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Fusobacterial brain abscess: a review of five cases and an analysis of possible pathogenesis.

OBJECT: The cases of five patients with fusobacterial brain abscess are presented. The authors discuss their attempt to determine the pathogenesis. METHODS: The clinical and microbiological features of five cases of fusobacterial brain abscess are reviewed. Isolates of 2031 Fusobacterium spp. and other anaerobes collected (1989-2002) at our institution were analyzed and compared for incidences and isolation sources. The findings were correlated with extensive literature on the subject. The five patients were men between 45 and 74 years of age. All experienced an insidious onset of the disease and probable hematogenous seeding of the organism(s). One patient had a monomicrobic Fusobacterium necrophorum abscess, whereas the others had polymicrobic F. nucleatum abscesses. Despite surgery and a regimen of antibiotic medications and dexamethasone, three patients experienced a paradoxical deterioration 3 days postoperatively that necessitated reevacuation of the lesion. The evacuants observed at that time contained numerous leukocytes but no microorganisms, suggesting intensified inflammation as the likely cause of deterioration. This explanation is supported by literature that fusobacteria strongly activate neutrophils. An analysis of the 2031 anaerobes from blood, wounds, and abscesses showed the considerable virulence of Fusobacterium spp., which were able to enter and/or sustain themselves in the blood circulation. This pattern was similar to that of Clostridium spp., but different from those of Peptostreptococcus spp., Bacteroides spp., and Prevotella spp., which were less invasive but more abundant. CONCLUSIONS: Some fusobacterial brain abscesses may be associated with a paradoxical postoperative deterioration, which is probably due to intensified inflammation following treatment. The blood-borne dissemination and invasive behavior of fusobacteria likely initiate such a brain abscess, and further seeding of other synergic bacteria leads to a polymicrobic abscess.

Aged↗

[Influence of the oral administration of indigenous microorganisms on the resistance of mice to Salmonella infection].

The influence of the oral administration of killed bifidobacteria, lactobacteria, bacteroids and fusobacteria on the anti- Salmonella resistance of mice, infected orally with S. dublin, was studied. Bifidobacteria and lactobacteria were shown to produce a dose-dependent immunostimulating effect. The oral administration of killed bifidobacteria and lactobacteria led to the enhanced resistance of mice to Salmonella infection. The oral administration of killed bifidobacteria was conductive to the normalization of the intestinal microflora in dysbacteriosis developing in cases of Salmonella infection. Bacteroids and fusobacteria were found to possess no such effect.

Administration, Oral↗

[Diagnosis of anaerobic bacteria in bronchial secretions in pulmonary diseases].

In 50 bronchoscopic examinations the microflora of bronchial secretions has been investigated especially in order to detect anaerobic microbes with the use of the glove-box-method. In 19 patients we found the bronchial secretions steril (particularly carcinomas). Eight patients showed anaerobic gramnegative rods (Bacteroides and Fusobacteria) as predominant germs. Also in eight patients we found a mixed culture consisting in several anaerobic gram-negative rods, anaerobic gram-positive sporeless rods, anaerobic cocci, partly Clostridia and aerobes (carcinomas, pneumonias). A contamination can be excluded. In a series of patients anaerobes must be considered as infectious agent, in abscessed pneumonias particularly Bacteroides and Fusobacteria. Repeatedly an impressive clinical improvement has been established under the treatment by Metronidazol. The evidence of anaerobes especially succeeded in cases with copious mucopurulent or pure purulent secretions. The accumulation of anaerobes in bronchial secretions in alcoholics is evident.

Adult↗

Impact of phenoxymethylpenicillin and clindamycin on microflora in recurrent tonsillitis.

A total of 75 patients with recurrent tonsillitis, between 15 and 44 years of age, were divided into three groups, two of which were treated with antibiotics before surgery. Bacteriological specimens were collected before treatment started and the microflora of the excised tonsils were analyzed. Bacteroides species were found in the tonsils of 83% of the patients, and 50% of these microorganisms were beta-lactamase producers. Other bacteria found were Staphylococcus aureus in 45%, beta-streptococci group A in 4%, and beta-streptococci groups C and G in 24%. Hemophilus species were isolated from 50%, but no strains produced beta-lactamase. Fusobacteria were recovered from 41%; one strain produced beta-lactamase. After administration of phenoxymethylpenicillin in doses of 1 g twice a day for nine days, the beta-streptococci were eliminated, but no change of the amount of S aureus, Hemophilus, Bacteroides, or fusobacteria was seen. Clindamycin in doses of 0.15 g four times daily for nine days diminished almost all bacteria except for the Hemophilus species.

Adolescent↗

[Etiology of perioral dermatitis].

The studies of Röckl und Schubert supported the theory that fusobacteria are often found in perioral dermatitis. When we characterize perioral dermatitis as fusobacteriosis, we do not have any doubt that fluorinated corticosteroids represent a very important pathogenetic factor. Corticoids enable opportune fusobacteria to become pathogenic. In our opinion without these bacteria the beginning of the perioral dermatitis seems impossible. Other supporting causes, which are relevant to sex distribution (oral contraceptives, moisturizing creams) are described.

Contraceptives, Oral↗

Metabolism of octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine by Clostridium bifermentans strain HAW-1 and several other H2-producing fermentative anaerobic bacteria.

Several H2-producing fermentative anaerobic bacteria including Clostridium, Klebsiella and Fusobacteria degraded octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) (36 microM) to formaldehyde (HCHO) and nitrous oxide (N2O) with rates ranging from 5 to 190 nmol h(-1)g [dry weight] of cells(-1). Among these strains, C. bifermentans strain HAW-1 grew and transformed HMX rapidly with the detection of the two key intermediates the mononitroso product and methylenedinitramine. Its cellular extract alone did not seem to degrade HMX appreciably, but degraded much faster in the presence of H2, NADH or NADPH. The disappearance of HMX was concurrent with the release of nitrite without the formation of the nitroso derivative(s). Results suggest that two types of enzymes were involved in HMX metabolism: one for denitration and the second for reduction to the nitroso derivative(s).

Anaerobiosis↗

Bacterial colonization during de novo plaque formation.

OBJECTIVE: To determine microbial changes that occur during plaque formation in a dentition free of gingival inflammation. MATERIAL AND METHODS: Ten subjects were recruited. The study included one preparatory period (2 weeks) and a plaque accumulation period (4 days). The volunteers exercised proper tooth cleaning methods, were scaled and received repeated professional mechanical tooth cleaning during the preparatory period. During the plaque accumulation period, the participants abstained from plaque control measures. Plaque was scored on the approximal surfaces of maxillary and mandibular premolars on Days 0, 1, 2 and 4 using a scale from 0 to 5 and according to the criteria of the Quigley and Hein Plaque Index (QHI). Supragingival plaque samples were obtained from the same intervals and surfaces and evaluated using a checkerboard DNA-DNA hybridization technique. RESULTS: The mean QHI increased from 0 to 1.6 (Day 4). The total number of organisms on Day 0 averaged 140 x 10(5) and increased to about 210 x 10(5) after 4 days without oral hygiene. The most dominant species on Day 0 were members of the genus Actinomyces. These organisms comprised almost 50% of the microbiota evaluated. None of the Actinomyces species increased significantly during the 4 days. Some Streptococcus species increased significantly over time as well as species of the genera Capnocytophaga, Campylobacter, Fusobacteria and Actinomyces actinomycetemcomitans. CONCLUSION: In the present investigation, the preparatory phase established a situation with minimal gingival inflammation and close to zero amounts of dental plaque. The Day 0 plaque samples exhibited high proportions of Actinomyces species. During the 4 days of no oral hygiene, there was a small increase in total numbers of organisms as well as a modest increase in the proportion of "disease-associated" taxa such as species of the "orange complex" species.

Actinomyces↗

Bacterial alpha2-macroglobulins: colonization factors acquired by horizontal gene transfer from the metazoan genome?

BACKGROUND: Invasive bacteria are known to have captured and adapted eukaryotic host genes. They also readily acquire colonizing genes from other bacteria by horizontal gene transfer. Closely related species such as Helicobacter pylori and Helicobacter hepaticus, which exploit different host tissues, share almost none of their colonization genes. The protease inhibitor alpha2-macroglobulin provides a major metazoan defense against invasive bacteria, trapping attacking proteases required by parasites for successful invasion. RESULTS: Database searches with metazoan alpha2-macroglobulin sequences revealed homologous sequences in bacterial proteomes. The bacterial alpha2-macroglobulin phylogenetic distribution is patchy and violates the vertical descent model. Bacterial alpha2-macroglobulin genes are found in diverse clades, including purple bacteria (proteobacteria), fusobacteria, spirochetes, bacteroidetes, deinococcids, cyanobacteria, planctomycetes and thermotogae. Most bacterial species with bacterial alpha2-macroglobulin genes exploit higher eukaryotes (multicellular plants and animals) as hosts. Both pathogenically invasive and saprophytically colonizing species possess bacterial alpha2-macroglobulins, indicating that bacterial alpha2-macroglobulin is a colonization rather than a virulence factor. CONCLUSIONS: Metazoan alpha2-macroglobulins inhibit proteases of pathogens. The bacterial homologs may function in reverse to block host antimicrobial defenses. Alpha2-macroglobulin was probably acquired one or more times from metazoan hosts and has then spread widely through other colonizing bacterial species by more than 10 independent horizontal gene transfers. yfhM-like bacterial alpha2-macroglobulin genes are often found tightly linked with pbpC, encoding an atypical peptidoglycan transglycosylase, PBP1C, that does not function in vegetative peptidoglycan synthesis. We suggest that YfhM and PBP1C are coupled together as a periplasmic defense and repair system. Bacterial alpha2-macroglobulins might provide useful targets for enhancing vaccine efficacy in combating infections.

Alphaproteobacteria↗

[Microecological aspects of small intestinal bacterial overgrowth syndrome].

Small intestinal bacterial overgrowth syndrome (SIBOS) means chronic recurrent diarrhea with malabsorption, intoxication and increased risk of endogenous infection. This syndrome are accompanied by increase of overall bacterial burden in biotope >10(5) CFU/ml in adults and >10(4) CFU/ml in children, emergence of different species of enterobacteria, bacteroides, clostridia and fusobacteria et al. in small intestine. Such characteristics of the syndrome allow to consider it as syndrome of disturbances of intestinal microflora (dysbacteriosis). Microecological changes are accompanied by B12 vitamin deficiency anemia, hypovitaminosis, protein deficiency, translocation of bacteria and their toxins from intestine in blood, emergence of endotoxinemia and possible generalization of infection. SIBOS is diagnosed by concentration of hydrogen in expiratory flow (lactulosa load test) or by bacteriological study of aspirate from proximal part of small intestine. Complex treatment includes containing lacto- and bifidobacteria probiotics and, in more severe cases, antimicrobial agents (vancomycine, metronidazole, aminoglycosides, amoxicillin clavulanate, tetracycline, and cephalosporines of 2nd generation) with following correction of disturbed microbiocenosis by different probiotics.

Adult↗

The behaviour of Fusobacterium nucleatum chemostat-grown in glucose- and amino acid-based chemically defined media.

Fusobacterium nucleatum is a Gram-negative anaerobe, found in a number of different areas of human and animal bodies as part of the resident microbiota. However, it also appears to be involved in polymicrobial infections in such sites. It occurs in the oral cavity where it is a prominent member of various bacterial consortia associated with periodontal diseases. Like most fusobacteria, it derives energy via the fermentation of amino acids which it can obtain through the dissimilation of small peptides. However, the role of simple carbohydrates, such as glucose, in its growth and metabolism are not well understood. Accordingly, the aim of the present study was to study the behaviour ofF. nucleatum grown anaerobically in continuous culture in two different chemically-defined media (CDM); one containing only amino acids as the energy source, the other containing glucose as the predominant energy provider. At various dilution rates the culture were assayed for dry weight, intracellular polyglucose (IP) content, residual amino acids and glucose and acidic metabolic end-products. In the carbohydrate-free CDM the acidic end-products were a constant acetate : butyrate : formate of 1.5 : 1 : 0.4. The values of Y(max)amino acids, maximum yield of bacteria per mol of amino acids consumed, for two strains were estimated to be 15.2 and 18.6 g dry wt/mol, respectively. Them(amino acids), maintenance energy requirement for growth on amino acids, for the two strains was 0.81 and 0.94 mmol/g dry wt/h, respectively. Growth of one strain in the glucose-based CDM gave an estimated Y(max)glucose of 67.2 and an m(glucose) of 0.38; the acidic end-products were a fairly constant acetate : butyrate : formate : lactate of 0.7 : 1 : 0.3 : 2.5. Only at low growth rates, and then only in small amount, was IP produced in this medium. Overall, it was concluded that the occurrence of F. nucleatum in widely-differing oral niches may be explained, at least in part, by its metabolic versatility.

Journal Article↗

Critical issues in bacterial phylogeny.

To understand bacterial phylogeny, it is essential that the following two critical issues be resolved: (i) development of well-defined (molecular) criteria for identifying the main groups within Bacteria, and (ii) to understand how the different main groups are related to each other and how they branched off from a common ancestor. These issues are not resolved at present. We have recently described a new approach, based on shared conserved inserts and deletions (indels or signature sequences) found in various proteins, that provides a reliable means for understanding these issues. A large number of conserved indels that are shared by different groups of bacteria have been identified. Using these indels, and based simply on their presence or absence, all of the main groups within Bacteria can be defined in clear molecular terms and new species could be assigned to them with minimal ambiguity. The analysis of these indels also permits one to logically deduce that the various main bacterial groups have branched off from a common ancestor in the following order: Low G+C Gram-positive ==> High G+C Gram-positive ==> Clostridium-Fusobacteria-Thermotoga ==> Deinococcus-Thermus-Green nonsulfur bacteria ==> Cyanobacteria ==> Spirochetes ==> Chlamydia-Cytophaga-Bacteroides-Green sulfur bacteria ==> Aquifex ==> Proteobacteria 1 (epsilon and delta) ==> Proteobacteria-2. (alpha) ==> Proteobacteria-3 (beta) and ==> Proteobacteria-4 (gamma). The validity of this approach was tested using sequence data from bacterial genomes. By making use of 18 conserved indels, species from all 60 completed bacterial genomes were assigned to different groups. The observed distribution of these indels in different species was then compared with that predicted by the model. Of the 936 observations concerning the placement of these indels in various species, all except one were in accordance with the model. The placement of bacteria into different groups using this approach also showed excellent correlation with the 16S rRNA phylogenies with nearly all of the species assigned to the same groups by both methods. These results provide strong evidence that the genes containing these indels have not been affected by factors such as lateral gene transfers. However, such events are readily detected by this means and some examples are provided. The approach described here thus provides a reliable and internally consistent means for understanding various critical and long outstanding issues in bacterial phylogeny.

Amino Acid Sequence↗

The effect of piperacillin prophylaxis on the colonic microflora In patients undergoing colorectal surgery.

Piperacillin was given parenterally in doses of 4 g every 8 h for two days to 20 patients undergoing colorectal surgery. A series of serum and fecal specimens were taken to analyse piperacillin concentrations. Tissue samples from the gut wall were taken during surgery. The maximum serum concentrations during surgery were reached 15 min after piperacillin administration. On Day 0 the mean half-life was 1.9 h and the mean area under the serum concentration curve was 536.8 mg/l. The piperacillin concentrations in the tissue samples ranged from 4.2 to 103.5 mg/kg. The tissue/serum ratio was 0.45. The piperacillin concentrations in the fecal samples ranged from not detectable to 101.2 mg/kg. Fecal samples were also collected during the investigation period for the cultivation of aerobic and anaerobic bacteria. Of the aerobic bacteria, enterococci, streptococci and enterobacteria decreased in on fourth of the patients during the prophylaxis period. Anaerobic bacteria, e. g. cocci, gram-positive rods, fusobacteria and bacteroides, decreased in two thirds of the patients during the same period. After the piperacillin administration period, the aerobic and anaerobic colon microflora returned to the pre-treatment pattern in most patients. Postoperative infections due to Escherichia coli, Morganella morganii, Bacteroides fragilis, peptococci and peptostreptococci occurred in two patients.

Aged↗

Bacteria, toxins, and the peritoneum.

Intraperitoneal infections are caused by members of the gastrointestinal flora, mainly Escherichia coli, enterococci, Klebsiella, Enterobacter, Proteus, Bacteroides, anaerobic cocci, Clostridia, and Fusobacteria. The Gram-negative aerobic bacteria exert their pathogenic potential mainly through endotoxin which acts by way of mediators, causing systemic septic response and, initially, the local response of the peritoneal cavity. The main virulence factors of anaerobic bacteria are exoenzymes and capsular polysaccharides. Peritoneal infections are truly synergistic infections. The most important synergistic mechanisms are protection against host defense and creation of a suitable environment by one member of the flora for another. Aside from bacteria, certain adjuvant substances, i.e., bile, gastric juice, blood, and necrotic tissue, play a role in the pathogenesis of peritonitis. The peritoneum deals with an infection in 3 ways: first, the direct absorption of bacteria into the lymphatics via the stoma of the diaphragmatic peritoneum; second, the local destruction of bacteria through phagocytosis by either resident macrophages or polymorphonuclear granulocytes attracted to the peritoneal cavity; and third, the localization of the infection in the form of an abscess.

Bacteria, Aerobic↗

Comparative in vitro activity of the new oral penem ALP-201 against aerobic and anaerobic bacteria.

The in vitro activity of the new penem derivative ALP-201 against 226 aerobic and 350 anaerobic clinical bacterial isolates was determined using agar dilution techniques. For comparison amoxicillin, cefaclor, ceftazidime, doxycycline, erythromycin, imipenem and trimethoprim/sulfamethoxazole were also tested with aerobic bacteria, and cefoxitin, chloramphenicol, clindamycin, imipenem, metronidazole and piperacillin with anaerobic bacteria. ALP-201 was found to be highly active against Escherichia coli, Klebsiella spp., Enterobacter spp., Haemophilus influenzae, Branhamella catarrhalis, Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, anaerobic cocci, Propioni-bacterium acnes, Clostridium perfringens, Bacteroides fragilis, Bacteroides spp. and fusobacteria. Pseudomonas aeruginosa and Clostridium difficile were resistant to ALP-201. When tested against aerobic bacteria using a high inoculum or using the broth dilution technique, the activity of ALP-201 showed little dependence on inoculum size and the bactericidal activity was similar to the inhibitory activity. Further investigations are warranted with ALP-201, which is absorbed from the gastrointestinal tract after oral administration.

Administration, Oral↗

beta-Lactamase production and susceptibility of US and European anaerobic gram-negative bacilli to beta-lactams and other agents.

The susceptibility of 1,476 US and European strains of anaerobic gram-negative bacilli to amoxicillin, amoxicillin/clavulanate, ticarcillin, ticarcillin/clavulanate, cefoxitin, imipenem and metronidazole was determined. All of the Bacteroides fragilis group and 51% of the non-Bacteroides fragilis group were beta-lactamase positive. Amongst the non-Bacteroides fragilis group, beta-lactamase positivity rates were higher for US strains (58%) than for European strains (39%). All strains were susceptible to imipenem and metronidazole. MIC90s of amoxicillin and ticarcillin for all beta-lactamase negative strains were 0.5 and 2 micrograms/ml, respectively. The addition of clavulanate reduced the MIC90s of amoxicillin (> or = 256 micrograms/ml) and ticarcillin (> or = 64 micrograms/ml) to 16 and 8 micrograms/ml, respectively, for the Bacteroides fragilis group, and to 4 micrograms/ml for both agents for the non-Bacteroides fragilis beta-lactamase producing group. Twenty-nine cefoxitin-resistant strains were found, mainly in the Bacteroides fragilis group, while 95 beta-lactamase producing strains (predominantly Bacteroides fragilis group and fusobacteria) did not show synergy between beta-lactams and clavulanate. Of the newe agents tested, meropenem and piperacillin-tazobactam were the most active (100% of strains susceptible), followed by amoxicillin-BRL 42715 (99% of strains susceptible); 94 to 98% of the strains were susceptible to cefoperazone-sulbactam, tosufloxacin, temafloxacin and clindamycin. Only 73% of the strains were susceptible to cefotetan, compared to 91% to cefoxitin; 88% of the strains were susceptible to trospectomycin. Overall, all of the beta-lactam/beta-lactamase inhibitor combinations, imipenem, meropenem, cefoxitin, tosufloxacin, temafloxacin and clindamycin had good activity against beta-lactamase producing strains, while all agents tested had good activity against beta-lactamase negative strains.

Anti-Bacterial Agents↗

Susceptibility of anaerobic bacteria to PD 131628.

The in vitro activity of PD 131628 against anaerobic cocci, Propionibacterium acnes, Clostridium perfringens, Clostridium difficile, Bacteroides fragilis, Bacteroides spp. and fusobacteria was determined by the agar dilution method. This activity was compared with that of ciprofloxacin, piperacillin, cefoxitin, imipenem, clindamycin, metronidazole and chloramphenicol. PD 131628, imipenem, clindamycin, metronidazole and chloramphenicol were the most active agents tested.

Anti-Infective Agents↗

In vitro activity of the new quinolone BAY y 3118 against anaerobic bacteria.

The in vitro activity of BAY y 3118 against anaerobic cocci, Propionibacterium acnes, Clostridium perfringens, Clostridium difficile, Bacteroides fragilis, other Bacteroides spp. and fusobacteria was determined by an agar dilution method. This activity was compared with that of ciprofloxacin, ofloxacin, piperacillin, cefoxitin, imipenem, clindamycin and metronidazole. BAY y 3118, imipenem, clindamycin and metronidazole were the most active agents tested. The in vitro activity of BAY y 3118 against anaerobic bacteria was superior to that of ciprofloxacin and ofloxacin.

Anti-Bacterial Agents↗

In vitro activity of L-627 against anaerobic bacteria.

The in vitro activity of L-627 against 370 anaerobic bacterial strains including anaerobic cocci, Propionibacterium acnes, Clostridium perfringens, Clostridium difficile, Bacteroides fragilis, other Bacteroides spp. and fusobacteria was determined by the agar dilution method. This activity was compared with that of piperacillin, cefoxitin, imipenem, meropenem, clindamycin, metronidazole and chloramphenicol. L-627, imipenem, meropenem, clindamycin, metronidazole and chloramphenicol were the most active agents tested. L-627 had in vitro activity similar to that of the other carbapenems tested.

Anti-Bacterial Agents↗