Brain Abscess Caused by Bordetella hinzii

PRACTICAL IMPLICATIONS

Consider Bordetella hinzii as a cause of intracranial abscess in both immunocompetent and immunocompromised patients.

Case

A 60-year-old, well-traveled botanist with a history of chronic sinusitis and treated stage IV follicular lymphoma presented to an outside facility with 2 weeks of progressive headache and nausea.

On initial presentation, brain MRI demonstrated a right anterior temporal lobe lesion (Figure 1A). The mass was resected. Pathology demonstrated a reactive inflammatory infiltrate with hemorrhage. Bacterial, fungal, and acid-fast bacterial (AFB) cultures were unremarkable. The local hospital initiated antibiotics and steroid therapy (see timeline Figure 2). MRI showed reduced edema and enhancement around the resection cavity in response to both treatments (Figure 1B).

Figure 1. Representative MRI Sequences.

(A) Initial pretreatment MRI shows an expansile lesion in the right anterior temporal lobe that contains intrinsic T1 hyperintensity (left, arrow), T2 hypointensity with surrounding T2 hyperintensity in a pattern consistent with vasogenic edema (middle, arrow), and heterogeneous gadolinium enhancement on T1 postcontrast images (T1+C; right, arrow). (B) MRI after first antibiotic and steroid treatment shows attenuation of enhancement on T1 postcontrast sequences and decreased T2 hyperintensity. (C) MRI at 3 months after presentation shows re-emergence of pathology after antibiotic discontinuation (see timeline figure 2), with enhancement on T1 postcontrast sequences (top, arrow) and T2 hyperintensity (bottom, arrow). (D) MRI after 3 months of trimethoprim sulfamethoxazole therapy shows stable reduction in enhancement and T2 hyperintensity. Note ventricular enlargement is presumed because of interval resection. Scale bar 2 cm.

Figure 2. Timeline.

Important symptoms (black), imaging findings (green), surgical procedures (red), and medical treatments (blue) are shown. abx = antibiotics; Bx = biopsy; Cx = culture; dex = dexamethasone (variable course); sz = seizure; TMP/SMX = trimethoprim sulfamethoxazole; WBC = white blood cell. Antibiotic regimens: Abx 1 = 6-week course of vancomycin, ceftriaxone, and metronidazole; Abx 2 = 10-week course of initially ceftriaxone, linezolid, and metronidazole, followed by ceftriaxone (later replaced by meropenem), voriconazole, and daptomycin; Abx 3 = 4-day course of ceftriaxone, vancomycin, metronidazole, and voriconazole. *Bordetella hinzii confirmed retrospectively by universal PCR on resected tissue. CSF studies: opening pressure 21 cm H₂O; protein 39 mg/dL; glucose 43 mg/dL (serum 94 mg/dL); WBC 69 cells/mm³ (58% neutrophils, 8% lymphocytes, and 34% monocytes); immunoglobulin G index 0.8; and no oligoclonal bands.

Two weeks later, the patient experienced a seizure with left hemibody shaking. MRI showed recurrent right temporal enhancement and edema (Figure 1C). He received additional antimicrobial and steroid therapies. His clinical symptoms and radiographic abnormalities improved but subsequently recurred when therapies were discontinued, leading to a second resection, further antimicrobial and steroid therapies, and transfer to our facility when he developed recurrent seizures and left-sided weakness despite treatments.

On transfer, his vital signs and general examination were normal. Neurologic examination was notable for pyramidal weakness of his left upper extremity. The results of broad serologic testing and whole body imaging were negative. CSF sampled 5 days after discontinuing antimicrobial medications demonstrated hypoglycorrhachia, normal protein, and a neutrophilic pleocytosis (Figure 2). Metagenomic next-generation sequencing of the CSF was negative.

Two weeks later, AFB blood culture and CSF fungal culture grew a fastidious Gram-negative rod, ultimately identified as Bordetella hinzii. The original biopsy specimen was sent for 16S bacterial sequencing and positive for B hinzii as well, confirming the presence of this organism in his presenting brain abscess. He started treatment with trimethoprim-sulfamethoxazole based on antimicrobial susceptibility reported in the literature.¹ He had sustained improvement in his radiographic abnormalities (Figure 1D) and clinical symptoms.

Discussion

We describe a case of B hinzii bacteremia and brain abscess. Similar to other brain abscesses, imaging was notable for a mass-like lesion with surrounding vasogenic edema. CSF analysis was typical of bacterial infection with hypoglycorrhachia and a neutrophilic pleocytosis. The patient ultimately responded to appropriate antimicrobial therapy. Although steroid therapy was initiated—theoretically to address an inflammatory process—steroid therapy is not indicated for abscess treatment and may have delayed the diagnosis and potentiated ongoing infection.

The Bordetella sp. consists of 9 Gram-negative rod-shaped species that infect various animals, including rodents, rabbits, dogs, birds, and humans.² Bordetella species most commonly cause respiratory tract disease but have also more rarely caused bacteremia, skin and soft tissue infections, and endocarditis.³ B hinzii was first isolated from human sputum in 1957 and deemed a new species in 1995 when it was identified in avian respiratory tracts.^4-6 The first described human B hinzii infection involved bacteremia and thrombophlebitis in a 42-year-old man with AIDS.² Additional reports of human infection are rare, including 6 reported respiratory infections;^1,7,e1-e3 5 reports of bacteremia, including 2 with endocarditis;^2,e4-e7 1 report of cholangitis;^e8 and 1 report of cutaneous abscess.^e9 Bordetella species, including B hinzii, have mainly been described to cause infection outside the CNS.

Our patient had multiple possible sources of B hinzii transmission and infection. Although B hinzii is found ubiquitously throughout the world, our patient had zoonotic exposure of birds through his travel in jungles in Southeast Asia. In addition, he had rodent exposure through his home. His chronic sinusitis was also a potential source of colonization and subsequent dissemination, given the strong affinity of B hinzii and other Bordetella species for the upper and lower respiratory tracts.^e10

The fastidious growth of B hinzii makes it challenging to isolate in culture.^e9 Multiple cultures may be required to successfully isolate the organism. In addition, the sensitivity of newer molecular techniques is unknown and likely variable. The yield of gene sequencing may be affected by external factors such as tissue processing. Pathogen identification also relies on the quality of the corresponding gene sequencing library. In our patient, B hinzii infection was confirmed through 16S ribosomal RNA sequencing, but initial metagenomic sequencing was aligned to a gene library that did not contain B hinzii, providing 1 explanation for his negative testing.

In conclusion, this is an unusual case of a brain abscess caused by B hinzii. B hinzii should be considered a potential cause of CNS infection in both immunocompetent and immunocompromised patients. When suspected, cultures should be repeated and held for a prolonged period of time, and a multimodal approach using novel molecular techniques can be crucial for increasing the likelihood of successfully identifying this rare pathogen.

Appendix. Authors

Study Funding

The authors report no targeted funding.

Disclosure

N. Mehta, J. Gerdts, and M. Fung report no disclosures relevant to the manuscript. E.L. Guterman received funding from the National Institute of Neurological Disorders and Stroke (1K23NS116128-01), the National Institute on Aging (5R01AG056715), and the American Academy of Neurology, consulting fees from Marinus Pharmaceuticals, Inc., and honoraria from Knowledge to Practice. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp.