourly.
or 2nd line Teicoplanin * IV (see dosing guideline) and Ciprofloxacin IV 400mg 12-hourly (or ORAL: 500mg 12-hourly if absorbing) and Metronidazole IV 500mg 8-hourly.

*Linezolid has a number of drug interactions/contraindications. Please see full guidance to check suitability for the patient. This is an off-label use of Linezolid and Teicoplanin ; the patient should be informed of this.

Hospital-acquired infection
In hospital-acquired empyema, additional cover against MRSA and Gram negative bacilli may be required until cultures become available. Please discuss with the duty microbiologist. In complex cases the Consultant Respiratory Physician should contact the on-call Microbiology Consultant.

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Empyema is defined as pus in the pleural space; it usually occurs as a complication of pneumonia but may also complicate thoracic surgery, penetrating chest trauma, oesophageal rupture or leaks from oesophageal anastamoses. Occasionally another focus of infection cannot be found - so called “primary empyema”. The development of empyema secondary to pneumonia evolves through stages beginning with a simple exudate, which then becomes turbid and subsequently frankly purulent (see classification)
In the UK over 20% of patients with empyema die and 40% require surgery because of failed catheter drainage (Ferguson, A 1996). Rapid evaluation and treatment appears to reduce mortality and cost¹.

Classification
Parapneumonic effusions may be simple, complicated or an empyema.

• A simple parapneumonic effusion is clear with pH >7.2 and will usually resolve with antibiotics alone, although a chest tube may be required for symptom relief. Other fluid characteristics are LDH <1000 IU/L, glucose >2.2 mmol/L and the absence of organisms on Gram-stain or culture.
• A complicated parapneumonic effusion is clear or turbid usually with a pH <7.2, and requires chest tube drainage. Other fluid characteristics are LDH >1000 IU/L and glucose <2.2 mmol/L. The Gram stain or culture may or may not be positive
• Frank pus is diagnostic of empyema and pH measurement is not required

Microbiology
Streptococci and Staphylococcus aureus are the most common causes of empyema. S. aureus is more commonly seen following surgery, trauma, healthcare associated infection and in immunocompromised patients¹. Among the streptococci, Streptococcus pneumoniae and Streptococcus anginosus group (often called “Streptococcus milleri”) are the most important.

Gram negatives such as Escherichia coli, Klebsiella species, Haemophilus influenzae and Pseudomonas aeruginosa are not uncommon but may be present as part of mixed infections, often with anaerobes. Yeasts are often involved if the empyema is secondary to oesophageal rupture or anastamotic leaks.

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History

• A parapneumonic effusion or empyema should be suspected in patients with pneumonia failing to respond to appropriate antibiotic therapy (persistently elevated CRP and/or temperature) or with examination findings suggestive of a pleural effusion. 

Examination
A reduction in breath sounds, tactile vocal fremitus can be useful in determining the presence of an effusion.

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• Blood tests - CRP and WCC are useful for monitoring progress of the infection but have no diagnostic value.
• Radiology

Step 1:Chest radiograph
The size and appearance of parapneumonic effusion on the chest x-ray is a poor guide as to how well patients will respond to antibiotics.

N.B. In the presence of consolidation it can be very difficult to tell from the chest radiograph that there is fluid present.

A CXR should be performed after chest tube insertion (see non-antimicrobial treatment section) or when there is a poor response to antibiotics. A parapneumonic effusion /empyema is not always seen on chest radiograph.

Step 2: Ultrasound
Ultrasound is more sensitive in detecting small effusions and in demonstrating loculations.  Small or localized effusions are best drained under ultrasound guidance.   Please discuss with the chest radiologists.  [Evidence level C]

Step 3: CT scan
A CT scan should be considered following ultrasound if the patient is not improving despite drainage and appropriate antibiotic therapy.  CT can demonstrate the full extent of the parapneumonic effusion, pleural enhancement and thickening, and distinguish empyema from a pulmonary abscess. Please discuss with the chest radiologists. [Evidence level C]

• Diagnostic Aspiration
• All patients with a pleural effusion associated with sepsis require a diagnostic pleural aspiration under ultrasound guidance. [Evidence level C]
• Fluid pH should be analysed immediately using a blood gas machine (not if fluid is very thick or presence of pus). [Evidence level B]
• Samples should be sent for microscopy/culture and sensitivity, LDH, Glucose, and Protein.  AAFB and cytology should be requested if TB or malignancy is suspected. Out-of-hours it may be advisable to contact the lab in advance to make sure that the Gram film is conducted urgently and phoned back to the sender.  [Evidence level C]

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• Insertion of Chest Drains

A chest tube should be inserted in the following situations:

• For symptomatic relief in large simple parapneumonic effusions [Evidence level C]
• Persistent pyrexia and/or elevated CRP [Evidence level B]
• Frank pus or cloudy/turbid fluid on diagnostic aspiration  [Evidence level B]
• Pleural pH <7.2 (caution – other conditions can cause low pH and as disease progresses pH falls.  A higher pH does not exclude complicated parapneumonic effusion)  [Evidence level B]
• Organisms identified in pleural fluid on Gram-stain or culture (Microbiology may be negative if patient is on antibiotics).  [Evidence level B]

Parapneumonic effusions which do not meet the above criteria should be treated with antibiotics alone.  However poor clinical progress or significant effusion should lead to prompt patient review and probably chest tube drainage.  [Evidence level B]

Fibrinolysis

The MIST-2 Protocol is followed [Evidence level B]:

The Treatment Regimen is:

• Alteplase 10mg in 30mL NaCl 0.9% TWICE a day for 3 days (i.e. 6 doses in total)
• Dornase 5mg in 30mL Water for Injection TWICE a day (i.e. 6 doses in total)

Give both intrapleurally via the chest drain.

• Alteplase is given first and then the chest drain is clamped for 1 hour, then allowed to drain freely for 1 hour. This is then repeated with dornase alfa.

Use of this therapy (Alteplase / Dornase intrapleurally) must be approved by a Consultant Respiratory Phsyician.

• Referral for Surgery

Early consultation with Thoracic surgeons  is important in the event of  failure of chest tube drainage

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Empirical therapy (microbiology negative or awaited)
Community-acquired infection
First line: Co-amoxiclav IV 1.2g 8-hourly
Penicillin allergy: Levofloxacin 500mg IV 12-hourly and Metronidazole IV 500mg 8-hourly

Prior to commencing Levofloxacin the possibility of tuberculosis should be considered and, if appropriate, sputum sent for AAFBs

Patients identified as ‘High Risk’ for MRSA: 1st line Linezolid * 600mg 12-hourly PO/IV and Ciprofloxacin IV 400mg 12-hourly (or ORAL: 500mg 12-hourly if absorbing) and Metronidazole IV 500mg 8-hourly.
or 2nd line Teicoplanin * IV (see dosing guideline) and Ciprofloxacin IV 400mg 12-hourly (or ORAL: 500mg 12-hourly if absorbing) and Metronidazole IV 500mg 8-hourly..
*Linezolid has a number of drug interactions/contraindications. Please see full guidance to check suitability for the patient. This is an off-label use of Linezolid and Teicoplanin ; the patient should be informed of this.

Hospital-acquired infection
In hospital-acquired empyema, additional cover against MRSA and Gram negative bacilli may be required until cultures become available.  Please discuss with the duty microbiologist.  In complex cases the Consultant Respiratory Physician should contact the on-call Microbiology Consultant.

Directed Therapy
Staphylococcus aureus : Flucloxacillin IV 2g 6-hourly

“Streptococcus milleri”, Streptococcus pneumoniae, β haemolytic streptococci:
Benzyl penicillin  IV 2.4g 6-hourly +/- Metronidazole IV 500mg 8-hourly (depending on gram stain results)

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If documented penicillin anaphylaxis and no alternative is recommended, please contact Microbiology.  In complex cases the Consultant Respiratory Physician should contact the on-call Microbiology Consultant.

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The duration of treatment has not been assessed in clinical trials. Antibiotics are often continued for several weeks. If there has been adequate pleural drainage and the patient is clinically improved treatment for approximately 3 weeks is probably appropriate. Please discuss with the duty microbiologist.

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Like most complex infections, there are no fixed rules regarding when to switch to oral antibiotics.  A decision should be made, tailored to each patient's need, based ideally on microbiological and clinical findings, close monitoring, and appropriate drainage being carried out. However oral switch should not be made before there has been a significant clearing of the empyema fluid

Recommended regimens
Community-acquired infection – empirical therapy (i.e. negative/no microbiology)

First choice:
ORAL:  Amoxicillin 1g 8-hourly and Metronidazole 400mg  8-hourly

Second choice (patient intolerant of Metronidazole :
ORAL: Co-amoxiclav  625mg  8-hourly and Amoxicillin 500mg 8-hourly

Penicillin allergic patients:
ORAL:  Levofloxacin 500mg once-daily and Metronidazole 400mg 8-hourly

Prior to commencing Levofloxacin the possibility of tuberculosis should be considered and , if appropriate, sputum sent for AAFBs

Oral switch therapy may also be guided by culture and sensitivity results e.g. oral Flucloxacillin may be used if the cause is identified as meticillin-susceptible S. aureus. Please seek Microbiology advice on a case-by-case basis.

Hospital-acquired infection - empirical therapy (i.e. negative/no microbiology)
In hospital-acquired empyema, additional cover against MRSA and Gram negative bacilli may be required -please discuss with the duty microbiologist.

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The chest drain can be removed if fluid is less than 25 ml/day (excluding flushes). It is sometimes useful to leave a drain in situ when undertaking CT in cases of treatment failure. This allows the drain position to be determined.

Davies HE, Davies RJO, Davies CWH, on behalf of the BTS Pleural Disease Guideline Group. Management of pleural infection in adults: British Thoracic Society pleural disease guideline 2010. Thorax 2010;65(Suppl 2):ii51-ii53

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Please contact Microbiology if the patient is not responding to the recommended antimicrobial regimens

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• All patients with a moderate/large simple parapneumonic effusion, complicated parapneumonic effusions or empyema should be managed by a Respiratory physician.
• Early consultation with Thoracic surgeons  is important in the event of  failure of chest tube drainage

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