Unraveling a Unique Encounter of Fusobacterium nucleatum With Empyema: A Case Report and Review of Literature

We report a case of Fusobacterium nucleatum (F. nucleatum) empyema in a 34-year-old male with no significant past medical history or obvious risk factors who presented with shortness of breath and chest pain. His imaging showed complicated parapneumonic effusion which grew F. nucleatum. He was started on piperacillin-tazobactam. The patient's clinical condition deteriorated despite initial therapeutic efforts, leading to escalated antibiotic therapy and further investigations. The patient's subsequent clinical course included pigtail catheter placement with drainage of fluid requiring tpa and dornase alpha, leading to significant improvement and eventual discharge on oral amoxicillin-clavulanic acid.


Introduction
Empyema, the accumulation of pus within the pleural space, is a severe complication of bacterial pneumonia and can lead to significant morbidity and mortality. The most common causative organisms are Streptococcus pneumoniae and Staphylococcus aureus. Fusobacterium nucleatum (F. nucleatum), an anaerobic gram-negative bacillus traditionally associated with oral and gastrointestinal diseases, has recently been implicated in various severe invasive infections, including empyema, a pus-filled infection in the pleural space [1,2]. While F. nucleatum infections are rare, their presentation is often atypical and associated with substantial morbidity and mortality [3]. The common infection caused by these bacteria include oral and periodontal infections. In recent years, emerging case reports have highlighted the need to consider F. nucleatum in the differential diagnosis of culture-negative empyemas, particularly when the standard empiric antibiotic therapy fails [4,5]. Here, we present a case of a young male with no risk factors who presented with complicated parapneumonic effusion and pleural fluid cultures grew F. nucleatum empyema.

Case Presentation
A 34-year-old male with no past medical history presented with shortness of breath at rest for three weeks. His shortness of breath was associated with productive cough and chest pain and he went to urgent care a week prior to admission to hospital, where he was given pain medications which did not help his symptoms. He smoked cigarettes about a half pack per day and drinks alcohol occasionally. He denied using illicit drugs. He worked in an oil factory and had exposure to dust, mold, and fumes for about three years.
On admission, his vitals are the following: blood pressure: 123/69 mmHg; heart rate: 130 bpm; and temperature: 102.5 F. His physical exam showed reduced breath sounds on the right side with dullness to percussion. He was tachypneic, tachycardic, and distressed from pain. His dentition was normal and no caries or cavities were noted on the exam. The rest of the exam was normal. He was given intravenous normal saline continuously 100 cc/hr and morphine 5 mg for pain. His lab analysis was significant for leukocytosis 20.8X 10*3/uL and elevated procalcitonin at 4.24 ng/mL. The rest of the labs including basic metabolic panel, liver-related tests, and urine analysis were normal. A chest X-ray on admission showed right-sided pleural effusion with atelectasis, as shown in Figure 1. CT of the chest showed a loculated rightsided large pleural effusion with associated atelectasis and consolidation as shown in  The patient was started on 4.5 grams of intravenous piperacillin-tazobactam and had a thoracentesis done in the emergency department for severe shortness of breath with the removal of 1.5 L of purulent pleural fluid. The repeat chest X-ray post thoracentesis showed persistent moderate effusion despite the patient's improved symptoms. Given his persistent effusion and leucocytosis, his antibiotics were escalated to linezolid and meropenem.
A repeat CT scan of the chest was done on day two and showed an anterior loculated effusion, as shown in Figure 3. A pigtail catheter was placed with draining of yellow purulent fluid. He was given tpa and dornase alpha via chest tube to clear the loculations for a total of six doses over three days, and he drained a total of 3 L of yellow straw-colored pleural fluid.

FIGURE 3: Repeat CT scan of chest showing reduced pleural effusion with anteriorly located loculated effusion (arrows)
The pleural fluid analysis showed Ph 6.87 (normal range: 7.25-7.45), pleural fluid glucose <20 mg/dl, and pleural fluid protein 5 g/dl consistent with exudative effusion by light's criteria. The pleural fluid cytology showed acute inflammatory cells and no malignancy. The fluid culture grew F. nucleatum which was pansensitive. His sputum culture did not show any organism. The other tests are summarized in Table 1. The antibiotics were deescalated to meropenem alone, and his leukocytosis trended down to 8x10*3/uL, procalcitonin dropped to 0.8 ng/ml, and he became afebrile.  The empyema was drained completely, and the chest tube output dropped to <10 ml/day. A repeat chest Xray showed improved lung aeration with atelectasis in the right lower lobe, as shown in Figure 4. The chest tube drain was removed eventually, and the patient was discharged home after two weeks of hospitalization, and he was given amoxicillin-clavulanic acid for seven days to finish a total of 21 days.  [4,6]. Molecular diagnostic methods, such as 16S rRNA sequencing, can help to overcome these challenges and have been instrumental in confirming the diagnosis in numerous cases [2,4].

Aspergillus galactomannan Ag
In recent literature, F. nucleatum has been increasingly associated with immunocompromised states, such as rheumatoid arthritis and other underlying co-morbidities [5,7]. This raises the question of whether immunosuppression might predispose individuals to F. nucleatum empyema, necessitating further research. F. nucleatum's pathogenic potential is also demonstrated by its association with various forms of empyema, such as pericardial empyema, pleural empyema, and concurrent infections like pyogenic liver abscesses and lung abscesses [6][7][8]. This pathogen can even extend its infection to skeletal structures, as reported by concurrent spondylodiscitis and osteomyelitis [9,10]. The factors that could have favored infection in our patient could be his occupational exposure and the possibility that he may have had an aspiration event when he had alcohol, and it is only speculation that cannot be definitively proved otherwise.
The role of F. nucleatum in severe pleural infections has yet to be fully understood. However, co-infection with other bacteria, such as Streptococcus intermedius, might lead to a distinct clinical entity of pleural infections [8]. Furthermore, intriguing correlations have been noted between F. nucleatum empyema and malignancies, particularly lung squamous cell carcinoma, which may have important implications for disease prognosis and patient management [11].
The treatment of F. nucleatum empyema involves both medical and surgical approaches. As F. nucleatum is an anaerobic bacterium, antimicrobial agents effective against anaerobes, such as metronidazole, βlactam/β-lactamase inhibitor combinations, carbapenems, or clindamycin, are commonly used [12]. Highdose penicillin has also been reported as an effective treatment. However, due to the increasing incidence of antimicrobial resistance, susceptibility testing is recommended to guide appropriate antibiotic therapy [13]. Surgical intervention, including thoracentesis, tube thoracostomy, or even video-assisted thoracoscopic surgery, may be required to evacuate the empyema. The optimal duration of antibiotic therapy for F. nucleatum empyema remains undetermined and depends on the individual patient's clinical response, the extent of infection, and whether surgical intervention is involved. However, as a general guideline, it is recommended that antibiotic treatment for pleural infections, such as empyema, be continued for four to six weeks [14]. Extended therapy may be warranted in more severe or complicated cases or in immunocompromised patients. Regular clinical assessment and follow-up imaging should guide the duration of therapy, with the goal of complete resolution of infection. Despite aggressive therapy, F. nucleatum empyema carries a significant risk of morbidity and mortality, emphasizing the importance of early recognition and timely initiation of treatment [15].

Conclusions
This growing body of literature underscores the importance of including F. nucleatum in the differential diagnosis of culture-negative empyema, especially in immunocompromised individuals and those with nonresolving symptoms under empirical therapy. Continued research will be crucial in further understanding the pathogenesis, risk factors, and optimal management strategies for F. nucleatum empyema.

Additional Information Disclosures
Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.