Pleural empyema with gas formation caused by mixed infection of Edwardsiella tarda with Streptococcus constellatus

Abstract Edwardsiella tarda is an anaerobic, gram‐negative rod bacterium associated with freshwater and marine life. Human E. tarda infections are rare, and most infections in humans cause gastroenteritis. Extraintestinal infections of E. tarda such as pleural empyema are particularly rare. A 72‐year‐old man was admitted with cough and purulent sputum. His medical history included periodontal disease and gastric cancer for which he had undergone total gastrectomy. Chest computed tomography showed left pleural effusion with foci of gas, and both E. tarda and Streptococcus constellatus were cultured from the pleural effusion. Thus, he was diagnosed with gas‐forming empyema. He was successfully treated with therapeutic thoracentesis and antibiotics. Our case suggests that a dietary habit of raw fish, undernutrition, gastrectomy and oral infection may be predisposing factors for empyema caused by E. tarda.


INTRODUCTION
Edwardsiella tarda is a motile, anaerobic, gram-negative rod bacterium associated with freshwater and marine life. Previous reports have indicated that E. tarda is a rare human pathogen and that its most common clinical manifestation is gastroenteritis. 1 However, E. tarda infrequently causes extraintestinal infections such as septicaemia, meningitis, cholecystitis and liver abscess, which can become systemic and potentially lethal. Empyema caused by E. tarda is particularly rare, 2 and gas production in such cases has not been previously reported. We herein present the first case of pleural empyema with gas formation caused by mixed infection of E. tarda with Streptococcus constellatus, a member of the Streptococcus milleri group.

CASE REPORT
A 72-year-old Japanese man was admitted because of a 2-week history of cough, purulent sputum and anorexia.
The patient was thin (height, 157 cm; weight, 34.5 kg; and body mass index, 14.0 kg/m 2 ), and his medical history included gastric cancer for which he had undergone total gastrectomy. He also had periodontal disease, but had discontinued the treatment for 2 years before the hospitalization. A dietary history revealed that he had eaten Paraplagusia japonica, a species of olive flounder, on a weekly basis. He had no history of taking immunosuppressive medication. His body temperature was 37.2 C and physical examination revealed coarse crepitations and reduced breath sounds in the left lower lung. Periodontal lesions were still detected. He had no gastrointestinal symptom or preceding history such as stomach pain, nausea and diarrhoea. Laboratory findings included a white blood cell count of 7100/μl with 82.5% neutrophils, C-reactive protein concentration of 5.36 mg/dl, procalcitonin concentration of 0.07 ng/ml (reference range, ≤0.05 ng/ml) and low serum albumin concentration of 2.1 g/dl (reference range, 4.1-5.1 g/dl). Chest computed tomography (CT) showed an infiltration shadow and suspended air bubbles within the pleural effusion with septations in the left lower lung lobe ( Figure 1A-C). Diagnostic thoracentesis was performed, and the pleural fluid was green, purulent and foul-smelling ( Figure 2A). The pleural fluid analysis was consistent with an exudative aetiology according to Light's criteria (Table 1). Microscopic examination revealed many neutrophils and gram-negative rods as well as gram-positive cocci. Furthermore, neutrophil-mediated phagocytosis of gram-negative rods was seen in the pleural effusion ( Figure 2B). A culture of the fluid grew E. tarda and S. constellatus. However, these bacteria were not cultured from either spontaneous sputum or blood specimen. Finally, he was diagnosed with gasproducing empyema caused by E. tarda, and treated with meropenem (2 g/day). In addition, therapeutic thoracentesis was performed, and a total of 105 ml of similarly appearing fluid was removed. Thereafter, the patient's clinical symptoms gradually improved and we found that the detected E. tarda was susceptible to meropenem we used and most other antibiotics including ampicillin, piperacillin, ceftriaxone, cefazoline and levofloxacin. Two weeks after the treatment, his C-reactive protein concentration had decreased to 0.17 mg/dl, and de-escalating antibiotic therapy of sulbactam/ampicillin was continued. Chest CT 4 weeks after the initial treatment showed marked shrinkage of the empyema, and no septations or gas foci were detected in the pleural effusion ( Figure 1D-F).

DISCUSSION
Risk factors for E. tarda infection include wounding in marine environments, exposure to infected reptiles and amphibians, a dietary habit of ingesting raw fish and immunodeficiencies. 1 In our case, the patient had no history of contact with wild animals or aquatic environments; however, he had a dietary habit of eating a species of olive flounder that was a known representative host of E. tarda. Furthermore, his medical history revealed gastric cancer for which he had undergone total gastrectomy. Previous case studies have reported that gastrectomy may increase the risk of E. tarda bacteraemia due to reduction of gastric acid secretion. 3 The patient also had a dental infection that served as a predisposing factor for pleural empyema. Interestingly, E. tarda was cultured only from the pleural effusion and not from the sputum. Therefore, E. tarda infection in the present case was considered to be foodborne, transmitted to the patient by ingestion of contaminated olive flounder with possible colonization in the oral cavity through periodontal disease followed by spread and establishment of purulent invasion in the pleural cavity. Pleural empyema with gas formation is rare. E. tarda is an anaerobic bacterium that can produce hydrogen sulphide in laboratory media; however, gas-forming infection caused by E. tarda is rare in the clinical setting. To the best of our knowledge, a case of empyema with gas formation caused by E. tarda infection has not been previously reported. In our patient, both E. tarda and S. constellatus were cultured from the pleural effusion. S. constellatus belongs to S. milleri group, which have been isolated from the mouth and nasopharynx. S. constellatus has low pathogenic potential and is less associated with severe infection including empyema than other S. milleri group subspecies such as Streptococcus intermedius. 4 The present case showed neutrophil-mediated phagocytosis of gram-negative rods such as E. tarda in the pleural effusion; thus, E. tarda could plausibly have been responsible for causing gas-producing empyema.
In conclusion, extraintestinal infections of E. tarda are rare; however, physicians should know that people with oral infections or poor nutrition who habitually ingest raw fish are at risk of empyema caused by this bacteria. Although E. tarda is sensitive to many antibiotics in vitro, E. tarda bacteraemia has a high mortality rate. 5 Thus, immediate intervention of pleural drainage and appropriate antibiotic therapy should be performed in patients with empyema caused by E. tarda.