https://orcid.org/0000-0001-9898-4172
QUESTION
A 47-year-old man underwent a right middle lobectomy for a lung abscess caused by methicillin-sensitive Staphylococcus aureus with a ruptured pseudoaneurysm. He initially received meropenem (1 g every 8 hours), followed by de-escalation to ampicillin-sulbactam (3 g every 6 hours) for a total of 4 weeks. Six months later, he experienced right-sided chest pain, followed by wound dehiscence, and was readmitted to our hospital. The patient had no other surgical history and was an former smoker with a 15-pack-year history. He also had a history of depression and alcoholism and consumed 1500 mL of beer daily.
Results of tests for immunodeficiency, including human immunodeficiency virus and hepatitis B and C, were negative. Physical examination revealed a body temperature of 36.8°C, a blood pressure of 122/81 mm Hg, a pulse rate of 82/min, a respiratory rate of 18/min, and percutaneous oxygen saturation of 99% on room air. Breathing and heart sounds were normal; however, wound dehiscence with pus was observed on the right lateral aspect of the patient’s chest (Figure 1A). Laboratory tests revealed a white blood cell count of 16 800/µL (83.8% neutrophils, 10.2% lymphocytes, 3.6% monocytes, and 2.0% eosinophils), a hemoglobin level of 10.3 g/dL, a platelet count of 842 000/µL, a C-reactive protein level of 17.6 mg/dL, and a procalcitonin level of 0.14 ng/mL. Chest computed tomography showed consolidation in the right upper and lower lobes, extrathoracic air leaking into the subcutaneous tissue and wound, and increased right-sided pleural thickening (Figure 1B).
A, Postsurgical wound from lung abscess, showing dehiscence with redness and pus 6 months after surgery. B, Computed tomographic scan findings demonstrating consolidation in the right upper and lower lobes, with extrathoracic air leaking into the subcutaneous tissue and wound, alongside exacerbated right-sided pleural thickening.
What is your diagnosis?
Diagnosis: Empyema necessitatis with cutaneous fistula caused by Aspergillus fumigatus.
On admission, the patient was initially treated with piperacillin-tazobactam. An open window thoracostomy and debridement were performed due to empyema with a lung fistula. We observed white pus covering the chest wall with a tendency to bleed (Figure 2A). Moreover, Gomori methenamine silver staining revealed extensive Y-shaped branching on the pleura (Figure 2B). Aspergillus sp. was isolated from pus in pleural space, and A. fumigatus was confirmed through β-tubulin partial sequencing [1]. Laboratory tests revealed elevated (1,3)-β-D-glucan levels at 11.7 pg/mL (cutoff value, <11.0 pg/mL) and Aspergillus antigen in serum at an index of 0.6 (cutoff, <0.5). Furthermore, the result of an Aspergillus precipitating antibody test was positive. Therefore, the diagnosed was empyema necessitatis with a cutaneous fistula caused by A. fumigatus.
A, Video-assisted thoracic surgery revealed pus covering the chest wall, prone to bleeding. The first postsurgical staple for the lung abscess is indicated by the arrow. An air leak was detected at the staple site, confirming the presence of a bronchopleural fistula. B, Thoracoscopic debridement and open thoracotomy findings demonstrating extensive Y-shaped branching fungal structures on the pleura, indicative of Aspergillus infection, as visualized using Gomori methenamine silver staining.
A delayed bronchopleural fistula was confirmed at the surgical staple site during the initial lung abscess surgery. This staple had loosened, which led to air leakage and identification of the fistula (arrow in Figure 2A). This fistula may have preceded the Aspergillus infection, or the infection may have caused tissue necrosis, leading to fistula formation. The patient's condition improved with voriconazole (800 mg initially, followed by 400 mg/d). Initially elevated Aspergillus antigen and (1,3)-β-D-glucan levels became negative after treatment, and the patient was discharged 21 days after surgery. The drug susceptibility testing for the clinical isolate of A. fumigatus revealed the minimum inhibitory concentrations of micafungin (≤0.015 μg/mL), caspofungin (0.25 μg/mL), amphotericin B (1 μg/mL), flucytosine (>64 μg/mL), fluconazole (>64 μg/mL), itraconazole (0.5 μg/mL), voriconazole (0.25 μg/mL), and miconazole (4 μg/mL).
The prolonged duration of therapy was necessary due to the extensive chest cavity infection and persistent lung fistula, which posed a high risk of recurrence. After 3 years, there was no recurrence, and voriconazole was discontinued (Figure 3). While the optimal treatment duration for Aspergillus empyema is not well defined, short-term antifungal treatment for chronic pulmonary aspergillosis worsens relapse-free survival rates [2]. Therefore, the chronicity and severity of the infection warranted extended therapy to ensure sustained clinical improvement in this case.
Posttreatment computed tomographic scan showing resolution of air leakage, reduction in pleural thickening, and improvement of the subcutaneous abscess after surgical intervention and a 3-year course of voriconazole.
This case highlights the importance of considering Aspergillus infection in patients with a history of lung disease or chest surgery. According to a Cochrane review, surgical treatment (video-assisted thoracic surgery) does not significantly reduce mortality rates compared with nonsurgical thoracostomy drainage therapy but does shorten the length of hospital stay, though this study is not specific to Aspergillus-induced empyema [3]. However, we believe that early surgical intervention combined with antifungal therapy can lead to favorable outcomes in Aspergillus-induced empyema.
Empyema is a heterogeneous disease with varying causes, comorbid conditions, and causative pathogens that depend on these factors and geographic location [4, 5]. Causes include infections secondary to pneumonia, aspiration, bronchopleural fistula, or postthoracotomy complications. The microbial causes involve various organisms, including gram-positive cocci (S. aureus and the most common pathogen, viridans streptococci), gram-negative rods (eg, Pseudomonas spp., Acinetobacter spp., and Enterobacteriaceae), anaerobes (eg, Bacteroides spp. and Fusobacterium spp.), and Mycobacterium species, especially in patients with tuberculosis [6].
In addition, fungi, mostly Candida spp. are recognized as pathogens causing empyema thoracis with a high mortality rate [7]. Aspergillus pleural infection is relatively uncommon; however, factors such as immunocompromised states (eg, neutropenia, hematologic cancers, and long-term corticosteroid use), chronic lung diseases (eg, chronic obstructive pulmonary disease and tuberculosis), and surgical interventions (eg, thoracic surgery) might increase susceptibility [7, 8]. Although comprehensive reports specifically on Aspergillus-induced empyema are lacking, these risk factors can be inferred from various studies on chronic pulmonary aspergillosis and general fungal empyema due to similar underlying mechanisms. Despite these risk factors, Aspergillus empyema necessitatis, wherein the infection extends from the pleural space into the subcutaneous tissue forming a cutaneous fistula, is rare in patients who are not immunocompromised [9].
In the current case, our patient had a history of smoking along with lung surgery and heavy alcohol consumption. Although direct evidence linking chronic alcohol consumption with S. aureus or Aspergillus-induced lung abscesses is limited, it is well established that chronic use of alcohol impairs immune function, which increases susceptibility to infections. Alcohol-induced oxidative stress weakens alveolar macrophages, impairing their ability to clear pathogens [10]. In this case, heavy alcohol consumption likely reduced lung immunity, facilitating the progression from a staphylococcal lung abscess to Aspergillus-induced empyema necessitatis and subsequent extrapulmonary spread. However, it is rare for such infections to penetrate the chest wall, especially in adults, and the definitive contributing factors remain unclear. The delayed presentation 6 months after surgery is notable and highlights the importance of vigilance and long-term follow-up after thoracic surgery. Effective management of Aspergillus-induced empyema necessitates prompt and adequate treatment, often requiring a combination of surgical debridement and targeted antifungal therapy.
Notes
Author contributions. T. A. and K. T. drafted the manuscript. K. T. and M. G. managed the clinical care, and K. T. obtained the patient’s consent for publication. Y. T. performed the surgical procedure. J. A. contributed to the manuscript review. All authors read and approved the final version of the manuscript.
Acknowledgments. The authors express their deep gratitude to Aya Komori, Takashi Tamura, PhD, and Koichi Makimura, MD, PhD, of Teikyo University Institute of Medical Mycology for their significant contributions to identifying the clinical isolate Aspergillus fumigatus and performing drug susceptibility testing.
Data availability. The data sets analyzed during this study are available from the corresponding authors on reasonable request.
References
Author notes
T. A. and K. T. contributed equally to this work.
Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
