Surreal illustration of lungs with C. difficile bacteria forming lung shapes, symbolizing atypical infection.

Beyond the Gut: When C. difficile Strikes the Lungs

Beau Callahan in Health & Wellness December 2025 • 4 min read.

"A rare case report sheds light on Clostridium difficile causing empyema, highlighting the importance of considering extraintestinal infections."

Clostridium difficile (C. difficile) is a bacterium most often associated with infections of the gut, causing symptoms like diarrhea and colitis. Typically, C. difficile infections occur after antibiotic use disrupts the natural balance of bacteria in the intestines. However, in very rare instances, C. difficile can manifest outside the gastrointestinal tract, leading to severe conditions like empyema—an accumulation of pus in the space between the lung and the surrounding membrane.

A recent case report published in Case Reports in Gastroenterology details an unusual occurrence of C. difficile causing empyema in a 42-year-old Hispanic male. This case is particularly noteworthy because the patient had no prior history of C. difficile infection, making the diagnosis challenging and emphasizing the importance of considering extraintestinal manifestations of common pathogens.

This article explores the details of this case report, shedding light on how C. difficile can cause lung infections, the potential mechanisms behind such rare occurrences, and what healthcare professionals and the public need to know about this unusual presentation of a common infection.

The Case: Atypical Presentation of C. difficile

Surreal illustration of lungs with C. difficile bacteria forming lung shapes, symbolizing atypical infection.

The 42-year-old patient presented with worsening shortness of breath, a cough producing green sputum, subjective fevers, and a notable 40-pound weight loss. He had a history of liver cirrhosis due to non-alcoholic fatty liver disease (NAFLD), hypothyroidism, and had undergone Roux-en-Y gastric bypass surgery seven years prior for morbid obesity. He had also developed achalasia, a condition affecting the esophagus, six years post-bypass, managed with Botox injections.

Initial examinations revealed diminished lung sounds in the right lower and middle lobes. A computed tomography (CT) scan of the chest indicated a thick-walled fluid collection in the right lower chest cavity, suggestive of empyema. The patient was admitted and started on broad-spectrum antibiotics, meropenem and linezolid. A pigtail catheter was inserted to drain the pleural fluid, which was thick and purulent. Cytology confirmed the diagnosis of empyema.

Diagnosis: C. difficile empyema confirmed via VATS procedure.
Treatment: Intravenous metronidazole.
Outcome: Patient recovered well after chest tube removal.

Due to decreased drainage and worsening respiratory status, a video-assisted thoracoscopic surgery (VATS) was performed. VATS revealed extensive empyema with numerous adhesions and a thickened pleural peel. During the procedure, pleural fluid analysis came back positive for C. difficile. Intravenous metronidazole was initiated, and the patient recovered well after the chest tubes were removed. Interestingly, stool samples tested negative for C. difficile toxin, highlighting the challenge in diagnosing such cases.

Implications and Future Directions

This case underscores the importance of considering C. difficile as a potential cause of empyema, even in the absence of typical risk factors or gastrointestinal symptoms. Clinicians should be vigilant in investigating atypical presentations of common infections, especially in patients with complex medical histories. Further research is needed to understand the mechanisms by which C. difficile can manifest outside the gut and to develop better diagnostic and treatment strategies for these rare but serious conditions.

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Everything You Need To Know

What is Clostridium difficile and why is it important in the context of lung infections?

Clostridium difficile, or C. difficile, is a bacterium primarily known for causing infections in the gut, leading to symptoms such as diarrhea and colitis. The bacterium is significant because, while typically associated with gastrointestinal issues, it can, in rare instances, cause infections outside the gut, such as empyema, a serious condition involving the accumulation of pus in the space between the lung and the surrounding membrane. This highlights the importance of recognizing that C. difficile infections are not limited to the gut and can manifest in other parts of the body, posing diagnostic and therapeutic challenges.

What is empyema and what role does Clostridium difficile play in it?

Empyema is a condition characterized by the accumulation of pus in the pleural space, which is the space between the lung and the surrounding membrane. It is significant because it can be caused by infections such as Clostridium difficile (C. difficile), leading to severe respiratory complications. Empyema's diagnosis often requires draining the pleural fluid, and treatment typically involves antibiotics and, in some cases, surgical intervention to remove the infected fluid and tissue. The implications of empyema can be serious, potentially leading to chronic lung problems or even death if not promptly and effectively treated.

What does 'atypical presentation of C. difficile' mean, and why is it important to recognize?

Atypical presentations of C. difficile refer to instances where the infection manifests outside of its typical location in the gastrointestinal tract, or when typical symptoms are not present. This is significant because it complicates the diagnostic process. For example, C. difficile causing empyema without gastrointestinal symptoms is an atypical presentation. It's important to be aware of these atypical presentations to ensure timely diagnosis and treatment, especially in patients with complex medical histories, where such unusual manifestations might be overlooked.

How is C. difficile empyema diagnosed, especially when typical risk factors are absent?

The first step in diagnosing C. difficile empyema involves considering it as a potential cause of lung infection, especially when typical risk factors for C. difficile, like recent antibiotic use or gastrointestinal symptoms, are absent. Diagnostic methods include a CT scan to identify fluid accumulation in the chest cavity and analyzing the pleural fluid for the presence of C. difficile. The absence of C. difficile in stool samples further complicates the diagnosis, underscoring the need for direct testing of the pleural fluid. Delayed diagnosis can lead to increased morbidity and mortality, emphasizing the need for vigilance and comprehensive testing.

What are the typical treatments for C. difficile empyema, and how is the effectiveness of the treatment monitored?

Treatment for C. difficile empyema typically involves a combination of approaches. Initially, broad-spectrum antibiotics like meropenem and linezolid are administered. Once C. difficile is confirmed, intravenous metronidazole is initiated. Additionally, drainage of the pleural fluid is crucial, often achieved through the insertion of a pigtail catheter or, in more severe cases, video-assisted thoracoscopic surgery (VATS) to remove adhesions and thickened pleural peel. The effectiveness of the treatment is monitored through improvements in the patient's respiratory status and the reduction of fluid accumulation in the pleural space. The absence of a response could result in chronic lung problems.