First report of spondylodiscitis caused by Bacillus circulans in an immunocompetent patient: Clinical case and review of the literature

Highlights • Vertebral osteomyelitis represents for clinicians a challenging infection to manage and treat.• Bacillus circulans is mainly considered as a rare, opportunistic pathogen in immunocompromised patients.• We report a spondylodiscitis caused by Bacillus circulans in an immunocompetent patient.• To date, this is the first case reported in literature.• The clinical case was described and all published Bacillus circulans infections were reviewed


Introduction
Bacillus circulans is a gram-positive, rod-shaped organism. It is motile via peritrichous flagella and produces endospores. Bacillus circulans is found in soil, sewage, food, and infant bile. This bacterium is also isolated from gut of bee larvae [1].
In the literature, few cases of infection caused by Bacillus circulans are described. It is mainly considered as an opportunistic pathogen in immunocompromised patients. However, many different infections have been reported: bacteremia, abscesses, meningitis, endophthalmitis, and wound infections.
Recently, we observed a spondylodiscitis caused by Bacillus circulans in an immunocompetent patient. To date, this is the first case reported in literature. For this reason, we described the clinical case and reviewed all published cases of infection caused by Bacillus circulans.

Case report
A 65-year-old Caucasian man with a history of hypertension, was evaluated in February 2020 for prolonged lower back pain. Before the evaluation, the patient reported a history of low-grade fever for 1 month associated with severe diarrhea for 2 weeks in the previous 2 months. At the visit, blood exams showed a Creactive protein (CRP) of 15 mg/l (normal value <5.0). He underwent a lumbar spine magnetic resonance imaging (MRI) that highlighted a suspected spondylodiscitis at L5-S1. Empirical antibiotic therapy with amoxicillin/clavulanate plus minocycline was started after percutaneous bone biopsy, without any improvement of symptoms and reduction of CRP value. After biopsy, blood cultures were collected. All other possible etiologies of spondylodiscitis were excluded (i.e., Mycobacterium tuberculosis, Brucella spp). A transthoracic echocardiography was performed, excluding the presence of endocarditis. Bone culture resulted sterile and patient was treated for 6 weeks with the same antibiotic regimen.
On the third month, clinical symptoms did not improve. Worsening lower back pain and a repeat increment of CRP required a new infectious diseases consultation. A new lumbar spine MRI was performed, showing the persistence of heterogeneous lesions in L5 and S1 with increased signal in T2-weighted ( Fig. 1-b,e), STIRweighted images ( Fig. 1-c), hypo-signal in T1-weighted images ( Fig. 1-a,d). The changes were registered at L5 and S1 vertebral bodies as bone edema and L5-S1 intervertebral disc as increased water content. After contrast administration, the images were highly suggestive for spondylodiscitis L5-S1 ( Fig. 1-f,g). No findings of inflammatory purulent process of the iliopsoas muscles and/or paraspinal or subdural/epidural phlegmon or abscess were detected.
Considering the clinical, radiological and laboratoristic findings, it was decided to perform another vertebral and disc biopsy. The patient was positioned in the prone position on the radiological table with the spine extended to increase the disc space in L5-S1. Two small skin incisions were made: one access for both L5 and S1 pedicles and the other, more lateral, for L5-S1 trans-foraminal disc  approach. Unilateral transpedicular approach was performed with a 13-gauge bone biopsy needle under fluoroscopical guidance (OEC Brivo Plus, GE Healthcare, USA). The needle was introduced first into L5 body through the left pedicle and bone biopsy was performed; another sterile needle was introduced into S1 body always through the left pedicle and a bone biopsy was obtained. At last, transforaminal L5-S1 disc biopsy was performed using percutaneous endoscopic forceps through an 11-gauge working cannula on the left side (Fig. 2). No intra-or post-procedure complications occurred. Left approaches were chosen because of previous L5 at the right side transpeduncolar biopsy 3 months before, that resulted negative. The duration of the whole procedure was about 70 min. Patient was discharged the day after.
Cultures of bone and disc showed the growth of Bacillus circulans. The organism was identified using MALDI-TOF mass pectrometry (MS) (Bruker Daltonics) and the Vitek 2 automated system (bioMérieux, Marcy l'Etoile, France) for antimicrobial susceptibility testing. Minimum inhibitory concentrations (MICs) were established according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints. The strain showed susceptibility to erythromycin, vancomycin, chloramphenicol, gentamicin and levofloxacin. It showed resistance to penicillin, clindamycin, tetracycline, cefazolin and cefotaxime.
After 2-week treatment with intravenous teicoplanin, the patient completed 4 weeks of oral levofloxacin, 750 mg once daily. At the end of therapy, the CRP value normalized with a complete resolution of clinical symptoms. A 18 F-Fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT), after 1 month, resulted negative.

Discussion and review of literature
To our knowledge, this is the first case described in the literature of vertebral osteomyelitis (VO) caused by Bacillus circulans.
Bacillus circulans is considered as an opportunistic pathogen [1]; in the described cases it was also recognized as the etiology of endocarditis, abscesses, endophthalmitis, and meningitis in humans as reported in Table 1. Moreover, a case of sepsis of unknown origin in an immunocompromised patient was described in 2011, which later led to patients' death. Finally, it was also associated with wound infection in 1985. In the literature there are reported 12 cases of documented infection caused by Bacillus circulans [2][3][4][5][6][7][8][9][10][11][12][13], and 3 cases in which Bacillus circulans was considered a possible etiology of infection [14].
Of importance, Bacillus spp are rarely implicated in infections and are frequently isolated as a culture contaminant. However, spores are found ubiquitously including in the hospital environment. The production of toxins and tissue invasion contribute to a range of diseases. Of interest, the spectrum of infections and susceptibility to antibiotics result similar to Bacillus cereus [1]. For this reason, a careful clinical evaluation is crucial to assess the significance of the isolation of a Bacillus organism from cultures. Clinical infections caused by Bacillus spp can mainly be categorized into gastrointestinal and non-gastrointestinal diseases; the latter are usually the etiology of local or systemic infections [1]. Although Bacillus spp. have not been recognized as major human pathogens, with recent advances in medical technology and an increased number of immunosuppressed patients they have been increasingly recognized as opportunistic pathogens especially in the hospitalized patient. Our patient reported a severe diarrhea for 2 weeks in the previous 2 months before diagnosis of spondylodiscitis. Probably, gastrointestinal inflammation with translocation of Bacillus circulans was favored to be the source of the lumbar osteomyelitis.
In the literature, in immunocompetent patients were described few cases of acute and chronic osteomyelitis caused by Bacillus cereus, the most important pathogen for humans among Bacillus spp. Interestingly, Fritzell and coworkers reported an experience about the detection of bacterial DNA in painful degenerated spinal discs. This in turn may be in patients without signs of clinical infection. One patient with disc hernia harbored DNA homologous to Bacillus cereus, and the authors concluded that 16S rRNA PCR can be a useful tool in search of bacterial DNA in degenerated discs, which in turn may be indicative of low-grade infection, manifesting itself only as pain rather than as clinical infection [15].
In conclusion, this clinical case represents a step toward a better knowledge of Bacillus spp, including Bacillus circulans and its related infections. As reported in the literature, Bacillus spp may be associated with indolent and/or chronic infections, also involving bone and causing osteomyelitis. Most cases of Bacillus circulans infection are associated with hospitalization in immunodeficient patients as reported in Table 1; however, we reported here a first case observed in immunocompetent patients from the community using a high-standard quality methodology for bone and disc biopsy.

Author statement
On behalf of all authors, I declare no conflict of interest for the manuscript "First report of spondylodiscitis caused by Bacillus circulans in an immunocompetent patient: clinical case and review of the literature".

Funding
No funding.

Concent
Consent: Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request

Ethical approval
None.

Author contribution
Please specify the contribution of each author to the paper, e.g. study design, data collections, data analysis, writing, others, who have contributed in other ways should be listed as contributors. Alessandro Russo and Riccardo Iundusi collected data and wrote the paper; Umberto Tarantino, Gabriella d'Ettorre, Carlo Della Rocca, Giancarlo Ceccarelli, Elena Gasbarra, Mario Venditti wrote and revised the paper.

Declaration of Competing Interest
The authors report no declarations of interest.