A case of bloodstream infection caused by Ruminococcus gnavus without gastrointestinal involvement

We report a case of bloodstream infection due to Ruminococcus gnavus (R. gnavus) associated with pelvic abscess in a 74-year-old female patient undergoing radiotherapy for cervical cancer. Gram staining of positive anaerobic blood cultures revealed short chains of gram-positive cocci. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry was performed directly on the blood culture bottle, and 16S rRNA sequencing identified the bacterium as R. gnavus. There was no leakage from the sigmoid colon to rectum on enterography, and R. gnavus was not found in the culture of her pelvic abscess. After the administration of piperacillin/tazobactam, her condition markedly improved. This patient with R. gnavus infection demonstrated no gastrointestinal involvement, whereas past published cases reported diverticulitis or intestinal damage. It is possible that bacterial translocation of R. gnavus occurred from the gut microbiota, due to damage to the intestinal tract caused by radiation.


Introduction
Ruminococcus gnavus is an anaerobic, non-spore-forming, gram-positive diplococcus that is part of the normal human intestinal flora [1]. R. gnavus is frequently found in human gut microbial communities and is present in more than 90% of all individuals [2]. Dysbiosis of the gut microbiota, with elevated R. gnavus counts, is strongly associated with Crohn's disease [3]. Human bloodstream infections caused by R. gnavus have been reported in only eight cases [4][5][6][7][8][9][10]. Two patients had a history of diverticulitis with concurrent bacteremia (Escherichia coli or Pseudomonas aeruginosa) [8], while two others had a history of intestinal damage [5,7]. Herein, we report a case of R. gnavus-related bloodstream infection where R. gnavus was the sole causative pathogen without any intestinal perforation.

Case description
A 74-year-old woman visited our hospital with fever. She had been treated with radiation for cervical cancer after total hysterectomy and had developed pelvic abscess due to bladder perforation 5 years ago. A drainage tube was placed to drain the pelvic abscesses. When she visited our hospital, purulent discharge was found in her drainage tube. Complete blood count revealed leukocytosis (14.6 × 10 9 cells/L) and anemia (hemoglobin 82 g/L); her C-reactive protein (CRP) level was elevated (3.9 × 10 4 μg/dL), and she was hospitalized. Ampicillin/sulbactam (3 g/kg bodyweight every 8 h) was initiated on admission because Enterococcus faecalis was identified in a pelvic abscess culture in the past. The blood culture test results were negative.
On days 2 and 3 of hospitalization, blood pressure measurement was difficult, and her pulse was 76 bpm. Computed tomography showed bleeding from the bilateral internal iliac arteries, and we performed embolization of the bilateral internal iliac arteries and stent insertion on the left external iliac artery. Her condition improved after the surgical procedure was performed without blood transfusion. On day 7 of hospitalization, she developed fever (39.1 • C). Her complete blood count revealed leukocytosis (92.00 × 10 9 cells/L) and elevated CRP level (18.2 × 10 4 μg/dL). We performed a blood culture again, and after incubation for 1.9 days (46 h), the two anaerobic samples were positive, while the two aerobic samples were negative. Gram staining revealed gram-positive cocci in small chains (Fig. 1). To directly identify the microorganism, blood culture extracts were analyzed using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS), performed using a BD MALDI Biotyper Sirius system (Becton, Dickinson and Company, Franklin lakes, NJ, USA) and MBT Compass 4.1, with the MBT Compass library: Ver.9.0.0.0 (8468MSPs) (Bruker Daltonik GmbH, Bremen, Germany) database.
MALDI-TOF MS yielded a score of 2.12 for R. gnavus. Positive blood culture extracts were then cultured on a solid medium at 35 • C and Brucella agar medium at 37 • C. The colonies were small and translucent. The MALDI-TOF MS analysis of these colonies identified R. gnavus with a score of 1.98. Subsequently, 16S rRNA gene sequencing (Data associated with this study has been deposited at figshare under the accession number. 10.6084/m9.figshare.22438999. https://doi.org/10.1016/j.jiac.2021.01.005) was performed via polymerase chain reaction using the universal primers 8UA and 1485B. The amplicons were sequenced using the primers 341A, 519B, and 907A [11], and the sequences obtained from GenBank® were compared using the BLAST program (https://blast.ncbi.nlm.nih. gov/Blast.cgi, accesion no.CP027002.1), confirming R. gnavus (BLAST score is 100%). R. gnavus was not identified in the pelvic abscess culture.
On day 12 after starting TAZ/PIPC administration, her temperature dropped to approximately 37 • C and her CRP decreased to the pretreatment level (5.58 × 10 4 μg/dL). Enterography revealed no leakage from the sigmoid colon to the rectum. She has not complained of abdominal pain or other abdominal symptoms for 2 years and the bacteremia caused by R. gnavus has not recurred.

Discussion
Anaerobic infections occur in 0.5-20% of all positive blood cultures. Anaerobic bacteremia usually occurs secondary to an infectious process that emanates from an intra-abdominal source, the oral cavity, female genital tract, respiratory tract, or skin or soft tissue infections. Anaerobic bacteremia remains associated with significant mortality, ranging from 15% to 60% [12]. R. gnavus is an anerobic gram-positive diplococci with 1-3 flagella [8].
Herein, we present the ninth reported case of R. gnavus bacteremia. Five cases of R. gnavus bacteremia were associated with gastrointestinal disease, of which two cases were associated with diverticulitis [8]. The other cases were associated with fecal peritonitis secondary to small bowel herniation and perforation [10], fecal peritonitis secondary to small bowel perforation [9], and intestinal perforation [5]. One patient with R. gnavus bacteremia had no gastrointestinal disease, and it was considered that R. gnavus bacteremia was caused by bacterial translocation of the gut microbiota due to prednisolone treatment of multiple myeloma and myelodysplastic syndrome [6]. In addition to blood, R. gnavus has been reported to be detected in the joint fluid of a prostatic implant [13] in a patient who had been previously treated for a pelvic abscess due to the effect of radiation therapy for cervical cancer and had no history of gastrointestinal perforation or intestinal disease. However, R. gnavus bacteremia was caused by the bacterial translocation of R. gnavus from the gut microbiota, which may have been due to damage to the intestinal tract caused by radiation. Thus, infection in the present case was possibly caused by translocation of R. gnavus from the intestinal tract damaged due to pelvic abscesses or radiation therapy for cervical cancer.
Previous R. gnavus infections reported susceptibility to penicillin and amoxicillin/clavulanic acid, meropenem, imipenem, cefotaxime, tetracycline, metronidazole, clindamycin, vancomycin, and piperacillin/tazobactam [5][6][7][8]10]. In the present case, the infection in the patient was susceptible to penicillin, ampicillin, ampicillin/sulbactam, imipenem, ceftriaxone, minocycline, vancomycin, piperacillin/tazobactam, and clindamycin. We obtained favorable results with TAZ/PIPC treatment. However, other antimicrobials are also sensitive to R. gnavus; Since there are few reports of Ruminococcus infections, it is considered necessary to accumulate a large number of cases in order to select the optimal antimicrobial drug. Since Ruminococcus is an intestinal bacterium, one must look for gastrointestinal lesions if one develops bacteremia with the organism. If there is no such cause, it is necessary to further search for causes such as the effects of radiation, immunosuppressive drugs, or immune disorders, and then bacterial translocation from the gastrointestinal tract should be suspected and treated.

Patient consent
Written informed consent was provided by the patient's legal guardian for the publication of this case report.

Author contribution statement
All authors listed have significantly contributed to the investigation, development and writing of this article.

Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.