The First Case Report of Mediastinal Abscess Caused by Gemella bergeri.

Most cases of mediastinal abscess occur as a postoperative complication of a thoracic surgical procedure or following trauma. The most common causative microorganism is Staphylococcus aureus, but it can be rarely caused by unusual microorganisms, such as Gemella species. These are relatively difficult-to-identify commensal microorganisms of the upper respiratory and gastrointestinal tracts and may cause several infections. A 66-year-old man was diagnosed with Gemella bergeri mediastinal abscess by the molecular detection of bacterial genes. He was successfully treated with penicillin antibiotic for eight weeks. To our knowledge, this is the first case report of mediastinal abscess caused by G. bergeri.

Introduction

There have been no reports of mediastinal abscess caused by Gemella bergeri in the literature. G. bergeri is one of the nine species of the genus Gemella (1) and is a Gram-variable coccus arranged in pairs, tetrads, clusters, or short chains. It was first isolated by Collins et al. in 1998 from the blood cultures of six patients, three of whom had bacterial endocarditis (2). It is relatively difficult to identify since conventional biochemical methods may result in misidentification as other Gemella species or viridans streptococci (3).

A few cases of mediastinal abscess caused by G. bergeri have recently been reported, including ones of infective endocarditis (2-9), Lemierre's syndrome (10), and cutaneous orbital abscess (11) in humans. However, the pathogenicity of G. bergeri has not been clarified.

We herein report the first case of mediastinal abscess caused by G. bergeri in Japan.

Case Report

A 66-year-old Japanese man with a history of gingivitis, acute appendicitis, and duodenal ulcer presented with a 3-month history of anorexia and loss of body weight at our hospital. His height and weight at the first visit were 159 cm and 55 kg, respectively [body mass index (BMI): 21.8]. He had no known allergies and had not been prescribed any recent medications. A detailed gastrointestinal examination revealed advanced carcinoma of the abdominal esophagus. After the second course of neoadjuvant chemotherapy (5-fluorouracil and cisplatin therapy; FP therapy), we conducted left trans-thoraco-abdominal retrosternal gastric tube reconstruction following subtotal esophagectomy with three-field lymphadenectomy. He developed a fever on the fourth day after the surgery for esophageal cancer.

He was alert (Glasgow Coma Scale 15) and presented with the following vital signs: temperature of 38.4 °C, blood pressure of 109/68 mmHg, heart rate of 110 beats/minute, respiratory rate of 22 breaths/minute, and oxygen saturation of 97% in ambient air. A physical examination revealed progressive destruction of the tooth-supporting apparatus on the right maxillary central incisor and hypoactive bowel sounds. The findings of other examinations, including those of the thoraco-abdominal wound, were all within normal limits.

Laboratory findings were as follows: albumin 2.1 g/dL, alanine transferase 38 U/L, aspartate aminotransferase 24 U/L, lactate dehydrogenase 155 U/L, blood urea nitrogen 9 mg/dL, creatinine 0.99 mg/dL, C-reactive protein 15.99 mg/dL, white blood cell count 13,200 /μL with 85.0% neutrophils, hemoglobin 6.4 g/dL, and platelet count 45.6×104/μL.

Chest computed tomography (CT) showed fluid collection and internal air bubbles in the left anterior mediastinum (Fig. 1). Consequently, aspiration and drainage of this area for Gram staining and culture were performed.

Figure 1.

Chest computed tomographic image showed fluid collection and internal air bubbles (white arrow) in the left anterior mediastinum.

Gram staining showed Gram-positive polymorphic cocci arranged in pairs, tetrads, clusters, or short chains. Based on the history of gingivitis and trans-thoraco-abdominal retrosternal gastric tube reconstruction after subtotal esophagectomy, findings of periodontitis, and Gram-positive polymorphic cocci, we suspected involvement of Gemella species or nutritional variant streptococci (NVS) rather than viridans streptococci (Fig. 2). There was no evidence of infective endocarditis by transthoracic echocardiography. Two sets of aerobic and anaerobic blood cultures (BacT/Alert FAN plus, bioMérieux, Marcy I'Etoile, France) were negative after incubation for 14 days. For drainage fluid cultures, no isolates grew on 5% sheep blood agar (Nihon Becton-Dickinson, Tokyo, Japan) or chocolate agar medium (Nissui Pharmaceutical, Tokyo, Japan) after 2 days of incubation under 5% CO2 at 35 °C, while pinhead colonies grew on 5% sheep blood agar medium after 3 days of incubation under 5% CO2 at 35 °C. In contrast, the isolates grew relatively well on 5% sheep blood agar medium after 2 days of anaerobic incubation at 35 °C (Fig. 3). The isolates were alpha-hemolytic, nonmotile, catalase-negative, leucine aminopeptidase (LAP)-positive, pyrrolidonylarylamidase (PYR)-positive, esculin-negative, urease-negative, and failed to type with Lancefield group A, B, C, D, F, or G antiserum (Kanto Chemical, Tokyo, Japan). The satellite test, known as satelliting, for NVS was negative. The bacteria were ultimately identified as G. bergeri by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) and 16S ribosomal ribonucleic acid (rRNA) gene sequencing (12)(Fig. 4). The E-test (bioMérieux) showed penicillin, ceftriaxone, and vancomycin with minimum inhibitory concentrations (MICs) of 0.008, 0.016, and 0.38 μg/mL, respectively, which indicated susceptibility to the breakpoint of related viridans streptococci.

Figure 2.

Gram staining (×1,000) revealed Gram-positive polymorphic cocci.

Figure 3.

The isolates grew on 5% sheep blood agar media after 2 days of anaerobic incubation at 35 °C.

Figure 4.

The results of 16S rRNA gene sequencing (GenBank BLAST database).

The patient was diagnosed with a mediastinal abscess due to G. bergeri and treated with a combination of intravenous sulbactam/ampicillin 3 g every 6 hours and metronidazole 500 mg every 8 hours. He became apyrexial on these combination therapies with drainage for two weeks, and metronidazole was discontinued (Fig. 5). After four weeks of intravenous therapy, sulbactam/ampicillin was changed to oral clavulanate/amoxicillin. Thereafter, the abscess disappeared on CT, and there has been no recurrence (Fig. 5).

Figure 5.

Clinical course. Based on the findings of Gram staining, a combination of intravenous sulbactam/ampicillin and metronidazole with drainage of the mediastinal abscess was started on Day 7. Esophagography on Day 9 revealed no leakage. Metronidazole was discontinued on Day 22. Follow-up CT on Day 33 revealed the shrinkage of the abscess. Sulbactam/ampicillin was changed to oral clavulanate/amoxicillin on Day 35. Thereafter, the abscess disappeared in CT.

Discussion

There are two clinical issues regarding the diagnosis of G. bergeri infections. G. bergeri is a part of the normal flora of the oral cavity and upper respiratory and gastrointestinal tracts. Nevertheless, there have been no reports of mediastinal abscess caused by G. bergeri in the literature. Furthermore, the conventional biochemical methods may lead to misidentification.

Regarding the first point, there have been few reports of mediastinal abscess or mediastinitis caused by Gemella species in the literature. Most cases of mediastinal abscess occur as a complication following surgery, trauma, esophageal perforation (e.g., Boerhaave's syndrome), or the development of cervical infections (e.g., descending cervical mediastinitis). The most common causative microorganism in mediastinitis following thoracic surgery is S. aureus (13). In contrast, there have been only three case reports of mediastinitis caused by G. morbillorum (14-16), and no cases caused by G. bergeri have been reported.

Regarding the second point, the conventional biochemical methods may result in misidentification. However, MALDI-TOF MS and 16S rRNA gene sequencing may be useful for the diagnosis of G. bergeri (3). To date, there have been 15 case reports of G. bergeri infections (2-11). Two reports did not mention how to identify the microorganisms. Of the remaining 13 cases, 8 were diagnosed by 16S rRNA gene sequencing, 2 were diagnosed by MALDI-TOF MS or MALDI-TOF MS+16S rRNA gene sequencing, 2 were diagnosed by conventional biochemical methods, and the last was diagnosed by real-time polymerase chain reaction. In brief, 10 of the 13 patients were diagnosed by MALDI-TOF MS or 16S rRNA gene sequencing. In our patient, the VITEK II system (bioMérieux) and BD BBL Crystal GP (Becton, Dickinson and Company, Sparks, USA) indicated an “Unidentified organism”. This strain was identified as G. haemolysans by API 20 strep v.8.0 (%ID 64.2, T index 0.97; bioMérieux) and Rapid ID 32 strep v.4.0 (%ID 93.4, T index 0.73; bioMérieux) with low discrimination. It was identified as G. bergeri with a confidence value of 99.9 by MALDI-TOF MS (VITEK MS; bioMérieux) and confirmed by 16S rRNA gene sequencing and the GenBank Basic Local Alignment Search Tool (BLAST) database (www.ncbi.nlm.nih.gov/genbank/) (Identities 1,397/1,397, Gaps 0/1,397, Score 2,580bits) (Fig. 4). Consequently, we diagnosed G. bergeri as the pathogen responsible for the mediastinal abscess in our case.

In general, Gemella species are known to be catalase-negative, slow-growing, fastidious, facultatively anaerobic, salt-tolerant, nonsatelliting, Gram-positive cocci. In addition, Gemella species have variable Gram staining patterns and may exhibit a polymorphic shape. These properties can lead to its misidentification as viridans streptococci or other related microorganisms. Before 1988, there were only two known Gemella species: G. haemolysans and G. morbillorum. G. bergeri was first isolated by Collins et al. in 1998 (2). It is believed that Gemella species are harmless commensal microorganisms in the oral cavity and upper respiratory, gastrointestinal, and genitourinary tract; however, there have been several reports of localized and generalized infections due to Gemella species. Of the nine species in the genus Gemella, seven (G. bergeri, G. morbillorum, G. haemolysans, G. sanguinis, G. asaccharolytica, G. parahaemolysans, G. taiwanensis) have been recognized as causative agents of infective endocarditis (2-9,17-19), brain abscess (20), septic arthritis (21), liver abscess (22), Lemierre's syndrome (10), and cutaneous orbital abscess (11) in humans. G. bergeri infection is especially rare and limited to a few case reports for this reason (2-11). In addition, because of limitations in conventional diagnostic testing and difficulty identifying G. bergeri, instances of this bacteria may have been misidentified as G. haemolysans, G. morbillorum, or viridans streptococci in the past (3,23), accounting for the rarity of G. bergeri.

Clinically, the involvement of anaerobic bacteria or Enterobacteriaceae should be considered because of air collection inside the abscess on chest CT (Fig. 1). In our case, Enterobacteriaceae did not grow on 5% sheep blood agar medium aerobically or anaerobically. Anaerobic transport devices and chambers were not available in our hospital. Therefore we prescribed metronidazole in combination with sulbactam/ampicillin based on the presumption of anaerobic bacteria. It is reported that the susceptibility rate of obligate anaerobes to sulbactam/ampicillin is high (24,25). However, some obligate anaerobes (e.g., Bacteroides species) may show resistance to sulbactam/ampicillin (25,26). We therefore prescribed metronidazole while being alert for encephalopathy in our case; consequently there was no evidence of antibiotic-associated encephalopathy (27).

Of the past 15 case reports of G. bergeri infections (2-11), 6 patients were treated with penicillin (3,6,8-11) and 4 with ceftriaxone, depending on the susceptibility (4-6,9); however, the antibiotics were not mentioned in 7 reports. Ceftriaxone may be a viable option for treating G. bergeri infection if susceptible. Microorganisms responsible for mediastinal abscess are related to the primary source. Gemella species are commonly recognized as a part of the normal oral flora and are frequently found in patients with white-spot lesions and gingivitis (28). Bacteremia after toothbrushing and dental procedures is associated with poor oral hygiene and gingival bleeding. Thus, they are known causes of bacterial entry into the bloodstream (29,30). Our patient had a history of gingivitis and a finding of chronic periodontitis, but 2 sets of blood cultures were negative despite a long 14-day incubation. In addition, he underwent ipsilateral trans-thoraco-abdominal retrosternal gastric tube reconstruction after subtotal esophagectomy. We concluded that this was the most likely source of infection in this case, as G. bergeri is part of the normal flora of the upper gastrointestinal tract (1). Obesity and diabetes mellitus are associated with mediastinitis following cardiac surgery (31). Furthermore, the risk of mediastinitis after surgical esophageal anastomosis is correlated with cervical anastomosis, female gender, and a pre-operative smoking habit (32). Our patient did not have a history of obesity, diabetes mellitus, or a smoking habit but had undergone cervical anastomosis, which may have been associated with this mediastinal abscess contaminated with intraesophageal G. bergeri. However, no leakage was found immediately after surgery by esophagography, and the abscess completely disappeared on the 62nd day, as revealed by CT.

A rare disease, mediastinal abscess caused by G. bergeri, was successfully treated with appropriate antibiotic therapy. The accurate diagnosis of rare or difficult-to-identify pathogens is challenging for clinical microbiological laboratories. In cases where pathogenic microorganisms cannot be identified by conventional methods, rare or difficult-to-identify pathogens can be identified using MALDI-TOF MS and 16S rRNA gene sequencing. There have been no reports of mediastinal abscess caused by G. bergeri in the literature. We herein report the first case of mediastinal abscess caused by G. bergeri in Japan.

Written informed consent was obtained from the patient for publication of this case report and accompanying images.

The authors state that they have no Conflict of Interest (COI).