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Fatal sepsis due to a beta-lactamase-producing strain of Fusobacterium nucleatum subspecies polymorphum.

A patient with Waldenström's macroglobulinemia was treated empirically with imipenem for sepsis related to oropharyngeal infection and responded within 24 hours. When blood cultures yielded Streptococcus agalactiae, the regimen was changed to ampicillin and gentamicin. The patient's condition rapidly deteriorated, and she died 3 days later. After her death, a strain of Fusobacterium nucleatum subspecies polymorphum producing beta-lactamase (PEN-Y; group 2a) was isolated from blood cultures. A literature review revealed increasingly frequent isolation of beta-lactamase-producing strains of F. nucleatum. Thus strains of F. nucleatum isolated from blood and other specimens from patients with serious infections should be tested for beta-lactamase production.

Fatal Outcome↗

Synergistic effect of bacteroides, Clostridium, Fusobacterium, anaerobic cocci, and aerobic bacteria on mortality and induction of subcutaneous abscesses in mice.

The potential for synergy between aerobic, facultative, and anaerobic bacteria was studied by subcutaneous inoculation of mixtures of these organisms into mice and observation of subsequent mortality and abscess formation. The anaerobic bacteria tested included 12 strains of gram-positive cocci and two strains each of Bacteroides species, Clostridium species, and Fusobacterium species. The facultative and aerobic bacteria included one strain each of Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis. Mortality increased significantly when each aerobic organism was inoculated along with either of the Bacteroides species. A similar increase occurred when the anaerobic gram-positive cocci were inoculated along with P. aeruginosa (four of six combinations) or S. aureus (four of six). The rate of abscess induction increased significantly when 10 of the 12 strains of anaerobic gram-positive cocci were injected along with B. fragilis and when nine of these strains were inoculated along with Bacteroides asaccharolyticus . The results demonstrate synergistic potential between Bacteroides species and all aerobic bacteria tested, between Bacteroides species and most anaerobic gram-positive cocci, and between most anaerobic gram-positive cocci and P. aeruginosa or S. aureus.

Abscess↗

Comparison of the effectiveness of bacterial culture, 16S rDNA directed polymerase chain reaction, and checkerboard DNA-dNA hybridization for detection of Fusobacterium nucleatum in endodontic infections.

Fusobacterium nucleatum is a Gram-negative, non-spore-forming, nonmotile, obligatory anaerobic rod that is normally isolated from the oral cavity. Epidemiological studies have shown that this species is one of the most prevalent in primary root canal infections. The purpose of this study was to compare the effectiveness of bacteriological culture, 16S rDNA directed polymerase chain reaction and checkerboard DNA-DNA hybridization for detection of F. nucleatum strains in infected teeth associated with periradicular lesions. Thirteen single-root teeth from adult patients, all having carious lesions, necrotic pulps, and radiographic evidence of periradicular bone loss were included in this study. Combining all methods, the results indicated that F. nucleatum was present in approximately 31% (4 of 13) of the specimens. Incidence of F. nucleatum in root canal infections, as evaluated in this study by polymerase chain reaction, culture, and DNA-DNA hybridization, was 15.4%, 15.4%, and 10.0%, respectively. Our data demonstrated that no method used herein could be considered superior for detecting F. nucleatum directly from clinical samples. However, the small number of samples examined and the low prevalence that was observed should be considered.

Adult↗

Fusobacterium osteomyelitis in a child with sickle cell disease.

Children who have sickle cell disease are at increased risk for osteomyelitis caused by Salmonella spp. and Staphylococcus aureus. We report a case of anaerobic osteomyelitis caused by Fusobacterium nucleatum in a child with sickle cell disease. The infection did not resolve with antibiotic therapy alone, but was cured after surgical debridement and hyperbaric oxygen therapy.

Anemia, Sickle Cell↗

Fusobacterium necrophorum septicemia without a primary focus.

We have presented a case of Fusobacterium necrophorum septicemia, an uncommon infection whose early course may be typified by vague diffuse symptoms or a seemingly benign upper respiratory tract inflammation mimicking acute viral syndromes or viral pharyngitis. The septicemia is most commonly, but not always preceded by an obvious oropharyngeal focus.

Adolescent↗

Fusobacterium necrophorum sepsis with cerebral infarction.

We have described the case of a 23-month-old female child in whom Fusobacterium sepsis progressed to cerebral infarction despite therapy with intravenous chloramphenicol and ampicillin. Some clinical improvement was noted upon addition of metronidazole to the treatment regimen. The child survived, but has severe neurologic sequelae. Physicians should suspect anaerobic infection in children who have signs of severe neurologic infection and in whom cultures are negative for aerobes. In selected cases, early treatment with metronidazole may be helpful.

Cerebral Infarction↗

Mesenteric adenitis and portal vein thrombosis due to Fusobacterium nucleatum.

We report the first description of portal and mesenteric vein thrombosis associated with suppurative mesenteric adenitis in a 71-year-old woman. The bacterium detected in mesenteric lymph nodes was Fusobacterium nucleatum, an anaerobic Gram-negative bacillus. Our patient had a clinical syndrome of pharyngitis and fever preceding portal vein thrombosis. Abdominal symptoms improved with antibiotics and anticoagulant therapy. This location of F. nucleatum in mesenteric lymph nodes provides an interesting insight into the occurrence of septic thrombosis in the portal vein following pharyngo-tonsillar infection.

Aged↗

Septic arthritis secondary to fusobacterium necrophorum in a 4-year-old girl: case report and review of the literature.

We report an unusual case of septic arthritis in a 4-year-old child caused by Fusobacterium necrophorum. In spite of aggressive parenteral antibiotic therapy with ampicillin-sulbactam after surgical drainage, disease recurred, requiring additional arthrotomies. The infection was eventually eradicated with parenteral meropenem and clindamycin, and additional surgical drainage.

Ampicillin↗

Robot-Assisted Stereotactic Aspiration of a Parietal Brain Abscess With Metagenomic Identification of Fusobacterium nucleatum.

Robot-assisted stereotactic aspiration offers a minimally invasive approach to brain abscesses near the eloquent cortex. We report a rare case of a left parietal abscess caused by Fusobacterium nucleatum in an immunocompetent adult, managed successfully with this approach. The patient, a 52-year-old man, presented with right-sided limb numbness. MRI and contrast-enhanced CT revealed a cystic, ring-enhancing lesion with diffusion restriction in the left parietal lobe. Despite empiric broad-spectrum antibiotics, neurological deterioration occurred due to progressive mass effect. Robot-assisted stereotactic aspiration enabled single-stage, precise drainage of the abscess. Metagenomic next-generation sequencing identified F. nucleatum , prompting adjustment of antibiotics to ceftriaxone plus metronidazole, followed by metronidazole monotherapy. The patient improved clinically, and a 6-month MRI confirmed complete resolution, underscoring the precision of robotic stereotaxy for eloquent-region abscesses and highlighting the diagnostic value of metagenomic sequencing in detecting anaerobic pathogens.

Humans↗

Fusobacterium necrophorum infections in England and Wales 1990-2000.

In response to a marked increase in both the number of Fusobacterium necrophorum bacteraemia reports to the PHLS Communicable Disease Surveillance Centre and the number of F. necrophorum isolates referred to the PHLS Anaerobe Reference Unit in 1999, the data from both sources on F. necrophorum infections were reviewed for the decade 1990-2000. There were 208 reports of F. necrophorum bacteraemia (average 19/year; range 14-34/year) with a peak in incidence in the late winter months; 68% were from male patients and the peak age range was 16-23 years. Of 205 referred isolates of F. necrophorum, 122 (59%) were from blood cultures and these represented 58% of the bacteraemia reports; the others were from brain and soft tissue abscesses, pleural and joint fluids, eyes, ears and lymphatic tissue. The average number of referrals was 19/year (range 9-37/year). The peak year for bacteraemia reports (34) and isolate referrals (37) was 1999; this increase was not sustained in 2000. All isolates were susceptible to metronidazole, but 2% were resistant to penicillin and 15% to erythromycin. F. necrophorum continues to be a regular but uncommon cause of bacteraemia and metastatic abscesses following an acute sore throat, especially in young, otherwise healthy adults.

Abscess↗

Cytotoxicity of Fusobacterium ulcerans.

A new species of Fusobacterium, F. ulcerans, was isolated from 46 tropical ulcers. All the isolates had shown identical soluble cell protein patterns on polyacrylamide gel electrophoresis although there were two morphological types with slightly different biochemical properties. A representative strain of each of the two groups was selected for in- vitro cytotoxicity testing on a range of tissue-culture cell lines. Both strains of F. ulcerans induced a marked cytotoxic effect on Vero and Int-407 cells. This effect may contribute to the pathogenesis of tropical ulcers.

Animals↗

A comparative study of Fusobacterium necrophorum strains from human and animal sources by phenotypic reactions, pyrolysis mass spectrometry and SDS-PAGE.

Fusobacterium necrophorum strains from human infection (21) were compared with strains from animals (17 biotype A, 2 biotype AB, 4 biotype B, 1 biotype unknown), and the type strain NCTC 10575 in conventional tests reaction patterns (CTRPs), SDS-PAGE and pyrolysis mass spectrometry (PMS). Classifications from the three approaches showed one major consensus group comprising all human strains, and another comprising animal biotype A strains. Animal biotype B strains and one animal strain, designated with some doubt to biotype A, were outliers of the consensus 'human strain' group. Again, animal biotype AB strains were outliers of the consensus 'animal biotype A group', as was the type strain, which was clearly atypical in conventional tests and PMS. Colonial and microscopic characters showed good discrimination between the major consensus groups. However, only haemagglutination and the API-ZYM leucine arylamidase of the biochemical tests discriminated well between these groups. The 'animal biotype A group' clearly corresponds to F. necrophorum subsp. necrophorum, but synonymy of F. necrophorum subsp. funduliforme with the group of human strains was less certain. The latter subspecies was described solely on the basis of animal strains, all of biotype B, but each of four animal biotype B strains in this study was an outlier of the 'human strain group' in one or more of the characterisation approaches. Strains of F. necrophorum causing human infection were clearly distinct from the biotype A strains commonly found in animal infection. This has implications for the validity of animal models of human necrobacillosis. In view of these differences, it would be useful to have a validated designation for strains causing human infection. However, it would be premature to assume that the definition of F. necrophorum subsp. funduliforme encompasses the human strains in the absence of confirmatory DNA-homology and 16S rRNA-sequencing studies.

Animals↗

Phenotypic characteristics and lipopolysaccharides of human and animal isolates of Fusobacterium necrophorum.

As part of a collaborative study, six culture collection isolates and 50 coded isolates of Fusobacterium necrophorum were examined for the types of lipopolysaccharides (LPS) they contained, and to see if this related to their reactions in a range of phenotypic tests and their susceptibility to a panel of six antimicrobial compounds. The biotype B type strain, putative biotype B isolates and human isolates were predominantly coccobacillary, had rough type LPS and some of these isolates (8 of 26) required incubation for > 2 days to demonstrate lipase activity. The biotype A type strain, putative biotype AB isolates and most putative biotype A isolates (16 of 18) were predominantly rod-shaped, had either smooth LPS or low M(r) rough type LPS and all demonstrated lipase activity within 2 days. The other two putative biotype A isolates were coccobacillary and had rough type LPS, and one of these required incubation for > 2 days to demonstrate lipase activity. The results of these latter two isolates more closely resembled biotype B. A few isolates were asaccharolytic, but most fermented one or more of glucose, fructose, maltose and galactose. There was no correlation between fermentation pattern and LPS type, biotype or source of isolate (animal or human) but, with the exception of two abberant isolates, there was good correlation between cellular morphology, type of growth in liquid media and LPS type.

Animals↗

Classification of human and animal strains of Fusobacterium necrophorum by their pathogenic effects in mice.

Forty-six strains of Fusobacterium necrophorum, 24 from animals and 22 of human origin, were examined by pathogenicity tests in mice, while the same strains were being examined in laboratories elsewhere by other methods. The pathogenicity tests consisted of (1) subcutaneous inoculation with a large dose of a pure culture, (2) subcutaneous inoculation with a small dose of F. necrophorum mixed with a large but relatively harmless dose of Staphylococcus aureus, and (3) intravenous inoculation with a large dose of a pure culture. Fourteen strains, all of animal origin, showed the characteristic behaviour of biotype A. Twenty-eight strains, 10 of animal origin and 18 from man, were classified as biotype B. The remaining four strains, all from man, produced a distinct type of infection in mice; these strains were referred to as 'A2433-like' because of their resemblance to a strain described in an earlier study. It would appear that biotype A strains, responsible for classical necrobacillosis in animals, do not infect man; that biotype B strains occur in both man and animals; and that 'A2433-like' strains are probably confined to man.

Animals↗

Clonal similarity of salivary and nasopharyngeal Fusobacterium nucleatum in infants with acute otitis media experience.

The environment of an infant's nasopharynx during acute otitis media (AOM) favours the growth of anaerobic bacteria, which can be recovered frequently during infection, but hardly at all if the infant is healthy. The aim of this investigation was to identify the potential source and inoculation route of anaerobes that were present in the nasopharynx. Eleven Fusobacterium nucleatum isolates that were collected through the nasal cavity from the nasopharynx of eight infants with a history of AOM, and 161 F. nucleatum isolates from the saliva of the same infants, were typed to the clonal level by using arbitrarily primed PCR (AP-PCR). In five of the eight infants examined, identical AP-PCR types were found among nasopharyngeal and salivary isolates. As anaerobes seem to be present only transiently in the nasopharynx and salivary contamination of the nasopharyngeal samples can be excluded, this observation indicates that the source of nasopharyngeal anaerobes is the oral cavity and that saliva is their transmission vehicle.

Acute Disease↗

Fusobacterium necrophorum infection associated with portal vein thrombosis.

This report describes a patient without obvious upper respiratory tract or gastrointestinal infection who developed portal vein thrombosis secondary to Fusobacterium necrophorum septicaemia. The patient responded well to systemic antibiotic therapy. The implications of F. necrophorum infection caudal to the head are discussed.

Anti-Bacterial Agents↗

Abscess forming ability of streptococcus milleri group: synergistic effect with Fusobacterium nucleatum.

The abscess forming abilities of "Streptococcus milleri" strains (Streptococcus constellatus, Streptococcus anginiosus, and Streptococcus intermedius) isolated from dentoalveolar abscesses and the synergistic effect of Fusobacterium nucleatum co-inoculated with the isolates were examined on a mouse subcutaneous abscess model. Five days after inoculation, all S. milleri strains formed abscesses, which showed less pathological spread to surrounding connective tissues than those formed by Staphylococcus aureus 209P strain and were similar to those by F. nucleatum ATCC25586. When each S. milleri strain and F. nucleatum were co-inoculated, abscess sizes and each bacterial number recovered from abscesses increased in comparison to those treated by bacterial mono-inoculation of each S. milleri strain or F. nucleatum alone. The strongest synergistic effect was observed in the combination of S. constellatus and F. nucleatum. In a time course experiment with this combination, the recovery of S. constellatus subsequently decreased after the decrement of F. nucleatum, and it appeared that the association with F. nucleatum maintained the bacterial number of S. constellatus in the abscess. The cell-free supernatant of F. nucleatum had a tendency to increase the abscess size caused by S. constellatus in this model. When S. constellatus was cultured with F. nucleatum culture supernatant in vitro, growth enhancement in the early phase was observed. Furthermore, the phagocytic killing of S. constellatus by human polymorphonuclear leukocytes (PMNs) was significantly suppressed and the PMN membranes appeared to be injured by addition of the F. nucleatum culture supernatant. These results suggest that the pathogenicity of S. milleri strains in odontogenic infections may be enhanced by the co-existence of F. nucleatum.

Abscess↗

Nitric oxide production and iNOS mRNA expression in mice induced by repeated stimulation with live Fusobacterium nucleatum.

There have been few studies on the detection of direct nitric oxide (NO) production and interferon-gamma (IFN-gamma) in vivo without using animal cell culture. We questioned whether NO and IFN-gamma could be produced at the site of infection. The peritoneal cavity of mice was used as the local infection model. NO and IFN-gamma in abdominal washings from these mice were measured directly at various times after injection of Fusobacterium nucleatum, a gram-negative rod periodontal pathogen. The mice were divided into three groups: those treated with live bacteria (LB), those treated with heat-killed bacteria (HKB) and those untreated: normal (N). These mice were compared on the basis of cell filtration, NO and IFN-gamma production by injection of live bacteria (LFn) or heat-killed bacteria (HKFn). In the LB group, the total cell number increased corresponding to an increase in neutrophils after injection of both LFn and HKFn. A low level of NO was constantly produced in abdominal washings, but a significant amount of NO was synthesized in the LB group only 12 hr to 24 hr after injection of LFn. At the same time iNOS enzyme activity and iNOS mRNA expression were detected. IFN-gamma, which may contribute to enhance NO production, was also secreted at a high level from peritoneal exudate cells (PEC) at 12 hr and 24 hr in the LB group by stimulation of LFn. At 12 hr and 24 hr, iNOS positive cells in the LB group by infection of LFn were identified and shown to contain mostly macrophages. These findings indicate that live bacteria play important roles in NO production by macrophages. It is suggested that NO may contribute to the inflammatory response during F. nucleatum infection in periodontitis.

Animals↗