Deep Brain Stimulator Infection by Oligella: A Case Report and Review of the Literature

Oligella is a commensal bacteria genus of the human urinary tract that rarely precipitates clinical infections. We report the case of an asymptomatic 24-year-old male with a medical history of Tourette syndrome and the recent placement of deep brain stimulator leads, which were found to be co-infected with Oligella species during hardware implantation. This is the first reported case of a deep brain stimulator infection by Oligella, a potentially under-recognized and emerging opportunistic bacteria. We review the previously published cases of extra-genitourinary Oligella infections and detail the clinical management of this uncommon pathogen.


Introduction
Oligella is a genus of aerobic Gram-negative coccobacilli comprising two species, O. ureolytica (formerly known as CDC group IVe) and O. urethralis (formerly known as Moraxella urethralis) [1]. These bacteria are particularly difficult to isolate using conventional laboratory techniques and knowledge of their antimicrobial susceptibility is limited [2]. Available data suggest that O. ureolytica are susceptible to far fewer antimicrobials than O. urethralis, yet both are generally susceptible to aminoglycosides and trimethoprim-sulfamethoxazole [2]. There is seldom cause to isolate Oligella species (spp.), as they are normally commensal within the human urinary tract and rarely precipitate clinical infections [2]. Pathogenic Oligella spp. are mostly encountered in the genitourinary tract, but both species have been implicated in respiratory infections of patients with cystic fibrosis, suggesting an additional tropism for the lower pulmonary tract [2]. Few other cases of extra-genitourinary infections by Oligella spp. have been reported in the literature and have included infections of the blood, lymphatics, and synovia [2][3][4][5][6][7][8][9][10][11][12]. Infections with Oligella spp. typically arise in patients with underlying medical conditions, particularly those associated with immunosuppression. Despite their low virulence, Oligella spp. may represent an under-recognized and emerging opportunistic pathogen [5]. Here we examine the first reported case of a deep brain stimulator (DBS) infection by Oligella spp. and provide a review of the literature on Oligella infections.

Case Presentation
A 24-year-old male with a past medical history of Tourette syndrome (diagnosed at the age of five years), depression, attention deficit hyperactive disorder, and obsessive-compulsive disorder were evaluated for the second procedure of elective DBS surgery. He was deemed a candidate for DBS placement because of uncontrolled tics of the bilateral upper extremities and head refractory to maximal medical management. In the first procedure, he underwent bilateral DBS leads implantation five weeks before the current admission, during which he was scheduled to have both leads connected to a pulse generator in the chest. This two-step process is the routine approach to DBS implantation. The patient denied any recent fever, chills or rigors, nausea, vomiting, or diarrhea, as well as any redness, pain, swelling, or drainage from the surgical site. A blood panel performed prior to surgery was notable for a white blood cell count of 11.0 x 10 9 cells/L (reference: 4-11 x 10 9 cells/L) and normal differential. During the procedure, the surgeon observed a significant amount of gelatinous material surrounding the connectors and harvested samples for a Gram stain. The stain showed Gram-positive cocci. Therefore, the hardware implantation procedure was aborted and the infected left-sided DBS hardware was explanted and sent for fungal, aerobic and anaerobic bacterial, and acid-fast bacilli cultures.
Broad-spectrum antimicrobials were initiated, including 750mg intravenous (IV) vancomycin every 12 hours, 2g IV cefepime every 12 hours, and 500mg IV metronidazole every eight hours. The aerobic cultures grew Corynebacterium spp., Oligella spp., and coagulase-negative Staphylococcus (CoNS) spp. Our laboratory does not perform the sensitivities for Corynebacterium spp. and so only the sensitivities for Oligella and CoNS are reported (Table 1). Unfortunately, due to temporary limitations of our laboratory, we were unable to 1 2 2  The patient admitted to vaping and occasional alcohol use but denied any history of illicit drug use. He suffered from tics and stated that if these occurred during micturition, urine would splatter and even reach his head. He further noted that he had not been applying surgical wound dressings since his initial DBS surgery. Once the sensitivities were finalized, the antimicrobials were narrowed to IV vancomycin and IV cefepime, which were continued for a total of six weeks following DBS lead removal. The patient did not report any side effects of treatment and vancomycin serum trough concentrations were monitored to maintain a level of 15-20mcg/mL. After the completion of antimicrobial therapy, the patient underwent reimplantation of the DBS lead and is now awaiting pulse generator placement.

Discussion
Tourette syndrome is a neuropsychiatric condition characterized by repetitive and non-rhythmic movements and vocalizations resulting from dysfunction in a basal ganglia-thalamo-cortical circuit [13]. In certain cases, these tics may be debilitating and resistant to medication, prompting the investigational use of DBSs [14]. The DBS is an implanted device consisting of a subcutaneous pulse generator, an extension wire, and an intracranial lead, which delivers electrical stimulations to target regions of the brain to treat movement disorders including Parkinson's disease, dystonia, and essential tremor [14]. As the clinical use of DBS increases, so does concern for infection of these devices with relatively common pathogens [15]. Estimates of DBS infection rates vary from 1% to 23%, with such a large range attributable to varying practices of antibiotic prophylaxis, surgical technique, and surveillance [15,16]. Infections may involve each of the three components of the DBS, though pulse generator infections occur most frequently [16].
DBS infections typically arise from common skin commensals, including Staphylococcus aureus, S. epidermidis, Pseudomonas aeruginosa, and Propionibacterium acnes [16]. Instances of DBS infections by atypical bacteria that are not skin commensals have been reported in the literature. However, in almost all cases, these have been with organisms common to the environment and have easily understood mechanisms of infection [16,17]. In this case, we found an intracranial lead infected by a combination of common skin flora (CoNS and Corynebacteria) and Oligella, an organism predominately found in the human urinary tract. Because the patient denied the use of surgical wound packing and reported occasional splashing of his head during micturition, we posit that a feasible source of infection was the patient's own urine.
A review of the literature yielded only 12 prior reported cases of infection by either Oligella spp. ( Table 2). In nearly all cases, infections occurred in patients with an identified source of immunosuppression, including malignancy, AIDS, and newborn status. Obstruction of the urinary tract also appeared to be a predisposing factor for Oligella bacteremia. In two cases (both infections with O. ureolytica), patients had wounds thought to be the nidus of infection, including one elderly woman who had fallen and spent four days laying in her own urine [4,5]. Oligella infections may be more common than reported, as many laboratories do not pursue the identification of uncommon bacteria to the genus level and few incubate cultures for the four days required by Oligella spp. [5].  Approaches to managing DBS infections are variable and depend upon the extent of the infection [17]. Initial empiric antibiotic therapy should cover commonly encountered pathogens, while treatment after susceptibility determination should target the identified organisms [16]. Antibiotic therapy is infrequently sufficient for treating DBS infections, and its combination with partial or complete removal of hardware is often required [17]. Complete system removal is necessary when there is evidence of intracranial lead infection [16]. In this case, with a Gram stain of gelatinous material surrounding the connector site showing Gram-positive cocci, the entire system was explanted and the patient was started on broad-spectrum IV antibiotics. The ultimate antibiotic choice was determined by sensitivity testing and the treatment duration of six weeks was chosen based on the typical approach to managing cerebritis. Without a complete device removal, however, the patient would have likely experienced recurrent infections following antibiotic treatments.

Conclusions
While the proposed mechanism of infection in the current case is extremely unlikely for most patients receiving DBS implantation, we believe that this case highlights the vulnerability of these systems to relatively avirulent organisms, as well as the growing recognition of Oligella as a source of opportunistic infection. Providers should appreciate the unusual causes of DBS infection and should consider Oligella as a potential pathogen when cultures are negative for common skin flora. Reporting novel cases of infection may be valuable for guiding provider decisions on antimicrobial treatment choices and methods of administration.

Additional Information Disclosures
Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.