Diagnostic Microbiology and Infectious Disease 78 (2014) 491–493
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Fusobacterium spondylodiscitis: case report and literature review Allen T. Grifﬁn a, b,⁎, Diana Christensen a a b
University of Louisville, School of Medicine, Department of Medicine, Division of Infectious Diseases, Louisville, KY 40292USA University of Utah, Associated Regional and University Pathologists, Division of Microbiology, Salt Lake City, UT 84108USA
a r t i c l e
i n f o
Article history: Received 4 July 2013 Received in revised form 21 August 2013 Accepted 23 August 2013 Available online 24 January 2014 Keywords: Fusobacterium nucleatum Vertebral osteomyelitis Discitis
a b s t r a c t Fusobacteria are obligate anaerobic bacilli residing in the oral cavity, female genital tract, and intestine. These pathogens are typical components of head, neck, and abdominal abscesses due to contiguous spread from adjacent mucosal surfaces. They are unusual etiologies, however, of bone and joint infections, particularly outside the cranial region. We report an unusual case of hematogenous lumbar spondylodiscitis caused by Fusobacterium nucleatum of suspected odontogenic origin. © 2014 Elsevier Inc. All rights reserved.
1. Introduction Fusobacteria are Gram-negative, obligate anaerobic bacilli indigenous to the oral cavity, female genital tract, and distal gastrointestinal tract. As a component of polymicrobial infections, these bacteria are commonly present in head, neck, and abdominal abscesses due to contiguous spread from their usual habitats (Citron, 2002). However, these organisms occasionally cause otitis media and its associated sequelae (Le Monnier et al., 2008); sinusitis (Brook and Hausfeld, 2011); pulmonary abscesses (Mori et al., 1993); bacteremia in those with neutropenia (Fanourgiakis et al., 2003); and, rarely, bone and joint infections (Brook and Frazier, 1993). Particularly unusual is the ﬁnding of fusobacteria as agents of vertebral osteomyelitis. We report an instance of Fusobacterium nucleatum as the sole etiology of vertebral osteomyelitis in which hematogenous acquisition from an odontogenic source is postulated. 2. Case report A 38-year-old Caucasian male was referred to the University of Louisville hospital for 2 months of back pain. Previous magnetic resonance imaging (MRI) performed at another institution demonstrated osteomyelitis of the third and fourth lumbar vertebrae with intervening discitis. Computed tomography (CT)–guided vertebral biopsy executed on an outpatient basis at this outside institution revealed negative aerobic and anaerobic cultures as well as Gram, fungal, and acid-fast staining, despite aspiration of purulent ﬂuid and no prior antibiotic administration. The referral to the University of Louisville hospital, a tertiary care center in Louisville, Kentucky, occurred due to inability to ascertain an etiology. ⁎ Corresponding author. Tel.: +1-801-583-2787x3592. E-mail address: allen.grifﬁ[email protected]
(A.T. Grifﬁn). 0732-8893/$ – see front matter © 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.diagmicrobio.2013.08.025
Upon referral, the patient relayed that his current back pain began 1 month subsequent to a rollover all-terrain vehicle (ATV) accident. During the accident, the patient had minor skin abrasions and a back strain. He recovered uneventfully until resurgence of back pain 1 month later that culminated in the aforementioned investigation and ultimate referral. His current episode of pain was associated with intermittent daily elevations of temperature to 102 °F, a 20-pound weight loss over 2 months, decreased appetite, night sweats, and malaise. In total, the current illness, beginning with resurgence of back pain after the ATV incident, spanned 2 months. The patient recalled no headache, vision changes, gastrointestinal complaints, skin lesions, urinary symptoms, arthralgias, or limb weakness. The patient had no previous medical or surgical history. He was taking acetaminophen and ibuprofen for pain but had taken no antibiotics in recent memory. He had had no formal dental evaluation in 2 years. While he consumed occasional alcohol, he had no history of tobacco or recreational drug use. He was raised in southern Virginia but currently resided in a suburban area outside Louisville, Kentucky, where he was employed in construction. He recounted remote, brief periods of travel to Madrid, Spain, and Cancun, Mexico. Finally, he had never been incarcerated, had never been homeless, and recalled no exposure to tuberculosis. Upon admission to our institution, physical examination was relevant for the following: temperature, 97.6 °F; pulse, 82 beats/ minute; respiratory rate, 18 breaths/minute; and blood pressure of 107/63 mm Hg. The patient did not appear acutely ill. He was noted to have gingivitis and exquisite tenderness upon palpation of the lumbar spine. He had normal cardiac, pulmonary, abdominal, genitourinary, neurologic, and dermatologic exams. Remarkable laboratory ﬁndings were a white blood cell count of 12,200 cells/mm 3 with 70% mature granulocytes, an erythrocyte sedimentation rate of 80 mm/h, a Creactive protein of 5.02 mg/dL (normal 0.00–0.49 mg/dL), and a procalcitonin of 2.4 ng/mL (normal b0.1 ng/mL). Electrolytes, serum
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creatinine, and liver functions tests were within normal limits. The MRI from our institution is depicted in Fig. 1. Antibiotics were not begun due to the patient's stability and indolent course. To elucidate the etiology of the osteomyelitis, 3 sets of standard aerobic and anaerobic blood cultures each held for 5 days, in addition to a lysis centrifugation blood culture held for 6 weeks, were performed and were negative. Serologies for Bartonella henselae, Bartonella quintana, Brucella species, and Blastomyces dermititidis were likewise negative, as was a QuantiFERON®-TB Gold In Tube (Cellestis, Hilden, Germany). Due to the continued inability to ascertain a pathogen, open surgical biopsies were procured. Five separate samples from the relevant vertebral bodies and disc were sent for aerobic and anaerobic cultures as well as Gram staining, Calcoﬂuor white staining for fungi, and auramine-O ﬂuorescent staining for mycobacteria. Aerobic specimens were placed in non-bacteriostatic saline, while anaerobic specimens were transported in anaerobic transport media. All stains were negative, and aerobic cultures yielded no growth after 5 days. However, upon 5 days of incubation, 2 of 5 anaerobic cultures (on Brucella blood agar plates) that contained material from both of the involved vertebrae and the disc produced a ﬁlamentous, Gram-negative bacillus later identiﬁed via the Rapid ID™ ANA II panel (Remel, Lenexa, KS, USA) as a Fusobacterium species. Subsequently, by 16 s-rRNA sequencing (Quest Laboratories, Chantilly, VA, USA), this pathogen was conﬁrmed as F. nucleatum. Mycobacterial and fungal cultures yielded no growth after 6 weeks. After conﬁrming the etiology, the patient was initiated on intravenous ertapenem at 2 grams per day pending susceptibility testing. The higher 2-gram-dosing strategy of ertapenem was chosen due to difﬁculties in general with antibiotic penetration in osseous tissue and the proclivity for protein binding with ertapenem speciﬁcally. Antibiotic sensitivities were subsequently performed
using anaerobic microbroth dilution with conﬁrmatory beta-lactamase testing with a nitroceﬁn disk. These results conﬁrmed the Fusobacterium to be susceptible to metronidazole and penicillin, but resistant to clindamycin; no beta-lactamase was detected. The patient later underwent extensive debridement of the lumbar spine that culminated in fusion of the second through the ﬁfth lumbar vertebrae with a cobalt chrome rod. Fusion was undertaken 5 days after antibiotic therapy was commenced; therefore, further microbiologic studies were not pursued. A colonoscopy and CT of the abdomen were subsequently performed to uncover a potential bowel lesion or ﬁstula that may have produced bacterial translocation, but only a single incidental tubular adenoma was discovered. An enzymelinked immunosorbent assay for antibodies to Strongyloides stercoralis that is endemic in Kentucky and may potentially lead to enteric bacterial translocation was likewise negative. Thus, given lack of an alternative site as the origin of the Fusobacterium, it was hypothesized that the patient had hematogenous seeding of the spine related to transient bacteremia from gingivitis. The previous back strain was thought to have created vulnerability in the lumbar spine. While it was suggested to the patient to switch to continuous infusion penicillin given the sensitivity of the Fusobacterium, he preferred the convenience of once-daily ertapenem. Chlorhexidine oral rinses were initiated for gingivitis, and a formal dental consultation with oral panoramic radiographs revealed no additional abnormalities. The patient was followed in a clinic and treated for a total of 6 weeks with ertapenem during which time his erythrocyte sedimentation rate declined to 5 mm/h and his C-reactive protein to b0.1 mg/ dL. At the conclusion of induction therapy with ertapenem due to retained orthopedic hardware, the patient was initiated on suppressive amoxicillin at 500 mg per day to continue indeﬁnitely. 3. Discussion
Fig. 1. MRI with gadolinium contrast (T2-weighted) demonstrating vertebral osteomyelitis at the third and fourth lumbar vertebrae with intervening discitis.
Fusobacteria are obligate anaerobic, Gram-negative, non–sporeforming bacilli of the Fusobacter phylum and Fusobacteriaceae family (Citron, 2002). Regarding pathogenic genera, fusobacteria are most closely related phylogenetically to Streptobacillus (Nolan et al., 2009) and Leptotrichia species (Ivanova et al., 2009). While found transiently on the skin, fusobacteria are present predominantly in the oral cavity, distal gastrointestinal tract, and female genital tract (Citron, 2002). Common infectious manifestations of these pathogens are polymicrobial in nature related to breach of adjacent mucosal barriers; therefore, abscesses of the mouth, female genital tract, and abdomen are usual. Fusobacteria have also been associated with sinusitis (Brook and Hausfeld, 2011); otitis media typically in young children (Le Monnier et al., 2008); mastoiditis (Yarden-Bilavsky et al., 2013), meningitis (Angelino et al., 2012), and brain abscess (Shimohata et al., 2012) related to contiguous spread from the middle ear, sinus, or oral cavity; and lung abscess in those prone to aspiration (Mori et al., 1993). Bacteremia in the setting of chemotherapy-induced mucositis and neutropenia has also been documented (Fanourgiakis et al, 2003). Lemierre's syndrome, a well-characterized clinical entity associated with Fusobacterium necrophorum speciﬁcally, is marked by a progressive peritonsillar abscess with resultant septic thrombophlebitis of the internal jugular vein and additional metastatic complications (Lemierre, 1936). Fusobacterial osteomyelitis or joint infection, while uncommon in any anatomic locale, is typically related to contiguous spread from an antecedent cranial infection, such as progressive otitis and mastoiditis (Gebhardt et al., 2011; Jacobsen et al., 2012), though hematogenous osteomyelitis of the long bones (Lee et al., 2012) and vertebrae (Ramos et al., 2013) has been documented exceptionally. Anaerobic vertebral osteomyelitis as a clinical entity in general is distinctly rare, regardless of organism. Bacteroides species, likely due to
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their enhanced pathogenicity compared to other obligate anaerobes, is the most prevalent etiology followed by anaerobic cocci, Propionibacterium acnes, clostridia, and fusobacteria (Saeed et al., 2005). Cases of F. nucleatum or F. necrophorum localized predominantly to the epidural and paravertebral structures without major concomitant bony involvement have been elucidated and were related to an odontogenic source (Goolamali et al., 2006; Guerrero et al, 1978; Park et al., 2006). Vertebral osteomyelitis, however, as the primary manifestation of spinal infection with fusobacteria has been described in the setting of Crohn's disease related to presumed hematogenous spread from the intestine (Ramos et al., 2013). Additional instances, primarily involving children and manifesting in the lumbar spine, were also presumed to be due to hematogenous seeding associated with Lemierre's syndrome or periodontal disease (Brook, 2001; Klinge et al., 2002; Le Moal et al., 2005; Peer Mohamed and Carr, 2010; Rubin et al., 1991; Wang et al., 1996). One of these instances simultaneously involved F. nucleatum and the Streptococcus anginosus group (Wang et al., 1996), while the remaining were monomicrobial. Though blood cultures were negative in the majority of these instances, as in the current case, hematogenous spread was inferred due to lack of an association with a contiguous infection at the spinal site involved. An additional case of fusobacterial vertebral osteomyelitis, in contrast, transpired in an elderly man with no clear source delineated (Soubrier et al., 1995). When identiﬁed to species level, the most common isolate in these cases was F. nucleatum followed by F. necrophorum, all of which did not produce beta-lactamase, except for a single F. nucleatum isolate (Brook, 2001). Finally, an instance of concomitant Actinomyces israelii and F. nucleatum spreading to the thoracic spine from a chest abscess has been elaborated (Honda et al., 2008). All of these reported cases resolved successfully with combined surgical intervention and beta-lactam therapy with or without metronidazole or clindamycin alone. 4. Conclusion We present an unusual case of lumbar vertebral osteomyelitis due to F. nucleatum from an odontogenic source. Our case resembles past reports in anatomic localization to the lumbar spine and the oral source. Our case was treated successfully with ertapenem and surgery but illustrates that clindamycin should be employed cautiously if sensitivities are not available, as resistance may exist. References Angelino G, Cantarutti N, Chiurchiù S, et al. Fulminant Fusobacterium necrophorum meningitis in an immunocompetent adolescent. Pediatr Emerg Care 2012;28: 703–4. Brook I, Hausfeld JN. Microbiology of acute and chronic maxillary sinusitis in smokers and nonsmokers. Ann Otol Rhinol Laryngol 2011;120:707–12.
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