Local management of pleural infection: a narrative review

Abstract

The management of pleural infection remains highly challenging. Rational selection of appropriate local treatment strategies is crucial for successful management. Local treatment decisions are primarily guided by clinical features, pleural fluid biochemical parameters, and imaging characteristics, with pleural fluid pH below 7.2 directly indicating the need for pleural drainage. When multiloculated pleural effusion develops, simple drainage frequently fails, necessitating advanced interventions including intrapleural fibrinolytic therapy (IPFT), medical thoracoscopy (MT), or surgical intervention. Current evidence supports the combination of recombinant tissue plasminogen activator (t-PA) and deoxyribonuclease (DNase) as the most validated fibrinolytic regimen. MT combined with IPFT offers a promising minimally invasive approach for selected patients. Video-assisted thoracoscopic surgery (VATS) remains an important treatment option, though recent evidence from the MIST-3 feasibility trial suggests that early IPFT may achieve better quality of life outcomes. Traditional open decortication remains a backup treatment option for patients with complex pleural infection. This review aims to summarize recent advances in local treatment of pleural infection and provide clinical reference for physicians in local treatment decision-making for pleural infection.

Introduction

Pleural infection, defined as an infectious disease caused by pathogenic bacteria invading and proliferating within the pleural cavity, primarily includes parapneumonic effusion (PPE) and empyema, representing a common cause of pleural effusion [1, 2]. Based on pleural fluid characteristics, PPE is further categorized into uncomplicated PPE (UPPE) and complicated PPE (CPPE) [3–5]. Although UPPE generally resolves with appropriate antibiotic treatment, approximately 10–20% of cases advance to CPPE or empyema. In such cases, systemic antibiotic therapy alone proves insufficient, necessitating active local interventions [4, 6–8]. A variety of local treatment modalities are available for the management of pleural infection (Fig. 1), including thoracentesis, chest tube drainage, intrapleural drug instillation, surgical intervention, and medical thoracoscopy [9–13]. Deciding on local treatment for pleural infection is a key challenge in clinical practice, making it crucial to understand their pathophysiology and treatment strategies.

Fig. 1.

Comprehensive treatment algorithm for local management of pleural infection. CPPE complicated parapneumonic pleural effusion; VATS video-assisted thoracoscopic surgery, t-PA tissue plasminogen activator, DNase deoxyribonuclease

Definitions and classification

The term “parapneumonic effusion” historically reflects a limited understanding of pleural infection, traditionally perceived as secondary to lung parenchyma infection. However, recent studies have indicated that approximately 30% of patients exhibit no definitive signs of pneumonia, leading to the classification of this subgroup as having primary pleural infection [14–17]. This finding has led clinicians to reconsider the definition of pleural infection, with contemporary medical practice favoring the use of the more precise term “pleural infection” to encompass all pathological conditions involving bacterial invasion of the pleural space [4, 5].

The distinction between UPPE and CPPE is primarily based on the biochemical and microbiological characteristics of the pleural fluid [4]. The pleural fluid in UPPE is typically clear, with pH > 7.20, glucose > 3.3 mmol/L, lactate dehydrogenase < 900 IU/L, and negative microbial culture. In contrast, CPPE is characterized by turbid pleural fluid, pH < 7.20, glucose < 3.3 mmol/L, lactate dehydrogenase > 900 IU/L, and positive microbial culture. Empyema typically shows purulent pleural fluid, pus cells under a microscope, and a positive microbial culture.

Loculations and septations arise due to fibrin deposition and inflammatory responses within the pleural space, resulting in compartmentalized fluid collections that substantially complicate drainage procedures [18]. The presence of loculations and septations can be evaluated using various imaging modalities, with ultrasound being a widely accessible and user-friendly diagnostic tool [6]. All loculations and septations discussed in this review refer to ultrasonographic findings on chest ultrasound examination. The presence of multiple loculated and septated collections significantly impacts treatment decisions, frequently necessitating more aggressive therapeutic interventions [19, 20].

Pathophysiology

The pathophysiological progression of pleural infection is a dynamic and continuous sequence that can be delineated into three distinct yet overlapping stages [10, 18].

During the initial exudative phase, a cascade of pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and vascular endothelial growth factor (VEGF), is released into the pleural cavity. Concurrently, neutrophils and monocytes infiltrate the pleural space. This sequence of events results in increased permeability of the visceral pleural capillaries and subsequent exudate formation. At this stage, the pleural fluid typically remains relatively clear, maintaining normal pH and glucose levels, with bacterial cultures generally yielding negative results. Prompt administration of effective antibiotic therapy can mitigate the inflammatory response, facilitating the spontaneous absorption of the pleural fluid.

In the fibrinopurulent stage, pleural permeability rises, allowing bacteria to multiply rapidly, increasing the bacterial load. This, along with neutrophil activity, lowers the pleural fluid pH due to lactic acid and carbon dioxide production. Glucose levels drop sharply due to bacterial and neutrophil glycolysis, while cell destruction raises lactate dehydrogenase levels. Concurrently, inflammatory mediators activate the extrinsic coagulation pathway, increasing tissue factor expression and thrombin production, which converts fibrinogen to fibrin, depositing it on the pleural surface. Stimulated by pro-inflammatory mediators, pleural mesothelial cells (PMCs) and myofibroblasts upregulate plasminogen activator inhibitor-1 (PAI-1), inhibiting fibrinolysis and worsening fibrin deposition [19]. This imbalance is crucial for forming loculations or septations (Fig. 2B–C) [18]. By the end of this stage, pleural fluid may become purulent due to cell degradation and bacterial debris.

Fig. 2.

Fibrin deposition, septations and loculations formation in pleural infection. A Schematic illustration of fibrin deposition pathophysiology in infected pleural space. B Ultrasound imaging demonstrating characteristic features of pleural infection with septations (arrows), pleural effusion (triangle), and loculations (asterisk). C Thoracoscopic view showing fibrinous septations (arrows) and pleural effusion (triangle). PAI-1 plasminogen activator inhibitor-1, uPA urokinase plasminogen activator, tPA tissue plasminogen activator, PGN plasminogen, PLN plasmin, TGF-β transforming growth factor-β, MesoMT mesenchymal-to-mesenchymal transition, α-SMA α-smooth muscle actin, Col-1 collagen-1, PMCs pleural mesothelial cells

In the organizing stage, fibroblasts produce large amounts of collagen and extracellular matrix. PMCs undergo a mesenchymal-to-mesenchymal transition (MesoMT), which is characterized by the upregulation of α-smooth muscle actin (α-SMA), collagen-1 (Col-1), and fibronectin, leading to their transformation into matrix-producing myofibroblasts (Fig. 2A). Consequently, the formation of loculations and septations due to fibrin deposition significantly hinders lung expansion and impairs chest drainage. Even with infection control, lung function may not fully recover, often requiring intrapleural fibrinolytic therapy, thoracoscopy, or surgical decortication [9, 11, 14, 21].

Local treatment strategies

Repeated therapeutic thoracentesis

Repeated therapeutic thoracentesis (RTT) has long been used in the local treatment of pleural infection and can avoid the need for chest tube drainage [5, 22]. In a series of five studies [23–27], a total of 260 patients with CPPE or empyema were included. All patients received RTT, and 76% of cases achieved favorable outcomes after an average of three interventions. The largest study included 79 patients [25], of whom 66% were empyema patients and 33% were CPPE patients. The study found that the success rate of RTT was 81%, with a median of three interventions. A first thoracentesis drainage volume of ≥ 450 mL and positive Gram stain of pleural fluid were independent risk factors for RTT treatment failure. The ACTion trial [27], the only randomized controlled trial (RCT) comparing RTT and chest tube drainage, involved 10 patients with non-loculated CPPE or empyema. The results demonstrated that this randomization was feasible and that RTT could significantly shorten hospital stay for patients with pleural infection (5.4 vs. 13.0 days), laying the foundation for subsequent large-scale trials. Consequently, it is advisable to employ this technique exclusively for small to moderate pleural infection that present with a negative Gram stain and are non-loculated.

Chest tube drainage

The continuous drainage of a chest tube effectively eliminates infected pleural effusion, thereby reducing bacterial presence and facilitating the administration of intrapleural medications. This technique is a widely utilized local treatment for CPPE and empyema.

The decision for chest tube drainage is guided by clinical evidence of infection and pleural fluid biochemistry. The presence of frank pus or positive bacterial culture universally mandates prompt drainage [4–6]. According to the British Thoracic Society (BTS) 2023 guideline, drainage is strongly recommended when pleural fluid pH is ≤ 7.2 [4]. For patients with a pH between 7.2 and 7.4, drainage should be considered if lactate dehydrogenase (LDH) is > 900 IU/L. When pH measurement is unavailable, BTS suggests pleural glucose < 3.3 mmol/L as a surrogate marker, whereas the ERS/ESTS and AATS guidelines utilize a stricter threshold of glucose < 2.2 mmol/L (40 mg/dL) combined with LDH > 1000 IU/L [4, 6, 8, 9]. Septations and loculations on ultrasound remain an important structural indication for drainage across all guidelines.

The optimal size of drainage tubes has been a key clinical focus. Traditionally, large-bore catheters (>  24 F) are thought to better drain high-viscosity effusions in pleural infection. Some studies link inadequate tube size to increased surgical intervention and drainage failure [3, 28, 29]. However, data from malignant pleural effusion treatments suggest that small-bore drainage tubes are associated with improved patient tolerance and reduced pain [30]. Rahman NM et al. [31] retrospectively analyzed the data of 405 patients in the MIST-1 trial and found no significant impact of chest tube size on clinical outcomes in pleural infection; specifically, there were no statistically significant differences in 3-month mortality, surgical intervention requirements, hospital stay duration, 3-month pulmonary function, or pleural shadow changes between patients utilizing small-bore versus large-bore drainage tubes. Consequently, the 2023 BTS guidelines recommend the use of small-bore drainage tubes (≤  14 F) for initial drainage in patients with pleural infection [4]. Small-bore drainage tubes are prone to blockage, and intermittent flushing with normal saline can prevent this problem [6].

Intrapleural drug instillation

Intrapleural drug instillation involves injecting substances into the pleural cavity to combat infection, promote effusion drainage, or remove necrotic tissue [4, 6, 8, 9]. This process works through mechanical irrigation, dilution, pus clearance, bactericidal effects, and fibrin breakdown (Table 1). Commonly used agents include normal saline [32, 33], electrolyte solutions [34], sodium bicarbonate [35, 36], and fibrinolytics [14, 21, 37].

Table 1.

Comparison of intrapleural agents for pleural infection

Category	Agent	Mechanism	Key evidence	Dosing regimen	Strengths	Limitations
Non-fibrinolytic	Normal saline	Mechanical irrigation; clearance of pus and necrotic tissue	RCT (n = 35): effusion reduction 32.3% vs 15.3%, surgical rate 11.1% vs 47.1% compared with standard care [32]	250 mL TID × 3 days	Simple; safe; low cost; guideline-recommended alternative when IPFT is contraindicated	Limited RCT data; passive mechanism
	Electrolyzed saline	Broad-spectrum antibacterial activity including drug-resistant bacteria	Retrospective (n = 20): 90% success rate with mini-thoracoscopy [34]	Combined with thoracoscopy	CDC-recognized disinfectant; effective against resistant pathogens	Limited clinical adoption; not standardized
	Sodium bicarbonate	Inhibits fibrin formation by binding calcium; disrupts bacterial membranes	Cohort: similar efficacy to urokinase [35]; ongoing prospective trial (n = 25) [36]	Not standardized	Low cost; available in resource-limited settings	Limited evidence; efficacy unconfirmed
Fibrinolytic	Streptokinase	Activates plasminogen to plasmin; degrades fibrin	MIST-1 RCT (n = 454): no benefit over placebo in mortality, surgery rate, or hospital stay [21]	250,000 IU daily	Low cost	No proven efficacy; not recommended
	Urokinase	Activates plasminogen to plasmin; degrades fibrin	Comparative: similar efficacy to t-PA/DNase; hemothorax 0% vs 17% [48]	250,000 IU BID × 5 days	Lower bleeding risk; cost-effective; readily available	Optimal dosing uncertain; limited high-quality evidence
	t-PA + DNase	t-PA activates plasminogen; DNase degrades extracellular DNA and reduces pus viscosity	MIST-2 RCT (n = 210): reduced surgical referral, shortened hospital stay [14]; meta-analysis: 12 RCTs (n = 993) [45]	Standard: 10 mg + 5 mg BID × 3 days; reduced: 5 mg or 2.5 mg t-PA	Most robust evidence; guideline-recommended	Bleeding risk 4.2%; higher cost

BID twice daily, CDC Centers for Disease Control and Prevention, IPFT intrapleural fibrinolytic therapy, RCT randomized controlled trial, TID three times daily, t-PA tissue plasminogen activator, DNase deoxyribonuclease

Normal saline

Intrapleural normal saline instillation is a simple, safe, and cost-effective adjunctive treatment that mechanically irrigates and clears intrapleural pus and necrotic tissue. This process improves the local microenvironment, reduces bacterial load, prevents fibrin deposition, and promotes healing of the empyema cavity, particularly in the fibrinopurulent stage.

Hooper et al. [32] randomized 35 patients with CPPE or empyema into a standard treatment group and a normal saline instillation group. The latter received 250 mL of saline three times daily for three days, while the former had 30 mL saline chest tube flushing with the same frequency and duration. After three days, chest CT revealed that pleural effusion volume reduction was significantly greater in the normal saline instillation group (32.3% vs. 15.3%), with a lower surgical conversion rate (11.1% vs. 47.1%). Porcel et al. [33] conducted a retrospective analysis involving 62 patients with CPPE or empyema, in which they compared the efficacy of small-bore catheter instillation of normal saline (n = 23) versus urokinase (n = 39). The group receiving saline showed reduced fibrinolytic drug use (15% vs. 44%, p = 0.019), shorter chest tube drainage (2 vs. 5 days, p < 0.01), and shorter hospital stays (6 vs. 8 days, p = 0.011).

While these findings are promising, a large randomized controlled trial is needed to confirm the effectiveness of saline instillation. Given its safety profile, low cost, and wide availability, current guidelines position saline irrigation as an alternative option when intrapleural fibrinolytic therapy is contraindicated (e.g., patients on therapeutic anticoagulation that cannot be discontinued) or when surgery is not feasible [4, 6].

Electrolyzed saline

Electrolyzed saline (ES) possesses broad-spectrum antibacterial activity and is effective against various pathogens, including drug-resistant bacteria. It has been listed as a novel irrigating and bactericidal agent in the guidelines of the US Centers for Disease Control and Prevention [38]. Nakamoto et al. [34] retrospectively studied 20 patients with pleural infection and showed that the success rate of mini-thoracoscopic surgery combined with ES infusion was as high as 90%, and the blood inflammatory markers also decreased significantly after surgery. The application of ES for local treatment of pleural infection is relatively new, and its use has not yet been widely adopted in clinical practice.

Sodium bicarbonate

Sodium bicarbonate can inhibit fibrin formation by binding calcium ions and can disrupt bacterial membranes, reducing their viability [35, 39]. Due to its easy availability, some resource-limited centers use it as an alternative fibrinolytic agent [35, 36]. However, clinical evidence remains limited. Zayed et al. [35] found no significant difference in success rates between sodium bicarbonate and urokinase for intrapleural therapy, indicating sodium bicarbonate as a potential alternative fibrinolytic agent. To further investigate, Suzukawa et al. [36] are conducting a prospective single-arm study planning to include 25 patients to evaluate the efficacy of intrapleural sodium bicarbonate instillation combined with continuous chest drainage for treating pleural infection. It is hoped that data from this ongoing study will provide evidence to support this treatment approach in the near future.

Fibrinolytic agents

Common fibrinolytic agents in clinical use are streptokinase, urokinase, tissue plasminogen activator (t-PA), and deoxyribonuclease (DNase). In pleural infection, increased fibrin leads to multiple loculations or septations (Fig. 2B–C). Intrapleural fibrinolytic therapy (IPFT) aids pleural effusion drainage by breaking down these fibrinous septations and loculations.

The MIST-1 study found no significant differences in three-month mortality, surgery rates, or hospital stay between streptokinase and placebo groups, leading to its limited clinical use [21]. In contrast, the MIST-2 study [14] demonstrated that the combination therapy of t-PA and DNase (10 mg t-PA, 5 mg DNase, twice daily for 3 days) significantly improved the 7-day pleural opacity change rate, reduced the 3-month surgical referral rate, and shortened hospital stay compared with placebo, while t-PA monotherapy and DNase monotherapy had no effect on the 7-day pleural opacity change rate. Subsequently, multiple studies have confirmed that t-PA/DNase combination therapy can effectively avoid surgical intervention and improve pleural effusion drainage and inflammatory markers [40–44]. Altman et al. [45] analyzed 12 RCTs with 993 pleural infection patients, finding no mortality difference between IPFT and placebo, but lower surgery and treatment failure rates.

Bleeding risk in IPFT is a significant clinical issue. Akulian et al. analyzed 1825 patients, finding a 4.2% bleeding risk, aligning with MIST-2 study results [14, 46]. Approximately 70% of bleeding patients can be controlled through blood transfusion. Factors such as high RAPID score, systemic anticoagulation therapy, renal failure, and low platelet count are independently associated with high bleeding complication risk. For those who cannot stop anticoagulation therapy, reducing the t-PA dose by half can lower bleeding risk [47]. To minimize bleeding complications while maintaining efficacy, several dose-reduction strategies have been investigated. The ADAPT-1 study found that a lower initial dose of 5 mg t-PA with 5 mg DNase was as effective as the standard 10 mg t-PA with 5 mg DNase [46]. The ADAPT-2 study showed that an even lower dose of 2.5 mg t-PA with 5 mg DNase achieved an 88.4% success rate [47]. These reduced-dose regimens can lower treatment costs and potentially decrease adverse reactions.

However, concerns about bleeding risk with t-PA/DNase combination therapy persist. Bédat et al. found that high-concentration urokinase therapy (250,000 IU, twice daily for 5 days) and t-PA/DNase combination therapy (10 mg t-PA combined with 5 mg DNase, twice daily for 3 days) had similar success rates in treating pleural infection, but the latter had a higher incidence of hemothorax (17% vs. 0%) [48]. However, the evidence for the efficacy of high-concentration urokinase therapy is currently limited.

Consequently, clinical decision-making should be individualized based on bleeding risk assessment. When initial pleural drainage fails to achieve clinical improvement, particularly with residual loculated effusion or persistent sepsis within 5–7 days, t-PA and DNase combination therapy should be considered [4, 8]. For patients at high bleeding risk, reducing the t-PA and DNase dose can be a choice. Compared to t-PA and DNase combination therapy, urokinase is more cost-effective, readily available, and associated with lower bleeding risk [37]. This makes urokinase an attractive alternative for resource-limited settings or patients with contraindications to t-PA/DNase therapy, though further high-quality evidence is needed to establish optimal dosing regimens and patient selection criteria.

Medical thoracoscopy

Medical thoracoscopy (MT) is a pivotal intervention in the management of pleural infection, offering capabilities beyond simple drainage [6, 49]. Through a single-port access, MT allows for direct visualization of the pleural cavity, enabling the effective disruption of fibrinous septations and debridement of necrotic tissue using endoscopic forceps. Unlike VATS, which mandates general anesthesia and single-lung ventilation, MT can be performed under local anesthesia with sedation in an endoscopy suite (Table 2). This distinct advantage makes it a viable option for elderly patients or those with significant comorbidities who are poor candidates for general anesthesia.

Table 2.

Comparison of procedural interventions for pleural infection

Category	Medical thoracoscopy	Video-assisted thoracoscopic surgery	Open decortication
Operator	Pulmonologist/interventional pulmonologist	Thoracic surgeon	Thoracic surgeon
Anesthesia	Local anesthesia with conscious sedation	General anesthesia with single-lung ventilation	General anesthesia with single-lung ventilation
Access	Single-port	Multiple ports	Thoracotomy
Success rate	~ 85% (meta-analysis); 58–100% depending on stage	Variable; conversion rate increases with treatment delay (EACTS: 28% at ≤ 10 days to 81% at 30–40 days)	Definitive; high technical success as rescue procedure
Strengths	Avoids general anesthesia; direct visualization; mechanical adhesiolysis; can be combined with IPFT; lower cost than surgery; shorter post-procedural LOS	Minimally invasive; effective debridement; shorter LOS than open surgery; preferred surgical approach	Most thorough debridement; reliable for complex/late-stage cases
Limitations	Limited decortication capability; not suitable for Stage III; less randomized evidence	Requires general anesthesia; risk of conversion if delayed	Most invasive; longest recovery
Guideline position	Alternative to IPFT; effective for multiloculated effusions in non-surgical candidates	Preferred first-line surgical approach for operable candidates	Reserved for failed VATS or complex/late-stage cases

EACTS European Association for Cardio-Thoracic Surgery, IPFT intrapleural fibrinolytic therapy, LOS length of stay, VATS video-assisted thoracoscopic surgery

Growing clinical evidence underscores the efficacy of MT. Kheir et al. demonstrated in an RCT that MT significantly shortened postoperative hospital stays compared to IPFT (2 versus 4 days, p = 0.026) [50]. Consistently, a meta-analysis by Mondoni et al. [11], encompassing eight studies, reported an 85% success rate for MT in the treatment of pleural infection, identifying negative pleural fluid cultures and concomitant use of IPFT as key predictors of success.

Most recently, the 2025 IMPLE observational study revealed that patients undergoing initial thoracentesis or chest tube drainage faced a 6- to eightfold higher risk of subsequent surgical referral compared to those treated with first-line MT (OR 6.0 and 7.8, respectively; p < 0.01) [51]. These findings reinforce current international consensus, validating the ERS/ESTS and BTS 2023 guidelines, which increasingly advocate for MT as an alternative to IPFT, particularly for multiloculated effusions or non-surgical candidates [4, 6] (Table 3).

Table 3.

Comparison of major international recommendations for pleural infection management

Category	BTS 2010	BTS 2023	EACTS 2015	AATS 2017	ERS/ESTS 2023
Drainage indications	pH < 7.2; purulent fluid; positive Gram stain/culture; loculated effusion	pH ≤ 7.2; pH 7.2–7.4 if LDH > 900 IU/L; Glucose < 3.3 mmol/L (if pH unavailable)	Stage I empyema (prompt drainage required)	pH < 7.2; Glucose < 2.2 mmol/L; LDH > 1000 IU/L; purulence	pH < 7.2 (or Glucose < 2.2 mmol/L + LDH > 1000 IU/L); Pus; positive microbiology
Catheter size	Small-bore (10–14F) adequate for most cases	Small-bore (≤  14 F) recommended as initial intervention	Not explicitly specified	Small-bore recommended for non-surgical candidates	Small-bore (12–14F) recommended; <  12 F usually avoided
IPFT indication	Not recommended for routine use	Consider if residual collection after initial drainage	For Stage II patients unsuitable for surgery	Not for routine use	Initiate within 48 h if standard care fails
Fibrinolytic regimen	Not specified	tPA 10 mg + DNase 5 mg bid × 3 days	tPA + DNase	Not specified	tPA 10 mg + DNase 5 mg bid × 3 days
Surgical referral timing	Consider if no improvement after 5–7 days	Failed medical therapy (precise criteria unclear)	Early referral	Not specified	Within 10 days of presentation
Surgical indication	Persistent sepsis with residual collection; effusion > 40% hemithorax	Individualized based on patient and empyema stage	Stage II/III fit for surgery	Chronic empyema in operable patients	Persistent sepsis, residual collection, or late-stage disease
Preferred surgical approach	Not specified	VATS preferred	VATS	VATS (Early intervention)	VATS
Medical thoracoscopy	Not addressed	Recognized for septated effusions	Not addressed	Limited discussion	Acknowledged as alternative to IPFT

“Not specified” indicates the topic was not explicitly addressed

AATS American Association for Thoracic Surgery, BTS British Thoracic Society, bid bis in die (twice daily), DNase deoxyribonuclease, EACTS European Association for Cardio-Thoracic Surgery, ERS European Respiratory Society, ESTS European Society of Thoracic Surgeons, F French (catheter gauge), IPFT intrapleural fibrinolytic therapy, LDH lactate dehydrogenase, tPA tissue plasminogen activator, VATS video-assisted thoracoscopic surgery

Despite these advances, protocol optimization remains necessary. Currently, only one prospective multicenter RCT has published its protocol for the combination of MT and IPFT, aiming to recruit 128 patients with CPPE or empyema, with the objective of evaluating the superiority of the combined MT and IPFT approach in comparison to IPFT alone [37]. Further rigorous studies are urgently needed to standardize these protocols and solidify the positioning of MT in future guidelines.

Surgical intervention

Surgical intervention, including video-assisted thoracoscopic surgery (VATS) and open decortication, effectively evacuates pleural effusion and re-expands the lung by tissue debridement or pleural decortication. These procedures are crucial for treating pleural infection and are suitable for patients with stage II and III empyema [9, 34].

VATS

While the American Association for Thoracic Surgery recommends VATS as the primary surgical treatment for acute stage II empyema, there remains insufficient evidence on the ideal candidates and timing for surgery [9].

Current guidelines reflect a divergence in strategy (Table 2). Some, such as the BTS 2010 guideline and the ERS/ESTS 2023 statement, propose specific temporal windows, recommending surgery if sepsis persists after 5–7 days or definitive treatment within 10 days of presentation, respectively [6, 8]. In contrast, the AATS 2017 and BTS 2023 guidelines eschew rigid timeframes in favor of individualized decision-making based on clinical response. However, the risks of delayed intervention are substantial. The EACTS 2015 consensus provides compelling evidence that delaying surgery beyond 30–40 days dramatically increases the rate of conversion from VATS to thoracotomy (81% vs. 28% when performed within 10 days), underscoring the critical window for effective minimally invasive intervention.

To date, the MIST-3 trial remains the only multicenter RCT comparing early VATS versus early IPFT for pleural infection [52]. Designed primarily as a feasibility pilot (n = 60), its main objective was to assess the practicality of randomization rather than to definitively establish treatment efficacy. The study successfully met its recruitment endpoints, demonstrating that randomizing patients between surgical and medical arms is acceptable to both participants and clinicians. Although underpowered for efficacy, the results offered notable exploratory signals: while median hospital stays were numerically similar between groups (7 days vs. 10 days for standard care; p = 0.70), quality of life outcomes significantly favored IPFT (EQ-5D index improvement: 0.83 vs. 0.59; p = 0.023). Ultimately, MIST-3 validates the viability of conducting large-scale surgical trials in this domain, laying the necessary groundwork for future definitive studies required to standardize evidence-based treatment protocols.

Open decortication

Open decortication has long been regarded as the gold standard for the surgical management of pleural infection [12]. However, evolving evidence challenges this dominance. A meta-analysis by Sokouti et al. [53], encompassing 13 studies with 2219 patients, demonstrated that VATS confers significant benefits in terms of shorter hospital stays and operative times, while maintaining comparable outcomes regarding mortality, prolonged air leakage, wound infection, and recurrence rates.

Despite these comparable outcomes, the choice of approach requires nuance. VATS carries an inherent risk of intraoperative conversion to thoracotomy, whereas open decortication serves as the definitive method with high primary technical success. The EACTS 2015 consensus highlights that conversion rates can exceed 40% in some series, noting that effective VATS decortication for stage III empyema demands a steep learning curve dependent on surgeon expertise [54]. Consequently, a strategic approach to pleural infection would prioritize VATS as the first-line surgical intervention to leverage its minimally invasive benefits, while reserving open decortication as a critical salvage option for cases where VATS fails or for patients presenting with complex stage III empyema.

Conclusions

The local management of pleural infection has evolved from simple thoracentesis to evidence-based multimodal therapeutic strategies. A pleural fluid pH of less than 7.2 serves as a critical threshold for drainage decisions, with small-bore tubes (≤  14 F) demonstrating efficacy comparable to large-bore drainage. When loculations or septations develop, mechanical or pharmacological interventions are required to address loculations or septations. The combination of recombinant tissue plasminogen activator and deoxyribonuclease is the most well-supported fibrinolytic regimen according to current evidence. The combination of medical thoracoscopy with intrapleural fibrinolytic therapy presents a promising alternative treatment modality. Video-assisted thoracoscopic surgery remains an important therapeutic modality, though recent MIST-3 feasibility study data suggest that early intrapleural fibrinolytic therapy may achieve comparable outcomes. Open decortication remains a vital salvage procedure for cases that are refractory to other treatments.

Author contributions

All authors contributed to the conception of the work and revised the manuscript. K.W.: Conceptualization, Writing—review and supervision. F.L. and W.L.: Conceptualization and supervision. L. Z., J.L. and M. Y.: Writing—original draft preparation, review, and editing.

Funding

This work was supported by Non-communicable Chronic Diseases-National Science and Technology Major Project (Grant Nos. 2024ZD0522604/2024ZD0522600 and 2023ZD0506102/2023ZD0506100).

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethics approval and consent to participate

Ethical approval was not required for this study.

Competing interests

The authors declare no competing interests.