Fusobacterium nucleatum Spondylodiscitis: Case Report and Literature Review An Joosten, M.D.,1 Jan Verhaegen, M.D., Ph.D.,1 and Eric Van Wijngaerden, M.D., Ph.D.,2 Departments of 1Microbiology and 2 Internal Medicine, University Hospitals Leuven, Leuven, Belgium Spondylodiscitis, also termed vertebral osteomyelitis, is uncommonly caused by anaerobic bacteria. In a study by McHenry et al. (1), only 2 of 255 (0.8%) cases of vertebral osteomyelitis were due to anaerobic bacteria. In both patients, Propionibacterium acnes was the causative organism (1), and it is the most frequent anaerobic bacterium responsible for spondylodiscitis (2). Spondylodiscitis is usually caused by facultative organisms, with Staphylococcus aureus being the bacterium Mailing address: Jan Verhaegen, M.D., Ph.D., Department of Microbiology, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium [email protected]
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most commonly isolated (1). We describe a 70-year-old patient with spondylodiscitis of the lumbar spine caused by Fusobacterium nucleatum.
Case Report A 70-year-old man was admitted to the emergency department of our university hospital in November 2009. His medical history included chronic rightsided brachialgia and numbness in the right C6 and C7 dermatomes. He complained of generalized weakness, loss of appetite, chills, and mild sweating for a week. On the day of admission, he experienced diffuse abdominal and lumbar back pain. His body temperature was 37.7°C. On physical examination, there was generalized tenderness on © 2011 Elsevier
palpation of the abdomen and abdominal rigidity, mainly in the right lower quadrant. There was tenderness on percussion over the spine from the second to the fourth lumbar vertebrae. Lasègue’s sign was positive on the right side. The patient had difficulty walking and had lumbar stiffness. Physical examination of the heart and lungs was normal. Laboratory tests showed a hemoglobin value of 12.6 g/dl, a white blood cell count of 5.8 x 109/L with 71.3% neutrophils, and a platelet count of 151 x 109/L. The C-reactive protein (CRP) level was 201.8 mg/L (normal value, <5 mg/L). Electrolytes and hepatic and renal function tests were normal. Chest and abdominal radiographs were unremarkable. An abdominal ultrasound and 0196-4399/00 (see frontmatter)
computed tomography scan of the abdomen showed no abnormalities and no evidence of appendicitis. Magnetic resonance imaging of the lumbar spine showed L3 to L4 edema and an epidural soft tissue structure at the right side of the L4 vertebral body level. An 18Ffluorodeoxyglucose (FDG) positronemission tomographic scan showed increased accumulation of FDG at the right side in the L3 and L4 vertebral bodies. These findings confirmed the clinical diagnosis of spondylodiscitis. Two anaerobic blood culture bottles of four sets collected at the time of admission became positive after 2 days of incubation using the BacT/ALERT 3D system (bioMérieux, Durham, NC). Three other anaerobic blood culture bottles of 10 sets taken during the 5 days before the start of antibiotic treatment also became positive. A needle aspiration of the spine was not performed, because the same organism was recovered from multiple blood culture bottles collected on different days. Bacterial growth on solid medium was observed after 3 days on Columbia blood agar medium incubated anaerobically at 37°C. Gram-stained smears showed the presence of fusiform, gram-negative bacilli. Therapy was begun with 1 g of amoxicillin-clavulanic acid administered intravenously (i.v.) three times a day, but this was changed the next day to 2 g of ceftriaxone i.v. daily and 500 mg of metronidazole orally twice daily (b.i.d). The isolate was further identified using the Anaerobe ID Mastring-S System MID8 (Mast Laboratories, Bootle, U.K.). Additional identification tests included a positive test for indole production but negative activities for lipase, catalase, urease, esculin hydrolysis, nitrate reduction, and beta-galactosidase. Negative fermentation reactions in CTA medium were observed for fructose, glucose, lactose, and mannose. By using these tests, the isolate was identified as F. nucleatum. We also identified the strain as F. nucleatum with the use of matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (Bruker Daltonics, Billerica, MA). The MICs of the strains determined by using the Etest (AB Biodisk, Solna, Sweden) on MuellerHinton blood agar were as follows: penicillin, <0.016 mg/L; clindamycin, 0.016 mg/L; metronidazole, <0.016 116
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mg/L; amoxicillin-clavulanic acid, 0.016 mg/L; chloramphenicol, 0.75 mg/L; piperacillin/tazobactam, <0.016 mg/L; meropenem, 0.003 mg/L; and tigecycline, 0.016 mg/L. Since the strain was susceptible to metronidazole, therapy with ceftriaxone was stopped after 3 days and monotherapy with 500 mg of metronidazole orally b.i.d. was initiated with an excellent clinical response. Because the patient developed mouth ulcers and an itchy skin rash on his chest and back after 3.5 weeks of treatment with metronidazole, therapy was switched to 600 mg of clindamycin orally three times a day. Therapy with clindamycin was stopped after 18 weeks. The patient improved symptomatically, The CRP level became normal, and an MRI showed decreased edema in the L4 vertebral body. He remained asymptomatic with a normal CRP level 6 weeks after discontinua-tion of all antibiotic therapy.
Discussion The genus Fusobacterium, which currently includes 13 species, is a heterogeneous group of gram-negative, non-spore-forming, nonmotile, anaerobic bacilli belonging to the family Bacteroidaceae, which includes the genera Bacteroides, Prevotella, Porphyromonas, Fusbacterium, and Leptotrichia. Fusobacteria are differentiated from the other genera by their production of major amounts of N-butyric acid alone; iso-butyric and iso-valeric acids are not produced (3,4). F. nucleatum is a member of the genus Fusobacterium. Five subspecies of F. nucleatum have been described from human flora: F. nucleatum subsp. nucleatum, F. nucleatum subsp. polymorphum, F. nucleatum subsp. vincentii, F. nucleatum subsp. fusiforme, and F. nucleatum subsp. animalis (3). Fusobacterium spp. are commonly found as normal flora of all mucosal surfaces, including the mouth, upper respiratory tract, gastrointestinal tract, and the female genital tract (4). Clinical infections with Fusobacterium spp. include infections of the head and neck, brain abscesses, and bacteremia (4-9). The most common Fusobacterium species found in clinical infections are F. nucleatum and F. necrophorum (610). F. nucleatum and F. necrophorum are also the most common causative © 2011 Elsevier
agents of Lemierre syndrome (11-16). We have described here a case of spondylodiscitis caused by F. nucleatum in a 70-year-old man. Spondylodiscitis caused by Fusobacterium spp. is rare. Thirteen cases have been reported in the literature (17-27). Eleven cases (1724,26) have been reviewed by Le Moal et al. (26). One case was excluded from the analysis because of the absence of description in the published series (25). Of the 13 remaining cases, including ours (17-24,26,27), F. nucleatum accounted for 7 (54%) of the cases, followed by F. necrophorum with 3 (23%), F. Varium with 1 (8%), and two species (15%) that were not further identified. The mean age of the patients was 50 years (range, 8 to 78 years), and the male/female ratio was 9:4. A previous ear, nose, or throat infection or maxillofacial problem was found in the nine (69%) patients without any other known portal of entry. Most patients with vertebral osteomyelitis have underlying risk factors, most commonly diabetes mellitus, intravenous drug abuse, immunosuppression, and malignancy (28). However, among the 13 patients with Fusobacterium sp. spondylodiscitis, only two had diabetes mellitus, and one had a history of alcohol abuse. The vertebral site of involvement was lumbar in eight (62%) patients, thoracic in two (15%), thoracolumbar in one (8%), lumbosacral in one (8%), and cervical in one (8%). Eight (62%) patients had a vertebral biopsy, and five of the eight (63%) were culture positive. A vertebral biopsy was not performed in the other five patients, because blood cultures permitted early identification of the bacterial cause of infection. Although they are infrequently isolated, anaerobic bacteria recovered from blood cultures should not be disregarded as a possible cause of spondylodiscitis. References 1. McHenry, M.C., K.A. Easley, and G.A. Locker. 2002. Vertebral osteomyelitis: long-term outcome for 253 patients from 7 Cleveland-area hospitals. Clin. Infect. Dis. 34:1342-1350. 2. Uçkay, I. et al. 2010. Spondylodiscitis due to Propionibacterium acnes: report of twenty-nine cases and a review of the literature. Clin. Microbiol. Infect. 16:353-358. 3. Citron, D.M. 2002. Update on the taxonomy and clinical aspects of the genus
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Fusobacterium. Clin. Infect. Dis. 35:S22-S27. Bennett, K.W. and A. Eley. 1993. Fusobacteria: new taxonomy and related diseases. J. Med. Microbiol. 39:246-254. Huggan, P.J. and D.R. Murdoch. 2008. Fusobacterial infections: clinical spectrum and incidence of invasive disease. J. Infect. 57:283-289. Su, C.P. et al. 2009. Fusobacterium bacteremia: clinical significance and outcomes. J. Microbiol. Immunol. Infect. 42:336-342. Brook, I. 1994. Fusobacterial infections in children. J. Infect. 28:155-165. Bourgault, A.M. et al. 1997. Fusobacterium bacteremia: clinical experience with 40 cases. Clin. Infect. Dis. 25(Suppl. 2):S181-S183. Epaulard, O. et al. 2006. The changing pattern of Fusobacterium infections in humans: recent experience with Fusobacterium bacteraemia. Clin. Microbiol. Infect. 12:178-181. Brazier, J.S. et al. 2002. Fusobacterium necrophorum infections in England and Wales 1990-2000. J. Med Microbiol. 51:269-272. Lemierre, A. 1936. On certain septicaemias due to anaerobic organisms. Lancet i:701-703. Syed, M.I. et al. 2007. Lemierre syndrome: two cases and a review.
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Laryngoscope 117:1605-1610. Riordan, T. and M. Wilson. 2004. Lemierre’s syndrome: more than a historical curiosa. Postgrad. Med. J. 80:328-334. Weeks, D.F. et al. 2010. Lemierre syndrome: report of five new cases and literature review. Emerg. Radiol. 17:323-328. Ridgway, J.M. et al. 2010. Lemierre syndrome: a pediatric case series and review of literature. Am. J. Otolaryngol. 31:38-45. Iwata, N. et al. 2010. Lemierre syndrome: a Japanese patient returning from Thailand. J. Infect. Chemother. 16:213-215. Fain, O. et al. 1989. Spondylodiscite à Fusobacterium nucleatum. A propos d’un cas. Rev. Rhum. Mal. Osteoartic. 56:339-340. Rubin, M.M., R.J. Sanfilippo, and R.S. Sadoff. 1991. Vertebral osteomyelitis secondary to an oral infection. J. Oral Maxillofac. Surg. 49:897-900. Soubrier, M. et al. 1995. Spondylodiscite à Fusobacterium nucleatum. A propos d’un cas. Presse Med. 24:989-991. Wang, T.D., Y.C. Chen, and P.J. Huang. 1996. Recurrent vertebral osteomyelitis and psoas abscess caused by Streptococcus constellatus and Fusobacterium nucleatum in a patient with atrial septal
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