Efficacy of Pleural Lavage With Antifungals in the Management of Fungal Empyema Thoracis: A Prospective Cohort Study

Empyema thoracis remains an important cause of morbidity and mortality worldwide. While the vast majority of pleural space infections are bacterial, fungal empyema is a distinct and increasingly recognized clinical entity that carries substantially higher mortality and a more complex therapeutic course than typical bacterial empyema. Fungal empyema most commonly occurs in patients with significant comorbidities or healthcare exposures (e.g., recent thoracic surgery, prolonged antibiotics, gastrointestinal perforation, or immunosuppression) and is frequently due to Candida or Aspergillus species. Reported crude mortality rates range between 40-70%, which are considerably higher than for bacterial empyema [1, 2].

Standard management of fungal empyema combines prompt pleural drainage with systemic antifungal therapy and, when indicated, surgical intervention (decortication or debridement) in the presence of loculation, trapped lung, or persistent sepsis [3]. However, surgical treatment is often high-risk because many patients are elderly, immunocompromised, or poor surgical candidates. Even when surgery is performed, fungal empyema is associated with increased intra- and postoperative complications and prolonged hospitalization compared with bacterial empyema [4]. These challenges underscore the need for adjunctive or alternative strategies that can enhance pleural sterilization, control sepsis, and either avert or optimize the timing of definitive surgery.

Voriconazole, a second-generation triazole antifungal, demonstrates excellent activity against Aspergillus and Candida species and has favorable pleural space penetration when administered systemically [5]. Local administration of antifungal agents directly into the pleural cavity has been described in isolated reports, with encouraging outcomes using agents such as amphotericin B and voriconazole [6-8]. Pleural lavage (intrapleural irrigation) allows high local drug concentrations at the infected pleural surface, improving fungal clearance while minimizing systemic toxicity. Case reports have demonstrated successful outcomes using intrapleural antifungal lavage as adjunct therapy or as a palliative measure in patients who could not undergo surgical decortication [7-9].

Despite these encouraging findings, there remains a paucity of prospective evidence evaluating the efficacy and safety of pleural lavage with voriconazole in fungal empyema. To address this gap, we designed a prospective cohort study to assess the outcomes of pleural lavage with voriconazole in patients with confirmed fungal empyema. The primary objectives are to evaluate (1) the effectiveness of intrapleural voriconazole lavage as an adjunct prior to surgical decortication and (2) its potential as a palliative option for patients unfit for surgery. Secondary outcomes include pleural sterilization rates, clinical improvement, conversion to surgery, length of hospital stay, and treatment-related adverse effects. This study aims to provide clinical evidence supporting the role of local antifungal therapy in optimizing the management of fungal empyema, particularly in high-risk and resource-limited settings.