Milky Tea-Colored Pleural Effusion: Empyema Complicated by Pneumothorax Due to Mixed Infection With Mycobacterium tuberculosis and Aspergillus fumigatus

Introduction

Empyema is the accumulation of pus within the pleural cavity, with gram-positive bacteria being the predominant causative pathogens. The incidence rate of tuberculous empyema is 8.8%, while that of fungal empyema is only 3%. Some communicate with the bronchi or chest wall, thereby forming empyema complicated by pneumothorax [1]. Empyema complicated by pneumothorax due to Mycobacterium tuberculosis combined with Aspergillus infection is extremely rare, and the diagnosis and management of this condition present significant challenges.

Case Report

The patient was a 76-year-old man who presented to the Department of Respiratory and Critical Care Medicine on August 1, 2025. His chief concern was fever with cough for 1 day. His temperature was 38.7°C at its highest, accompanied by chest tightness and shortness of breath after activity. The patient was admitted with a temperature of 36.6°C, a heart rate of 101 beats per minute, a respiratory rate of 21 breaths per minute, and a blood pressure of 91/63 mmHg. Five years ago, he was diagnosed with squamous cell lung carcinoma at an external hospital. Regular treatment with tislelizumab was administered, with the most recent treatment occurring approximately 10 days before the current admission. He had a history of hypertension and cerebral infarction. Due to recent episodes of hypotension, antihypertensive medication was discontinued. Regular oral administration of aspirin and atorvastatin was maintained for management of cerebral infarction. A chest CT scan (August 1, 2025) revealed a right hilar mass with obstructive inflammation, bilateral pulmonary emphysema, and a small amount of right pleural effusion (Figure 1). Laboratory test results were white blood cell count 8.05×109/L, C-reactive protein 218.29 mg/L, and COVID-19 nucleic acid test positive (ORF gene Ct value: 21.73; N gene Ct value: 21.63). In the hospital he received meropenem combined with teicoplanin for anti-infective therapy and saquinavir/ritonavir for antiviral treatment, but the, intermittent fever persisted, accompanied by coughing that produced white sputum. A follow-up chest CT scan (August 11, 2025) indicated progression of right-sided pneumonia compared to 1 August 2025, with increased right-sided pleural effusion (Figure 2). Right-sided thoracentesis with tube placement was performed, yielding a milky-tea-colored turbid fluid. Pleural fluid analysis revealed nucleated cell count 66 001×106/L, polymorphonuclear cell percentage 83.9%, adenosine deaminase (ADA) 44.9 U/L, lactate dehydrogenase (LDH) 7528 U/L, and total protein: 28.1 g/L. Cultures for bacteria, fungi, and Mycobacterium tuberculosis were negative. The patient declined to undergo bronchoscopy. tNGS analysis of submitted sputum detected Acinetobacter baumannii (2.15×103 copies/ml), Stenotrophomonas maltophilia (1.32×103 copies/ml), Klebsiella pneumoniae (2.99×103 copies/ml), Streptococcus pneumoniae (1.13×103 copies/ml), Aspergillus fumigatus (1.59×104 copies/ml), Aspergillus flavus (1.37×104 copies/ml), and SARS-CoV-2 (<100 copies/ml). Among these, Acinetobacter baumannii exhibited resistance to carbapenems, cephalosporins, penicillin, and cephamycin, while Klebsiella pneumoniae demonstrated resistance to cephalosporins, penicillin, and monobactams. Therefore, treatment was switched to cefoperazone/sulbactam combined with moxifloxacin and voriconazole for anti-infective therapy. On August 15, the drainage bag contained a significant volume of gas. A chest X-ray revealed a right-sided pneumothorax and subcutaneous air accumulation in the right pleural cavity. Consequently, subcutaneous needle decompression and continuous negative-pressure drainage were administered. On August 17, a chest CT scan revealed a right pneumothorax with incomplete expansion of the right lung, along with extensive air accumulation in the cervical region, chest wall, and mediastinum (Figure 3). Following a thoracic surgery consultation recommending conversion to a larger-bore tube for continuous negative-pressure drainage, the fever subsided, and the subcutaneous emphysema diminished. The patient declined further treatment and was discharged. Following discharge, thoracic fluid tNGS detected Mycobacterium tuberculosis complex (1.06×103 copies/ml) and Aspergillus fumigatus (9.29×102 copies/ml). He died 5 days after discharge.

Discussion

Empyema is a serious and potentially life-threatening condition characterized by the accumulation of infected fluid within the pleural cavity. It can arise from various underlying conditions, such as pneumonia, lung abscess, chest trauma, esophageal rupture, or postoperative complications [2]. Microbiological culture of pleural fluid is crucial for identifying the causative pathogen and determining the treatment regimen; however, up to 40% of patients with pleural infection have negative culture results [3]. A recent systematic review involving 10 241 patients revealed that the most common pathogen was Staphylococcus aureus, followed by Streptococcus species [1]. The use of broad-spectrum antibiotics, transplant surgery, and anti-tumor treatments had compromised our patients’ immune system, leading to a gradual worsening of tuberculous and fungal empyema [4]. Our patient had pulmonary malignancy following immunotherapy, complicated by concurrent COVID-19 and compromised immunity, increasing the risk of tuberculosis and fungal infections. Empyema caused by different pathogens exhibits distinct clinical presentations and varying prognoses. Studies indicate that patients with fungal empyema have worse overall survival than those with bacterial and tuberculous empyema [2,5].

Tuberculous empyema is uncommon, typically arising from rupture of subpleural lesions, lymphatic spread from primary pulmonary disease, or hematogenous dissemination. With the influx of neutrophils and subsequent development of purulent effusion, extensive pleural thickening and calcification can occur [6]. The diagnosis of tuberculous empyema primarily relies on acid-fast staining of pleural fluid smears, culture, and nucleic acid amplification testing. Acid-fast staining and culture of tuberculous pleural fluid have low sensitivity, at 3% and 17%, respectively [7]. Nucleic acid amplification testing is costly, with moderate sensitivity (28–81%) but high specificity (90–100%) [8]. Tuberculous empyema, containing substantial quantities of mycobacteria, has a higher bacteriological detection rate than tuberculous pleural effusion. No specific treatment guidelines currently exist for tuberculous empyema, and high-quality data linking interventions to prognosis remain lacking. Tuberculous empyema presents greater challenges than non-tuberculous empyema, potentially leading to frequent bronchopleural fistulae, anorexia, and poor nutritional status due to the adverse effects of anti-tuberculosis drugs. The mortality rate for tuberculous empyema is comparable to that of non-tuberculous empyema [9].

Aspergillosis pulmonis is an invasive form of aspergillosis, with or without pulmonary involvement. It typically occurs in the context of chronic pulmonary disease, including pulmonary infection, prior pulmonary surgery, or in immunocompromised patients [10]. Research indicates that respiratory viral infections such as influenza A, influenza B, COVID-19, and respiratory syncytial virus are also associated with invasive aspergillosis. These respiratory viral infections damage the airway epithelium, facilitating invasion through colonization by Aspergillus species [11]. Even in this patient cohort, aspergillotic empyema remains uncommon. The prognosis for empyema caused by Aspergillus is markedly worse than that for bacterial or tuberculous empyema, potentially due to the compromised immune function observed in such patients [4]. Regrettably, our patient died 5 days after discharge.

Conclusions

This case report presents a relatively uncommon clinical scenario of empyema complicated by pneumothorax, arising from a mixed infection with Mycobacterium tuberculosis and Aspergillus fumigatus. The patient exhibited atypical symptoms, posing diagnostic challenges and resulting in a poor prognosis. Clinicians should heighten vigilance for tuberculous and fungal empyema, striving for early diagnosis based on medical history, imaging studies, and laboratory findings. Prompt treatment is essential to improve outcomes.