Fusobacteria are non–spore-forming, nonmotile, pleomorphic, gram-negative ( Fig. 193.1 ), obligate anaerobic bacilli that can cause a wide spectrum of human disease ranging from mild pharyngitis to sepsis, and these organisms are most notorious for causing septic thrombophlebitis of the internal jugular vein, commonly referred to as Lemierre syndrome. Fusobacterium infections in children and adolescents often are associated with abscess formation and intracranial complications. F. nucleatum and F. necrophorum subspecies funduliforme are the most common fusobacteria identified in human disease. , , ,

FIGURE 193.1
Gram stain of Fusobacterium nucleatum , magnification ×1000.

From Baron EJ, Peterson LR, Finegold SM [eds]. B ailey and Scott’s Diagnostic Microbiology , 8th ed. St. Louis: Mosby; 1990.

Description Of The Pathogen

The genus Fusobacterium includes 9 disease-causing species that are part of the normal flora of the human oropharynx and the upper respiratory, gastrointestinal, and female genitourinary tracts: F. nucleatum (subspecies nucleatum, polymorphum, vincentii, animalis, fusiforme, and canifelium ), F. necrophorum (subspecies necrophorum and funduliforme ), F. ulcerans, F. gonidiaformans, F. mortiferum, F. naviforme, F. necrogenes, F. russii, and F. varium . , , Because molecular techniques are redefining the taxonomy and role of fusobacteria as commensals and pathogens, this compilation is evolving. ,

Unlike other anaerobes, F. necrophorum produces lipopolysaccharide, which contributes to its intrinsic virulence. , Overall, one third of fusobacterial infections are polymicrobial, and animal studies demonstrated increased virulence of F. necrophorum in the presence of fecal organisms. Additional, less well-characterized virulence factors include production of leukocidins, hemolysins, lipases, DNases, hemagglutinins, and β-lactamases (by F. nucleatum ) and the ability to aggregate platelets ( F. necrophorum ). , , , Molecular thrombophilic predisposition has been identified in children with invasive fusobacteriosis. Whole-genome sequencing of a diverse set of Fusobacterium spp. revealed that actively invading species have larger genomes than passively invading species and possess a complement of genes that have evolved to enable host cell adherence and invasion. A single nucleotide polymorphism in the toll-like receptor 5 gene was found in 1 affected child, a finding suggesting that underlying host factors also may predispose to infection.

Epidemiology

Well recognized in the preantibiotic era, invasive fusobacteriosis was rarely reported after the advent of antibiotic therapy for pharyngitis, and it became a forgotten disease. Since the 1990s, both incidence and disease reporting have been increasing. , The increase in incidence may be the result of decreased empiric use of antibiotics for sore throat, increased use of corticosteroid therapy for mononucleosis or sore throat, superior blood culture methods, improved techniques for diagnosis of anaerobic infections, and use of non–culture-based molecular diagnostic tools. , , , Fewer tonsillectomies also could contribute to the increased incidence. , However, a Swedish study in adolescents and adults found persistent pharyngeal colonization with F. necrophorum despite tonsillectomy (30% versus 16% in pre-tonsillectomy versus post-tonsillectomy throat cultures). Estimates of disease incidence range from 0.8–3.6 cases per million people. , , A prospective study in Denmark demonstrated an incidence of Lemierre disease of 14.4 cases per million people 15–24 years of age. The infection may have a peak in late winter. Boys and men are more commonly afflicted. ,

Three age-related disease patterns are observed for fusobacteriosis ( Table 193.1 ). , , , Localized head and neck disease tends to arise from the middle ear (and, occasionally, cervical lymph nodes) in young children, the throat and tonsil in adolescents, and the sinuses and carious teeth and gums in adults. Similarly, invasive or disseminated fusobacterial infection tends to vary with age. Children tend to develop infection, often associated with otitis media, that can disseminate systemically but more often results in intracranial complications. , , , Otogenic Lemierre disease was reported in patients 2 months to 51 years of age (median, 5 years), whereas pharyngitis-associated Lemierre disease occurred in patients 8 months to 63 years of age (median, 19 years). Other investigators have noted peak ages for Lemierre disease of 16–23 years (median age range, 17–21.5 years). , , In another series of cases in patients ranging in age from 2 months to 78 years, distribution of cases was 51%, 20%, and 8% in the second, third, and first decades of life, respectively. In a prospectively collected series of 391 isolates of F. necrophorum from localized and disseminated infections, 343 isolates had subspeciation performed; >99% were F. necrophorum subspecies funduliforme, and a single isolate was F. necrophorum subspecies necrophorum . ,

TABLE 193.1
Prospectively Collected Series of 388 Cases of Fusobacterium necrophorum Infection
Data from Hagelskjær Kristensen L, Prag J. Lemierre’s syndrome and other disseminated Fusobacterium necrophorum infections in Denmark: a prospective epidemiological and clinical survey. Eur J Clin Microbiol Infect Dis . 2008;27:779–789; and Hagelskjær Kristensen L, Prag J. Localised Fusobacterium necrophorum infections: a prospective laboratory-based Danish study. Eur J Clin Microbiol Infect Dis. 2008;27:733–739.
Classification Source of Infection Number of Cases Age Range (Yr) Median Age (Yr)
Localized disease (n = 288) Otogenic source 7 0–26 4
Cervical lymphadenitis 9 0–46 3
Tonsillitis 26 13–57 20
Peritonsillar abscess 215 4–72 19
Sinus- or teeth-associated source 10 29–73 44
Localized disease caudal to the head and neck 21 9–83 38
Disseminated disease (n = 100) Otogenic Lemierre disease 5 0–16 2
Oropharyngeal-associated Lemierre disease 37 6–66 20
Disseminated disease originating from sinus or teeth 16 7–89 24–55 a
Disseminated disease originating from the gastrointestinal tract 30 5–89 61
Disseminated disease originating from the genitourinary tract 6 25–96 78
Disseminated disease originating from an unknown focus 6 66–87 76

a Group subdivided with 2 medians reported in Hagelskjær Kristensen L, Prag J. Lemierre’s syndrome and other disseminated Fusobacterium necrophorum infections in Denmark: a prospective epidemiological and clinical survey. Eur J Clin Microbiol Infect Dis . 2008;27:779–789.

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