Rare Case of Bacteremia and Pleural Empyema Originating from a Burn Ulcer in a 16-Year-Old Female Patient

Introduction

Fusobacterium necrophorum is a gram-negative anaerobic bacterium primarily present in the oral cavity. The frequency of F. necrophorum infections has gradually increased. In referrals of isolates of F. necrophorum to the United Kingdom Anaerobe Reference Laboratory, the annual average number of infections confirmed to be due to F. necrophorum has increased since 1999 [1,2]. Additionally, the incidence of all invasive infections caused by F. necrophorum in Sweden increased from 2010 to 2017 [3]. The increased incidence has been attributed to changing patterns of antibiotic use, poor nutrition, and poor oral hygiene [4]. However, there have been no reports regarding recent comprehensive data on the incidence rate of F. necrophorum in Asia, including Japan, to the extent of our investigation. Approximately two-thirds of F. necrophorum infections are in male patients, and the incidence is highest in individuals aged 16 to 23 years [1]. Adolescents and young adults can be more severely affected, with mortality rates ranging from 4% to 18% [2]. F. necrophorum is commonly implicated in Lemierre syndrome; this syndrome often starts with a sore throat that progresses to pharyngeal abscess, followed by thrombosis of the internal jugular vein, metastatic foci of infection in the lungs and joints, and sepsis [5].

F. necrophorum infections from sources other than the head and neck region are rare. Kristensen and Prag [6] reported that the infection originated from sources other than the head and neck region in only 21 of 291 cases documented from 1998 to 2001 in Denmark, including 2 cases of appendicitis and 19 cases of subcutaneous wounds. From 2010 to 2017, a total of 300 cases of invasive F. necrophorum infections in Sweden were reported, of which 94 were not localized to the head and neck region [3]. In the 94 patients with non-localized infections, the median age was 64 years, and the mortality within 30 to 180 days of infection onset was significantly higher in the non-localized infection group than in the head and neck infection group [3]. Another study found that infections originating from sources other than the head and neck region were common in older men, while pulmonary complications were uncommon [7].

Herein, we report a unique case of F. necrophorum infection due to a post-burn ulcer on the lower leg that resulted in bacteremia and empyema in a previously healthy adolescent girl.

Case Report

The patient was a previously healthy 16-year-old Japanese girl, with no relevant medical history, who had sustained a burn on her left shin caused by a hot water bottle in late December 2022. An ulcer had formed, but the patient did not seek medical help and cared for the wound with occasional use of topical benzethonium chloride. On January 21, 2023, she developed a fever of 38 °C and left chest pain accompanied by dyspnea, and visited a physician on January 25, 2023. Chest radiography (Figure 1) and computed tomography (CT; Figure 2) revealed an infiltrative shadow in the left lung; therefore, the patient was hospitalized in the first hospital. No abnormal findings were noted on examination of the head, neck, and oral cavity. Although no microbial swabs or cultures were taken from the burn ulcer or the head and neck region earlier, 2 sets of blood cultures performed after admission showed the presence of F. necrophorum. Antimicrobial susceptibility test results revealed that the infection was sensitive to all antimicrobial agents evaluated, except for levofloxacin. After admission, the patient was immediately treated with sulbactam sodium/ampicillin sodium (9 g/day) intravenously (i.v.) for 5 days; however, the fever did not resolve. The treating physicians switched treatment to combination therapy with meropenem (3 g/day) and metronidazole (1500 mg/day) i.v., but right chest pain also developed, and the infiltrate shadow worsened on CT (Figure 3). Because of the progressing bilateral pleural effusion and deteriorating respiratory condition (oxygen saturation: 92% oxygen, 2 L/min via a nasal catheter), the patient was transferred to our hospital on February 6, 2023, twelve days after admission to the first hospital, for further evaluation and multidisciplinary treatment.

On admission to our hospital, it was noted that the patient had an ulcer measuring 25 × 16 mm on her left shin (Figure 4) that was diagnosed as a second-degree burn. At the time of hospital transfer, the blood test results showed an elevated white blood cell (WBC) count (13 200 cells/µL) and elevated levels of C-reactive protein (CRP; 7.60 mg/dL), D-dimer (14.6 µg/mL), and procalcitonin (84 ng/mL), indicating the presence of bacteremia and tendency toward thrombus formation. Sputum examination was performed, but no causative organism was detected. Furthermore, upper extremity venous ultrasonography to differentiate Lemierre syndrome from F. necrophorum infections due to sources other than the head and neck region showed no thrombi in the bilateral common jugular and brachiocephalic veins. Echocardiography showed no obvious evidence of infective pericarditis, a normal ejection fraction (60%), and no congenital heart disease. The antimicrobial therapy was switched to i.v. administration of tazobactam/piperacillin (tazobactam: 13.5 g/day; piperacillin: 1.69 g/day). As there was no improvement in left pleural effusion (Figure 5), left diagnostic and therapeutic thoracentesis was performed on February 7, and revealed exudative (serum lactate dehydrogenase [LDH]: 180 U/L, pleural fluid LDH: 2183 U/L), neutrophil-predominant (neutrophils: 77%, eosinophils: 0%, basophils: 0%, monocytes: 15%, lymphocytes: 8%), and glucose-depleted pleural fluid (57 mg/dL; reference range 70–105 mg/dL), leading to a diagnosis of pleural empyema. However, only 20 mL could be punctured, due to high viscosity. Skin abrasions, which had not been collected by the previous physician, were collected and submitted for culture on February 9. However, no causative organisms were detected in the wound culture. Furthermore, right pleural fluid had increased gradually after admission to our hospital. Chest radiograph on February 13 showed more right pleural fluid (Figure 6); thus, right therapeutic thoracentesis was performed on February 15. Right diagnostic and therapeutic thoracentesis revealed exudative (serum LDH: 153 U/L, pleural fluid LDH: 328 U/L), eosinophil-predominant (neutrophils: 4%, eosinophils: 28%, basophils: 5%, monocytes: 10% lymphocytes: 53%) pleural fluid, and glucose concentrations of 76 mg/dL; the amount of right pleural fluid drained by puncture was 500 mL. Bacterial cultures of both pleural fluids were negative. Following thoracentesis, the patient became afebrile and her chest pain resolved. Her WBC, CRP, D-dimer, and procalcitonin levels decreased markedly (6100 cells/µL, 0.3 mg/dL, 3.4 µg/mL, and 0.05 ng/mL, respectively). A blood culture test performed on February 19 showed negative results, and CT (Figure 7) and chest radiography (Figure 8) showed decreased bilateral pleural effusion.

We administered tazobactam/piperacillin i.v. for 15 consecutive days. The patient no longer required oxygen inhalation and was discharged on February 27. The patient’s condition remained stable after discharge, and on March 6, she visited our outpatient hospital fully recovered, with no evidence of recurrence.

Discussion

In this case, given the absence of abnormal findings on examination of the head, neck, and oral cavity, F. necrophorum infection is thought to have resulted from the burn wound. Fusobacterium also occurs on the skin and can cause skin and soft tissue infections. In a previous study, Mousa [8] investigated the organisms responsible for burn wound infections and identified anaerobic bacteria and other strains of Fusobacterium. Of the 127 patients with burn wounds studied, 17 developed septic shock, of whom 15 had positive anaerobic bacterial cultures; furthermore, of the 377 strains identified from cultures of subcutaneous exudates, 116 were anaerobic, including 3 F. nucleatum and 2 F. mortiferum strains. However, no cases of F. necrophorum infection were detected [8].

In this case, the physician at the previous hospital did not collect a burn wound sample from the patient, because burns were not considered a source of infection; nevertheless, F. necrophorum was detected in blood cultures before initiation of antimicrobial therapy. Bacterial cultures of pleural fluid collected from the 2 thoracentesis procedures and wound culture at our hospital did not reveal the causative organism; however, both thoracentesis procedures and wound culture were performed after the patient had commenced antimicrobial treatment, which may explain the negative culture of pleural fluid. Therefore, in this case, while the burn ulcer was assumed to be the source of the infection, this could not be proven, due to the lack of positive microbial wound cultures. In a previous study, blood culture was the only indicator of F. nucleatum infection presumed to originate from the gastrointestinal tract [7]. In another study, F. necrophorum infections in 285 of 300 patients were diagnosed on the basis of positive blood culture results [3].

Bilateral pleural effusion has been reported in Lemierre syndrome [9], and the hematogenous spread of F. necrophorum can lead to the appearance of lung nodules, cavities, infiltrates, pleural effusion, empyema, and abscesses [5]. Of the 300 patients with F. necrophorum infection in the study by Nygren and Holm [3], 39 required thoracic drainage, 35 had Lemierre syndrome, and 4 had invasive non-head and neck infection [3]. Furthermore, comorbidities were common in the invasive non-head and neck infection group, which may have contributed to the high mortality rate [3]; however, in the present case, the patient was an adolescent girl with no comorbidities, and she recovered well following appropriate treatment.

Another previous study reported that 3 of 75 patients with F. necrophorum infection required pleural fluid drainage [10]. In the present case, the patient required drainage of bilateral pleural effusion, probably caused by F. necrophorum bacteremia. The right pleural effusion was eosinophil predominant, possibly because of the pleural infection, as shown by Krenke et al [11]. The present case may be unique, as we did not find any previous reports of F. necrophorum infection due to burn wounds. Second-degree burns with elevated pH levels are more likely to develop bacteriosis, and gram-negative bacilli grow better in high pH areas [12,13]. Therefore, appropriate treatment of second-degree burns is important. Our patient did not seek medical care immediately after sustaining the burn injury and did not receive antimicrobial treatment within the first 3 weeks. This might have contributed to the development and invasiveness of the F. necrophorum infection.

Conclusions

In the present case, a burn ulcer was the likely origin of infection, although this could not be proven, due to the lack of positive microbial cultures. The reported case is rare and suggests that F. necrophorum can enter the body through burn wounds, resulting in severe bacteremia and pleural empyema. The patient, a 16-year-old girl, was successfully treated with tazobactam/piperacillin therapy and bilateral thoracentesis. This case highlights the importance of proper management and treatment of post-burn wounds.