tetracycline and Fusobacterium-Infections

Previous work has demonstrated that intestinal bacteria, such as Fusobacterium varium (F. varium), contribute to the clinical activity in ulcerative colitis (UC); thus, an antibiotic combination therapy (amoxicillin, tetracycline, and metronidazole (ATM)) against F. varium can induce and maintain UC remission. Therefore, we investigated whether ATM therapy induces a long-term alteration of intestinal microbiota in patients with UC. Patients with UC were enrolled in a multicenter, randomized, double-blind, placebo-controlled study. Biopsy samples at the beginning of the trial and again at 3 months after treatment completion were randomly obtained from 20 patients. The terminal restriction fragment length polymorphism (T-RFLP) in mucosa-associated bacterial components was examined to assess the alteration of the intestinal microbiota. Profile changes of T-RFLP in mucosa-associated bacterial components were found in 10 of 12 patients in the treatment group and in none of 8 in the placebo group. Dice similarity coefficients using the unweighted pair group method with arithmetic averages (Dice-UPGMA) confirmed that the similarity of mucosal microbiota from the descending colon was significantly decreased after the ATM therapy, and this change was maintained for at least 3 months. Moreover, at 3 months after treatment completion, the F. varium/β-actin ratio, examined by real-time PCR using nested PCR products from biopsy samples, was reduced less than 40% in 8 of 12 treated patients, which was higher, but not significantly, than in 4 of 8 patients in the placebo group. Together, these results suggest that ATM therapy induces long-term alterations in the intestinal microbiota of patients with UC, which may be associated, at least in part, with clinical effects of the therapy.

Topics: Actins; Adolescent; Adult; Aged; Amoxicillin; Anti-Bacterial Agents; Colitis, Ulcerative; Double-Blind Method; Drug Therapy, Combination; Female; Fusobacterium; Fusobacterium Infections; Humans; Intestinal Mucosa; Male; Metronidazole; Microbiota; Middle Aged; Tetracycline

Fusobacterium varium may contribute to ulcerative colitis (UC). We conducted a double-blind placebo-controlled multicenter trial to determine whether antibiotic combination therapy induces and/or maintains remission of active UC.. Patients with chronic mild-to-severe relapsing UC were randomly assigned to oral amoxicillin 1500 mg/day, tetracycline 1500 mg/day, and metronidazole 750 mg/day, vs. placebo, for 2 weeks, and then followed up. The primary study end point was clinical response (Mayo score at 3 months after treatment completion) and secondary end points were clinical and endoscopic score improvements at 12 months. Anti-F. varium antibodies were measured by enzyme-linked immunosorbent assay.. Treatment and placebo groups each had 105 subjects. At the primary end point, response rates were significantly greater with antibiotics than with placebo (44.8 vs. 22.8%, P=0.0011). Endoscopic scores significantly improved at 3 months (P=0.002 vs. placebo). Remission rates were 19.0% (antibiotics) vs. 15.8% (placebo) at 3 months (P=0.59). At the secondary end point, response rates were significantly greater with antibiotics than with placebo (49.5 vs. 21.8%, respectively, P<0.0001). Endoscopic scores were significantly improved at 12 months after antibiotic treatment (P=0.002 vs. placebo). Remission rates had improved to 26.7% with antibiotics vs. 14.9% for placebo, at 12 months (P=0.041). F. varium antibody titers decreased in responders but not in nonresponders, and more in the antibiotic than in the placebo group. More pretreatment steroid-dependent UC patients discontinued corticosteroids after treatment completion (6 months: 28.6 vs. 11.8%, respectively, P=0.046; 9 months: 34.7 vs. 13.7%, respectively, P=0.019; and 12 months: 34.7 vs. 13.7%, respectively, P=0.019). These effects were greater in the subanalysis of the active group (Mayo scores of 6-12) than in that of total cases (0-12). No serious drug-related toxicities occurred.. The 2-week triple antibiotic therapy produced improvement, remission, and steroid withdrawal in active UC more effectively than a placebo.

Topics: Administration, Oral; Adrenal Cortex Hormones; Adult; Amoxicillin; Colitis, Ulcerative; Double-Blind Method; Drug Therapy, Combination; Endoscopy, Gastrointestinal; Enzyme-Linked Immunosorbent Assay; Female; Fusobacterium Infections; Humans; Male; Metronidazole; Placebos; Statistics, Nonparametric; Tetracycline; Treatment Outcome

We proposed that Fusobacterium varium is one of the causative agents in ulcerative colitis.. To examine the efficacy of antibiotic combination therapy against F. varium and to investigate the mucosa-associated bacteria before and after the therapy using a new molecular approach.. Twenty patients with ulcerative colitis were randomly assigned into the antibiotic treatment group (amoxicillin, tetracycline and metronidazole for 2 weeks) and no-antibiotics group. Clinical assessment, colonoscopic and histological evaluations were performed at 0 and 3-5 months after the treatment. DNA from mucosal bacteria was isolated from biopsy specimens. We investigated the mucosa-associated bacterial components by terminal restriction fragment length polymorphism with the restriction enzyme HhaI and MspI, and quantified the change in the number of bacteria by real-time polymerase chain reaction. Immunohistochemical detection of F. varium in biopsy specimens was also performed.. After the treatment, the clinical assessment, colonoscopic and histological scores improved in the antibiotic group compared with the control group. Three peaks of terminal restriction fragment length polymorphism decreased after treatment only in the antibiotic group. Eubacterium rectale, Dorea formicigenerans, Clostridium clostridioforme and F. varium were included in these peaks. Based on the real-time polymerase chain reaction study, only F. varium was significantly reduced after treatment. In the immunostaining, post-treatment scores in treatment group were significantly lower than that in control group.. Antibiotics combination therapy was effective for ulcerative colitis. The number of mucosa-associated F. varium significantly decreased after the treatment.

Topics: Amoxicillin; Colitis, Ulcerative; Drug Therapy, Combination; Fusobacterium; Fusobacterium Infections; Humans; Intestinal Mucosa; Metronidazole; Tetracycline

It is proposed that Fusobacterium varium might be one of the elusive pathogenic factors in ulcerative colitis (UC). Our goal was to assess whether an antibiotic combination therapy against F. varium is effective for induction and maintenance of remission of UC.. Twenty chronic, active UC patients with F. varium infection were enrolled consecutively and were randomly assigned to receive amoxicillin, tetracycline or metronidazole per os for 2 weeks (treatment group; n=10), or no antibiotics (control group; n=10). F. varium was sensitive to the antibiotics. Symptom assessment, endoscopic and histological evaluations were performed blind before enrollment at 3-5 months and 12-14 months after the treatment. Serum immunoglobulins to F. varium were measured using an enzyme-linked immunosorbent assay (ELISA). Immunohistochemical detection of F. varium in biopsy specimens was carried out using the avidin-biotin complex method.. The clinical activity, endoscopic and histological scores in the treatment group decreased significantly at 3-5 and 12-14 months after the end of treatment compared with those in the control group (p=0.001-0.036). The remission rate in the treatment group was higher than that in the control group (p=0.037). In addition, the titers of antibody to F. varium and the F. varium density in the mucosa decreased at both the short- and long-term follow-ups in the treatment group (p=0.0002-0.049). No serious drug-related toxicity was observed during the trial.. The 2-week antibiotic combination therapy against F. varium was effective and safe in patients with chronic, active ulcerative colitis in this long-term follow-up study.

Topics: Adolescent; Adult; Amoxicillin; Anti-Bacterial Agents; Colitis, Ulcerative; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; Fusobacterium; Fusobacterium Infections; Humans; Male; Metronidazole; Middle Aged; Probability; Reference Values; Risk Assessment; Severity of Illness Index; Statistics, Nonparametric; Tetracycline; Treatment Outcome

Gram-negative anaerobes belonging to the genera Fusobacterium, Prevotella and Porphyromonas were investigated for the presence of tetQ and ermF, which have been shown to be spread by conjugal elements. One hundred isolates from either sites of infection or various body sites in healthy subjects were studied. PCR was used to detect tetQ, and DNA-DNA hybridization studies on EcoRI chromosomal digests were undertaken to detect the presence of tetQ and ermF. Antibiotic sensitivity assays were performed on selected isolates to detect tetracycline, erythromycin and penicillin resistance. Twenty Fusobacterium isolates lacked tetQ, and were tetracycline sensitive. Twenty per cent of Prevotella spp. isolates both from clinical specimens and from healthy subjects were found to possess tetQ. Of 20 Porphyromonas isolates tested, one (Porphyromonas levii) from a case of bacterial vaginosis was shown to possess tetQ in the chromosome. The presence of tetQ was always associated with tetracycline resistance. Four isolates of Prevotella melaninogenica and one isolate of Prevotella were ermF-positive, although expression of erythromycin resistance was not consistently associated with detection of this gene. Antibiotic resistance phenotypes of Prevotella isolates were shown to be related to specific chromosomal restriction patterns by hybridization studies: tetracycline resistance and tetracycline/erythromycin resistance are conferred by Bacteroides tetracycline-resistant ERL elements, whereas the tetracycline/penicillin resistance phenotype could be due to spread of elements identified in Prevotella only. Tetracycline/erythromycin-resistant and tetracycline/erythromycin/penicillin-resistant P. melaninogenica isolates were found in this study. It appeared that the presence of tetQ and ermF in Bacteroides and Prevotella contributed to the persistence of antibiotic resistance isolates within the host and to potential spread to other organisms through conjugal elements.

Topics: Anti-Bacterial Agents; Bacteroidaceae Infections; Drug Resistance, Microbial; Erythromycin; Fusobacterium; Fusobacterium Infections; Genes, Bacterial; Humans; Microbial Sensitivity Tests; Nucleic Acid Hybridization; Penicillins; Polymerase Chain Reaction; Porphyromonas; Prevotella; Tetracycline; Tetracycline Resistance

A study of the predominant microflora in active sites of noma (cancrum oris) lesions was carried out in eight noma patients 3-15 years of age in Sokoto State in northwestern Nigeria. Paper point sampling and conventional anaerobic microbiologic techniques were used. Fusobacterium necrophorum was recovered from 87.5% of the noma lesions. Oral microorganisms included Prevotella intermedia, alpha-hemolytic streptococci, and Actinomyces spp. which were isolated from 75.0%, 50.0%, and 37.5% of the patients, respectively. Peptostreptococcus micros, Veillonella parvula, Staphylococcus aureus, and Pseudomonas spp. were each recovered from one lesion. The F. necrophorum and P. intermedia isolates were tested for antibiotic sensitivity to clindamycin, tetracycline, metronidazole, and penicillin using the E-test, and all strains were observed to be sensitive to all of the antibiotics tested with the exception of one strain of P. intermedia, which showed resistance to penicillin. The first reported isolation from human noma lesions of F. necrophorum, a pathogen primarily associated with animal diseases, may have important etiologic and animal transmission implications.

Topics: Adolescent; Anti-Bacterial Agents; Bacteroidaceae Infections; Child; Child, Preschool; Clindamycin; Culture Media; Drug Resistance, Microbial; Fusobacterium Infections; Fusobacterium necrophorum; Humans; Metronidazole; Microbial Sensitivity Tests; Nigeria; Noma; Nutrition Disorders; Penicillins; Prevotella intermedia; Tetracycline

Minocycline has demonstrated greater in vitro activity against anaerobic bacteria than its parent compound, tetracycline. In vivo therapeutic efficacy of the two drugs was tested against a mixed anaerobic infection in a mouse model. Fusobacterium necrophorum plus F. nucleatum injected intraperitoneally produced progressive intrahepatic and occasional extrahepatic abscesses, which were measured at autopsy. Three treatment regimens were tested, single daily doses of antibiotic being administered by oral gavage: four doses begun at 2 or 24 h after challenge and 14 doses begun 3 weeks after challenge when abscesses were well developed. Autopsy was not performed until several weeks after completion of treatment to assess long-term effects. Based on the number of mice without lesions, the median effective dose (ED(50)) in milligrams per kilogram per dose for minocycline was significantly lower than that for tetracycline with each regimen tested. With the 2-h (immediate therapy) regimen and the 24-h-delayed therapy regimen, minocycline was 30 and 6 times, respectively, more effective against hepatic abscesses than tetracycline on a weight basis. With each antibiotic, abscesses outside the liver were more resistant to therapy, although again minocycline was more effective. In the treatment of developed abscesses (3-week-delayed regimen), minocycline was effective (ED(50) <16 mg/kg), whereas tetracycline was ineffective (ED(50) >256 mg/kg). Minocycline has demonstrated greater therapeutic efficacy in vivo than tetracycline in this experimental infection, which is similar, in certain aspects, to human anaerobic infection. These data support further evaluation of the clinical usefulness of minocycline.

Topics: Animals; Fusobacterium; Fusobacterium Infections; Fusobacterium necrophorum; Humans; Male; Mice; Minocycline; Species Specificity; Tetracycline; Tetracyclines

Topics: Animals; Animals, Newborn; Anti-Bacterial Agents; Arthritis, Infectious; Cattle; Cattle Diseases; Cystitis; Diarrhea; Escherichia coli Infections; Female; Foot Diseases; Fusobacterium Infections; Liver Abscess; Mastitis, Bovine; Meningitis; Osteomyelitis; Pasteurella Infections; Pneumonia; Respiratory Tract Infections; Salmonella Infections, Animal; Sheep; Sheep Diseases; Streptococcal Infections; Sulfonamides; Tetracycline; Uterine Diseases

An experimental animal model for testing antibiotics in vivo against Fusobacterium (Sphaerophorus) necrophorum has been developed. It incorporates the subcutaneous injection of the bacteria into mice followed by intraperitoneal administration of the antibiotic at 24, 48, 72, and 96 h. Mean effective dose values are based on the number of survivors 21 days after challenge. Tetracycline was the most effective drug tested, with a mean effective dose of 5.0 mg/kg, compared with mean effective dose values of 11.1 for clindamycin, 11.8 for penicillin-G, and 52.9 for lincomycin.

Topics: Animals; Anti-Bacterial Agents; Clindamycin; Disease Models, Animal; Fusobacterium; Fusobacterium Infections; Lincomycin; Male; Mice; Penicillins; Tetracycline

Topics: Animals; Anti-Bacterial Agents; Chlortetracycline; Fusobacterium Infections; Sheep; Sheep Diseases; Tetracycline

Topics: Animals; Fusobacterium Infections; Reindeer; Tetracycline

Topics: Animals; Fusobacterium Infections; Reindeer; Tetracycline

Topics: Animals; Chlortetracycline; Fusobacterium Infections; Sheep; Sheep Diseases; Tetracycline

Topics: Animals; Bacteria; Drug Resistance, Microbial; Fusobacterium Infections; Microbial Sensitivity Tests; Reindeer; Tetracycline

Topics: Animals; Fusobacterium Infections; Reindeer; Tetracycline