Empyema

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

All patients with empyema and complicated parapneumonic effusion require antibiotic treatment and urgent pleural fluid drainage.[1][8][36] The key goal of treatment is sterilisation of the pleural space.

Patients may be septic at presentation and require emergency fluid resuscitation and urgent intravenous antibiotics even before the diagnosis is established. Standard initial medical management also includes tube thoracostomy with continuous drainage of the infected pleural space.[37] The largest multi-centre prospective observational study (PILOT) demonstrates that this standard therapy fails in over 30% of cases.[38]

In patients who fail to respond to chest tube drainage and antibiotics, either intrapleural enzyme therapy and/or surgery should be considered.[18] Patients should be under the care of a respiratory physician or thoracic surgeon.

One Cohrane review found no statistically significant difference in mortality between primary surgical and non-surgical management of pleural empyema for all age groups.[39] Although video-assisted thoracoscopic surgery (VATS) reduced the length of hospital stay compared with thoracostomy drainage alone, there was insufficient evidence about the impact of fibrinolytic therapy.[39] As of November 2023, there has yet to be a randomised controlled trial comparing intrapleural enzyme therapy to early surgery, although a feasibility study was recently published (MIST-3), and set the framework for future evaluation.[37]

Adults

Initial antibiotic treatment[8]

All adults should initially receive empirical intravenous antibiotics based on local microbiology guidelines to cover the likely causative organisms, both aerobic and anaerobic. Clinicians should keep in mind differences between community-acquired and hospital-acquired pathogens.
Penicillins, penicillins combined with beta-lactamase, cephalosporins, and metronidazole penetrate the pleural space well. Aminoglycosides should be avoided due to their poor penetration of the pleural space and decreased efficacy in acidic environments. Clindamycin can be used as an alternative to metronidazole.
Intrapleural administration of antibiotics is not recommended.
If possible, antibiotic choice should be based on bacterial culture from the pleural fluid.
Even when anaerobic cultures are negative, continuation of empirical antibiotics covering both common community-acquired bacterial pathogens and anaerobic organisms should be considered, because anaerobes frequently infect empyemas and because anaerobes are not always cultured successfully.
In general, empirical antibiotics with activity against atypical organisms are not necessary.
For patients with community-acquired empyemas in whom the risk for methicillin-resistant Staphylococcus aureusand highly resistant gram-negative infection is low, the recommended treatment is with a second- or third-generation cephalosporin (e.g., cefuroxime, ceftriaxone) or an aminopenicillin with a beta-lactamase inhibitor (e.g., amoxicillin/clavulanate). However, due to emerging resistance patterns clinicians should familiarise themselves with a local antibiogram. Amoxicillin/clavulanate is active against a range of anaerobes, but ceftriaxone requires the addition of an antibiotic with anaerobic cover, such as metronidazole. Clindamycin may be used as an alternative to metronidazole.
Empirical antibiotic treatment for hospital-acquired empyema should include antibiotics active against methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa (e.g., vancomycin plus cefepime, and metronidazole; or vancomycin plus piperacillin/tazobactam) and keep in mind increasing resistance patterns. Vancomycin plus meropenem may be indicated if there is a history or suspicion of extended spectrum beta-lactamase-producing organisms. As up to 25% of cases of hospital-acquired empyema are associated with MRSA, all patients (particularly postoperative and post-traumatic) should receive anti-staphylococcal cover.

Subsequent antibiotic therapy[8]

Once culture results from the pleural fluid are obtained, antibiotics should be tailored to the sensitivities of the grown culture. Antibiotics should not be discontinued following a negative culture, as pleural fluid cultures are negative in 40% of cases. In these patients, prolonged empirical antibiotic therapy may be required.

If the patient has responded to intravenous treatment, the source of infection has been controlled, the organism is susceptible to oral antibiotics, and the patient’s oral intake is acceptable, then a transition to oral treatment can be made.
Although the optimum duration of treatment is unknown, antibiotic therapy is generally continued for at least 3 weeks. The Working Group of the American Association for Thoracic Surgery recommends a minimum of 2 weeks from the time of drainage and settling of the fever, and states that clinical response, source control, and pathogen should all play a role in treatment decisions. Inflammatory markers (white blood cell count [WBC] and C-reactive protein [CRP]) are useful as guides to the required duration of antibiotic treatment.

Prolonged courses of antibiotics may be necessary and can be administered after discharge.

Supportive care

Antipyretics and analgesics should be administered as indicated. The authors make no recommendations for specific antipyretics and analgesics. Agents should be used in accordance with local protocols. Good nursing care, ensuring maintenance of appropriate dietary intake with nutritional supplements if necessary, is paramount. Early mobilisation is also essential.

Chest tube drainage

Urgent chest drain insertion is essential in all adults with empyema or complicated parapneumonic effusion. In most cases thoracentesis alone is not sufficient.
Chest drains should be inserted by competent personnel under imaging (ultrasound) guidance to reduce the risk of complications that include organ damage, haemorrhage, subcutaneous emphysema, and death.[40]
There is no consensus on the optimal chest tube size for drainage, although it is likely that small-bore chest drains (10-14F) are as effective as large-bore drains (20-28F).[8][41] Small-bore drains have also been shown to be less painful for patients.[42]
Regular flushing with saline is recommended for small-bore chest drains and if the chest drain becomes blocked.
The chest drain should remain in place until the effusion has resolved and drainage has stopped.

Surgery

Patients who do not respond to antibiotics and tube thoracostomy (chest drain insertion) should be referred to a thoracic surgeon for consideration of surgical intervention. [ ] Failure to respond is a clinical decision based on ongoing fever, failure of pleural fluid drainage, and persistently raised inflammatory markers. Approximately 30% of patients will require surgery.[23]
The optimal time at which to refer for surgery is unclear. Some authorities advocate immediate surgery for all patients. The American Association for Thoracic Surgery recommends VATS as the first-line approach in all patients with stage 2 acute empyema.[8] However, some experts support a trial of combination therapy with a fibrinolytic drug and dornase alfa before considering surgery for patients with stage 2 empyema, or for patients with stage 3 empyema awaiting a surgical consultation.[43] In patients with stage 2 and 3 empyema, a beneficial effect of surgical debridement or decortication has been found over tube thoracostomy alone in terms of treatment success and reduction in hospital stay. [ ] For patients with stage 3 empyema VATS has been shown in some studies to be as effective as open decortication. However, there were some series reporting high conversion rate to open decortication (about 40%). Stage 3 empyema decortication should be performed by open technique, particularly in symptomatic patients over 5 weeks; in experienced units VATS may be an option, especially in early surgical referrals.[22]
The first-line surgical option is VATS, as it is a less invasive procedure, with less post-operative pain, shorter hospital length of stay, less blood loss, less respiratory compromise, fewer post-operative complications, and lower cost compared with open thoracotomy.[8]
Local anaesthetic thoracoscopy may be useful for the treatment of empyema, allowing division of septations and adhesions and facilitating accurate tube placement and drainage, but is not routinely used, as large prospective randomised trials are still needed to elucidate its role for empyema.
A thoracic surgeon should be involved in assessment of the patient, even for anaesthesia. Less radical surgical interventions, depending on surgical expertise and access, such as rib resection and placement of a large-bore drain, may be considered in unstable patients and can be performed in some cases with epidural or local anaesthesia.[8]
In patients with ineffective effusion drainage and persistent sepsis who cannot tolerate general anaesthesia, re-evaluation with re-imaging of the thorax and, after discussion with a thoracic surgeon, placement of another image-guided small-bore catheter or a larger bore chest tube, or intrapleural enzyme therapy may be considered.[8]
If VATS is not available, intrapleural enzyme therapies should be considered, and if these do not result in adequate resolution of the empyema, further surgical options should be discussed with a thoracic surgeon. These include mini-thoracotomy, decortication (a major thoracic operation involving the evacuation of pus and debris from the pleural space and removal of fibrous tissue from the visceral and parietal pleura), and open thoracic drainage. Intrapleural fibrinolytic drugs should be considered for patients who are not surgical candidates.

Intrapleural enzyme therapy

As of November 2023 there has not been a head to head randomised controlled trial comparing early surgery to chest tube thoracostomy with intrapleural enzyme therapy. However, it is likely that early intervention in general has significant benefit and is associated with shorter hospital length of stay.[37]
Standard medical therapy with chest tube thoracostomy and antibiotics fail in approximately 30% of adult patients. These patients should be treated with either surgical intervention, or intrapleural enzyme therapy with a combination of alteplase (recombinant tissue plasminogen activator [t-PA]) and dornase alfa (deoxyribonuclease [DNAse]). The medicines are instilled into the chest tube and allowed to dwell for 1 hour.

Intrapleural enzyme therapy may be indicated for the decompression of multiloculated and tube drainage-resistant pleural effusions that are responsible for dyspnoea or respiratory failure if a thoracic surgeon identifies that surgery is not immediately possible (e.g., patient comorbidity or other clinical or logistical reasons).[44] Some experts support routine consideration of intrapleural enzyme therapy for either initial or subsequent treatment of empyema, but only following multidisciplinary risk-benefit discussion and depending on local expertise and the availability of minimally invasive surgical services.[43]

Intrapleural enzyme therapy (such as streptokinase or urokinase) should be considered in haemodynamically unstable and older patients, patients who are not candidates for surgery (e.g., due to comorbidity), in those with a large effusion not relieved by chest tube drainage and causing respiratory compromise, and in institutions where VATS is not available.[45][46] American Association for Thoracic Surgery guidelines do not support routine use of intrapleural fibrinolytics for complicated pleural effusions and early empyemas.[8]
The bleeding risk from intrapleural enzyme therapy is low. In one large multi-centre retrospective review of 1833 patients, there was a 4.1% bleeding risk associated with intrapleural enzyme therapy. Increased risk of bleeding was associated with therapeutic anticoagulation, increased RAPID [Renal (urea), Age, fluid Purulence, Infection source, Dietary (albumin)] score, increased serum urea, and thrombocytopenia (<100 × 10⁹/L).[47]
Most experts support use of a combination of a fibrinolytic and dornase alfa in place of monotherapy.[43]

Indwelling pleural catheters

These may rarely have a role in maintaining drainage of a chronically infected pleural space that is not readily treated in other ways such as surgery.[48]
Patients with existing indwelling pleural catheters placed for malignant pleural effusion who develop pleural space infections can often be treated with antibiotics and pleural fluid drainage without removal of the indwelling pleural catheter.[49] The catheter should likely be removed if patients present with sepsis.

Children

Antibiotic therapy

All children with empyema should be treated with empirical intravenous antibiotics covering Streptococcus pneumoniae and Staphylococcus aureus, based on local microbiology guidelines.[26][27] Antibiotics should be administered intravenously in high doses initially to ensure adequate pleural penetration.[27] Once culture results from the pleural fluid are obtained, antibiotics may be tailored to the sensitivities of the grown culture. Antibiotics should not be discontinued following a negative culture, as pleural fluid cultures are negative in 40% of cases. In these patients, prolonged empirical antibiotic therapy may be required.[50]
Antibiotic selection for empyemas varies and selection should be based on local microbiology guidelines; however, suitable choices include cefotaxime or ceftriaxone or amoxicillin, depending on local guidelines or antibiograms.[26] The addition of vancomycin or linezolid is usually reserved for culture-proven or severe suspected MRSA infection.[26]
When drainage has been completed, and the patient is clinically improving and off oxygen, the route of antibiotic administration may be changed to oral.[26] Inflammatory markers (WBC count and CRP) are useful as guides to the required duration of antibiotic treatment.