Pleural infection affects over 15,000 patients per year in the UK, with a 12-month mortality of approximately 15% — outcomes that have not improved in 15 years. About a third of patients fail standard medical therapy and require either intrapleural enzyme therapy or surgery. The right operation, at the right point in the disease, by a team that does this often, is the difference between resolution in days and a problem that lingers for weeks. Dr Okiror is first author of the 2014 European Journal of Cardio-Thoracic Surgery paper on decortication outcomes; a named co-author of the MIST-3 feasibility trial (Am J Respir Crit Care Med 2023); and Lead Surgeon and Co-PI at Guy’s and St Thomas’ for the MIST-4 Phase III randomised trial — the trial that will define the surgical answer for this disease.
Last reviewed: April 2026 · Dr Lawrence Okiror FRCS(CTh) FRCSEd(CTh) · GMC 6150382
Pleural infection — the broader umbrella term for what becomes empyema — usually starts as a complication of pneumonia. Bacteria cross from the lung into the pleural space. Fluid accumulates around the lung. The fluid becomes infected. Without effective treatment, it organises into loculated pockets of pus, then into a thick fibrous peel that encases the lung and prevents it from re-expanding.
Across the UK, more than 15,000 patients are admitted with pleural infection each year. The 12-month mortality is approximately 15%. The median hospital stay is 14 days. Around 14.5% require surgical referral. About one third fail the standard medical pathway of antibiotics and chest drain alone. These figures have not changed materially over the past 15 years — despite advances in antibiotics, intrapleural enzyme therapy, and minimally invasive surgery.
UK incidence rose by 61% between 2008 and 2017. The burden falls hardest on elderly and frail patients, and on those with diabetes, immunosuppression, or significant comorbidities. Around 30% of cases occur in otherwise healthy individuals.
UK patients per year, and rising
12-month mortality
Medical therapy failure rate
Median hospital stay
UK national pleural infection epidemiology data; figures consistent with the population assumptions of the MIST-4 trial protocol.
Empyema is not a single bacterial disease. The organisms involved differ between community-acquired and hospital-acquired infection — and that difference matters for antibiotic choice, surgical urgency, and prognosis.
Community-Acquired Pleural Infection
Streptococci & AnaerobesThe dominant organisms are the Streptococcus milleri group (often the single most common isolate in UK community-acquired empyema), Streptococcus pneumoniae, and a substantial proportion of anaerobes including Fusobacterium and Bacteroides species. Mortality is comparatively lower. Surgical resolution is generally good when intervention is timely.
Empirical antibiotic cover follows BTS and local microbiology guidance, with broad-spectrum agents that cover anaerobes pending culture.
Hospital-Acquired Pleural Infection
Gram-negatives, MRSA & PolymicrobialHospital-acquired pleural infection involves a different microbiological profile — gram-negative organisms (E. coli, Klebsiella, Pseudomonas), MRSA, and polymicrobial infection are all more common. Mortality is substantially higher. Time to surgical intervention often matters more in this group, and antibiotic cover must reflect local resistance patterns.
The infection source — community versus hospital — is one of the five components of the validated RAPID risk score and one of the stratification factors in MIST-4.
Why this matters for the surgical decision: patients with hospital-acquired pleural infection, multi-resistant organisms, or significant comorbidities cannot afford a prolonged trial of failing medical therapy. Earlier surgical involvement — not necessarily earlier surgery — allows the surgical option to be planned in parallel with the medical trial, rather than as a salvage step after weeks of failure. The 2023 GIRFT Cardiothoracic Surgery report recommends that surgery for empyema be performed within 48 hours of surgical referral.
The evidence base for pleural infection has been built by four major UK trials over twenty years — the MIST series, run by the Oxford Respiratory Trials Unit. Each trial has answered one piece of the puzzle. The fourth and final question — whether surgery or intrapleural enzyme therapy should be first when medical management fails — is what MIST-4 is now testing in a definitive Phase III randomised trial across multiple UK sites including Guy’s and St Thomas’.
MIST 1 · 2005
MIST 1 trial group · New England Journal of Medicine · 2005 · 454 patients
The First Multicentre Intrapleural Sepsis Trial randomised patients with pleural infection to intrapleural streptokinase or placebo. There was no difference in mortality, the need for surgery, or hospital stay. Streptokinase alone was abandoned as a treatment option. The question of whether a different fibrinolytic combination might work was left open.
A negative trial that closed one door and opened the question that MIST 2 would answer.
MIST 2 · 2011
MIST 2 trial group · New England Journal of Medicine · 2011 · 210 patients
A 2×2 factorial trial of intrapleural tPA plus DNase versus either alone or placebo in pleural infection. The combination significantly improved pleural fluid drainage on imaging and reduced the need for surgical referral and hospital stay. Either drug alone was no better than placebo. This established intrapleural enzyme therapy — alteplase plus DNase — as the medical escalation step before surgery.
Published failure rate of intrapleural enzyme therapy in subsequent real-world data: approximately 18%.
MIST-3 · 2023
Bedawi et al. · Am J Respir Crit Care Med · 2023 · 60 patients · 8 UK centres · ISRCTN18192121
The Third Multicentre Intrapleural Sepsis Trial established the feasibility of randomising patients with pleural infection to early VATS surgery, early IET, or standard care. It met its predefined feasibility criteria, demonstrated potential length-of-stay reduction with early surgery and earlier symptom resolution with IET, and confirmed that a definitive Phase III RCT was feasible. Dr Okiror is a named co-author of MIST-3, contributing the Guy’s and St Thomas’ surgical centre data.
MIST-3 is the bridge that made MIST-4 possible — the feasibility evidence on which the Phase III definitive trial was designed.
MIST-4 · Phase III · Recruiting
Phase III multicentre RCT · 604 patients · Oxford Respiratory Trials Unit · ISRCTN16328099
The Fourth Multicentre Intrapleural Sepsis Trial is the definitive Phase III comparison: early VATS debridement versus early intrapleural enzyme therapy in adult patients with pleural infection that has failed initial medical management. Run by the Oxford Respiratory Trials Unit. Stratified by RAPID score and by surgical facilities on site.
Dr Okiror is Lead Surgeon and Co-PI at Guy’s and St Thomas’ for MIST-4.
The arc in one sentence
MIST 1 ruled out streptokinase. MIST 2 established intrapleural enzyme therapy as the medical step before surgery. MIST 3 demonstrated that randomising patients to early VATS versus early IET was feasible. MIST-4 now answers the question definitively. Dr Okiror is a named co-author on MIST-3 and Lead Surgeon and Co-PI at Guy’s and St Thomas’ for MIST-4.
The right surgical decision in pleural infection is not "VATS or thoracotomy." It is "what stage of disease is this, what has already failed, and which operation will reliably re-expand the lung."
First-line treatment per BTS guidelines. Appropriate empirical antibiotic cover for community-acquired or hospital-acquired infection. Image-guided chest drain. Most Stage I exudative effusions and many early Stage II cases will respond. Failure to defervesce, persistently raised CRP (failure to fall by 50% in 5 days), or persistent collection on imaging signals failure and the need to escalate.
For fibrinopurulent Stage II disease where loculations are established, or when intrapleural enzyme therapy has failed or is not appropriate. Single-port or multi-port VATS, with breakdown of all loculi and washout until clear. Hospital stay typically 4–7 days. Early VATS — within 48 hours of surgical referral per the GIRFT December 2023 recommendation — is associated with lower failure rates and shorter overall hospital stay. The MIST-4 trial mandates VATS by Day 4 from randomisation.
For organised Stage III empyema where a fibrous peel has formed and the lung will not re-expand without removal of that peel. VATS alone is no longer adequate at this stage. Thoracotomy provides the access required to free the visceral pleura cleanly without injuring the underlying lung. This is the operation studied in Dr Okiror’s 2014 EJCTS publication on outcomes of decortication for culture-positive empyema.
The RAPID risk score
The validated RAPID score — Renal function (urea), Age, Purulence of pleural fluid, Infection source (community vs hospital), and Dietary status (serum albumin) — predicts 90-day mortality from pleural infection and identifies patients who may benefit from earlier escalation to surgery. RAPID score is one of the two stratification factors in the MIST-4 trial randomisation.
If your treating team has not used the RAPID score to guide escalation decisions, that is a reasonable question to ask. It is the single best validated tool for matching the intensity of treatment to the severity of disease.
Pleural infection is not a high-volume condition for any private thoracic practice. It is a disease that comes through the NHS first — via A&E, respiratory medicine, or intensive care — and patients see a surgeon only when escalation is needed. What matters most when choosing where to be treated is whether the surgeon has done this often, has published on it, and is connected to the network that defines current and future practice.
Okiror L, et al. Thoracotomy and decortication: impact of culture-positive empyema on the outcome of surgery. European Journal of Cardio-Thoracic Surgery 2014;46(5):901–906.
Cited in international guidelines including the 2023 Japanese Association for Chest Surgery guidelines and major systematic reviews of pleural infection.
Bedawi et al. Early VATS or Intrapleural Enzyme Therapy in Pleural Infection: The Third Multicenter Intrapleural Sepsis Trial — MIST-3. Am J Respir Crit Care Med 2023;208(12):1305–1315.
Trial registry: ISRCTN18192121. Multicentre feasibility trial across 8 UK centres including the Guy’s and St Thomas’ surgical site.
Lead Surgeon and Co-PI at Guy’s and St Thomas’ for the multicentre Phase III MIST-4 trial — the definitive UK randomised comparison of early VATS surgery versus early intrapleural enzyme therapy in adult pleural infection.
Trial registry: ISRCTN16328099. Run by the Oxford Respiratory Trials Unit.
Teaching and faculty roles. Dr Okiror teaches pleural disease and the surgical management of empyema annually on the SCTS Education Revision and Viva Course for the FRCS (Cardiothoracic) — the national examination preparation course for senior thoracic trainees — most recently in April 2026. He has also delivered the chest wall and pleural disease module on national specialty examination preparation programmes, alongside leading authorities in pleural disease, including authors of the BTS pleural guidelines.
The combination — first-author publication, current Phase III trial leadership, and active national teaching role — is uncommon in private thoracic surgical practice in London for this specific condition. For patients and referring physicians who want a surgeon connected to the evidence base for pleural infection, that combination is worth checking against any alternative.
VATS debridement and washout for pleural infection is performed at London Bridge Hospital and The Lister Hospital Chelsea. Both have full thoracic surgical capability and the level of perioperative support appropriate for patients who are systemically unwell at the time of surgery.
For chronic Stage III empyema requiring thoracotomy and decortication — or for patients with significant comorbidities, persistent sepsis, or multi-organ involvement — surgery takes place at London Bridge Hospital, where the level of intensive care and respiratory medicine support matches the complexity of the operation and the underlying illness.
Outpatient consultations — including for patients seeking a second opinion on a chest drain that has not resolved or a recommendation against surgery they want to question — are also available at HCA outpatients in Canary Wharf and the City of London. Same-day or next-day virtual consultations can be arranged for urgent cases.
Insurance and self-pay: Dr Okiror is recognised by all major UK private medical insurers including AXA, BUPA, WPA, Vitality, Cigna, and Aviva. Pleural infection often requires prolonged inpatient care — transparent estimates covering surgical, hospital, anaesthetic, and intensive care costs are provided by Jo Mitchelson before any commitment is made — 020 7952 2882 or pa@lungsurgeon.co.uk.
Patients with chronic empyema are sometimes told that surgery is too risky — or that the only option left is long-term antibiotics or an indwelling drain. Those answers are sometimes correct. They are also sometimes wrong, given by units without high-volume experience in decortication. Three questions are worth asking before accepting them.
RAPID is the validated tool for stratifying risk in pleural infection. If it has not been calculated, the assessment of "too risky" is being made by clinical impression rather than by the validated framework that the field uses. That is a reasonable question to raise.
There is a difference between “too risky” assessed by a chest physician and “too risky” assessed by a thoracic surgeon who performs decortication regularly. For complex cases, a specialist surgical opinion is the right standard — and is reasonable to ask for.
Antibiotics and chest drain. Intrapleural enzyme therapy with alteplase and DNase. VATS debridement. Decortication. Each is a different rung on the ladder. If only one or two have been tried, options remain. If all have been tried and failed, that is a different conversation — but it should be one had with a surgeon experienced in the disease.
A second opinion appointment with Dr Okiror is typically available within 2–3 days. For acutely unwell patients, virtual consultations can be arranged same-day. Bring CT and chest X-ray imaging, the inflammatory marker trend, microbiology results, and any treatment recommendation already made.
If your problem is pleural fluid, not infection
Pleural effusion, pleural thickening, or suspected mesothelioma?Non-infective pleural disease — recurrent effusions, undiagnosed pleural thickening, and mesothelioma assessment — follows a different pathway. The dedicated pleural disease page covers VATS pleurodesis, pleural biopsy, and the diagnostic work-up for malignant pleural disease.
Common questions from patients with pleural infection that has not resolved on antibiotics, from families of patients with chronic empyema seeking a second surgical opinion, and from referring physicians considering early surgical involvement.
Book a Consultation →Or call Jo Mitchelson:
020 7952 2882
Appointments within 2–3 days. Same-day virtual consultations possible for urgent pleural infection cases. Surgery at London Bridge Hospital and The Lister Hospital Chelsea.
Jo Mitchelson, Private PA · 020 7952 2882 · pa@lungsurgeon.co.uk
St Thomas’ Hospital #1 UK · Guy’s Hospital #2 UK · London Bridge Hospital #10 UK · Newsweek World’s Best Hospitals 2026
Pleural effusions, pleural thickening, mesothelioma assessment — the non-infective pleural pathway
Specialist Second OpinionIndependent review for patients told surgery is not possible — within 2–3 days, same-day virtual for urgent cases
For Referring GPs & PhysiciansDirect surgical referral pathway for chest physicians and ICU teams managing failing pleural infection