Lemierre's syndrome and other disseminated Fusobacterium necrophorum infections in Denmark: a prospective epidemiological and clinical survey.

In a 3-year prospective study, all cases of disseminated Fusobacterium necrophorum infections found in Denmark from 1998 to 2001 were analysed, with the aim of describing the epidemiology and clinical features of the variants of Lemierre's syndrome and disseminated non-head-and-neck-associated F. necrophorum infections. Fifty-eight cases of Lemierre's syndrome were reported in previously healthy persons, with an incidence of 14.4 cases per million per year in youngsters aged 15-24 years old. There was no increase during the study period. Lemierre's syndrome originating from an oropharyngeal infection was seen in 37 youngsters. An otogenic variant of Lemierre's syndrome was seen in 5 children with dissemination to nearby regions, and other variants of Lemierre's syndrome, e.g. from the sinuses and teeth, were seen in 16 adults. Patients often had metastatic infections already on admission and needed prolonged hospitalisation. The overall mortality of Lemierre's syndrome was 9%. Forty-two elderly patients had disseminated F. necrophorum infections originating from foci in lower parts of the body. They frequently had predisposing diseases, e.g. abdominal or urogenital cancers, which contributed to the high mortality of 26%. This study shows that the incidence of Lemierre's syndrome is higher than that previously found and has a characteristic age distribution. Early suspicion of the diagnosis, several weeks of antibiotic therapy, often combined with surgical drainage, is mandatory to lower the mortality. In disseminated non-head-and-neck-associated F. necrophorum infections, underlying cancers must be considered.

Localised Fusobacterium necrophorum infections: a prospective laboratory-based Danish study.

During a 3-year prospective laboratory-based study in Denmark from 1998 to 2001, all patients who were diagnosed with localised Fusobacterium necrophorum infections were registered with the purpose of describing the variety of localised infections caused by F. necrophorum, especially in the head. We found 267 patients, most of them previously healthy, with localised F. necrophorum infections in the head and neck. In children, F. necrophorum caused otitis media and solitary abscess formation in cervical lymphadenitis. In adolescents, F. necrophorum was found in 21% of peritonsillar abscesses. We also found F. necrophorum in young adults with tonsillitis and in middle-aged adults with sinusitis. F. necrophorum was found in substantial amounts and as the only bacterial pathogen in the majority of patients. All 267 patients recovered without sequelae. We found another 21 localised non-head-and-neck-associated F. necrophorum infections, mainly subcutaneous wound infections in adults. This study shows that F. necrophorum causes a variety of localised infections, especially in the head and neck region, with a characteristic age distribution. We recommend that anaerobic culture is performed on swabs from children with recurrent otitis media and adolescents with non-streptococcal group A tonsillitis.

Minimum requirements for a rapid and reliable routine identification and antibiogram of Fusobacterium necrophorum.

Three hundred fifty-seven isolates of Fusobacterium necrophorum from human infections in Denmark were consecutively collected over a 3 year period for the purpose of establishing the minimum requirements for rapid and reliable routine identification of Fusobacterium necrophorum using phenotypic characters. The first 40 isolates were fully characterized by the most common phenotypic tests mentioned in the literature, while the last 317 where identified solely by the established minimum requirements for rapid and reliable routine identification of Fusobacterium necrophorum. All but one isolate were identical in all phenotypic tests. The outlying strain differed in morphology and the ability to agglutinate erythrocytes. On the basis of our findings it should be possible within 3-4 days to identify and differentiate F. necrophorum from other species including other Fusobacterium spp. by the unique but subspecies specific colony morphology, susceptibility to kanamycin and metronidazole, the smell of butyric acid, chartreuse colour fluorescence, and beta-haemolysis on horse blood agar. Three-hundred fifty-six isolates were identified as F. necrophorum subsp. funduliforme while one strain was F. necrophorum subsp. necrophorum. The species and subspecies level was confirmed for the first 40 isolates by real-time PCR. MIC in mg/l was determined for the 40 isolates. MIC(90) was 0.047 for penicillin, 0.047 for clindamycin, 0.25 for metronidazole, 0.38 for cefuroxime, >32 for imipenem, 0.012 for meropenem, and 2 for erythromycin. All 357 isolates were susceptible to penicillin and metronidazole indicating that these antibiotics are still the drugs of choice in antibiotic therapy of F. necrophorum infections, but therapy with clindamycin may be an alternative. Erythromycin should be avoided.

Detection of Fusobacterium necrophorum subsp. funduliforme in tonsillitis in young adults by real-time PCR.

Throat swabs from 61 patients, aged 18-32 years, with non-streptococcal tonsillitis (NST) and 92 healthy controls were examined for the presence of Fusobacterium necrophorum DNA using a novel TaqMan-based real-time quantitative PCR assay for F. necrophorum subspecies. The assay was based on the gyrB subunit gene, and detected F. necrophorum DNA in 48% of patients with NST and in 21% of controls (p <0.001). F. necrophorum subsp. funduliforme was the only subspecies found in both patients and controls. The load of F. necrophorum DNA on swabs from patients with NST was significantly higher than that on swabs from controls (p <0.001). Furthermore, patients with recurrent NST had a significantly higher load of F. necrophorum DNA compared to patients with acute NST (p 0.04). In addition, 26 patients with tonsillitis and group C streptococci (GCS) had a significantly higher load of F. necrophorum DNA compared to the NST group (p <0.001). It was concluded that F. necrophorum subsp. funduliforme is present in small numbers as part of the normal human throat flora, and that F. necrophorum in large quantities may cause tonsillitis, especially recurrent tonsillitis. In addition, the study suggests that the concomitant presence of GCS may aggravate F. necrophorum tonsillitis.

Human necrobacillosis, with emphasis on Lemierre's syndrome.

Lemierre's syndrome is the classical presentation of human necrobacillosis. It is characterized by a primary infection in the head in a young, previously healthy person who subsequently develops persistent high fever and disseminated metastatic abscesses, frequently including a septic thrombophlebitis of the internal jugular vein. The main pathogen is Fusobacterium necrophorum, an obligate anaerobic, pleomorphic, gram-negative rod. Clinical microbiologists have a key role in alerting clinicians and advising proper antibiotic treatment when the characteristic microscopic morphology of the pleomorphic F. necrophorum is seen in Gram stains from positive anaerobic cultures of blood and pus. Early diagnosis and prolonged appropriate antibiotic treatment with good anaerobic coverage are crucial to reduce morbidity and mortality. F. necrophorum also causes human necrobacillosis with foci caudal to the head, mainly in elderly patients with high mortality related to age and predisposing diseases, such as cancers of the primary focus.