JOHNS HOPKINS
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Department of Pathology
600 N. Wolfe Street / Baltimore MD 21287-7093
(410) 955-5077 / FAX (410) 614-8087
Division of Medical Microbiology
Case Presentation
The patient is a 55-year-old man with a history of granulocytic sarcoma diagnosed in 2005
and is admitted for recurrence of the same disease. In 2005, he presented with acute myeloid
leukemia (AML) at multiple locations outside of the bone marrow which included the mandible,
neck, and chest wall. He achieved complete remission after chemotherapy but recently was found
to have thrombocytopenia which prompted a bone marrow biopsy showing recurrent AML. The
patient was then treated again with chemotherapy; however, residual AML continued to persist.
Furthermore, he developed scrotal bleeding and neutropenic fever. The blood culture was drawn
and he was treated with pipercillin/tazobactam, tobramycin, and vancomycin. The blood culture
from the anaerobic bottle grew out Fusobacterium nucleatum.
Organism
Fusobacterium species are gram negative, non-spore forming, and non-motile bacilli.
Although they are anaerobes, they can grow in the presence of up to 6% oxygen. Its name comes
from fusus, a spindle, and bacterion, a small rod; literally, it is a small spindle-shaped rod. The
species name of nucleatum was given due to its nucleated appearance from the light microscope
from their intracellular granules. Most of the bacteria are 5 to 10 m in length with pointed ends.
The production of butyric acid from fermentation of glucose and peptone is unique among its
family of Bacteroidaceae. Fusobacterium species reside in the genitourinary tract, mouth, and
gastrointestinal tract as normal flora.
Clinical Significance
Fusobacterium nucleatum has been strongly associated with periodontal disease. Studies
have shown that Fusobacterium nucleatum is commonly found in patients with periodontal
disease and the formation of plaque. Interestingly, the butyric acid that is produced by this
bacteria inhibits the proliferation of human gingival fibroblast which could contribute to
periodontitis.
In addition, both Fusobacterium nucleatum and Fusobacterium necrophorum can also
cause the Lemierre’s syndrome. This syndrome occurs when an infection of the mouth or throat
creates an abscess. The overgrowth of anaerobes in the abscess then penetrates into the venous
system forming a bacterial thrombus which can disseminate as emboli throughout the body. Most
of the cases of Lemierre’s syndrome are caused by Fusobacterium necrophorum but cases caused
only by Fusobacterium nucleatum have been documented.
Besides the association with oral diseases, severe systemic infections have been found to
be caused by F. nucleatum in patients with neutropenia and mucositis following chemotherapy.
Unfortunately, the exact cause and source of the systemic infection is unknown. In contrast to F.
nucleatum, other Fusobacterium species are found frequently in skin ulcers, animal-bite
infections and abdominal infections.
Laboratory Diagnosis
When colonies are identified on the plates grown under anaerobic conditions, a gram stain
is performed. A long, slender gram negative rod is highly suspicious of Fusobacterium species.
At this point, an API test can be performed which differentiates different bacteria by various
biochemical reactions. In addition, the profile of antibiotic susceptibility can also aide in the
identification of Fusobacterium species. Specifically, among the family of Bacteroidaceae, only
Bilophila and Fusobacterium are resistant to vancomycin (5 g) but sensitive to kanamycin (1000
g) and colistin (10 g). Luckily, it is relatively easy to distinguish Fusobacterium from
Bilophila, since the former is catalase, nitrate and 20% bile salt negative, and indole and lipase
positive, whereas the latter is exactly the opposite (i.e. catalase, nitrate and 20% bile salt positive,
and indole and lipase negative). Fatty acid analysis by gas liquid chromatography or molecular
analysis of the 16S rRNA can also be used to identified Fusobacterium nucleatum. Recent studies
show that rapid identification of Fusobacterium nucleatum and Fusobacterium necrophorum might
be possible by using fluorescence in-situ hybridization (FISH). The FISH analyses rely on
fluorescent labeled rRNA-targeted oligonucleotide probes specific for Fusobacterium nucleatum
and Fusobacterium necrophorum.
Treatment
Management of fusobacterial infections usually begins with a beta-lactam. However, with
the increase of beta-lactamase production in Fusobacterium species including F. nucleatum, F.
mortiferum, and F. varium, the addition of metronidazole or clindamycin is recommended. If an
abscess is present, drainage can help control the infection. Similarly, debridement of devitalized
tissue can also be helpful. In cases of Lemierre’s syndrome or septic thrombophlebitis, heparin can
shorten the course of illness.
REFERENCES:
1. Sigge A, Essig A, Wirths B, Fickweiler K, Kaestner N, Wellinghausen N, Poppert S (2007).
Rapid identification of Fusobacterium nucleatum and Fusobacterium necrophorum by
fluorescence in situ hybridization. Diag Micro Infect Dis 58:255-259.
2. Bolstad AI, Jensen HB, Bakken V (1996). Taxonomy, Biology, and Periodontal Aspects of
Fusobacterium nucleatum. Clinical Microbiology Reviews, 9 (1): 55-71.
3. Duncan MJ (2005). Oral microbiology and genomics. Periodontology 2000 38:63-71.
4. Lemierre A (1936). On certain septicemias due to anaerobic organisms.
Lancet 1:701-3.
5. Fanourgiakis P, Vekemans M, Georgala A, Grenier P, Aoun M (2003) Febrile neutropenia and
Fusobacterium bacteremia: clinical experience with 13 cases. Supp Care Cancer 11(5):332-335.