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FINAL DIAGNOSIS: Fusobacterium necrophorum bacteremia, rule out Lemierre's Syndrome
Summary of Hospital Course
This patient presented with fever, headache, and pain on the right side of his neck and face with localization to the right mandible. A lumbar puncture and nonconstrast CT of the head, performed to evaluate for meningitis, were negative. He was subsequently given one dose of intravenous ceftriaxone. The growth of gram-negative rods in an aneorobic blood culture prompted additional antibiotic treatment consisting of ampicillin/sulbactum and gentamicin. The patient's antibiotic regiment was then switched to penicillin once the identification of the microbe as Fusobacterium necrophorum on hospital day two was established. Panex radiographs revealed abscesses of the periapical right 2nd molar and right sublingual space. He was taken to the OR on hospital day four, where extractions of teeth 30 and 32 and incision and drainage of the right sublingual space abscess was performed under general anesthesia. The patient's symptoms improved and he was discharged home on hospital day five.
Fusobacterium necrophorum and Lemierre's Syndrome
Fusobacterium organisms are anaerobic, non-motile, gram-negative bacilli and include F. necrophorum, F. nucleatum, F. mortiferu, F. varium, F. gonidaformans, F. alocis, F. pseudonecrophorum, F. salci, and F. ulcerans. Microscopically, they are characterized by slender or fusiform rods with tapered ends, though some species may be pleomorphic. Fusobacterium is included in the genera of anaerobic, gram-negative, non-spore-forming bacteria, which include Bacteroides, Prevotella, and Porphyromonas. Fusobacterium can be differentiated from these other gram-negative, obligate anaerobes by its ability to produce significant amounts of butyric acid from glucose, giving cultured colonies a characteristic odor. Identification in the laboratory is made by morphology and the following biochemical assays:
| Indole | Positive |
| Lipase | Positive |
| Hydrogen sulfide | Negative |
| Catalase | Negative |
| Esculin | Negative |
| Catalase | Negative |
Fusobacterium species are normal inhabitants of all mucosal surfaces, including the mouth, upper respiratory tract, gastrointestinal tract, and urogenital tract. Worldwide, F. nucleatum is the most common Fusobacterium species found in clinical infections, while F. necrophorum is the most virulent. The species is generally susceptible to penicillin, clindamycin, and chloramphenicol and resistant to erythromycin and macrolides.
Though part of the normal flora of human tissues, Fusobacterium can invade tissues after surgical or accidental trauma, edema, anoxia, and/or tissue destruction. F. necrophorum contains particulary powerful endotoxic lipopolysaccharides in its cell wall and produces a coagulase enzyme that encourages clot formation. Additionally, it produces a variety of exotoxins, including leukocidin, hemolysin, lipase, and cytoplasmic toxin, all of which likely contribute to its pathogenicity.
In the case presented, the patient's long history of poor oral hygiene resulting in gingival breaks provided ample access for bacterial penetration, bacteremia, and abscess formation. Thus, the obvious source for the patient's F. necrophorum bacteremia was the oral cavity. Once this diagnosis is made, it is imperative to evaluate for the presence of Lemierre's syndrome.
Lemierre's syndrome (LS), or postanginal septicemia, typically occurs in healthy young adults and is caused by an acute oropharyngeal infection with secondary septic thrombophlebitis of the internal jugular vein and frequent metastatic infections. Fusobacterium necrophorum is the usual etiologic agent. There is little data on its epidemiology, though one Danish study reported an incidence of 0.8/1,000,000.
LS was first described by the French physician Lemierre in a Lancet article published in 1936. In describing 20 cases of the syndrome, Lemierre said:
"To anyone instructed as to the nature of these septicemias it becomes relatively easy to make a diagnosis on the simple clinical findings. The appearance and repetition several days after the onset of a sore-throat . . . of severe pyrexial attacks with an initial rigor, or still more certainly the occurrence of pulmonary infarcts and arthritic manifestations, constitute a syndrome so characteristic that mistake is almost impossible. Certain diagnosis is established by bacteriological examination. Bacteroides fundiliformis (now known as F. necrophorum) is easy to discover . . . blood culture on anaerobic media . . . gives the earliest definite information."
The disease progresses in several steps. Pharyngitis typically occurs first followed by local invasion of the lateral pharyngeal space and internal jugular vein thrombophlebitis (IJVT). During this stage, patients often complain of a tender neck. Confirmation of IJVT may be made with contrasted CT or MRI scan of the neck, or with Doppler ultrasound (Figure A). Metastatic complications, most often occuring in the lung in the form of non-cavitating pulmonary infiltrates, is the last stage and is documented in 90% of cases at the time of diagnosis. In contrast to Lemierre's preantibiotic era, cavitating pulmonary infarcts and septic arthritis are now relatively uncommon. Other complications include vocal cord palsy, splenic/hepatic abscesses, soft tissue infection, vesiculopustular rash, meningitis, disseminated intravascular coagulation, acute renal failure, and acute respiratory distress syndrome (see Table 2).
Fig. A Axial contrast-enhanced CT image of the neck shows left-sided internal jugular vein thrombosis (arrow).
Table 2. Clinical characteristics of Lemierre syndrome
(IJV = internal jugular vein. From: Chirinos JA, et al: Medicine, 2002, Vol. 81:458-465)
It is important to recognize the signs and symptoms of LS since early treatment greatly decreases the incidence of complications and death. As noted above, F. necrophorum has been traditionally susceptible to penicllin and clindamycin. Treatment failures with penicillin have been reported, postulated to result from beta-lactamase production. The reported mortality rate of LS is 15% with a 23-50% morbidity.
In our patient, pharyngitis was followed by periapical teeth and sublingual space abscesses. Since suppurative jugular vein thrombophlebitis was not present on CT, Lemierre's syndrome was ruled out. The patient was counseled on the importance of good dental hygiene and an appointment was made for follow-up with a dentist.
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Contributed by Nicole Esposito, MD
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