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PubMed1982

Infection with Bacteroides fragilis: pathogenesis and immunoprophylaxis in an animal model.

Organisms of the genus Bacterioides represent the major group of obligate anaerobes involved in human infections. Bacteroides usually cause either bacteremia or localized abscesses. Of the numerous species of Bacteroides, Bacteroides fragilis is the single most frequent clinical isolate. B. fragilis and Bacteroides melaninogenicus have chemically incomplete lipopolysaccharides as compared with the lipopolysaccharides (endotoxins) of aerobic bacteria, and the lipopolysaccharides of Bacteroides lack of biologic potency characteristic of endotoxin. This inactivity may account for the very infrequent occurrence of disseminated intravascular coagulation or purpura that can accompany sepsis due to these organisms. Furthermore, strains of B. fragilis have an immunologically common capsular polysaccharide. In an animal model of intraabdominal sepsis, the encapsulated strains caused abscesses when given without other organisms. But abscess formation from unencapsulated strains of Bacteroides generally required the administration of a synergistic aerobe. The abscesses caused by encapsulated strains were shown to be directly attributable to the capsular polysaccharide, which is an important virulence factor of this organism. Antibody against the capsular antigen is protective against bacteremia due to B. fragilis, but T cell mediated immunity is protective against experimental intraabdominal abscesses.

Animals↗
PubMed1978

Carbenicillin for treatment of Bacteroides fragilis infections: why not penicillin G?

Carbenicillin has been advocated for treatment of infections caused by Bacteroides fragilis and other anaerobic bacteria. Wide-scale use of the drug in this setting could result in a substantial increase in carbenicillin-resistant Pseudomonas aeruginosa, an effect that would have serious implications. Thirty-four strains of B. fragilis, one-half from bacteremic infections, were tested in vitro, and penicillin G was found to be twice as active as carbenicillin on an equal weight basis; 94% of the strains were inhibited by 32 microgram of penicillin/ml, a level easily achieved therapeutically. Penicillin killed B. fragilis organisms as rapidly as carbenicillin. In two subjects given equivalent doses (100 mg/kg intravenously) of carbenicillin and aqueous penicillin G, the bactericidal activity of serum against B. fragilis after administration of each drug was the same. Controlled clinical trials of treatment of anaerobic bacterial infections with penicillin G in high dosage, carbenicillin (or closely related ticarcillin), clindamycin, and chloramphenicol should be undertaken. Carbenicillin (and ticarcillin) for the present would seem better reserved for P. aeruginosa infections.

Bacteroides Infections↗
PubMed1983

Detection of a specific bacterial antigen in urine of rats with Bacteroides fragilis infection.

Human intra-abdominal infections frequently yield Bacteroides fragilis and require specific antimicrobial and surgical therapy. Noninvasive immunologic assessment of this organism might allow more optimum therapy. Therefore we raised antisera in goats to Bacteroides fragilis ATCC 23745 and allowed it to react with a solid-phase capsular polysaccharide-protein antigen extracted from the same organism. Preliminary work disclosed that 10 ng/ml antigen could be detected in competition assays in both saline and dialyzed rat urine. Results were manifest by diminution of bound antiglobulin alkaline phosphatase conjugate in an antigen-mediated antibody-inhibition enzyme-linked immunosorbent assay. Rats were then infected intra-abdominally with (1) B. fragilis ATCC 23745; (2) one of eight recent clinical isolates of B. fragilis; or (3) one of nine isolates representative of Enterobacteriaceae. Seventy-two rat urine samples obtained prior to infection disclosed essentially no assay inhibition: 98.3% +/- 10.3 (1 S.D.). Mean values of reagent antibody activity after incubation with urine aliquots from 24 hr samples collected between 24 and 72 hr were (1) strain 23745 (n = 35) 70.9% +/- 2.6 (S.E.); (2) eight isolates of B. fragilis (n = 49) 86.8% +/- 1.9; (3) nine isolates of Enterobacteriaceae (n = 47) 100.9% +/- 1.0; and (4) shams (n = 29) 95.5% +/- 1.55. Ascribing values less than or equal to 77.7% (2 S.D.) as positive, seven of the eight clinical B. fragilis isolates causing infection were detected in at least one 24 hr urine sample (sensitivity = 87% by organism); 12 of 17 infected rats were correctly identified as positive by at least one urine (sensitivity = 70.6% by rat). Specificity, as assessed in the Enterobacteriaceae group, was 89% (by organism) and 94.5% (by rat). Collectively, these results suggest the presence of a potentially specific, soluble antigen excreted in the urine of rats with B. fragilis infection.

Animals↗
PubMedDate not supplied

Surface antigens as virulence factors in infection with Bacteroides fragilis.

Organisms of the genus Bacteroides represent the major group of obligate anaerobes involved in human infections. Bacteroides usually cause either bacteremia or localized abscesses. Of the numerous species of Bacteroides, Bacteroides fragilis is the single most frequent clinical isolate. B. fragilis and Bacteroides melaninogenicus have chemically incomplete lipopolysaccharides as compared with the lipopolysaccharides (endotoxins) of aerobic bacteria, and the lipopolysaccharides of Bacteroides lack the biologic potency characteristic of endotoxin. This inactivity may account for the very infrequent occurrence of disseminated intravascular coagulation or purpura that can accompany sepsis due to these organisms. Furthermore, strains of B. fragilis have an immunologically common capsular polysaccharide. In an animal model of intraabdominal sepsis, the encapsulated strains caused abscesses when given without other organisms, but abscess formation from unencapsulated strains of Bacteroides generally required the administration of a synergistic aerobe. The abscesses caused by encapsulated strains were shown to be directly attributable to the capsular polysaccharide, which is an important virulence factor of this organism. Patients or experimental animals infected with B. fragilis develop antibodies to the capsular polysaccharide, and these antibodies can be detected in a radioactive antigen-binding assay.

Animals↗
PubMed1987

Role of anaerobic beta-lactamase-producing bacteria in upper respiratory tract infections.

Bacteroides sp. (Bacteroides melaninogenicus, Bacteroides oralis and Bacteroides fragilis), peptostreptococci and Fusobacterium sp. are important pathogens in upper respiratory tract infections. A recent increase in numbers of beta-lactamase-producing strains of anaerobic Gram-negative bacteria in upper respiratory tract infections has been associated with increased failure rates of penicillins in eradication of these infections. These infections include chronic otitis media, chronic sinusitis and mastoiditis, chronic recurrent tonsillitis and lung abscesses. The indirect pathogenicity of these organisms is apparent through their ability not only to survive penicillin therapy but also to protect penicillin-susceptible pathogens from the drug. These direct and indirect virulence characteristics of anaerobic bacteria require the administration of appropriate antimicrobial therapy directed against all pathogens in mixed infections.

Bacteroides↗
PubMed1979

The humoral antibody response to Bacteroides fragilis infections in humans.

The humoral antibody response to Bacteroides fragilis infections in humans, with particular reference to ss. fragilis, was studied using an enzyme immunosorbent assay (EIA). Phenol-water extracted polysaccharide fractions (PS) from B. fragilis ss. fragilis, ss. ovatus, ss. distasonis and ss. vulgatus were used as antigens. Antibody titer determinations were done on sera collected from 57 patients where B. fragilis had been cultured and from 50 controls. In patients with septicemia caused by B. fragilis ss. fragilis a significant titer increase (greater than or equal to doubling) against PS from strain 9343 was seen during the course of the illness. In sera from patients with appendicitis, and where B. fragilis was isolated from the appendix, a titer increase against B. fragilis ss. fragilis 9343 was observed for 6 of 17 patients. However, in sera from 9 of the 17 patients a titer increase against B. fragilis ss. ovatus was also seen. No titer increase was observed in sera from most of the patients with salpingitis where B. fragilis had been isolated. In sera from 10 patients with Crohn's disease the median antibody titer against all four B. fragilis antigens was slightly higher than in sera from the controls. The median antibody titer against B. fragilis ss. ovatus was, however, significantly higher. Our experience is that a humoral antibody response against B. fragilis ss. fragilis can be expected in patients where the organism is isolated from blood. In diseases like appendicitis and salpingitis titer increases are less common. When they occur they are not necessarily directed against ss. fragilis only but are as frequent against ss. ovatus. Titer increases against ss. vulgatus and ss. distasonis are also seen. This raises the question if the observed titer increases are a consequence of a specific pathogenic role of B. fragilis in these infections, or if they merely represent the result of an antigenic stimulus as a result of an increased permeability of the mucosal barriers caused by inflammation and/or surgical manipulation.

Antibodies, Bacterial↗
PubMed1976

Use of semisolid agar from initiation of pure Bacteroides fragilis infection in mice.

The development of a pure Bacteroides fragilis infection in mice is described. The infection produces large subcutaneous abscesses at the site of injection which can be observed grossly within 7 days after injection. The infection was initiated by infection of pure cultures grown in semisolid agar medium. Similar infections were also produced with pure cultures of B. distasonis, B. ovatus, B. thetaiotaomicron, and B. vulgatus. However, a distinct deoxyribonucleic acid homology group, formerly classified as B. thetaiotaomicron, did not produce abscesses in any of the mice tested.

Agar↗
PubMed1979

[Bacteriological and clinical studies on metronidazole in Bacteroides fragilis infections (author's transl)].

The antimicrobial activity of 24 Bacteroides fragilis, 13 Bacteroides thetaiotaomicron and 5 Bacteroides vulgatus, all of which were recent clinical isolates, was determined by the agar dilution technique. These three species had similar susceptibility patterns, but the B. thetaiotaomicron strains were generally less susceptible than the B. fragilis strains. Clindamycin was very active against 81% of the Bacteroides strains at 3.1 mcg/ml of less while 21% of the Bacteroides strains had MICs of 100 mcg/ml or above. Metronidazole was active against all Bacteroides strains at 1.6 mcg/ml or less. The patients with decubitus ulcers and B. fragilis septicemia, who responded satisfactorily to the combination of metronidazole and tobramycin, were presented.

Aged↗
PubMed1981

The effect of hyperbaric oxygenation on experimental Bacteroides fragilis infection in the rat liver.

An experimental intra-abdominal model for producing Bacteroides fragilis abscesses in the rat liver was used to evaluate the therapeutic effect of hyperbaric oxygenation (HO) at 3 ATA (atmospheres absolute). Two different experiments were performed. In the first experiment one half of the animals were inoculated with B. fragilis, and the other half were sham-operated. Whether the inoculated or sham-operated animals were given single or repeated HO treatment at 3 ATA for 90 min, the bacteriological pattern was about the same. In the second experiment all the animals were inoculated with B. fragilis; half of the animals were given HO at 3 ATA for 90 min as single or repeated treatments, and the other half acted as controls receiving no HO. Even if the HO treatment was given every day during 21 days, B. fragilis could be recovered in all inoculated animals 22 days after inoculation.

Animals↗
PubMed1983

Relative efficacy and critical interval of antimicrobial agents in experimental infections involving bacteroides fragilis.

Activity of seven antimicrobial agents was examined using a mouse model of a subcutaneous infection that involved Bacteroides fragilis. Untreated mice had encapsulated abscesses with approximately 10(10) bacteria. Pharmacokinetic studies showed that all drugs tested penetrated into abscesses to provide mean peak levels that were 17% to 53% of mean peak serum levels. In vivo efficacy v 15 strains was measured by the reduction in counts of viable organisms when treatment was initiated one hour after challenge. This showed that the most active agents, in order of activity, were metronidazole hydrochloride, clindamycin phosphate, moxalactam disodium, and cefoxitin sodium. A delay in treatment of eight to 120 hours after challenge showed a noticeable reduction in activity, except with metronidazole. It is presumed that bacteria within an abscess are in a stationary growth phase, and this has an important influence on in vivo efficacy.

Abscess↗
PubMed1985

Failure of oral zinc therapy to alleviate Bacteroides nodosus infections in cattle and sheep.

Cattle and sheep with Bacteroides nodosus infection were treated orally with both high (65 mg Zn/kg and 82 mg Zn/kg) and low (1 mg Zn/kg and 8.6 mg Zn/kg) doses of zinc sulphate respectively. The lower dose rates administered weekly for one month, in the case of cattle, or daily for 2 weeks, in the case of sheep, had no effect either on serum zinc levels or the prevalence or severity of infection in treated animals. High dose rates of zinc (approximately 2.5 g Zn per head per day) were required to elevate serum levels above those normally present in both cattle and sheep. Even these dose rates continued daily for about 2 weeks had no beneficial effect on B. nodosus infection in either species.

Administration, Oral↗
PubMed1977

Chemotherapy of an experimental Bacteroides fragilis infection in mice.

The efficacies of five common antimicrobial agents were determined for a pure Bacteroides fragilis infection in mice. Therapy was begun 4 h after bacterial injection and given every 8 h thereafter for 5 days. Blood levels were determined over an 8-h period for each concentration of antibiotic tested. Clindamycin and tetracycline were the most effective in preventing the formation of abscesses. Chloramphenicol, penicillin G, and cephalothin were not effective in protecting the mice from infection.

Abscess↗
PubMed1984

Quantification of the effect of anti-anaerobic drugs in experimental Bacteroides fragilis infection in mice.

As a basis for the quantitation of the effect of anti-anaerobic drugs in vivo, an experimental thigh infection in mice was developed in which co-inoculation of Bacteroides fragilis and Escherichia coli is obligatory for proliferation of Bact. fragilis. The inhibitory effect of metronidazole and tinidazole on the proliferation of Bact. fragilis was assessed in this model. Both metronidazole and tinidazole showed a significant dose-effect relationship with respect to the outgrowth of Bact. fragilis but not that of E. coli. The effect of both drugs on Bact. fragilis was similar and at all dosage levels a significant correlation was found between the numbers of Bact. fragilis and E. coli.

Animals↗
PubMed1982

A new model of experimental Bacteroides fragilis infection in mice and rats.

We describe a method, based on Selye's granuloma pouch, for establishing reproducible Bacteroides fragilis infections in both mice and rats starting from rather low inocula. The infected pouches resemble abscesses and phlegmons. This model is promising for studies of antibiotic therapy in that both bacterial kinetics and antibiotic levels can be followed in the exudates.

Animals↗
PubMed1993

In vivo effects of rufloxacin and ciprofloxacin on T-cell subsets and tumor necrosis factor production in mice infected with Bacteroides fragilis.

We investigated the in vivo effects of rufloxacin and ciprofloxacin on T-cell subsets and tumor necrosis factor production in mice infected with Bacteroides fragilis. These quinolones did not alter the helper/suppressor ratio but did modulate the kinetics of tumor necrosis factor production in infected animals. This result correlated with the observed therapeutic efficacies of the quinolones.

Animals↗